Index

What is human organ transplant?

Why need of authority?
Organs transplanted: eyes; heart; liver
http://applications.emro.who.int/emhj/v16/s
upp/16_S_2010_159_166.pdf?ua=1
http://traccc.gmu.edu/wp-content/uploads/2013/06/Pakistans-Kidney-
Bazaar.pdf

http://www.senate.gov.pk/uploads/documents/1363266625_535.pdf

https://books.google.com.pk/books?id=ARnTXJhnl-
sC&pg=PA18&lpg=PA18&dq=pdf+pakistan+human+organ+transplant&s
ource=bl&ots=oH94sodi3S&sig=5SbQq77-
lYDhuIE6_WU1sL2Gbvo&hl=en&sa=X&ved=0ahUKEwj-
jMOBvdrSAhWGuBoKHYL3DO04ChDoAQg_MAE#v=onepage&q=pdf
%20pakistan%20human%20organ%20transplant&f=false

http://pubmedcentralcanada.ca/pmcc/articles/PMC2500247/pdf/391.pdf

http://www.ghgj.org/Living%20Organ%20Transpl.pdf

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http://epress.lib.uts.edu.au/journals/index.php/portal/article/view/1833/25
15

http://apmc.com.pk/Download/APMC/apmc_v9n4/08-Kidney
%20Donation,%20Preference%20and%20Determinants%20in
%20Pakistan.pdf

http://www.sjkdt.org/temp/SaudiJKidneyDisTranspl201154-
1565967_042059.pdf

http://organdonorincentives.org/wordpress/wp-
content/uploads/2010/01/AST-Pakistan.pdf

https://www2.warwick.ac.uk/fac/arts/history/ecc/events/writingrights/work
shopprogramme/readingmaterials/moazam_et_al-selling_kidneys.pdf

http://www.ejmanager.com/mnstemps/155/155-1458018754.pdf

http://www.ghgj.org/Living%20Organ%20Transpl.pdf

http://www.ejmanager.com/mnstemps/155/155-1458018754.pdf

http://ijme.in/wp-content/uploads/2016/11/1987-5.pdf

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https://www.moh.gov.sg/content/moh_web/home/policies-and-
issues/human_organ_transplantacthota/National_Organ_Transplant_Uni
t.html

https://www.google.com.pk/url?
sa=t&rct=j&q=&esrc=s&source=web&cd=2&cad=rja&uact=8&ved=0ahU
KEwikrcaGltrSAhXhCMAKHdnIBVQQFggdMAE&url=http%3A%2F
%2Fwww.prime.edu.pk%2Fpdc%2Farticles%2FOrgan
%2520Transplantation%2520Professor%2520Najibul
%2520Haq.doc&usg=AFQjCNHHXo91_YT3HANwLHWyeD-
Z3y5jow&sig2=cueQTPPu1J7tUT3Bnkc_cA&bvm=bv.149397726,bs.1,d.
d24

http://piler.org.pk/wp-
content/uploads/2017/02/Brief_Baldia_Factory_Fire-_Incident.pdf

http://piler.org.pk/wp-
content/uploads/2017/02/Brief_Baldia_Factory_Fire-_Incident.pdf

https://s3.amazonaws.com/s3.documentcloud.org/documents/2070301/s
tatus-labour-rights-in-pakistan-the-year-2014.pdf

https://www.google.com.pk/url?
sa=t&rct=j&q=&esrc=s&source=web&cd=23&cad=rja&uact=8&ved=0ah
UKEwjG08uUy-7SAhXIqo8KHQNXC_Q4FBAWCCUwAg&url=http%3A
%2F%2Findusvalley.edu.pk%2Flibrary1%2FArch%2FPUF%2520EVENT
%2FVenue%25204%2FDay%25203%2Fsession%252025%2FAkhlaque
%2520Qureshi.ppt&usg=AFQjCNEOQRbKVKmV2t2fO8L7QnEok0t7QQ
&sig2=X_dwpf4Soy_xOjHGk9T_aQ
Page 3 of 87
http://www.ecoi.net/file_upload/1930_1434536558_g1511523.pdf

Page 4 of 87
Baldia factory fire: Rauf Siddiqui gets pre-arrest bail Pakistan Today, December 31, 2016 An
Anti-Terrorism Court-II (ATC-II) on Saturday granted an interim pre-arrest bail to Muttahida
Qaumi Movement-Pakistan (MQM-P) leader and MPA Rauf Siddiqui in Baldia factory inferno
case. After the revelations made by Abdul Rehman alias Bhola, the main suspect in the Baldia
factory fire case, Siddiqui had approached ATC administrative judge to avoid his possible arrest,
but he was directed to approach the trial court. The applicant through his counsel, Shaukat Hayat,
submitted in ATC-II that Bhola in his confession named him for allegedly lodging a case against
the factory owners. Hayat contended that his client was neither nominated in the FIR nor named
in the charge sheets or any joint investigation report, adding that the factory owners had also not
named Siddiqui in the case. The counsel added: Siddiqui is ready to join the investigation, but
he would be arrested as the detained suspect named him during his confession on the basis of
hearsay. After a preliminary hearing, the in-charge judge of ATC-II granted him pre-arrest bail
against a surety bond of Rs 100,000 till January 12, 2017. According to a report, 259 people were
burnt alive when a private factory located in Karachis Baldia area was set ablaze in September
2012

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Karachi Baldia Factory fire case By 31 December 2015, more than three years after the Baldia
factory fire that killed 258 workers, the investigation of the case lingered on. A Joint
Investigation Team (JIT) report, submitted to the Sindh High Court on 7 February 2015, said that
a political party was involved in the deadly fire because the factory owners had reportedly
refused to pay extortion money. Three earlier inquiries, conducted by a committee of police
officers, FIA and the Sindh High Court, had earlier investigated the possibility of sabotage for
extortion but rejected it as a cause of fire. In January 2015, on the order of the Sindh High Court,
each of the deceased workers family was awarded Rs 500,000 as compensation. In February, the
public prosecutor withdrew from the case over what he called non-cooperation of the
investigating officer. In April, the Sessions Court directed the Sindh police to submit a
reinvestigation report by August. The court observed that the government had turned a blind eye
towards the case as a new public prosecutor had not been appointed despite repeated orders.

http://hrcp-web.org/hrcpweb/wp-content/uploads/2016/04/Labour-
2016.pdf

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Promulgation of Ordinance on Human Cell and Tissue Transplantation by President Musharraf (4
September 2007), now the Transplantation Bill HOTMA, Human Organ Transplantation
Monitoring Authority is actively enforcing the law

Contact HOTA

Street Address: Opposit NORI Hospital , Hanna Road, G8/4, Islamabad.

Dr. Fazl-e-Moula Administrator HOTA

Ph #: 051 9107652
Cell # : 0345 5000111
Fax: 051 9107653

Dr. Badr us Saleheen

Sr. Director
Ph # : 051 9107654
Cell#: 0331 5091872

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Pledge Your Organs - Donor Card
The Donor Card enables people to express their wish to become an organ donor. It is
like making a will. By signing the 'Donor Card' you have agreed to organ donation. Keep
the Donor Card with you always in your purse or wallet. Inform your close relatives
about your wish to be an organ donor. The Donor Card also substitutes as an emergency
card as it has the contact number in case of any emergency.

HUMAN ORGAN TRANSPLANT AUTHORITY Protocol/Guidelines for Stem Cell

Research/Regulation in Pakistan In Collaboration with the National Bioethics
committee, Pakistan INTRODUCTION The ability to cultivate a special class of cells
known as stem cells and the possibility to use them as therapeutic tools has
ushered in the era of what is known as regenerative medicine. All across the world
research and clinical applications of stem cells involving human subjects are
regulated by well established international guidelines with country specific details
mandated by religious and social mores. Origin and Properties of Stem Cells: During
the development of multi-cellular organisms a fertilized egg undergoes repeated
cellular divisions to produce a mass of unspecialized cells known as embryonic stem
cells. They are uncommitted primordial cells which ultimately give rise to adult stem
cells most of which differentiate into characteristic cells of organs and tissues. Stem
cells are defined by their ability to keep dividing and renewing their population and
thus are not exhausted. In contrast some of the differentiated specialized cells often
do not divide and once damaged are depleted. Potential of stem cells to renew and
differentiate offers exciting possibilities to reverse tissue and organ damages
caused by metabolic and degenerative diseases and aging. Where are Stem Cells
found? Gametes/ blastocysts/ fetal tissues/ placenta/umbilical cord cells/ adult
tissues serve as sources of stem cells. Classification of Stem Cells according to their
Differentiation Potential Totipotent stem cells: These are stem cells with absolute
developmental plasticity which can give rise to all cell types that are found in an
embryo, fetus or developed organism including the trophoblast and the placenta.
The zygote and the cells of the very early stage (i.e. the 2-cell stage) are totipotent.
Pluripotent stem cells: as the zygote undergoes further mitotic divisions a mass of
cells develops. This mass consists of unspecialized cells that can give rise to most,
but not all, the tissues necessary for fetal development. Further specialization gives
rise to multipotent cells that are committed to give rise to cells that have a
particular function (e.g. multipotent cells committed to giving rise to the red cells,
white cells and platelets). Unipotent stem cells These self renew as well as give rise
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to a single mature cell type; e.g., spermatogenic stem cells. They can proceed only
along one developmental pathway. Induced Pluripotent Stem Cells (iPS): A recently
developed technique has made it possible to develop multipotent stem cells from
adult skin cells by genetic reprogramming (Yamanaka, 2006). The iPS resemble
embryonic stem cells in their ability to differentiate into myriad of cells that
constitute tissues and organs of the body and offer the advantage that they can be
developed and put back in the same individual from whom they were derived. They
therefore escape immune surveillance. Sources of Stem cells are as follows: There
are many sources of stem cells and appendix 1 details some of the issues related to
stem cell research. i) Adult Stem Cells: Derived from peripheral blood, tissue or
bone marrow ii) Cord Blood Cells: Derived from placenta iii) Embryonic Stem Cells:
Derived either from blastocysts or foetal tissues I. Adult stem cells: Adult bone
marrow cells have been used for more than a decade. Stem cells in adult tissue are
often multi-potent and can produce many, but not all cell types. These cells can be
multiplied but do not have an unlimited capacity for renewal like embryonic stem
cells. Adult stem cell therapy (ASCT) by qualified and experienced staff using
appropriate validated technology, has become well established in certain
hematological disorders such as very severe aplastic anemia, chronic granulocytic
leukemia and thalassaemia major (well chelated, Pessaro category 1). ASCT has also
been used for other hematological conditions such as relapsed childhood acute
lymphoblastic leukemia and acute myeloid leukemia, but its use is not established
as standard of care. Research is ongoing to determine whether these adult stem
cells can also be made to differentiate into other tissues but in contrast to ASCT in
hematological disorders, the use of such cells for nonhematological indications is
experimental. The same applies to emerging techniques of modification of adult
stem cells such as retro-differentiation, which are experimental at this stage. II. Cord
Blood Cells: Cord blood stem cells (CSC) are also obtained from aborted fetal tissue
and umbilical cord blood and have shown to be successful in reconstitution of bone
marrow in children in many disease conditions. These stem cells and those from the
adults are pluripotent in nature. They can be multiplied and maintained in culture
and do not have unlimited capacity for renewal like the embryonic stem cells.
Research is ongoing to determine whether these cells can also be made to
differentiate into other tissues. Use of fetal stem cells will reduce the amount of
foetal tissue used for various therapies. TERMINATION OF PREGNANCY FOR
OBTAINING FOETUS FOR STEM CELLS research or for transplantation will not be
permitted. III. Embryonal Stem cells: These are pluripotent and have the capacity to
develop into any cell of the body. These are obtained from the very early stages of
the embryonic development probably up to 2-4 cell stage in humans i.e. within 5-7
days of conception. While scientists believe that these cells can be directed in the
laboratory to differentiate into any cell or tissue to treat many diseases affecting
various tissues and organs, these applications are still experimental. The main
source of embryonic stem cells is currently IVF clinics dealing with infertility
treatment, where SPARE OR SUPERNUMERARY embryos (at a very early stage) may
be available for these purposes. However no embryo should be CREATED for the
sole purpose of obtaining stem cells. Stem Cells at the Center Stage of Biology and
Medicine The journey of a stem cell as it traverses the trajectory of its life reveals
the molecular and genetic events underlying growth, differentiation and
development from a single fertilized egg to a complex multicellular organism. It also
provides understanding of disease, aging and death. Stem cells have generated a
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new medical paradigm known as stem cell therapies. Some of these such as bone
marrow transplant (BMT) using adult hematopoietic stem cells are well established.
Certain cell based treatments for ophthalmologic and musculoskeletal conditions
are also being used. Geron Corporation, one of the leading stem cell companies is
awaiting FDA clearance for the first ever trial of treatment for spinal cord injury. But
treatment modalities for other diseases such as Parkinsons and Alzeimers ,
immuno-genetic conditions and stroke and cardiac repair are still at the stage of
animal studies and are unlikely to develop into routine bed side therapies in
foreseeable future. Promise and Problems: on the one hand there is no doubt that
the yet far from fully realized potential of stem cells holds great promise for many
life threatening and debilitating diseases and on the other they have been hyped as
magic bullets for rejuvenating aged human skins. Claims abound as to the
effectiveness of skin treatment with stem cells without proof of the principle. There
is a need to regulate the diverse aspects of stem cell research and therapy where
the immense power to cure and rejuvenate is harnessed and possible harm is
avoided. THE NEED FOR NATIONAL REGULATORY AUTHORITY AND INSTITUTIONAL
OVERSIGHT AND MONITORING COMMITTEES Stem cell research and its applications
pose serious ethical, social, legal and safety concerns and call for exceptional care
and vigilance particularly when it comes to human embryonic stem cells (hES)
derived from embryos. Research and therapy with adult stem cells is not embroiled
in serious controversies but unrelenting watchfulness is indicated. Detailed National
and institutional guidelines should be formulated to protect patients and donors
from possible harm. It is extremely important that persons drafting guidelines are
professionals with adequate understanding of scientific, ethical, legal and social
aspects of SCRT and that all stakeholders are represented. As the field is new and
rapidly advancing it is equally important that once the guidelines are developed
they are reviewed at appropriate intervals. It is imperative to develop mechanisms
for implementing guidelines/Regulatory Frame Work and to invest the Implementing
Authority with adequate powers to punish violations. Human Organ Transplant
Authority (HOTA) for cell based research & therapy: The guidelines have to be in
accordance with religious sensitivities and cultural norms of our people. PMRC
should remain the main Regulatory Authority in the area of stem cell and related
medical research. HOTA will set up an advisory subcommittee of the National
Bioethics Committee in Research (NBCR) for cell based Research & Therapy. Given
the wider application of such technologies by sector other than the Ministry of
Health such as educational and research institutions and Ministry of Science &
Technology, the HOTA Sub-Committee will have additional representation from these
sectors. The membership of this HOTA Sub-Committee will be derived from the
membership of the National Bioethics Committee for Research and shall also consist
of additional co-opted members representing the fields of reproductive health,
hematology and representatives of all organ transplant societies/ institutions. All
centers performing stem cell research and therapy should be registered with the
HOTA for accreditation, on the basis of their technical competence (in stem cell
collection procedures, enumeration, cryopreservation, stem cell viability studies)
and ethical review and oversight procedures. All proposals involving stem cells of
any source for research or non-approved therapy (see Appendix 1 for approved
therapeutic indications), should be cleared by Human Organ Transplant Authority
(HOTA) Sub-Committee, through the National Bioethics Committee. Scope: The
HOTA will have the responsibility to examine the scientific, technical, ethical, legal
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and social issues in the area of cell based research and therapy. Scientific/Technical
Issues: All proposals, from public or private sector, for research or non-approved
stem cell therapy (SCT) should be placed before the HOTA Sub-Committee for
approval after due clearance through appropriate institutional ethical review
committee and scientific peer review process. Ethical, legal and social issues:
Institutional Ethics Committees should keep in view the ethical, legal and social
issues and should adhere to the ethical guidelines as per the Pakistan National
Guidelines for Human Research (2006), the Helsinki Declaration (2000), the CIOMS
guidelines (2002) as well as the WHO publication on Genomics and Global Health
(2003) GUIDELINES Adult stem cells: While the approved use of specific adult stem
cells does not pose major ethical problems at present their use must be considered
experimental except for specific hematological indications. As indicated above, all
centers doing stem cell treatment and research should register with HOTA. Bone
marrow, peripheral, blood, skin, limbal cells are some of the tissues in use for
procuring adult stem cells. No commercial sale or transaction for stem cell use or
research will permitted All clinical use or therapeutic trails of stem cell must be
conducted by institutions and qualified specialists who must be registered with
HOTA. Proper informed consent procedures are to be followed as given in
international ethical guidelines. Standard Operating Procedures, as outlined in the
Appendix I, should be followed for procurement, cataloguing, source identification,
storage and preservation. In vivo Studies: Experimental work on stimulation of
adult stem cells also has tremendous future. However, approval from HOTA must be
sought for carrying out all such experiments. Cord Blood stem cells: For using
umbilical cord blood from a live fetus or a neonate it must be ensured that no harm
should occur to the fetus or the neonate. Since the exact timing of the clamping of
the umbilical cord has a significant impact on the neonate and early clamping may
cause an abrupt surge in arterial pressure resulting in cerebral intraventricular
haemorrhage, particularly in premature neonates, normal clamping protocol
(Appendix II) will be followed when collecting foetal blood for transplantation. There
is a risk that the neonate donor may need his or her own cord blood later in life.
Parents will be informed of the risks of donation and a written consent will be
obtained from them on behalf of the fetus. Cord blood stem cells are generally used
for hematopoietic stem cell transplantation. For any other form of therapy detailed
protocol has to be submitted for approval. The following points should be
specifically considered while collecting umbilical cord blood for banking: No harm
should occur to the fetus or the neonate. Exact timing of the clamping of umbilical
cord should be defined. Early clamping may lead to cerebral haemorrhage. Normal
clamping protocol should always be followed. Parents should be correctly informed
regarding risks and benefits involved. Free informed consent should be obtained
from both parents. If there is disagreement between the parents, the mothers wish
shall prevail. ID card should be issued for voluntary donation to enable
access/benefit in future in case required for self/relatives. Cord blood stem cell
banking is permissible. However, all Cord Blood Banks should be registered as per
guidelines applicable to the blood banks. Commercial exploitation of stored blood
should be regulated strictly. Special care must be taken in collection, processing and
storage of umbilical cord stem cells to avoid transmission of infections. Maternal
screening should be carried out for transmissible infections. Purpose of banking

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should be clearly explained to couples interested in storing cord blood. The ideal
use of these cells at present is for allogenic hematopoietic stem cell transplantation.
Expansion of umbilical cord stem cells for transplantation in adult and use for non-
hematopoietic indications is still in exploratory phase. When it comes to registries
and banking, the commercial aspects pose additional problems. The advertisement
related to collection of samples should be carefully looked into with respect to
conflict of interest, utility of samples, accessibility and affordability Fetal stem
cells/tissue: These can be processed from spontaneously aborted fetus or from
fetuses obtained from hospitals. International guidelines for fetal tissue
transplantation should be followed. DNA fingerprinting of the cell line should be
preserved and it is advised to keep it in cell repository. Generally fetal stem cell use
is presently experimental. Any therapeutic fetal cell transplantation will not be
permitted at present and this possibility will be examined at an appropriate time
later. Termination of pregnancy should not be sought with a view to donate fetal
tissue in return for possible financial or therapeutic benefits. Informed consent to
have a termination of pregnancy and the donation of fetal material for purpose of
research or therapy should be taken separately. The wishes of the mother will
prevail in case of any difference of opinion. Embryonic stem cells (ES Cells): No
Embryo should be generated for the sole purpose of obtaining stem cells. Only
surplus or spare or supernumerary embryos (under 16 weeks gestation), can be
used with the permission of the couple from IVF clinics. Cell lines generated should
be registered. At present only research program relating to in vitro induction of
differentiation into various cell lines will be cleared by the NRC on case to case
basis. Any therapeutic trial will be examined in detail before approval. Reproductive
cloning will not be permitted on ethical grounds. Human cloning is not permitted for
the purpose of creating a new individual. Monitoring Mechanism: The HOTA will be
authorized to make site visits as required and receive annual reports of cleared
projects. These annual reports should be submitted in appropriate format for further
continuation of the project by the 10th month of commencement of the project
decision and review should be communicated in 4-6 weeks. Any violation of
guidelines would be strictly dealt with and procedures will be established to enforce
such regulations and penalties in the event of violation through the PMDC and the
Ministry of Health. Commercialization and Patent issues: Established stem cell lines
can have considerable commercial value as wide ranging potential benefits for large
number of patients is possible. Patent issues need wider discussions and public
debates should be held on who should be the beneficiary and what type of patents
can be taken. Exploitation of Pakistani biological material by foreign commercial
interests is not permitted. IPR protection should be accorded to commercially
utilizable materials and procedures. Benefits of commercialization should be
extended to community including patients, researchers and institutions engaged in
research and applications. Regulation of stem cell lines: All cell lines should be
registered with HOTA. All proposals for therapeutic trial should be cleared by this
committee before submitting to national or international funding bodies.
International collaboration: National guidelines of respective countries should be
followed and all research protocols for sponsored research must be cleared with
appropriate ethical review committees in the sponsoring country. Collaboration will
be permitted only after the joint proposal with appropriate MOU is approved by the
National Research ethics Committee following clearance by the HOTA. No export of
cell lines per se will be permitted. Generation of embryonic stem cells from non-
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human sources: Embryonic stem cells for experimental purposes cal also be
obtained from sources such as rodents. Primates, domestic animals, farm animals
etc. Research in these areas should be encouraged but is strictly experimental and
must undergo similar ethical review and clearance. Check list to be submitted to the
Human Organ Transplant Authority (HOTA) for any proposal 1. Title of the proposal.
2. Institution concerned. 3. Investigators name with brief bio-data and relevant
publications. 4. Source of funding. 5. An assurance signed by the responsible
institutional head that the pluripotent stem cells were derived from human embryos
in accordance with the guidelines. 6. Informed consent document duly signed by
appropriate individuals. 7. Brief summary of the proposed work. 8. IRB/IEC clearance
(if sponsored, ethical review and clearance from appropriate ethical review
committees in the sponsoring countries). 9. Certificate that no undue inducements/
incentive is provided for donation of embryo. 10. Separate consent for infertility
treatment and donation of embryos to be taken. 11. Certificate that only spare
embryos are being used. Private sector involved in such research should also come
under the purview of this committee and it should comply with due safeguards and
standards and submit all proposals for clearance. Permissible Research on Stem
Cells 1. Use of human stem cell lines derived from hES, hEG, hSS or fetal/adult stem
cells is permitted for in vitro investigations. 2. In vivo studies of human cell lines
and their differentiated derivatives are allowed in small non-primate animals at
various stages of development (embryonic, fetal, postnatal, adult). The animals
derived from these experiments shall not be allowed to breed especially when there
is a possibility that human cells could significantly contribute to development of
gonads and/brain. 3. Animal studies for pre-clinical evaluation of efficacy and safety
of human stem cell lines is also allowed as per above mentioned criteria. 4.
Informed consent from donors is required for: in- vivo animal studies when using
stem cells from donors of bone marrow, peripheral blood, umbilical cord blood, skin,
limbal cells, dental cells, bone cells, cartilage cells or any other organ (including
placenta) Establishment of fetal/adult hSS and new hES cell lines from spare,
supernumerary embryos. Establishment of Umbilical Cord Stem Cell banks Clinical
Grade Stem Cells for Biomedical Research and Therapy Clinical grade stem cells
are classified as therapeutics and are required to be produced under international
GMP/GTP conditions. The cells should be well characterized about their stemness
and safety. Prohibited Research Creation of a zygote by IVF, SCNT or any other
method with the specific aim of deriving a hES cell line for any purpose.
Introduction of hESCs into non-human primate blastocysts in vitro culture of any
intact human embryo for longer than 14 days or until formation of the primitive
streak begins, whichever occurs first Breeding of animals that have had hESCs
introduced into the germ line Germ line genetic engineering or reproductive
cloning. Transfer of human blastocysts generated by SCNT or parthenogenetic or
androgenetic techniques into a human or non-human uterus. Animals in which any
of human stem cells have been introduced at any stage of development should not
be allowed to breed. Research involving directed non- autologous donation of any
stem cells to a particular individual is also prohibited. Any research involving
implantation of human embryo into uterus after in vitro manipulation, at any stage
of development, in humans or primates. Ref: Ethical Guidelines for Biomedical
Research in human Subjects. 2000, 2006 ICMR Application of blood and marrow
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transplantation (BMT) Introduction: The clinical use of progenitor cell transplantation
technology has been instrumental in the treatment and cure of thousands of
patients with haematological and non haematological malignant disorders.
However, the procedure still carries significant morbidity and mortality. It is also at
risk of commercial exploitation and unethical practices. The setting up of centres for
BMT must be strictly regulated and their working should be periodically and
objectively monitored. The following guidelines are for the infrastructure of these
centres: BMT Centre This centre must be located in a tertiary care hospital which
will provide a wide range of support and patient care services including critical care
management, haemodialysis, advanced imaging facilities, cardiac support facilities,
infection surveillance and management facilities. Dedicated areas, according to
workload will be earmarked for BMT patients in these hospitals. The BMT Centre will
have A clinic to perform pre-donation physical examination and specialized tests
(X-ray, ECG, Echo etc) Indoor facilities which must have dedicated operation
theatres and isolation rooms with state-of-art ventilation facilities. The BMT Centre
must have harvesting facilities for bone marrow and progenitor cells. There should
be atleast two cell-separators, facilities for quantitative and qualitative evaluation of
harvested progenitor cells and facilities for cryo preservation and storage of
progenitor cells. The Centre must have direct access to the following accredited
facilities. HLA Typing Laboratory Microbiology Laboratory Biochemistry
Laboratory Blood Transfusion Laboratory Histopathology Laboratory I. Essential
Personal a. Medical Director The centre must be under the control of a medical
doctor who has accredited post-graduate qualification in haematology, a minimum
of 15 years experience in laboratory and clinical haematology and demonstrable
knowledge and interest of BMT. b. Transplant Physician At least two transplant
physicians should be full time employees of the centre. They must be medical
graduates and have accredited post-graduate qualification in haematology. They
must have 10 years experience of clinical haematology, have worked under the
supervision of a transplant physician for atleast 2-years at a centre doing a
minimum of 10 BMT per year. They should have exposure to atleast 10 bone marrow
harvesting procedures. c. Program Coordinator Master in Social Sciences, having
working knowledge of statistics, computers and record keeping. II. Support Medical
Faculty 1. Anesthetist 2. Pulmonologist 3. Gastroenterologist 4. Nephrologist 5.
Cardiologist 6. Neurologist 7. Infection Disease Physician II. Support Services 1.
Pharmacy 2. CSSD 3. Nutritionist 4. Social Worker III. Monitoring of Services The
services of the centre must be supervised by a regulatory body which will include;
1. Medical Director 2. Program Coordinator 3. Legal Expert 4. Financial Advisor 5.
Ethical Service Advisor 6. Social Service Advisor 7. Womens Representative 8.
Donor Representative IV. Accreditation of the Centre It should be mandatory for all
BMT centres to allow access to inspectors for the purpose of accreditation. The
inspection team, to be constituted by HOTA, must ensure that the centre is located
in an institution at a fixed physical site, is equipped and staffed as per regulation,
and is not involved in unethical commercial practices. The centre must maintain a
record of donors of blood, aphaeresis progenitor cells and bone marrow. It should be
carrying out management activities including education, counseling, rehabilitation
of patients and should be capable of dealing with medical screening and
confidentiality issues. Appendix I GUIDELINES FOR THE COLLECTION, PROCESSING
AND STORAGE OF HUMAN BONE MARROW, PERIPHERAL STEM CELLS FOR

Page 14 of 87
TRANSPLANTATION General principles: Each stem cell transplant unit shall establish,
document and maintain an effective and economical quality system to ensure and
demonstrate that adequate and appropriate standards of work are maintained.
Procedural step Related to Bone Marrow Harvest: Donor suitability must be ensured.
The donation may be an autograft or an allograft from a related or unrelated donor.
The allogenic donor should be counseled and a full medical examination carried out
to establish that the donor is fit for anesthesia. Routine haematological, biochemical
and virological parameters are checked. A chest X-ray and ECG should be
performed. Written informed consent must be obtained from the donor before the
recipient commences pretransplant conditioning. It is a cardinal principle that
unrelated donors should be anonymous, unpaid and not pregnant. The donor is
admitted, night before harvest to the transplant centre or hospital experienced in
marrow harvests. The donor receives a unique donor identification number (DIN)
and this must be assigned to the marrow, both primary and secondary collection
packs and all the sample tubes used. Marrow Collection: Before the start of harvest
the identity of the donor must be checked. Collection of marrow should be by
aseptic technique into pyrogen-free containers with sufficient anticoagulant for the
quantity of marrow to be collected and appropriate for the subsequent processing.
The container label should state the amount of anticoagulant and the maximum
amount of marrow that can be collected and required storage temperature. The
marrow should be anticoagulated with ACD-A unless preservative free heparin is
requested by the transplant centre. In the latter case marrow should be returned to
the patient within 12 h. The anticoagulant solution must be clear, free from deposit.
Harvest should only be undertaken by trained medical staff. Personnel required are
an anesthetist; operators to harvest marrow, haematological scrub nurse and
theatre staff. Harvest lists should be dedicated or at the beginning of the operating
list. The volume of marrow withdrawn from the donor must be controlled. The
volume taken should be such that a target cell count appropriate to transplant is
reached. Records: A record of the total volume of marrow removed from the donor
must be documented in the patients notes. The most efficient way of measuring
the volume in plastic bags is by weight of 1 ml. Of marrow is 1.06g; a unit
containing 405-495 ml should therefore weigh 430-522 g plus the weight of the
container and its anticoagulant. Operating procedure: The anaesthetized patient is
positioned on the operating table with pelvis supported to make the iliac crest
prominent. The choice of harvest needle is one of personal preference and can very
from conventional needles for diagnostic aspiration from iliac crests through to
designed harvest needles with holes along the lateral aspect of the shafts (e.g.
(Islam). No more than 5 ml of bone marrow should be collected into a 20 ml syringe
containing preservative free heparin and the needle then repositioned after each
aspiration. It is usually possible to take marrow at several different depths from one
site. The needle is then withdrawn and resited, samples being taken as widely as
possible along the posterior iliac crest. If an inadequate cell count is obtained from
both posterior iliac crests the patient should be turned over and further aspirates
taken from the anterior iliac crests and the sternum. Marrow Processing: A closed
system is preferred in which the syringe is emptied directly into 500ml or 1L bags
containing anticoagulant. Marrow should be filtered in accordance with the harvest
centers routine practice to remove fat, aggregates, clots or bone spicules if it is not
processed further by centrifuge or sedimentation. During and after harvesting
samples of marrow can be obtained from the bag and nucleated cell count carried
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out to ascertain the anticipated volume needed to produce engraftment. Estimation
of Marrow dose at harvest: The present recommended dose of nucleated cells is
expressed per kilogram of recipient body weight. 1. Autografts: minimum dose 1.5 x
108 cells /kg. 2. HLA identical sibling allografts for aplastic anaemia: minimum dose
3 x 108 cells /Kg (Storb et al, 1977). 3. HLA identical sibling for leukemia
haemoglobinopathies and inborn errors of metabolism: minimum dose 1.5-2 x 108
cells/kg 4. Unrelated donor allograft: minimum dose 2-3 x 108 nucleated cells/Kg A
minimum number of marrows (nucleated cells) per kilogram recipient body weight
should be stated by each transplant unit to permit engraftment. The weight of the
recipient must be ascertained. Post-Harvest Marrow Processing: In allogeneic
transplantation the completed barrow bag is rendered airtight, labeled and its
contents may then be infused intravenously into the recipient where both donor and
recipient are ABO compatible or cryopreserved. If volume reduction is required buffy
coat cells can be separated and transferred to a second sterile pack. When there is
no major blood group incompatibility between donor and recipient then a cell
fraction known to contain the repopulating stem cells and low in haematocrit should
be obtained by density separation. If removal of T cells is required to prevent graft
versus host disease the volume of the donation is reduced before incubation with
monoclonal antibodies. An appropriate method is to use blood cell washer or cell
separator. Processing also may be modified to collect donor red cells for autologous
reinfusion. Autologous marrow can be similarly separated to leave a buffy coat or
further processed to a mononuclear cell fraction which may be purged before
storage. Purging involves incubation of the marrow with most commonly the
cyclophosphamide antimetabolite, 4 hydoxy-per-oxycyclophosphamide (4 H-C;
Kaizer et al., 198) or with monoclonal antibodies. Monoclonal antibodies may also
be used for positive selection of putative progenitor stem cells (e.g. anti-CD34
antibodies). The purged / unpurged marrow is then cryopreserved (see below).
Biological methods of purging such as long-term bone marrow culture are still
experimental. Peripheral Blood Stem Cell Collection: Haemopoietic cells are present
at low concentration in steady-state blood. Such cells can be mobilized from the
bone marrow into peripheral blood during the recovery phase from
myelosuppressive chemotherapy or following administration of haemopoietic
growth factors or by a combination of the two. They are collected by leukapheresis
on a blood cell separator set to obtain sufficient mononuclear cells for engraftment.
A suggested value is 7x 108mononuclear cells/kg but this will vary according to the
centre and whether myeloablative treatment is given. Some centers use lower
values of 2 x 108 mononuclear cells /kg. Mobilized blood progenitor autografts are
usually associated with very rapid haemopoietic reconstitution. Timing of the
leukapheresis may be guided by the appearance of CD34 positive cells is the blood,
or by surrogate markers such as white blood cell and platelet counts. During
recovery from myelosuppressive therapy a white count greater than 1 x 109 /1 and
platelets greater than 70 x 109 /l are generally taken as the time to initiate
leukapheresis but absolute counts will very with the chemotherapy regime and
whether or not growth factors are employed. Mobilized blood stem cells collections
are usually assessed by their CD34 positive cells or CFUGM. Threshold doses need
to be determined by each centre by the recommended minimum number of CFU-GM
and is usually in the range 5-20 x 104 /kg (Craig et al., 1992). It is usual that the
donor is an autograft recipient and that the material is stored by cryopreservation.
Nucleated cell collection: The technique for procurement of the nucleated cell layer
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rich in stem cells depends on the cell separator machine used. The aim is to collect
the buffy coat interface between plasma and red cell. The total nucleated cell
volume collected is determined from the total blood volume of the donor
ascertained from their height/ weight prior to apheresis. It is recommended that in
adults 7-15 /l is processed. Where the nucleated cell yield is greater than 100 x
109 /l dilutions in plasma are needed to prevent aggregation during the process of
freezing (see Storage). When the collection is complete the residual volume of blood
is returned to the donor. Appendix II GENERAL SPECIFICATION FOR IDENTIFICATION,
STORAGE AND TRANSPORTATION OF BONE MARROW AND PERIPHERAL BLOOD STEM
CELLS Identification: The unit containing stem cells must be labeled with the name
of the product, the donors name and hospital number, unique donation number,
date of collection, the presence and type of anticoagulant and additive media if any,
ABO and Rh D group and the volume of the product. Storage (Rowley & Davis.1990;
Reiman & Sacher, 1991) An SOP should be written to include the following: a
designated storage area: a procedure for quarantine of bone marrow and peripheral
blood stem cells: a procedure for validating the conditions of storage achieved in
any given storage area. This should include temperature control and preventation of
microbiological contamination. If, as a result of microbiological screening, the donor
is positive for any of the mandatory microbiological marker (table 1) then that unit
should be stored in isolation to avoid cross contamination of other units. Storage
unfrozen. Unmanipulated bone marrow and peripheral blood stem cells may be
stored unfrozen for up to 72 h at 4 + 2C. The anticoagulant conventionally used in
ACD. Heparin is unsuitable. Storage at 4C will, however, reduce leukocyte viability
and cellular aggregation may occur. Preparation of frozen marrow and peripheral
blood haemopoietic cells Haemopoietic cells in bone marrow are enriched and
concentrated by differential centrifugation into a buffy coat. Further enrichment
using a density gradient may be required. Peripheral blood cells are not normally
concentrated. The cell concentration frozen should be less than 100 *109 /1 (see
above Nucleated Cell Collection). The above products are cryopreserved using one
of the established cryoprotectants, for example 10 or 15% v/v dimethyl sulphoxide
(DMSO) or 5% v/v DMSO plus 6% w/v hydroxyethyl starch (HES). DMSO should be
added slowly to its diluents to avoid a rise in temperature since desired final
concentration of DMSO is isotonic in molar terms. This requires the addition of
albumin solution (HAS) is used additional salts or a suitable impermeable sugar are
necessary (Pagg. 1984). The diluent is then cooled on ice to 0-4C, DMSO added
and the cryoprotectant mixed with an equal volume of haemopoietic cells. The
freezing process: A feedback-controlled cooling machine (controlled rate freezer)
will provide reproducible, standardized cooling conditions. The cooling program
should be one that has been shown to be effective (e.g. 2 C/ min to -30C, followed
by 4C/min to -70C with adequate control of freezing plateau: Gorin, 1986). Passive
cooling methods may also be effective providing that they produce acceptable
cooling profiles (Makino et al., 1991). The bags in which the marrow is cooled should
be made from plates ton produce a thickness of about 3 min to facilitate heat
transfer. Temperature should be recorded in a control bag and the data kept with
the processing records. Peripheral blood cells may be cryopreserved by the same
methods. Once below -70C the bone marrow and peripheral blood stem cells
should be transferred for storage. Such deep frozen is fragile and container bags
may fracture. Thawing of frozen bone marrow/peripheral blood cells: 1.
Contamination of the marrow/peripheral blood bag with water bath fluid is to be
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avoided and it is essential that double bags are used. 2. Thaw in a water bath at 37-
40C with gentle agitation. Observe carefully for rapid expansion of the bag during
thawing which will suggest that liquid nitrogen has leaked into the bag during
storage. If this occurs release the pressure immediately by puncturing the bag with
a sterile needle. 3. DMSO toxicity is temperature dependent ( Goring 1986). It is
therefore important to remove the bags from the waterbath soon as the last ice has
melted and not to allow the marrow to reach the waterbath temperature. Keep the
thawed marrow cool until administration and infuse within 5 min of complete
thawing. Current practive is not to remove the DMSO before injection into the
patient (Rowley & Anderson, 1993). Premedication of the patient with steroid/
antihistamine is recommended. 4. Any thawing incidents should be documented
and reported to the clinician in charge of the recipient who will decide whether
action is required. Testing: Testing of frozen products may be performed utilizing 1-
or 2-ml aliquots of material frozen at the same time under conditions that are as
close as possible to the bulk product. It should be noted that small ampoules will not
cool at the same rate as large bags. Assay may be performed to determine short-
term progenitor growth post-cryopreservation. Specific Laboratory Procedures
Related to Provision of Haemopoietic Cells for Engraftment Serology: The ABO and
RhD blood groups of all donors should be performed as set out in the Guidelines for
Compatibility Testing in Hospital Blood Banks (Boulton et al, 1987). Cell Counting:
The minimum information required is the total nucleated cell count obtained at
stem cell harvest. If counts are corrected for peripheral blood dilutions, this should
be clearly indicated to avoid confusion with uncorrected nucleated counts. Such
counts should be performed on a cell counting machine by validated methods or
performed manually. The volume of bone marrow or peripheral blood harvest is best
calculated by weight. Cell Viability The quality of frozen cells can be assessed by the
trypan blue exclusion test or automated techniques using a flow cytometer and
propidium iodide. These results do not correlate with in vitro growth, but given
indication of consistency of the technique. Red Cell Depletion: Red cell depletion of
the donor graft is strongly recommended in ABO mismatched allogenic transplant.
This can be carried by HES sedimentation or differential centrifugation (Braine et al.,
1982: Ho et al., 1984). An alternative is to plasma exchange the recipient and/or to
give A/B antigen rich secretor plasma prior to the transplant. Microbiology and
Virology: The sterility of the bone marrow/ peripheral blood product at various
stages should be ascertained using liquid and semi-solid culture medium. This is
especially important prior to freezing and at the final stage of processing after
freezing before the product is infused into the patient. A pilot tube is thawed and
cultured. The clinician should be informed if the cultures are positive. Donor bone
marrow can transmit infectious disease and all donors should have the mandatory
tests (shown on table 1) carried out and where possible the serological tests
repeated at not less than 90 days from the first screening sample. Table-1: 1.
Mandatory HBsAg (hepatitis B surface antigen) HIV 1+2 antibody (human immune
deficiency virus) Anti-HCV (Hepatitis C virus antibody) VDRL or equivalent test for
syphilis 2. Advisable CMV antibody Toxoplasma gondii antibody 3. Desirable HSV
(herpes simplex antibody) HZV (herpes zoster antibody) HTLV-1 (Human T-
Lymphotrophic virus) Appendix III PRE-REQUISITES FOR A STEM CELL
TRANSPLANTATION CENTRE Standard Operating Procedures (SOPs): Standards for
collection, processing and storage of cells for clinical use: For the consistence and
reliable results International standard procedures should be adopted. These
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standards are designed to provide minimum guidelines for facilities and individuals
performing collection, processing and storage of cells for clinical use or providing
support services for such procedures. These standards are not intended to include
all procedures and practices that a facility or individual should implement if the
standard of practice in the community or governmental laws or regulations establish
additional requirements. Each facility and individual should analyze their practices
and procedures to determine whether additional standards may apply. Protocols
shall be developed, implemented, and documented for the validation or
qualification of significant products of facilities, processes, equipment, reagents,
labels, containers, packaging materials, and computer systems. For this purpose
training of the staff in renowned stem cell/transplantation centers is recommended.
There shall be procedures for biological, chemical, and radiation safety, as
appropriate, and a system for monitoring training and compliance. Personnel 1.
There shall be a Collection Facility Head / Officer in-charge an individual with a
doctoral degree, qualified by postdoctoral training or experience for the scope of
activities carried out in the facility. This individual is responsible for all technical
procedures and administrative operations of the collection facility. This individual
should participate regularly in educational activities related to the field of cell
collection and / or processing. 2. The Collection or Processing Facility Head / Officer
in-charge with a doctoral degree, n shall have at least one years experience in the
collection procedure. This individual shall have performed or supervised at least 10
collection procedures of each type that are to be carried out at the facility. 3. There
shall be a Collection Facility Medical Head/Director who is a physician licensed in the
jurisdiction in which the facility is located. This individual is directly responsible for
the precollection evaluation of the donor, final approval of the prospective donor for
the collection procedure, conduct of the collection / processing procedure, care of
any complications arising from collection and compliance of the collection facility
with these Standards. 4. There shall be adequate numbers of trained support
personnel available at the facility where the collection is performed. 5. The training,
continued education and continued competency for the performance of operations
shall be documented. Ethical issues: Informed consent from the donor shall be
obtained and documented by a licensed physician or other health care provider
familiar with the collection procedure before the high dose therapy of the recipient
is initiated. The procedure shall be explained in terms the donor can understand,
and shall include information about the significant risks and benefits of the
procedure and tests performed to protect the health of the donor and recipient and
the rights of the donor to review the results of such tests. The donor shall have an
opportunity to ask questions and the right to refuse to donate. In the case of a
minor donor, informed consent shall be obtained from the donors parents or legal
guardian in accord with applicable law and shall be documented. Laboratory
facilities for cell processing The facility responsible for cell processing shall be of
adequate space and design for the intended procedures. The operation of the
facility shall be divided into defined areas of adequate size for each operation to
prevent improper labeling and/ or contamination of the product. The facility shall
be operated in a manner to minimize risks to the health and safety of employees,
patients, donors and visitors. The facility shall have written policies and
procedures for infection control, biosafety, chemical and radiological safety,
emergency response to worksite accidents, and waste disposal. Instructions for
Page 19 of 87
action in case of exposure to communicable disease or to chemical, biological and
radiological hazards shall be included in the safety manual. Decontamination and
disposal techniques for medical waste shall be described. Human tissue shall be
disposed in such a manner as to minimize any hazard to facility personnel or the
environment in accordance with applicable governmental laws and regulations.
Eating, drinking, smoking, the application of cosmetics or the insertion or removal of
contact lenses shall not be permitted in work areas. Gloves and protective clothing
shall be worn while handling human specimens. Such protective clothing shall not
be worn outside the work area. There shall be adequate equipment for the
procedures performed at the facility. The facility shall be maintained in a clean and
orderly manner as established in SOPs. The facility shall be secure to prevent the
admittance of unauthorized personnel. Equipment Equipment used in the
processing, testing, freezing, storage, transportation, and transplantation of
products shall be maintained in a clean and orderly manner and located so as to
facilitate cleaning, calibration and maintenance. Each collection facility shall be
operated in a manner to minimize risks to the health and safety of employees,
donors, volunteers, and patients. Suitable environment and equipment shall be
available to maintain safe operations. Environmental control lab facilities of
international standards are must. Equipments used in the collection of products
shall be maintained in a clean and orderly manner and located so as to facilitate
cleaning, calibration and maintenance. The equipments shall be observed,
standardized and calibrated on a regularly scheduled basis as described in the SOPs
Manual and according to the Manufacturers recommendations. Sterilization
equipments shall be designed, maintained and used to ensure the destruction of
contaminating microorganisms. Refrigerators and freezers used for the storage of
specimens, cell products, blood products, human tissues, or reagents shall not be
used for any other purpose. Consumables Reagents used in collection of products
shall be of appropriate grade for the intended use and shall be sterile. Procedures
for production of in-house reagents shall be validated. Each supply and reagent
used in the collection of the product shall be examined visually for damage or
evidence of contamination as it comes into inventory and this review shall be
documented. Such examination shall include inspection for breakage of seals,
abnormal color and expiration date. All supplies and reagents used in the
collection of products shall be stored in a safe, sanitary, and orderly manner. Lot
numbers and expiration dates of reagents and disposables shall be recorded.
Supplies and reagents should be used in a manner consistent with instructions
provided by the manufacturer. Tissue processing Human tissue refers to cells
obtained from any living or cadaveric human donor or organ. The cell processing
facility shall have written policies and procedures addressing all appropriate aspects
of the operation including processing; emergency and safety procedures; donor and
patient confidentiality; quality management and improvement; errors, accidents
and adverse reactions; corrective actions; personnel training; competency
assessment; outcome analysis; audits; labeling; storage, including alternative
storage if the primary storage device fails; transportation; expiration dates; release
and exceptional release; disposal of medical and biohazard waste; equipment and
supplies; maintenance and monitoring; cleaning and sanitation; and a disaster plan.

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 All open cell handling procedures must be performed in class 100 environment.
More than minimal manipulation of products should only be performed in a clean-
room environment. Environmental monitoring of such rooms must be performed and
documented. There shall be a written request from the recipients physician
before processing is initiated. Processing of cellular therapy products shall be
performed according to protocols defined in the facilitys SOPs. Methods for
processing shall employ aseptic technique and be validated to result in acceptable
cell viability and recovery. There shall be written documentation of an interim
assessment of donor suitability for the collection procedure by a qualified person
immediately prior to each collection procedure. For donors of peripheral blood
aphaeresis products, a complete blood count, including platelet count, shall be
performed within 72 hours prior to the first collection and within 24 hours before
each subsequent aphaeresis. For progenitor and other adult cell collection,
methods for collection shall employ aseptic technique and shall use procedures
validated to result in acceptable progenitor cell viability and recovery. The
collected cells shall be packaged in a closed sterile container / transfer packs
approved for human cells and labelled. Bone Marrow shall be filtered to remove
particulate material prior to final packaging, distribution or transplantation using
sterile filters that are non-reactive with blood. Labelling control Labelling
operations shall be conducted in a manner adequate to prevent mislabelling of
products that shall include the following quality management elements: Container
labels shall be held upon receipt from the manufacturer pending review and
proofing against a copy approved by the Collection Facility In-charge or designee to
ensure accuracy regarding identity, content, and conformity. Stocks of unused
labels representing different products shall be stored in an orderly manner to
prevent errors. Stocks of obsolete labels shall be destroyed. A system of checks in
labelling procedures shall be used to prevent errors in translating information to
container labels. All labelling shall be clear and legible and printed using moisture-
proof ink. Labels shall be affixed or attached firmly to the container. The proper
name and significant modification(s) shall be noted on the label. Products that are
subsequently re-packaged into new containers shall be labelled with new labels as
appropriate. Records to allow tracking of products including collection or processing
facility identity, unique numeric or alphanumeric identifier, collection date and time,
product identity, donor and recipient information on the original container shall be
maintained. When the label has been affixed to the container, a sufficient area of
the container shall remain uncovered to permit inspection of the contents. The
product label shall be complete. Not applicable (NA) may be used when appropriate.
Stem cell storage and transportation facilities: Cell collections shall be handled and
discarded with precautions that recognize the potential for transmission of
infectious agents. Issues of donor health that pertain to the safety of the collection
procedure shall be communicated in writing to the collection facility staff.
Prospective donors shall be evaluated by medical history, physical examination by a
trained physician and laboratory testing for the risks of the collection procedure
including the possible need for central venous access and/or mobilization therapy
for collection of blood cells and anaesthesia for collection of marrow. This evaluation
shall be documented. Cryopreservation Sample aliquots of the product,

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cryopreserved and stored under the same conditions as the product, should be
available for testing for 5 years. Cryopreservation procedures shall be included in
the cell processing facilitys SOPs and shall describe: The name and freezing
criteria of the cell product or aliquot. The cryoprotectant solution and its final
concentration. Cryopreservation container & acceptable range of product volume
for reproducible cryopreservation. Acceptable range of nucleated cell
concentration of the final product after cryopreservation. Cooling rate and product
temperature at endpoint of controlled cooling. The cooling rate achieved shall be
recorded, if a rate-controlling device is used. Acceptable temperature range for
storage. Storage Materials that may adversely affect cell products shall not be
stored in the same refrigerators or freezers. For products immersed in liquid
nitrogen, procedures to minimize the risk of microbial crosscontamination of
products shall be employed. Refrigerators and freezers for product storage shall
have a system to monitor the temperature continuously or at least every 8 hours.
For products fully immersed in liquid nitrogen continuous temperature monitoring is
not required. There shall be a mechanism to ensure that levels of liquid nitrogen in
liquid nitrogen freezers are maintained. Storage devices for products or reagents
for product processing shall have alarm systems that are continuously active. The
alarm systems shall have audible signals. If laboratory personnel are not always
present in the immediate area of the storage device, a remote alarm device shall be
required at a location staffed 24 hours a day. Alarms shall be set to activate at
temperatures or an unsafe level of liquid nitrogen to allow time to salvage products.
There shall be written instructions to be followed if the storage device fails. These
instructions shall be displayed in the immediate area containing the storage device.
Alarm systems shall be checked periodically for function. Additional storage
devices of appropriate temperature shall be available for product storage if the
primary storage device fails. The storage device shall be located in a secure area.
Locking capability for the device or the storage location should be used when the
area is unattended. Transportation Procedures for transportation of the collected
product shall be designed to protect the integrity of the product being shipped and
the health and safety of facility personnel. The primary product container shall be
placed in a secondary container and sealed to prevent leakage. The outer shipping
container shall be thermally insulated and shall conform to the regulations
regarding the mode of transport. Frozen or non-frozen products that leave the
facility or are transported on public roads shall be shipped in an outer shipping
container. The outer shipping container should be made of material adequate to
withstand leakage of contents, shocks, pressure changes, and other conditions
incident to ordinary handling in transportation. Cryopreserved products with an
indicated storage temperature below -80C shall be shipped in a validated liquid
nitrogen dry shipper that contains adequate absorbed liquid nitrogen to maintain
temperature at least 48 hours beyond the expected time of arrival at the receiving
facility. The product shall be shipped to the processing laboratory at a temperature
defined in the SOP Manual. The transit time should be minimized. If the intended
recipient has received high-dose therapy, the product shall be hand-carried by a
suitably informed courier in the passenger compartment. There shall be plans for
alternative transport in an emergency. The products should not be passed through
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X-Ray irradiation devices designed to detect metal objects. If inspection is
necessary, the contents of the container shall be inspected by hand. Appendix IV
TRANSPLANT REGISTRY FORM STEM CELL TRANSPLANT FIRST REPORT FORM-16(c)
Refer Rule 10(4) Transplant Centre Name of Physician Recipient Name Recipients
Age/Sex Recipients Fathers Name Recipients CNIC number/Form B Address
Donors name (if applicable) Donors Age/Sex Donors CNIC number/Form B
Donors Fathers name Relationship of recipient Indication for transplant Source of
stem cells i) Adult stem cells: a. Bone Marrow b. Blood c. Tissue If source is blood or
tissue please mention by what process stems are harvested. Is this harvesting
procedure experimental YES NO accepted norm YES NO ii) Cord Blood Cells: iii)
Embryonal stem cells: Derived either from blastocytes or foetal tissues Date of
Procedure_________________________ Date reported: ____________________ Signature:
___________________ Signature: ___________________________________ Head Transplant
Centre Member Evaluation Committee Name: Name: Note: In case donor/recipient is
a married woman, Name of husband as well as father will be endorsed. Fax/Mail to
Administrator, Monitoring Authority Transplantation of Human Organs& Tissues,
House-80, Street-23, F-10/2, Islamabad. On the day of Transplantation on Fax: 051-
0266107 followed by a copy by Courier/post. REFERENCES 1. Jones, R. & Burnett,
A.K. (1992) How to harvest bone marrow for transplantation. Journal of Clinical
Pathology; 45, 1053-1057. 2. Makino, S., Harada, M., Akashi, K., Taniguchi, S.,
Shibuya, T., Inaba, S. & Nilo, Y. (1991) A simplified method for cryopreservation of
peripheral blood stem cellsat -80OC without ratecontrolled freezing. Bone Marrow
Transplantation, 8, 239-244. 3. Pegg, D.E. (1984) Red Cell volume in glycerol/sodium
chloride/water mixtures. Cryobiology, 21, 234-239. 4. Braine, H.G., Sensenbrenner,
L.L., Wright, S.K., Tutschka, P.J., Sasal, R. & Santos, G. (1982) Bone marrow
transplantation with major ABO blood group incompatibility using erythrocyte
depletion of marrow prior to infusion. Blood. 60, 420-425. 5. Commission of the
European Communities (1989). Rules Governing Medical Products in the European
Community, Vol. IV, Guide to Good Manufacturing Practice for Medicinal Products.
Consumer Protection Act. (1987) Chapter 43, Part I, HMSO, London. 6. Reiman, E.M.,
& Sacher, R.A. (1991) Bone marrow processing for transplantation. Transfusion
Medicine Reviews, 5, 214-227. 7. Gorin, N.C. (1986) Collection, manipulation and
freezing of haemopoietic stem cells. Clinics in Haematology, 15, 19-48. 8. Craig,
J.I.O., Turner, M.L. & Parkar A.C. (1992) Peripheral blood stem cell transplants. Blood
Reviews, 6, 59-67. 9. Hrowitz, M.M., Przepiorka, D., Champlin, R.E., Gale, R.P.,
Gratwohl, R.H., Prentice, G.H.,Rimm, A.A., Ringden, O. & Bortin, M.M. (1992) Should
HLA identical sibling bone marrow transplants for leukaemia be restricted to large
centres? Blood, 79, 2771-2774. 10. Gluckman, E., Wagner, J., Hows, J., Kerman, N.,
Bradley, N., & Broxmeyer, H.E. (1993) Cord blood banking for haematopoietic stem
cell transplantation: an introductional cord blood transplant registry. Bone Marrow
Transplantation, 11, 199-200. 11. Boulton, F.E., et al. (1987) Guidelines for
compatibility testing in hospital blood banks. Clin. lab. Haemat. 9, 331-341.

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To provide rules and regulations for removal, surgery and transplantation of human organs and
tissues for therapeutic purposes.

To control and ban organ trade.

To stop illegal organ selling to foreigners from Pakistani citizens.

To improve the quality of transplantation.

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Human Organs Transplant Authority, HOTA
January 19, 2016

HOTA Projects

Projects
The Federal Human Organ Transplant Authority is committed to work against the
menace of organ trade. The Federal HOTA has recently taken following steps / actions.

Federal HOTA has issued an Advisory letter to foreign office regarding provision of a
mandatory certificate by foreigners visiting Pakistan that they are not having renal
failure and are not on hemodialysis and their stay in Pakistan will not involve any illegal
activity such as seeking a donor for organ trade.

Federal HOTA has created the public awareness by sponsoring the FIRST NATIONAL
TRANSPLANT CONFERENCE ON DECEASED DONOR PROGRAM which was held from
JANUARY 11-13, 2013. Public awareness is being created by conferences and media
involvement.

Federal HOTA has formulated rules and regulations including consent forms regarding
deceased donor program in Pakistan. These are published in the Gazette of Pakistan.
This will provide an alternative choice to live organ donation.

Federal HOTA is soon launching its dynamic, broad based and independent website
supporting National Organ Sharing Network, Organ Procurement Organization and
National Database / registry for recipients and donors.

Federal HOTA has formally approved the creation of Headquarters of NOSN and OPO
Secretariat in HOTA office.
To check the fake identity (of foreigners and donors), the federal HOTA has applied for
CNIC VERISYS (Computerized National Identification Cards verification system).

Federal HOTA is planning to establish a Central HOTA Laboratory to avoid fake blood and
serum reports deposited by unfit donors. The HLA tissue typing and cross match facility
may be provided centrally.

Federal HOTA has established a Monitoring and Enforcement Cell to monitor the
transplant activities. HOTA surveillance teams are being established for regular strict
inspection of transplant centers and doctors.

Federal HOTA has issued a circular to nation wide transplant centers to provide
certificates, the details of which include:
Certificate that Hospitals and the concerned doctors are not involved in any form
directly or indirectly in violating the provision of transplantation of Human Organs and
Tissues Act, 2010.

Certificate that Hospitals and the concerned doctors are not exploiting the vulnerable
segment of society financially in bad condition by indulging into sale / purchase of
Human Organs by luring them into selling of their organs.

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Certificate that Hospitals and the concerned doctors are not indulging in the nefarious
act of organ trade violative of provisions of transplantation of human organs and tissues
act, 2010 and are not running the business of exploiting the poor and needy into selling
their organs against petty amounts.

Certificate that no donation of organs / tissues by Pakistani citizen has been permitted
to any citizen of any other country in the hospital / institution.

Federal HOTA is planning to establish a media cell for proper awareness of public.
Federal HOTA is planning to establish a legal section for proper legal prosecutions of
culprits.
Federal HOTA is planning to establish HOTA TRUST for the welfare of poor patients.

In view of all of the above, it is clearly evident that the federal HOTA is committed to
effective implementation / enforcement of the law prohibiting the sale and trade of the
human organs in Pakistan.

HOTA Ordinance/ Act

4th September 2007 is a milestone in the history of Pakistan. About five years back an Ordinance
titled, Transplantation of Human Organs and Tissues Ordinance 2007 was promulgated. Most of
the people welcomed this move, which brought Pakistan into a comity of nations where human
dignity is prized and valued. Some people were skeptical as to whether this law would bring a
change or not and Pakistan would continue to be a hotspot for notorious organ trade.

On 17 March 2010, after the assent of the President of Pakistan the said law has
become an act of the parliament, titled, Transplantation of Human Organs and Tissues
Act,2010

The Government of Pakistan and Human Organ Transplant Authority (HOTA) are
committed to bring to an end the organ trade and restore the dignity of human life. The
figures speak for themselves. In 2006 it was reported that approximately 2000 kidneys
transplants were performed, out of which nearly 1500 were foreigners. Now no foreigner
is being provided kidneys from poor Pakistanis because of the efforts done by HOTA to
stop illegal trade.

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HUMAN ORGAN TRANSPLANT AUTHORITY Protocol/Guidelines for Stem Cell
Research/Regulation in Pakistan 2 AMMENDED These guidelines have been adopted
from the Guidelines originally developed by the National Bioethics Committee,
Pakistan with some modifications 3 INTRODUCTION The ability to cultivate a special
class of cells known as stem cells and the possibility to use them as therapeutic
tools has ushered in the era of what is known as regenerative medicine. All across
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the world research and clinical applications of stem cells involving human subjects
are regulated by well established international guidelines with country specific
details mandated by religious and social mores. Origin and Properties of Stem Cells:
During the development of multi-cellular organisms a fertilized egg undergoes
repeated cellular divisions to produce a mass of unspecialized cells known as
embryonic stem cells. They are uncommitted primordial cells which ultimately give
rise to adult stem cells most of which differentiate into characteristic cells of organs
and tissues. Stem cells are defined by their ability to keep dividing and renewing
their population and thus are not exhausted. In contrast some of the differentiated
specialized cells often do not divide and once damaged are depleted. Potential of
stem cells to renew and differentiate offers exciting possibilities to reverse tissue
and organ damages caused by metabolic and degenerative diseases and aging.
Where are Stem Cells found? Gametes/ blastocysts/ fetal tissues/ placenta/umbilical
cord cells/ adult tissues serve as sources of stem cells. Classification of Stem Cells
according to their Differentiation Potential Totipotent stem cells: These are stem
cells with absolute developmental plasticity which can give rise to all cell types that
are found in an embryo, fetus or developed organism including the trophoblast and
the placenta. The zygote and the cells of the very early stage (i.e. the 2-cell stage)
are totipotent. Pluripotent stem cells: as the zygote undergoes further mitotic
divisions a mass of cells develops. This mass consists of unspecialized cells that can
give rise to most, but not all, the tissues necessary for fetal development. Further
specialization gives rise to multipotent cells that are committed to give rise to cells
that have a particular function (e.g. multipotent cells committed to giving rise to the
red cells, white cells and platelets). Unipotent stem cells These self renew as well as
give rise to a single mature cell type; e.g., spermatogenic stem cells. They can
proceed only along one developmental pathway. Induced Pluripotent Stem Cells
(iPS): A recently developed technique has made it possible to develop multipotent
stem cells from adult skin cells by genetic reprogramming (Yamanaka, 2006). The
iPS resemble embryonic stem cells in their ability to differentiate into myriad of cells
that constitute tissues and organs of the body and offer the advantage that they
can be developed and put back in the same individual from whom they were
derived. They therefore escape immune surveillance. 4 Sources of Stem cells are as
follows: There are many sources of stem cells and appendix 1 details some of the
issues related to stem cell research. i) Adult Stem Cells: Derived from peripheral
blood, tissue or bone marrow ii) Cord Blood Cells: Derived from placenta iii)
Embryonic Stem Cells: Derived either from blastocysts or foetal tissues I. Adult stem
cells: Adult bone marrow cells have been used for more than a decade. Stem cells in
adult tissue are often multi-potent and can produce many, but not all cell types.
These cells can be multiplied but do not have an unlimited capacity for renewal like
embryonic stem cells. Adult stem cell therapy (ASCT) by qualified and experienced
staff using appropriate validated technology, has become well established in certain
hematological disorders such as very severe aplastic anemia, chronic granulocytic
leukemia and thalassaemia major (well chelated, Pessaro category 1). ASCT has also
been used for other hematological conditions such as relapsed childhood acute
lymphoblastic leukemia and acute myeloid leukemia, but its use is not established
as standard of care. Research is ongoing to determine whether these adult stem
cells can also be made to differentiate into other tissues but in contrast to ASCT in
hematological disorders, the use of such cells for nonhematological indications is
experimental. The same applies to emerging techniques of modification of adult
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stem cells such as retro-differentiation, which are experimental at this stage. II. Cord
Blood Cells: Cord blood stem cells (CSC) are also obtained from aborted fetal tissue
and umbilical cord blood and have shown to be successful in reconstitution of bone
marrow in children in many disease conditions. These stem cells and those from the
adults are pluripotent in nature. They can be multiplied and maintained in culture
and do not have unlimited capacity for renewal like the embryonic stem cells.
Research is ongoing to determine whether these cells can also be made to
differentiate into other tissues. Use of fetal stem cells will reduce the amount of
foetal tissue used for various therapies. TERMINATION OF PREGNANCY FOR
OBTAINING FOETUS FOR STEM CELLS research or for transplantation will not be
permitted. III. Embryonal Stem cells: These are pluripotent and have the capacity to
develop into any cell of the body. These are obtained from the very early stages of
the embryonic development probably up to 2-4 cell stage in humans i.e. within 5-7
days of conception. While scientists believe that these cells can be directed in the
laboratory to differentiate into any cell or tissue to treat many diseases affecting
various tissues and organs, these applications are still experimental. The main
source of embryonic stem cells is currently IVF clinics dealing with infertility
treatment, where SPARE OR SUPERNUMERARY embryos (at a very early stage) may
be available for these purposes. However no embryo should be CREATED for the
sole purpose of obtaining stem cells. 5 Stem Cells at the Center Stage of Biology
and Medicine The journey of a stem cell as it traverses the trajectory of its life
reveals the molecular and genetic events underlying growth, differentiation and
development from a single fertilized egg to a complex multicellular organism. It also
provides understanding of disease, aging and death. Stem cells have generated a
new medical paradigm known as stem cell therapies. Some of these such as bone
marrow transplant (BMT) using adult hematopoietic stem cells are well established.
Certain cell based treatments for ophthalmologic and musculoskeletal conditions
are also being used. Geron Corporation, one of the leading stem cell companies is
awaiting FDA clearance for the first ever trial of treatment for spinal cord injury. But
treatment modalities for other diseases such as Parkinsons and Alzeimers ,
immunogenetic conditions and stroke and cardiac repair are still at the stage of
animal studies and are unlikely to develop into routine bed side therapies in
foreseeable future. Promise and Problems: on the one hand there is no doubt that
the yet far from fully realized potential of stem cells holds great promise for many
life threatening and debilitating diseases and on the other they have been hyped as
magic bullets for rejuvenating aged human skins. Claims abound as to the
effectiveness of skin treatment with stem cells without proof of the principle. There
is a need to regulate the diverse aspects of stem cell research and therapy where
the immense power to cure and rejuvenate is harnessed and possible harm is
avoided. 6 THE NEED FOR NATIONAL REGULATORY AUTHORITY AND INSTITUTIONAL
OVERSIGHT AND MONITORING COMMITTEES Stem cell research and its applications
pose serious ethical, social, legal and safety concerns and call for exceptional care
and vigilance particularly when it comes to human embryonic stem cells (hES)
derived from embryos. Research and therapy with adult stem cells is not embroiled
in serious controversies but unrelenting watchfulness is indicated. Detailed National
and institutional guidelines should be formulated to protect patients and donors
from possible harm. It is extremely important that persons drafting guidelines are
professionals with adequate understanding of scientific, ethical, legal and social
aspects of SCRT and that all stakeholders are represented. As the field is new and
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rapidly advancing it is equally important that once the guidelines are developed
they are reviewed at appropriate intervals. It is imperative to develop mechanisms
for implementing guidelines/Regulatory Frame Work and to invest the Implementing
Authority with adequate powers to punish violations. Human Organ Transplant
Authority (HOTA) for cell based research & therapy: The guidelines have to be in
accordance with religious sensitivities and cultural norms of our people. PMRC
should remain the main Regulatory Authority in the area of stem cell and related
medical research. HOTA will set up an advisory subcommittee of the National
Bioethics Committee in Research (NBCR) for cell based Research & Therapy. Given
the wider application of such technologies by sector other than the Ministry of
Health such as educational and research institutions and Ministry of Science &
Technology, the HOTA Sub-Committee will have additional representation from these
sectors. The membership of this HOTA Sub-Committee will be derived from the
membership of the National Bioethics Committee for Research and shall also consist
of additional co-opted members representing the fields of reproductive health,
hematology and representatives of all organ transplant societies/ institutions. All
centers performing stem cell research and therapy should be registered with the
HOTA for accreditation, on the basis of their technical competence (in stem cell
collection procedures, enumeration, cryopreservation, stem cell viability studies)
and ethical review and oversight procedures. All proposals involving stem cells of
any source for research or non-approved therapy (see Appendix 1 for approved
therapeutic indications), should be cleared by Human Organ Transplant Authority
(HOTA) Sub-Committee, through the National Bioethics Committee. Scope: The
HOTA will have the responsibility to examine the scientific, technical, ethical, legal
and social issues in the area of cell based research and therapy. 7
Scientific/Technical Issues: All proposals, from public or private sector, for research
or non-approved stem cell therapy (SCT) should be placed before the HOTA Sub-
Committee for approval after due clearance through appropriate institutional ethical
review committee and scientific peer review process. Ethical, legal and social
issues: Institutional Ethics Committees should keep in view the ethical, legal and
social issues and should adhere to the ethical guidelines as per the Pakistan
National Guidelines for Human Research (2006), the Helsinki Declaration (2000), the
CIOMS guidelines (2002) as well as the WHO publication on Genomics and Global
Health (2003) 8 GUIDELINES Adult stem cells: While the approved use of specific
adult stem cells does not pose major ethical problems at present their use must be
considered experimental except for specific hematological indications. As indicated
above, all centers doing stem cell treatment and research should register with
HOTA. Bone marrow, peripheral, blood, skin, limbal cells are some of the tissues in
use for procuring adult stem cells. No commercial sale or transaction for stem cell
use or research will permitted All clinical use or therapeutic trails of stem cell must
be conducted by institutions and qualified specialists who must be registered with
HOTA. Proper informed consent procedures are to be followed as given in
international ethical guidelines. Standard Operating Procedures, as outlined in the
Appendix I, should be followed for procurement, cataloguing, source identification,
storage and preservation. In vivo Studies: Experimental work on stimulation of
adult stem cells also has tremendous future. However, approval from HOTA must be
sought for carrying out all such experiments. Cord Blood stem cells: For using
umbilical cord blood from a live fetus or a neonate it must be ensured that no harm
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should occur to the fetus or the neonate. Since the exact timing of the clamping of
the umbilical cord has a significant impact on the neonate and early clamping may
cause an abrupt surge in arterial pressure resulting in cerebral intraventricular
haemorrhage, particularly in premature neonates, normal clamping protocol
(Appendix II) will be followed when collecting foetal blood for transplantation. There
is a risk that the neonate donor may need his or her own cord blood later in life.
Parents will be informed of the risks of donation and a written consent will be
obtained from them on behalf of the fetus. Cord blood stem cells are generally used
for hematopoietic stem cell transplantation. For any other form of therapy detailed
protocol has to be submitted for approval. The following points should be
specifically considered while collecting umbilical cord blood for banking: No harm
should occur to the fetus or the neonate. Exact timing of the clamping of umbilical
cord should be defined. Early clamping may lead to cerebral haemorrhage. Normal
clamping protocol should always be followed. Parents should be correctly informed
regarding risks and benefits involved. Free informed consent should be obtained
from both parents. If there is disagreement between the parents, the mothers wish
shall prevail. ID card should be issued for voluntary donation to enable
access/benefit in future in case required for self/relatives. Cord blood stem cell
banking is permissible. However, all Cord Blood Banks should be registered as per
guidelines applicable to the blood banks. Commercial exploitation of 9 stored blood
should be regulated strictly. Special care must be taken in collection, processing and
storage of umbilical cord stem cells to avoid transmission of infections. Maternal
screening should be carried out for transmissible infections. Purpose of banking
should be clearly explained to couples interested in storing cord blood. The ideal
use of these cells at present is for allogenic hematopoietic stem cell transplantation.
Expansion of umbilical cord stem cells for transplantation in adult and use for non-
hematopoietic indications is still in exploratory phase. When it comes to registries
and banking, the commercial aspects pose additional problems. The advertisement
related to collection of samples should be carefully looked into with respect to
conflict of interest, utility of samples, accessibility and affordability Fetal stem
cells/tissue: These can be processed from spontaneously aborted fetus or from
fetuses obtained from hospitals. International guidelines for fetal tissue
transplantation should be followed. DNA fingerprinting of the cell line should be
preserved and it is advised to keep it in cell repository. Generally fetal stem cell use
is presently experimental. Any therapeutic fetal cell transplantation will not be
permitted at present and this possibility will be examined at an appropriate time
later. Termination of pregnancy should not be sought with a view to donate fetal
tissue in return for possible financial or therapeutic benefits. Informed consent to
have a termination of pregnancy and the donation of fetal material for purpose of
research or therapy should be taken separately. The wishes of the mother will
prevail in case of any difference of opinion. Embryonic stem cells (ES Cells): No
Embryo should be generated for the sole purpose of obtaining stem cells. Only
surplus or spare or supernumerary embryos (under 16 weeks gestation), can be
used with the permission of the couple from IVF clinics. Cell lines generated should
be registered. At present only research program relating to in vitro induction of
differentiation into various cell lines will be cleared by the NRC on case to case
basis. Any therapeutic trial will be examined in detail before approval. Reproductive
cloning will not be permitted on ethical grounds. Human cloning is not permitted for
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the purpose of creating a new individual. Monitoring Mechanism: The HOTA will be
authorized to make site visits as required and receive annual reports of cleared
projects. These annual reports should be submitted in appropriate format for further
continuation of the project by the 10th month of commencement of the project
decision and review should be communicated in 4-6 weeks. Any violation of
guidelines would be strictly dealt with and procedures will be established to enforce
such regulations and penalties in the event of violation through the PMDC and the
Ministry of Health. Commercialization and Patent issues: Established stem cell lines
can have considerable commercial value as wide ranging potential benefits for large
number of patients is possible. Patent issues need wider discussions and public
debates should be held on who should be the beneficiary and what 10 type of
patents can be taken. Exploitation of Pakistani biological material by foreign
commercial interests is not permitted. IPR protection should be accorded to
commercially utilizable materials and procedures. Benefits of commercialization
should be extended to community including patients, researchers and institutions
engaged in research and applications. Regulation of stem cell lines: All cell lines
should be registered with HOTA. All proposals for therapeutic trial should be cleared
by this committee before submitting to national or international funding bodies.
International collaboration: National guidelines of respective countries should be
followed and all research protocols for sponsored research must be cleared with
appropriate ethical review committees in the sponsoring country. Collaboration will
be permitted only after the joint proposal with appropriate MOU is approved by the
National Research ethics Committee following clearance by the HOTA. No export of
cell lines per se will be permitted. Generation of embryonic stem cells from non-
human sources: Embryonic stem cells for experimental purposes cal also be
obtained from sources such as rodents. Primates, domestic animals, farm animals
etc. Research in these areas should be encouraged but is strictly experimental and
must undergo similar ethical review and clearance. Check list to be submitted to the
Human Organ Transplant Authority (HOTA) for any proposal 1. Title of the proposal.
2. Institution concerned. 3. Investigators name with brief bio-data and relevant
publications. 4. Source of funding. 5. An assurance signed by the responsible
institutional head that the pluripotent stem cells were derived from human embryos
in accordance with the guidelines. 6. Informed consent document duly signed by
appropriate individuals. 7. Brief summary of the proposed work. 8. IRB/IEC clearance
(if sponsored, ethical review and clearance from appropriate ethical review
committees in the sponsoring countries). 9. Certificate that no undue inducements/
incentive is provided for donation of embryo. 10.Separate consent for infertility
treatment and donation of embryos to be taken. 11.Certificate that only spare
embryos are being used. Private sector involved in such research should also come
under the purview of this committee and it should comply with due safeguards and
standards and submit all proposals for clearance. 11 Permissible Research on Stem
Cells 1. Use of human stem cell lines derived from hES, hEG, hSS or fetal/adult stem
cells is permitted for in vitro investigations. 2. In vivo studies of human cell lines
and their differentiated derivatives are allowed in small non-primate animals at
various stages of development (embryonic, fetal, postnatal, adult). The animals
derived from these experiments shall not be allowed to breed especially when there
is a possibility that human cells could significantly contribute to development of
gonads and/brain. 3. Animal studies for pre-clinical evaluation of efficacy and safety
of human stem cell lines is also allowed as per above mentioned criteria. 4.
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Informed consent from donors is required for: in- vivo animal studies when using
stem cells from donors of bone marrow, peripheral blood, umbilical cord blood, skin,
limbal cells, dental cells, bone cells, cartilage cells or any other organ (including
placenta) Establishment of fetal/adult hSS and new hES cell lines from spare,
supernumerary embryos. Establishment of Umbilical Cord Stem Cell banks Clinical
Grade Stem Cells for Biomedical Research and Therapy Clinical grade stem cells
are classified as therapeutics and are required to be produced under international
GMP/GTP conditions. The cells should be well characterized about their stemness
and safety. Prohibited Research Creation of a zygote by IVF, SCNT or any other
method with the specific aim of deriving a hES cell line for any purpose.
Introduction of hESCs into non-human primate blastocysts in vitro culture of any
intact human embryo for longer than 14 days or until formation of the primitive
streak begins, whichever occurs first Breeding of animals that have had hESCs
introduced into the germ line Germ line genetic engineering or reproductive
cloning. Transfer of human blastocysts generated by SCNT or parthenogenetic or
androgenetic techniques into a human or non-human uterus. Animals in which any
of human stem cells have been introduced at any stage of development should not
be allowed to breed. Research involving directed non- autologous donation of any
stem cells to a particular individual is also prohibited. Any research involving
implantation of human embryo into uterus after in vitro manipulation, at any stage
of development, in humans or primates. Ref: Ethical Guidelines for Biomedical
Research in human Subjects. 2000, 2006 ICMR 12 Application of blood and marrow
transplantation (BMT) Introduction: The clinical use of progenitor cell transplantation
technology has been instrumental in the treatment and cure of thousands of
patients with haematological and non haematological malignant disorders.
However, the procedure still carries significant morbidity and mortality. It is also at
risk of commercial exploitation and unethical practices. The setting up of centres for
BMT must be strictly regulated and their working should be periodically and
objectively monitored. The following guidelines are for the infrastructure of these
centres: BMT Centre This centre must be located in a tertiary care hospital which
will provide a wide range of support and patient care services including critical care
management, haemodialysis, advanced imaging facilities, cardiac support facilities,
infection surveillance and management facilities. Dedicated areas, according to
workload will be earmarked for BMT patients in these hospitals. The BMT Centre will
have A clinic to perform pre-donation physical examination and specialized tests
(X-ray, ECG, Echo etc) Indoor facilities which must have dedicated operation
theatres and isolation rooms with state-of-art ventilation facilities. The BMT Centre
must have harvesting facilities for bone marrow and progenitor cells. There should
be atleast two cell-separators, facilities for quantitative and qualitative evaluation of
harvested progenitor cells and facilities for cryo preservation and storage of
progenitor cells. The Centre must have direct access to the following accredited
facilities. HLA Typing Laboratory Microbiology Laboratory Biochemistry
Laboratory Blood Transfusion Laboratory Histopathology Laboratory I. Essential
Personal a. Medical Director The centre must be under the control of a medical
doctor who has accredited postgraduate qualification in haematology, a minimum of
15 years experience in laboratory and clinical haematology and demonstrable

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knowledge and interest of BMT. 13 b. Transplant Physician At least two transplant
physicians should be full time employees of the centre. They must be medical
graduates and have accredited post-graduate qualification in haematology. They
must have 10 years experience of clinical haematology, have worked under the
supervision of a transplant physician for atleast 2-years at a centre doing a
minimum of 10 BMT per year. They should have exposure to atleast 10 bone marrow
harvesting procedures. c. Program Coordinator Master in Social Sciences, having
working knowledge of statistics, computers and record keeping. II. Support Medical
Faculty 1. Anesthetist 2. Pulmonologist 3. Gastroenterologist 4. Nephrologist 5.
Cardiologist 6. Neurologist 7. Infection Disease Physician II. Support Services 1.
Pharmacy 2. CSSD 3. Nutritionist 4. Social Worker III. Monitoring of Services The
services of the centre must be supervised by a regulatory body which will include;
1. Medical Director 2. Program Coordinator 3. Legal Expert 4. Financial Advisor 5.
Ethical Service Advisor 6. Social Service Advisor 7. Womens Representative 8.
Donor Representative IV. Accreditation of the Centre It should be mandatory for all
BMT centres to allow access to inspectors for the purpose of accreditation. The
inspection team, to be constituted by HOTA, must ensure that the centre is located
in an institution at a fixed physical site, is equipped and staffed as per regulation,
and is not involved in unethical commercial practices. The centre must maintain a
record of donors of blood, aphaeresis progenitor cells and bone marrow. It should be
carrying out management activities including education, counseling, rehabilitation
of patients and should be capable of dealing with medical screening and
confidentiality issues. 14 Appendix I GUIDELINES FOR THE COLLECTION,
PROCESSING AND STORAGE OF HUMAN BONE MARROW, PERIPHERAL STEM CELLS
FOR TRANSPLANTATION General principles: Each stem cell transplant unit shall
establish, document and maintain an effective and economical quality system to
ensure and demonstrate that adequate and appropriate standards of work are
maintained. Procedural step Related to Bone Marrow Harvest: Donor suitability must
be ensured. The donation may be an autograft or an allograft from a related or
unrelated donor. The allogenic donor should be counseled and a full medical
examination carried out to establish that the donor is fit for anesthesia. Routine
haematological, biochemical and virological parameters are checked. A chest X-ray
and ECG should be performed. Written informed consent must be obtained from the
donor before the recipient commences pretransplant conditioning. It is a cardinal
principle that unrelated donors should be anonymous, unpaid and not pregnant. The
donor is admitted, night before harvest to the transplant centre or hospital
experienced in marrow harvests. The donor receives a unique donor identification
number (DIN) and this must be assigned to the marrow, both primary and
secondary collection packs and all the sample tubes used. Marrow Collection: Before
the start of harvest the identity of the donor must be checked. Collection of marrow
should be by aseptic technique into pyrogen-free containers with sufficient
anticoagulant for the quantity of marrow to be collected and appropriate for the
subsequent processing. The container label should state the amount of
anticoagulant and the maximum amount of marrow that can be collected and
required storage temperature. The marrow should be anticoagulated with ACD-A
unless preservative free heparin is requested by the transplant centre. In the latter
case marrow should be returned to the patient within 12 h. The anticoagulant
solution must be clear, free from deposit. Harvest should only be undertaken by
trained medical staff. Personnel required are an anesthetist; operators to harvest
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marrow, haematological scrub nurse and theatre staff. Harvest lists should be
dedicated or at the beginning of the operating list. The volume of marrow withdrawn
from the donor must be controlled. The volume taken should be such that a target
cell count appropriate to transplant is reached. Records: A record of the total
volume of marrow removed from the donor must be documented in the patients
notes. The most efficient way of measuring the volume in plastic bags is by weight
of 1 ml. Of marrow is 1.06g; a unit containing 405-495 ml should therefore weigh
430-522 g plus the weight of the container and its anticoagulant. 15 Operating
procedure: The anaesthetized patient is positioned on the operating table with
pelvis supported to make the iliac crest prominent. The choice of harvest needle is
one of personal preference and can very from conventional needles for diagnostic
aspiration from iliac crests through to designed harvest needles with holes along the
lateral aspect of the shafts (e.g. (Islam). No more than 5 ml of bone marrow should
be collected into a 20 ml syringe containing preservative free heparin and the
needle then repositioned after each aspiration. It is usually possible to take marrow
at several different depths from one site. The needle is then withdrawn and resited,
samples being taken as widely as possible along the posterior iliac crest. If an
inadequate cell count is obtained from both posterior iliac crests the patient should
be turned over and further aspirates taken from the anterior iliac crests and the
sternum. Marrow Processing: A closed system is preferred in which the syringe is
emptied directly into 500ml or 1L bags containing anticoagulant. Marrow should be
filtered in accordance with the harvest centers routine practice to remove fat,
aggregates, clots or bone spicules if it is not processed further by centrifuge or
sedimentation. During and after harvesting samples of marrow can be obtained
from the bag and nucleated cell count carried out to ascertain the anticipated
volume needed to produce engraftment. Estimation of Marrow dose at harvest: The
present recommended dose of nucleated cells is expressed per kilogram of
recipient body weight. 1. Autografts: minimum dose 1.5 x 108 cells /kg. 2. HLA
identical sibling allografts for aplastic anaemia: minimum dose 3 x 108 cells /Kg
(Storb et al, 1977). 3. HLA identical sibling for leukemia haemoglobinopathies and
inborn errors of metabolism: minimum dose 1.5-2 x 108 cells/kg 4. Unrelated donor
allograft: minimum dose 2-3 x 108 nucleated cells/Kg A minimum number of
marrows (nucleated cells) per kilogram recipient body weight should be stated by
each transplant unit to permit engraftment. The weight of the recipient must be
ascertained. Post-Harvest Marrow Processing: In allogeneic transplantation the
completed barrow bag is rendered airtight, labeled and its contents may then be
infused intravenously into the recipient where both donor and recipient are ABO
compatible or cryopreserved. If volume reduction is required buffy coat cells can be
separated and transferred to a second sterile pack. When there is no major blood
group incompatibility between donor and recipient then a cell fraction known to
contain the repopulating stem cells and low in haematocrit should be obtained by
density separation. If removal of T cells is required to prevent graft versus host
disease the volume of the donation is reduced before incubation with monoclonal
antibodies. An appropriate method 16 is to use blood cell washer or cell separator.
Processing also may be modified to collect donor red cells for autologous reinfusion.
Autologous marrow can be similarly separated to leave a buffy coat or further
processed to a mononuclear cell fraction which may be purged before storage.
Purging involves incubation of the marrow with most commonly the
cyclophosphamide antimetabolite, 4 hydoxy-per-oxy-cyclophosphamide (4 H-C;
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Kaizer et al., 198) or with monoclonal antibodies. Monoclonal antibodies may also
be used for positive selection of putative progenitor stem cells (e.g. anti-CD34
antibodies). The purged / unpurged marrow is then cryopreserved (see below).
Biological methods of purging such as long-term bone marrow culture are still
experimental. Peripheral Blood Stem Cell Collection: Haemopoietic cells are present
at low concentration in steady-state blood. Such cells can be mobilized from the
bone marrow into peripheral blood during the recovery phase from
myelosuppressive chemotherapy or following administration of haemopoietic
growth factors or by a combination of the two. They are collected by leukapheresis
on a blood cell separator set to obtain sufficient mononuclear cells for engraftment.
A suggested value is 7x 108mononuclear cells/kg but this will vary according to the
centre and whether myeloablative treatment is given. Some centers use lower
values of 2 x 108 mononuclear cells /kg. Mobilized blood progenitor autografts are
usually associated with very rapid haemopoietic reconstitution. Timing of the
leukapheresis may be guided by the appearance of CD34 positive cells is the blood,
or by surrogate markers such as white blood cell and platelet counts. During
recovery from myelosuppressive therapy a white count greater than 1 x 109 /1 and
platelets greater than 70 x 109 /l are generally taken as the time to initiate
leukapheresis but absolute counts will very with the chemotherapy regime and
whether or not growth factors are employed. Mobilized blood stem cells collections
are usually assessed by their CD34 positive cells or CFU-GM. Threshold doses need
to be determined by each centre by the recommended minimum number of CFU-GM
and is usually in the range 5-20 x 104 /kg (Craig et al., 1992). It is usual that the
donor is an autograft recipient and that the material is stored by cryopreservation.
Nucleated cell collection: The technique for procurement of the nucleated cell layer
rich in stem cells depends on the cell separator machine used. The aim is to collect
the buffy coat interface between plasma and red cell. The total nucleated cell
volume collected is determined from the total blood volume of the donor
ascertained from their height/ weight prior to apheresis. It is recommended that in
adults 7-15 /l is processed. Where the nucleated cell yield is greater than 100 x
109 /l dilutions in plasma are needed to prevent aggregation during the process of
freezing (see Storage). When the collection is complete the residual volume of blood
is returned to the donor. 17 Appendix II GENERAL SPECIFICATION FOR
IDENTIFICATION, STORAGE AND TRANSPORTATION OF BONE MARROW AND
PERIPHERAL BLOOD STEM CELLS Identification: The unit containing stem cells must
be labeled with the name of the product, the donors name and hospital number,
unique donation number, date of collection, the presence and type of anticoagulant
and additive media if any, ABO and Rh D group and the volume of the product.
Storage (Rowley & Davis.1990; Reiman & Sacher, 1991) An SOP should be written to
include the following: a designated storage area: a procedure for quarantine of bone
marrow and peripheral blood stem cells: a procedure for validating the conditions of
storage achieved in any given storage area. This should include temperature control
and preventation of microbiological contamination. If, as a result of microbiological
screening, the donor is positive for any of the mandatory microbiological marker
(table 1) then that unit should be stored in isolation to avoid cross contamination of
other units. Storage unfrozen. Unmanipulated bone marrow and peripheral blood
stem cells may be stored unfrozen for up to 72 h at 4 + 2C. The anticoagulant
conventionally used in ACD. Heparin is unsuitable. Storage at 4C will, however,
reduce leukocyte viability and cellular aggregation may occur. Preparation of frozen
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marrow and peripheral blood haemopoietic cells Haemopoietic cells in bone marrow
are enriched and concentrated by differential centrifugation into a buffy coat.
Further enrichment using a density gradient may be required. Peripheral blood cells
are not normally concentrated. The cell concentration frozen should be less than
100 *109 /1 (see above Nucleated Cell Collection). The above products are
cryopreserved using one of the established cryoprotectants, for example 10 or 15%
v/v dimethyl sulphoxide (DMSO) or 5% v/v DMSO plus 6% w/v hydroxyethyl starch
(HES). DMSO should be added slowly to its diluents to avoid a rise in temperature
since desired final concentration of DMSO is isotonic in molar terms. This requires
the addition of albumin solution (HAS) is used additional salts or a suitable
impermeable sugar are necessary (Pagg. 1984). The diluent is then cooled on ice to
0-4C, DMSO added and the cryoprotectant mixed with an equal volume of
haemopoietic cells. The freezing process: A feedback-controlled cooling machine
(controlled rate freezer) will provide reproducible, standardized cooling conditions.
The cooling program should be one that has been shown to be effective (e.g. 2 C/
min to -30C, followed by 4C/min to -70C with adequate control of freezing
plateau: Gorin, 1986). Passive cooling methods may also be effective providing that
they produce acceptable cooling profiles (Makino et al., 1991). The bags in which
the marrow is cooled should be made from plates ton produce a 18 thickness of
about 3 min to facilitate heat transfer. Temperature should be recorded in a control
bag and the data kept with the processing records. Peripheral blood cells may be
cryopreserved by the same methods. Once below -70C the bone marrow and
peripheral blood stem cells should be transferred for storage. Such deep frozen is
fragile and container bags may fracture. Thawing of frozen bone marrow/peripheral
blood cells: 1. Contamination of the marrow/peripheral blood bag with water bath
fluid is to be avoided and it is essential that double bags are used. 2. Thaw in a
water bath at 37-40C with gentle agitation. Observe carefully for rapid expansion
of the bag during thawing which will suggest that liquid nitrogen has leaked into the
bag during storage. If this occurs release the pressure immediately by puncturing
the bag with a sterile needle. 3. DMSO toxicity is temperature dependent ( Goring
1986). It is therefore important to remove the bags from the waterbath soon as the
last ice has melted and not to allow the marrow to reach the waterbath
temperature. Keep the thawed marrow cool until administration and infuse within 5
min of complete thawing. Current practive is not to remove the DMSO before
injection into the patient (Rowley & Anderson, 1993). Premedication of the patient
with steroid/ antihistamine is recommended. 4. Any thawing incidents should be
documented and reported to the clinician in charge of the recipient who will decide
whether action is required. Testing: Testing of frozen products may be performed
utilizing 1-or 2-ml aliquots of material frozen at the same time under conditions that
are as close as possible to the bulk product. It should be noted that small ampoules
will not cool at the same rate as large bags. Assay may be performed to determine
short-term progenitor growth post-cryopreservation. Specific Laboratory Procedures
Related to Provision of Haemopoietic Cells for Engraftment Serology: The ABO and
RhD blood groups of all donors should be performed as set out in the Guidelines for
Compatibility Testing in Hospital Blood Banks (Boulton et al, 1987). Cell Counting:
The minimum information required is the total nucleated cell count obtained at
stem cell harvest. If counts are corrected for peripheral blood dilutions, this should
be clearly indicated to avoid confusion with uncorrected nucleated counts. Such
counts should be performed on a cell counting machine by validated methods or
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performed manually. The volume of bone marrow or peripheral blood harvest is best
calculated by weight. 19 Cell Viability The quality of frozen cells can be assessed by
the trypan blue exclusion test or automated techniques using a flow cytometer and
propidium iodide. These results do not correlate with in vitro growth, but given
indication of consistency of the technique. Red Cell Depletion: Red cell depletion of
the donor graft is strongly recommended in ABO mismatched allogenic transplant.
This can be carried by HES sedimentation or differential centrifugation (Braine et al.,
1982: Ho et al., 1984). An alternative is to plasma exchange the recipient and/or to
give A/B antigen rich secretor plasma prior to the transplant. Microbiology and
Virology: The sterility of the bone marrow/ peripheral blood product at various
stages should be ascertained using liquid and semi-solid culture medium. This is
especially important prior to freezing and at the final stage of processing after
freezing before the product is infused into the patient. A pilot tube is thawed and
cultured. The clinician should be informed if the cultures are positive. Donor bone
marrow can transmit infectious disease and all donors should have the mandatory
tests (shown on table 1) carried out and where possible the serological tests
repeated at not less than 90 days from the first screening sample. Table-1: 1.
Mandatory HBsAg (hepatitis B surface antigen) HIV 1+2 antibody (human immune
deficiency virus) Anti-HCV (Hepatitis C virus antibody) VDRL or equivalent test for
syphilis 2. Advisable CMV antibody Toxoplasma gondii antibody 3. Desirable HSV
(herpes simplex antibody) HZV (herpes zoster antibody) HTLV-1 (Human T-
Lymphotrophic virus) 20 Appendix III PRE-REQUISITES FOR A STEM CELL
TRANSPLANTATION CENTRE Standard Operating Procedures (SOPs): Standards for
collection, processing and storage of cells for clinical use: For the consistence and
reliable results International standard procedures should be adopted. These
standards are designed to provide minimum guidelines for facilities and individuals
performing collection, processing and storage of cells for clinical use or providing
support services for such procedures. These standards are not intended to include
all procedures and practices that a facility or individual should implement if the
standard of practice in the community or governmental laws or regulations establish
additional requirements. Each facility and individual should analyze their practices
and procedures to determine whether additional standards may apply. Protocols
shall be developed, implemented, and documented for the validation or
qualification of significant products of facilities, processes, equipment, reagents,
labels, containers, packaging materials, and computer systems. For this purpose
training of the staff in renowned stem cell/transplantation centers is recommended.
There shall be procedures for biological, chemical, and radiation safety, as
appropriate, and a system for monitoring training and compliance. Personnel 1.
There shall be a Collection Facility Head / Officer in-charge an individual with a
doctoral degree, qualified by postdoctoral training or experience for the scope of
activities carried out in the facility. This individual is responsible for all technical
procedures and administrative operations of the collection facility. This individual
should participate regularly in educational activities related to the field of cell
collection and / or processing. 2. The Collection or Processing Facility Head / Officer
in-charge with a doctoral degree, n shall have at least one years experience in the
collection procedure. This individual shall have performed or supervised at least 10
collection procedures of each type that are to be carried out at the facility. 3. There
shall be a Collection Facility Medical Head/Director who is a physician licensed in the
jurisdiction in which the facility is located. This individual is directly responsible for
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the pre-collection evaluation of the donor, final approval of the prospective donor
for the collection procedure, conduct of the collection / processing procedure, care
of any complications arising from collection and compliance of the collection facility
with these Standards. 4. There shall be adequate numbers of trained support
personnel available at the facility where the collection is performed. 21 5. The
training, continued education and continued competency for the performance of
operations shall be documented. Ethical issues: Informed consent from the donor
shall be obtained and documented by a licensed physician or other health care
provider familiar with the collection procedure before the high dose therapy of the
recipient is initiated. The procedure shall be explained in terms the donor can
understand, and shall include information about the significant risks and benefits of
the procedure and tests performed to protect the health of the donor and recipient
and the rights of the donor to review the results of such tests. The donor shall
have an opportunity to ask questions and the right to refuse to donate. In the case
of a minor donor, informed consent shall be obtained from the donors parents or
legal guardian in accord with applicable law and shall be documented. Laboratory
facilities for cell processing The facility responsible for cell processing shall be of
adequate space and design for the intended procedures. The operation of the
facility shall be divided into defined areas of adequate size for each operation to
prevent improper labelling and/ or contamination of the product. The facility shall
be operated in a manner to minimize risks to the health and safety of employees,
patients, donors and visitors. The facility shall have written policies and
procedures for infection control, biosafety, chemical and radiological safety,
emergency response to worksite accidents, and waste disposal. Instructions for
action in case of exposure to communicable disease or to chemical, biological and
radiological hazards shall be included in the safety manual. Decontamination and
disposal techniques for medical waste shall be described. Human tissue shall be
disposed in such a manner as to minimize any hazard to facility personnel or the
environment in accordance with applicable governmental laws and regulations.
Eating, drinking, smoking, the application of cosmetics or the insertion or removal of
contact lenses shall not be permitted in work areas. Gloves and protective clothing
shall be worn while handling human specimens. Such protective clothing shall not
be worn outside the work area. There shall be adequate equipment for the
procedures performed at the facility. The facility shall be maintained in a clean and
orderly manner as established in SOPs. The facility shall be secure to prevent the
admittance of unauthorized personnel. Equipment Equipment used in the
processing, testing, freezing, storage, transportation, and transplantation of
products shall be maintained in a clean and orderly manner and located so as to
facilitate cleaning, calibration and maintenance. 22 Each collection facility shall be
operated in a manner to minimize risks to the health and safety of employees,
donors, volunteers, and patients. Suitable environment and equipment shall be
available to maintain safe operations. Environmental control lab facilities of
international standards are must. Equipments used in the collection of products
shall be maintained in a clean and orderly manner and located so as to facilitate
cleaning, calibration and maintenance. The equipments shall be observed,
standardized and calibrated on a regularly scheduled basis as described in the SOPs

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Manual and according to the Manufacturers recommendations. Sterilization
equipments shall be designed, maintained and used to ensure the destruction of
contaminating micro-organisms. Refrigerators and freezers used for the storage of
specimens, cell products, blood products, human tissues, or reagents shall not be
used for any other purpose. Consumables Reagents used in collection of products
shall be of appropriate grade for the intended use and shall be sterile. Procedures
for production of in-house reagents shall be validated. Each supply and reagent
used in the collection of the product shall be examined visually for damage or
evidence of contamination as it comes into inventory and this review shall be
documented. Such examination shall include inspection for breakage of seals,
abnormal colour and expiration date. All supplies and reagents used in the
collection of products shall be stored in a safe, sanitary, and orderly manner. Lot
numbers and expiration dates of reagents and disposables shall be recorded.
Supplies and reagents should be used in a manner consistent with instructions
provided by the manufacturer. Tissue processing Human tissue refers to cells
obtained from any living or cadaveric human donor or organ. The cell processing
facility shall have written policies and procedures addressing all appropriate aspects
of the operation including processing; emergency and safety procedures; donor and
patient confidentiality; quality management and improvement; errors, accidents
and adverse reactions; corrective actions; personnel training; competency
assessment; outcome analysis; audits; labelling; storage, including alternative
storage if the primary storage device fails; transportation; expiration dates; release
and exceptional release; disposal of medical and biohazard waste; equipment and
supplies; maintenance and monitoring; cleaning and sanitation; and a disaster plan.
All open cell handling procedures must be performed in class 100 environment.
More than minimal manipulation of products should only be performed in a clean-
room environment. Environmental monitoring of such rooms must be performed and
documented. There shall be a written request from the recipients physician before
processing is initiated. 23 Processing of cellular therapy products shall be
performed according to protocols defined in the facilitys SOPs. Methods for
processing shall employ aseptic technique and be validated to result in acceptable
cell viability and recovery. There shall be written documentation of an interim
assessment of donor suitability for the collection procedure by a qualified person
immediately prior to each collection procedure. For donors of peripheral blood
aphaeresis products, a complete blood count, including platelet count, shall be
performed within 72 hours prior to the first collection and within 24 hours before
each subsequent aphaeresis. For progenitor and other adult cell collection,
methods for collection shall employ aseptic technique and shall use procedures
validated to result in acceptable progenitor cell viability and recovery. The
collected cells shall be packaged in a closed sterile container / transfer packs
approved for human cells and labelled. Bone Marrow shall be filtered to remove
particulate material prior to final packaging, distribution or transplantation using
sterile filters that are non-reactive with blood. Labelling control Labelling
operations shall be conducted in a manner adequate to prevent mislabelling of
products that shall include the following quality management elements: Container
labels shall be held upon receipt from the manufacturer pending review and

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proofing against a copy approved by the Collection Facility In-charge or designee to
ensure accuracy regarding identity, content, and conformity. Stocks of unused
labels representing different products shall be stored in an orderly manner to
prevent errors. Stocks of obsolete labels shall be destroyed. A system of checks in
labelling procedures shall be used to prevent errors in translating information to
container labels. All labelling shall be clear and legible and printed using moisture-
proof ink. Labels shall be affixed or attached firmly to the container. The proper
name and significant modification(s) shall be noted on the label. Products that are
subsequently re-packaged into new containers shall be labelled with new labels as
appropriate. Records to allow tracking of products including collection or processing
facility identity, unique numeric or alphanumeric identifier, collection date and time,
product identity, donor and recipient information on the original container shall be
maintained. When the label has been affixed to the container, a sufficient area of
the container shall remain uncovered to permit inspection of the contents. The
product label shall be complete. Not applicable (NA) may be used when appropriate.
Stem cell storage and transportation facilities: Cell collections shall be handled and
discarded with precautions that recognize the potential for transmission of
infectious agents. Issues of donor health that pertain to the safety of the collection
procedure shall be communicated in writing to the collection facility staff. 24
Prospective donors shall be evaluated by medical history, physical examination by a
trained physician and laboratory testing for the risks of the collection procedure
including the possible need for central venous access and/or mobilization therapy
for collection of blood cells and anaesthesia for collection of marrow. This evaluation
shall be documented. Cryopreservation Sample aliquots of the product,
cryopreserved and stored under the same conditions as the product, should be
available for testing for 5 years. Cryopreservation procedures shall be included in
the cell processing facilitys SOPs and shall describe: The name and freezing
criteria of the cell product or aliquot. The cryoprotectant solution and its final
concentration. Cryopreservation container & acceptable range of product volume
for reproducible cryopreservation. Acceptable range of nucleated cell
concentration of the final product after cryopreservation. Cooling rate and product
temperature at endpoint of controlled cooling. The cooling rate achieved shall be
recorded, if a rate-controlling device is used. Acceptable temperature range for
storage. Storage Materials that may adversely affect cell products shall not be
stored in the same refrigerators or freezers. For products immersed in liquid
nitrogen, procedures to minimize the risk of microbial cross-contamination of
products shall be employed. Refrigerators and freezers for product storage shall
have a system to monitor the temperature continuously or at least every 8 hours.
For products fully immersed in liquid nitrogen continuous temperature monitoring is
not required. There shall be a mechanism to ensure that levels of liquid nitrogen in
liquid nitrogen freezers are maintained. Storage devices for products or reagents
for product processing shall have alarm systems that are continuously active. The
alarm systems shall have audible signals. If laboratory personnel are not always
present in the immediate area of the storage device, a remote alarm device shall be
required at a location staffed 24 hours a day. Alarms shall be set to activate at
temperatures or an unsafe level of liquid nitrogen to allow time to salvage products.

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 There shall be written instructions to be followed if the storage device fails. These
instructions shall be displayed in the immediate area containing the storage device.
Alarm systems shall be checked periodically for function. Additional storage
devices of appropriate temperature shall be available for product storage if the
primary storage device fails. The storage device shall be located in a secure area.
Locking capability for the device or the storage location should be used when the
area is unattended. 25 Transportation Procedures for transportation of the collected
product shall be designed to protect the integrity of the product being shipped and
the health and safety of facility personnel. The primary product container shall be
placed in a secondary container and sealed to prevent leakage. The outer shipping
container shall be thermally insulated and shall conform to the regulations
regarding the mode of transport. Frozen or non-frozen products that leave the
facility or are transported on public roads shall be shipped in an outer shipping
container. The outer shipping container should be made of material adequate to
withstand leakage of contents, shocks, pressure changes, and other conditions
incident to ordinary handling in transportation. Cryopreserved products with an
indicated storage temperature below -80C shall be shipped in a validated liquid
nitrogen dry shipper that contains adequate absorbed liquid nitrogen to maintain
temperature at least 48 hours beyond the expected time of arrival at the receiving
facility. The product shall be shipped to the processing laboratory at a temperature
defined in the SOP Manual. The transit time should be minimized. If the intended
recipient has received high-dose therapy, the product shall be hand-carried by a
suitably informed courier in the passenger compartment. There shall be plans for
alternative transport in an emergency. The products should not be passed through
X-Ray irradiation devices designed to detect metal objects. If inspection is
necessary, the contents of the container shall be inspected by hand. 26 Appendix IV
TRANSPLANT REGISTRY FORM STEM CELL TRANSPLANT FIRST REPORT FORM-16(c)
Refer Rule 10(4) Transplant Centre Name of Physician Recipient Name Recipients
Age/Sex Recipients Fathers Name Recipients CNIC number/Form B Address
Donors name (if applicable) Donors Age/Sex Donors CNIC number/Form B Donors
Fathers name Relationship of recipient Indication for transplant Source of stem cells
i) Adult stem cells: a. Bone Marrow b. Blood c. Tissue If source is blood or tissue
please mention by what process stems are harvested. Is this harvesting procedure
experimental YES NO accepted norm YES NO ii) Cord Blood Cells: iii) Embryonal
stem cells: Derived either from blastocytes or foetal tissues Date of
Procedure_________________________ Date reported: ____________________ Signature:
___________________ Signature: ___________________________________ Head Transplant
Centre Member Evaluation Committee Name: Name: Note: In case donor/recipient is
a married woman, Name of husband as well as father will be endorsed. Fax/Mail to
Administrator, Monitoring Authority Transplantation of Human Organs& Tissues, Al-
Farabi Special Education Complex, G-8/4, Islamabad. On the day of Transplantation
followed by a copy by Courier/post. 27 REFERENCES 1. Jones, R. & Burnett, A.K.
(1992) How to harvest bone marrow for transplantation. Journal of Clinical
Pathology; 45, 1053-1057. 2. Makino, S., Harada, M., Akashi, K., Taniguchi, S.,
Shibuya, T., Inaba, S. & Nilo, Y. (1991) A simplified method for cryopreservation of
peripheral blood stem cellsat -80OC without rate-controlled freezing. Bone Marrow
Transplantation, 8, 239-244. 3. Pegg, D.E. (1984) Red Cell volume in glycerol/sodium

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chloride/water mixtures. Cryobiology, 21, 234-239. 4. Braine, H.G., Sensenbrenner,
L.L., Wright, S.K., Tutschka, P.J., Sasal, R. & Santos, G. (1982) Bone marrow
transplantation with major ABO blood group incompatibility using erythrocyte
depletion of marrow prior to infusion. Blood. 60, 420-425. 5. Commission of the
European Communities (1989). Rules Governing Medical Products in the European
Community, Vol. IV, Guide to Good Manufacturing Practice for Medicinal Products.
Consumer Protection Act. (1987) Chapter 43, Part I, HMSO, London. 6. Reiman, E.M.,
& Sacher, R.A. (1991) Bone marrow processing for transplantation. Transfusion
Medicine Reviews, 5, 214-227. 7. Gorin, N.C. (1986) Collection, manipulation and
freezing of haemopoietic stem cells. Clinics in Haematology, 15, 19-48. 8. Craig,
J.I.O., Turner, M.L. & Parkar A.C. (1992) Peripheral blood stem cell transplants. Blood
Reviews, 6, 59-67. 9. Hrowitz, M.M., Przepiorka, D., Champlin, R.E., Gale, R.P.,
Gratwohl, R.H., Prentice, G.H.,Rimm, A.A., Ringden, O. & Bortin, M.M. (1992) Should
HLA identical sibling bone marrow transplants for leukaemia be restricted to large
centres? Blood, 79, 2771- 2774. 10.Gluckman, E., Wagner, J., Hows, J., Kerman, N.,
Bradley, N., & Broxmeyer, H.E. (1993) Cord blood banking for haematopoietic stem
cell transplantation: an introductional cord blood transplant registry. Bone Marrow
Transplantation, 11, 199- 200. 11.Boulton, F.E., et al. (1987) Guidelines for
compatibility testing in hospital blood banks. Clin. lab. Haemat. 9, 331-341.

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3. Authorization for removal of human organ,- Any donor may authorize the
removal, before his death, of any organ of his/her body for therapeutic purposes in
the manner and on such conditions as specified in Form 1, 2 or 3, as the case may
be. 4. Duties of the recognized transplant surgeon or physician.- (1) A recognized
transplant surgeon or physician shall, before removing a human organ from the
body of a donor before his death, satisfy himself that,- (a) the donor has given
his/her authorization in the relevant Form 1, 2 or 3; (b) the donor is in proper state
of health and is fit to donate the organ or tissues. Thereafter the recognized
transplant surgeon or physician shall sign a certificate as specified in Form 4; (c) in
case the recipient is spouse of the donor, the donor has given a statement to the
effect that they are so related by signing a certificate in Form 2. Thereafter the
recognized transplant surgeon or physician shall sign a certificate as specified in
Form 5; and (d) the donor has submitted an application in Form 10 jointly with the
recipient to grant approval for removal and transplantation of a human organ to the
Evaluation Committee. (2) A recognized transplant surgeon or physician shall,
before removing a human organ or tissue from the body of a person after his/her
death satisfy himself that.- (a) the donor had, in the presence of two or more
witnesses (at least one of whom is a close blood relative of such donor),
unequivocally authorized as specified in Form 6 before his death, the removal of the
human organ of his body, after his death, for therapeutic purposes and there is no
reason to believe that the donor had subsequently revoked the authority as
aforesaid; and (b) that the person lawfully in possession of the dead body has
signed a certificate as specified in Form 7. (3) A recognized transplant surgeon or
physician shall, before removing a human organ from the body of a person in the
event of his brain-stem death, satisfy himself that.- (a) a certificate as specified in
Form 8 has been signed by all the members of the Board; (b) in the case of brain-
stem death of a person of less than eighteen years of age, an authority as specified
in Form 9 has been signed by either of the parents or close blood relatives of such
dead person. 5. Board.- (1) The Evaluation Committees shall ensure that every
hospital or institution shall have a Board to be constituted by that Hospital or
Institution for deceased donor, which shall consist of: (a) Executive Director or
Medical Superintendent or Head of the Hospital; (b) a neurosurgeon or
neurophysician; and (c) an intensivist. Provided that no medical practitioner who
shall be part of transplant team shall be part of the Board. (2) The quorum of the

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Evaluation Committee should be four. However, quorum shall not to be considered
to be complete without the participation of one of the members from category (b)
above. (3) At the time of the meeting, the Evaluation Committee should take note of
all relevant contents and documents in the course of its decision making process
and in the event any document or information is found to be inadequate or doubtful,
explanation should be sought from the applicant and if it is considered necessary
that any fact or information requires to be verified in order to confirm its veracity or
correctness, the same be ascertained through the concerned officer of the
Government concerned. 6. Donation from close blood relatives:- (1)Where the
proposed transplant is between close blood relative, as specified in sub-section (1)
of Section (3) of the Act, the concerned Evaluation Committee shall ensure and
evaluate,-- (i) results of tests for Human Leukocyte Antigen (HLA), alleles A, B and
DR performed by serology or DNA-PCR methods and if necessary further testing by
contemporary technology to confirm relationship i.e. micro satellite gene analysis;
(ii) documentary evidence of relationship e.g. relevant National Identity Card, birth
certificate and marriage certificate; (iii) documentary evidence of .identity and
residence of the proposed donor e.g. computerized National Identify Card, passport,
driving license or bank account where possible: Provided that where such
relationship is not conclusively established after evaluating the above evidence, the
Evaluation Committee, may in its discretion direct further medical tests as
applicable in that case under the current medical best practices and where these
test referred to above do not establish a genetic relationship between the donor and
the recipient, the same tests are to be performed on preferably both parents or at
least one parent. If parents are not available, same tests are to be performed on
such relatives of donor and recipient as are available and are willing to be tested
failing which, genetic relationship between the donor and the recipient shall be
deemed to have not been established. (2) The papers for approval of
transplantation should be processed by the recognized transplant surgeon or
physician and administrative division of the recognized institution while the
approval hall be granted by the Evaluation Committee concerned. (3) Where the
proposed donor or the recipient or both are foreigners; (a) a senior Embassy official
of the country of origin has to certify the relationship between the donor and the
recipient; and (b) Evaluation Committee shall examine the cases of Pakistani donors
consenting to donate organs to a foreign national (who is a close blood relative),
including a foreign national of Pakistani origin, with greater caution. Such cases
should be considered on case to case basis. 7. Transplants between married couple.-
Where the proposed transplant is between a married couple, the Evaluation
Committee shall evaluate all available evidence to establish the factum and
duration of marriage and ensure that relevant documents including marriage
certificate, is placed before the committee along with the information on the
number and age of children and birth certificate of children containing the
particulars of parents, if any. 8. Donation from non close blood relatives.- (1)Where
the proposed transplant is between individuals who are non close blood relatives
the Evaluation Committee shall evaluate that,- (a) there is no commercial
transaction between the recipient and the donor. No payment of money or moneys
worth as referred to in Act, has been made to the donor or promised to be made to
the donor or any other person. In this connection, the Evaluation Committee shall
take into consideration,- (i) an explanation of the link between recipient and donor
and the circumstances which led to the offer being made; (ii) documentary evidence
Page 49 of 87
of the link e.g. proof that they have lived together etc; and (iii) reason why the
donor wishes to donate; (b) there is no middleman / tout involved; (c) that financial
status of the donor and the recipient is probed by asking them to give appropriate
evidence of their vocation and income for the previous three financial years. Any
gross disparity between the status of the two, must be evaluated in the backdrop of
the objective of preventing commercial dealing; (d) the donor is not a drug addict or
a known person with criminal record; and (e) the next of kin of the proposed
altruistic unrelated donor is interviewed regarding awareness about his / her
intention to donate an organ, the authenticity of the link between the donor and the
recipient and the reasons for donation. Any strong views of disagreement or
objection of such kin may also be recorded and taken note of. (2) In the course, of
determining eligibility of the applicant to donate, the applicant should be personally
interviewed by the Evaluation Committee and minutes of the interview should be
recorded. The final interview with the donor should be video recorded. (3) In case of
female donor, her identity and independent consent should be confirmed by a
person other than the recipient. (4) Any document with regard to the proof of the
residence or domicile and particulars of parentage should be relatable to the photo
identify of the applicant in order to ensure that the documents pertain to the same
person, who is the proposed donor and in the event of any inadequate or doubtful
information to this effect, the Evaluation Committee may in its discretion seek such
other information or evidence as may be expedient and desirable in the peculiar
facts of the case. (5) The Evaluation Committee should state in writing its reason for
rejecting or approving, as the case may be, the application of the proposed donor
and all approvals should be subject to the following conditions; namely:- (a) the
approved proposed donor should be subject to all such medical tests as required at
the relevant stages to determine his biological capacity and compatibility to donate
the organ in question; (b) the psychiatrist clearance shall also be mandatory to
certify his mental condition, awareness, absence of any over or latent psychiatric
disease and ability to give free consent; (c) all prescribed forms have been filled up
by all relevant persons involved in the process of transplantation; and (d) final
interview to be video recorded. (6) The Evaluation Committee shall expedite its
decision making process and use its discretion judiciously and pragmatically in all
such cases where, the patient requires transplantation on medical priority. (7) The
secretariat of the Monitoring Authority shall evaluate and recommend the cases
referred to it by the respective Evaluation Committee through treating hospital
citing cogent reasons viz: non availability or non compatibility of any close blood
relative as a donor after ensuring that no monitory transaction is involved between
recipient and the donor. The Evaluation Committee shall proceed in accordance with
section 5 read with sub-section 2 of section 3 of the Act. Each application such
referred shall be accompanied by a processing fee of ten thousand rupees to be
paid into Authoritys authorized bank account to be used on the activities of the
Authority. (8) Every recognized institution shall have its own website. The Evaluation
Committee is required to take final decision about donor selection within thirty six
hours of holding the meeting for grant of permission or refusal for transplant. The
decision of the Evaluation Committee shall reflect transparency and the same shall
be posted on the website of the recognized institution within thirty six hours of the
decision. Apart from this, the website of the recognized institution must be updated
regularly in respect of the total number of the transplantations done in that
recognized institution along with the essential details of each transplantation. The
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same data should be accessible for compilation, analysis and further use by
Authority. 9. Preservation of organs and tissues.-The organ or tissue removed shall
be preserved according to the best scientific methods in order to ensure viability for
the purpose of transplantation. FORM 1 [See rule 3] (To be completed by the
prospective close blood related donor) Name of the
Donor Photograph of the Donor
(Attested by Notary Public) Permanent address:-

.. .
Tel: .. Present address:-

..
..... ....... Tel:.. Date of birth .
.(day/month/year) * National Identity
Card number and Date of issue & place: (Photocopy attached)
and/or * Form B of National Data Registration Authority (NADRA) of that family unit.
and/or * Passport number and country of
issue where available (Photocopy attached)
and/or * Driving License number, Date of issue, licensing
authority. where available (Photocopy attached) and/or *
Other proof of identity and address . I
hereby authorize removal for the therapeutic purposes/consent to donate my
(state which organ) to my relative .. (specify son /
daughter / father / mother / brother / sister), whose name is
. and who was born on
(day/month/year) and whose particulars are as follows: Photograph of the Recipient
To be affixed and attested by Notary Public after it is affixed. To be affixed and
attested by Notary Public after it is affixed. (Attested by Notary Public) * National
Identity Card number and Date of issue & place: (Photocopy
attached) and/ or * Form B of National Data Registration Authority (NADRA) of that
family unit. and/or * Passport number and country of
issue.. where available (Photocopy attached)
and/ or * Driving License number, Date of issue, licensing
authority. where available (photocopy attached) and/or *
Other proof of identity and address . I
solemnly affirm and declare that: Sections 2, 3 and 11 of The Transplantation of
Human Organs and Tissues Act, 2010 (VI of 2010) have been explained to me and I
confirm that: 1. I understand the nature of criminal offences referred to in the
sections. 2. No payment of money or moneys worth as referred to in the Sections of
the Ordinance has been made to me or will be made to me or any other person. 3. I
am giving the consent and authorization to remove my ..
(organ) of my own free will without any undue pressure, inducement, influence or
allurement. 4. I have been given a full explanation of the nature of the medical
procedure involved and the risks involved for me in the removal of my
..(organ). That explanation was given by
(name of recognized transplant surgeon or physician). 5.
I understand the nature of that medical procedure and of the risks to me as
explained by that practitioner. 6. I understand that I may withdraw my consent to
the removal of that organ at any time before the operation takes place. 7. I state
Page 51 of 87
that particulars filled by me in the form are true and correct to my knowledge and
nothing material has been concealed by me. ..
. Signature of the prospective donor Date Note: To be sworn
before Notary Public, who while attesting shall ensure that the person/persons
swearing the affidavit(s) signs(s) on the Notary Register, as well. FORM 2 [See rule
3] (To be completed by the prospective spousal donor) I
Photograph of the
Donor (Attested by Notary Public) Permanent address:
..
..
Tel: . Present address
... ..
Tel :
Date of birth ..(day/month/year) I
authorize to remove for therapeutic purposes/consent to donate my .
(state which organ) to my husband/wife.. whose full
name is . .and who was
born on (day/month/year) and whose particulars are
Photograph of the Recipient (Attested by Notary Public) * National Identity Card
number and Date of issue & place: (photocopy attached)
and/or * Passport number and country of
issue.. where available (photocopy
attached) and/or * Driving License number, Date of issue, licensing
authority. where available (photocopy attached) and/or To
be affixed and attested by Notary Public after it is affixed. To be affixed and attested
by Notary Public after it is affixed. * Other proof of identity and address
. I submit the following as evidence of
being married to the recipient:- (a) a certified copy of a marriage certificate or (b)
an affidavit of a close blood relative confirming the status of marriage to be sworn
before Class-I Magistrate/Notary Public. (c) Family photographs / marriage
photographs (d) Letter from Nazim / Councilor certifying factum and status of
marriage. (e) Other credible evidence including the Form B of National Data
Registration Authority (NADRA) of that family unit. I solemnly affirm and declare
that: Sections 2, 3 and 11 of The Transplantation of Human Organs and Tissues Act,
2010 (VI of 2010) have been explained to me and I confirm that 1. I understand the
nature of criminal offences referred to in the Sections. 2. No payment of money or
moneys worth as referred to in the Sections of the Ordinance has been made to me
or will be made to me or any other person. 3. I am giving the consent and
authorisation to remove my ..(organ) of my own free will
without any undue pressure, inducement, influence or allurement. 4. I have been
given a full explanation of the nature of the medical procedure involved and the
risks involved for me in the removal of my ..(organ). That
explanation was given by (name of recognized
transplant surgeon or physician). 5. I understand the nature of that medical
procedure and of the risks to me as explained by that practitioner. 6. I understand
that I may withdraw my consent to the removal of that organ at any time before the
operation takes place. 7. I state that particulars filled by me in the form are true and
correct to my knowledge and nothing material has been concealed by me.
.. . Signature of the prospective donor
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Date Note : To be sworn before Notary Public, who while attesting shall ensure that
the person /persons swearing the affidavit(s) signs(s) on the Notary Register, as
well. FORM 3 [See rule 3] (To be completed by the prospective non close blood
related donor) Name of the Donor
Photograph of the Donor (Attested by Notary Public) Permanent address:
..
..
Tel: . Present address ...
..
Tel :
Date of birth ..(day/month/year) *
National Identity Card number and Date of issue and place:..
(photocopy attached) and/or * Passport number and country of
issue... where available (photocopy
attached) and/or * Driving License number, Date of issue, licensing authority..
... where available (photocopy attached) and/or * Other proof of
identity and address . * Details of last
three years income and vocation of donor
.. * A
description of the relationship / interaction with the recipient in the past.

. I
hereby authorize to remove for therapeutic purposes/consent to donate my
. To be affixed and attested by Notary Public after it is affixed. (state which
organ) to a person whose full name is
. and who was born on
(day/month/year) and whose particulars are. Photograph of
the Recipient (Attested by Notary Public) To be affixed and attested by Notary Public
after it is affixed. * National Identity Card number and Date of issue & place:
(photocopy attached) and/or * Passport number and
country of issue.. where available
(photocopy attached) and/or * Driving License number, Date of issue, licensing
authority. where available (photocopy attached) and/or *
Other proof of identity and address . I
solemnly affirm and declare that: Sections 2, 3 and 11 of The Transplantation of
Human Organs and Tissues Act, 2010 (VI of 2010) have been explained to me and I
confirm that 1. I understand the nature of criminal offences referred to in the
Sections. 2. No payment of money or moneys worth as referred to in the Sections
of the Ordinance has been made to me or will be made to me or any other person.
3. I am giving the consent and authorization to remove my ..
(organ) of my own free will without any undue pressure, inducement, influence or
allurement. 4. I have been given a full explanation of the nature of the medical
procedure involved and the risks involved for me in the removal of my
..(organ). That explanation was given by
(name of recognized transplant surgeon or physician). 5.
I understand the nature of that medical procedure and of the risks to me as
explained by that practitioner. 6. I understand that I may withdraw my consent to
the removal of that organ at any time before the operation takes place. 7. I state
that particulars filled by me in the form are true and correct to my knowledge and
Page 53 of 87
nothing material has been concealed by me. ....
. Signature of the prospective donor Date Note : To be sworn
before Notary Public, who while attesting shall ensure that the person/persons
swearing the affidavit(s) signs(s) on the Notary Register, as well. * wherever
applicable. FORM 4 [See rule 4(1)(b)] (To be completed by the recognized transplant
surgeon or physician) I, Dr..possessing qualification of
.. registered as medical practitioner at serial no.
..by the .. Medical
Council, certify that I have examined Mr./Mrs./Ms.
..S/o, D/o, W/o ..aged who
has given informed consent about donation of the organ,
namely. to Mr./Mrs./Ms ..who is a
close blood relative of the donor/non close blood relative of the donor, who had
been approved by the Evaluation Committee and that the said donor is in proper
state of health and is medically fit to be subjected to the procedure of organ
removal. Place: . Signature of Doctor Date:
. Seal Photograph of the Donor Photograph of the recipient (Attested
by doctor) (Attested by the doctor) To be affixed and attested by the doctor
concerned. The signatures and seal should partially appear on photograph and
document without disfiguring the face in photograph. To be affixed and attested by
the doctor concerned. The signatures and seal should partially appear on
photograph and document without disfiguring the face in photograph. FORM 5 [See
rule 4 (1](c)] (To be completed by the recognized transplant surgeon or physician) I,
Dr..possessing qualification of ..
registered as medical practitioner at serial no. ..by
the .. Medical Council, certify that- (i). Mr..
..S/o Mr. aged
resident of
and Mrs. ..d/o., w/o. Mr. .
aged . resident of
.. are related to each other as
spouse according to the statement given by them and their statement has been
confirmed by means of following evidence before effecting the organ removal from
the body of the said Mr/ Mrs/Ms. Place:
. Signature of Doctor Date: .
Seal FORM 6 [See rule 4 (2)(a)] (To be completed by person in his/her lifetime and
willing to donate his/her organs/ tissues after death) I,
..s/o, d/o, w/o. Mr. aged.
resident of .. ..
. in the presence of persons mentioned below hereby unequivocally authorize the
removal of my organ/organs, namely, ...
from my body after my death for therapeutic purposes. ..
Signature of the donor Date: . (Signature) .
(1). Mr./Mrs/Ms . ..s/o, d/o, w/o, Mr.
aged resident of
..
Tel
(Signature) . (2). Mr./Mrs/Ms .

Page 54 of 87
..s/o, d/o, w/o, Mr. aged
resident of ..
Tel
is a close blood relative to the donor as ..
Date FORM 7 [See rule 4 (2)(b)] (To be filled by a person
having lawful possession of the dead body) I, ..s/o, d/o,
w/o. Mr. aged. resident of ..
... having lawful possession of
the dead body of Mr./Mrs/Ms. . s/o./d/o/w/o. Mr.
aged of resident of ..
. having known that the
deceased has not expressed any objection to his/her organ/organs being removed
for therapeutic purposes after his/her death and also having reasons to believe that
no close blood relative of the said deceased person has objection to any of his/her
organs being used for therapeutic purposes, authorize removal of his/her body
organs, namely . . Signature
Date Place.. Person in lawful
possession of the dead body Address:
.
. FORM 8 [See rule 4 (3)
(a)] (To be filled by the Board of Medical Experts) We, the following members of the
Board of Medical Experts after careful personal examination, hereby certify that
Mr/Mrs/Ms . aged . s/o, d/o., w/o. Mr.
. resident of
.. is dead on account of permanent and
irreversible cessation of all functions of the brain-stem. The tests carried out by us
and the findings therein are recorded in the brain-stem death certificate annexed
hereto. Date.. Signature. 1. Medical
Director or Medical Superintendent of the Hospital 2. A neurosurgeon/
neurophysician; and 3. An intensivist. BRAIN-STEM DEATH CERTIFICATE (A). Patient
Details: 1. Name of the patient: Mr./Mrs./Ms. . s/o,
d/o. w/o. . Sex: Male Female Age .. years
2. Address:
.
Tel
#..................................................... 3. Hospital Number
. 4. Name and
address of next of kin or person responsible for the patient (if none exist, this must
be specified). resident of
.

5. Has the patient or next of kin agreed to any transplant ?
.. 6. Is this a police case ? Yes No (B) Pre-conditions: 1.
Diagnosis: Did the patient suffer from any illness or accident that led to irreversible
brain damage? Specify
details .............................................................................................. ...........................
................................................................................................................ Date and
time of accident/onset of illness ............................................................................
Date and onset of no-responsible
Page 55 of 87
coma ?........................................................................... 2. Finding of Board of
Medical Experts : (1) The following reversible causes of coma have been excluded:
Intoxication (Alcohol) Depressant Drugs Relaxants (Neuromuscular blocking agents)
Others First Medical Examination Second Medical Examination 1 st 2 nd 1 st 2 nd
Primary hypothermia Hypovolaemic shock Metabolic or endocrine disorders Tests for
absent of brain stem functions 2) Coma 3) Cessation of spontaneous breathing 4)
Pupillary Size 5) Pupillary light reflexes 6) Doll's head eyes movement 7) Corneal
reflexes (Both Sizes) 8) Motor response in any cranial nerve distribution, any
responses to simulation of face, limb or trunk 9) Gag reflex 10) Cough (Tracheal) 11)
Eye movements on caloric testing bilaterally 12) Apnoea tests as specified 13) Were
any respiratory movements seen?

. Date and Time of first testing ........................................................................ Date

and Time of second testing ........................................................................ This to
certify that the patient has been carefully examined twice after an interval of about
six hours and on the basis of findings recorded above,
Mr/Mrs/Ms. ................................................................. is declared brain-stem dead. 1.
Medical Director or Medical Superintendent of the Hospital 2. A neurosurgeon/
neurophysician; and 3. An intensivist. NB. The minimum time interval between the
first testing and second testing will be six hours. FORM 9 [See 4 (3)(b)] (to be filled
by either parent of dead child under 18 years) I,
Mr/Mrs/Ms. ...........................................son of / wife of..........................................
resident
of..................................................................................................................................
............. hereby authorize removal of the organ/organs
namely..................................for therapeutic purposes from the dead body of my
son/daughter, Mr/Ms......................................................... aged.........................whose
brain stem death has been duly certified in accordance with the law.
Signature................................................... Name.........................................................
Place.......................................................... Date........................................ FORM 10
[See 4 (1)(d)] Application for Approval for Transplantation (Live Donor) (To be
completed by the proposed recipient and the proposed donor) Photograph of the
Donor Photograph of the recipient (Self-attested) (Self-attested) Whereas I
.s/o, d/o, w/o, ... aged
. residing at .. have
been advised by my doctor . that I am suffering
from .. . and may be benefited by transplantation
of into my body. And whereas I .s/o,
d/o, w/o, ... aged . residing at
.. by the following reason(s):- a) by
virtue of being a close blood relative i.e. __________________ b) by reason of
affection/attachment/other special reason as explained below :-

I would
therefore like to donate my ..to Mr./Mrs./Ms. . ...
We .and .
(Donor) (Recipient) hereby apply to Evaluation Committee for permission for such
transplantation to be carried out. We solemnly affirm that the above decision has
Page 56 of 87
been taken without any undue pressure, inducement, influence or allurement and
that all possible consequences and options of organ transplantation have been
explained to us. To be self attested across the affixed photograph To be self attested
across the affixed photograph Instructions for the applicants:- 1. Form 10 must be
submitted along with the completed Form 1, or Form 2 or Form 3 as may be
applicable. 2. The applicable Form i.e. Form 1 or Form 2 or Form 3 as the case may
be, should be accompanied with all documents mentioned in the applicable form
and all relevant queries set out in the applicable form must be adequately
answered. 3. Laboratory reports of tissue typing. 4. The doctors advice
recommending transplantation must be enclosed with the application. 5. In addition
to above, in case the proposed transplant is between non close blood relative,
appropriate evidence of vocation and income of the donor as well as the recipient
preferably for the last three years must be enclosed with this application. It is
clarified that the evidence of income does not necessarily mean the proof of income
tax returns, keeping in view that the applicant(s) in a given case may not be filing
income-tax returns. 6. The application shall be accepted for consideration by the
Evaluation Committee only if it is complete in all respects and any omission of the
documents or the information required in the forms mentioned above, shall render
the application incomplete. 7. A brief description of relationship / interaction in the
past in case of non close blood relative. We have read and understood the above
instructions. . ..
Signature of the Prospective Donor Signature of Prospective Recipient Date :
. Date : .. Place :
.. Place : .

Achivements of HOTA

Page 57 of 87
A total of 44 hospital/medical institutes have been accorded recognition to perform
transplant operations (22 in public Sector, 22 in private sector). HOTA is regulating
following organs transplants

1. Kidney
2. Liver
3. Bone Marrow
4. Cornea
5. Heart

Total number of 4033 kidney transplants have been performed in about six years
period (5 Sept 2007 to 28 August, 2013). In 2247 cases the donors were male,
whereas in 1786 cases the donors were female i.e. 55.72% male donors and 44.28%
female donors. 3729 were Live Related Donors (LRD) and 300 were Live Unrelated
Donors (Cases in which there was no eligible/fit/compatible donor within the
Close/Non Close Blood Relatives) and 04 cases of deceased Donors.

Breakdown of the Kidney Transplants performed in the country is as follows:

1. Sindh 2218 (SIUT= 2185)

2. Punjab 1768
3. NWFP 46
4. Balochistan 01

http://www.hota.pk/AchivementsofHOTA.aspx
HUMAN ORGAN TRANSPLANT AUTHORITY Protocol/Guidelines for Stem Cell
Research/Regulation in Pakistan 2 AMMENDED These guidelines have been adopted
from the Guidelines originally developed by the National Bioethics Committee,
Pakistan with some modifications 3 INTRODUCTION The ability to cultivate a special
class of cells known as stem cells and the possibility to use them as therapeutic
tools has ushered in the era of what is known as regenerative medicine. All across
the world research and clinical applications of stem cells involving human subjects
are regulated by well established international guidelines with country specific
details mandated by religious and social mores. Origin and Properties of Stem Cells:
During the development of multi-cellular organisms a fertilized egg undergoes
repeated cellular divisions to produce a mass of unspecialized cells known as
embryonic stem cells. They are uncommitted primordial cells which ultimately give
rise to adult stem cells most of which differentiate into characteristic cells of organs
and tissues. Stem cells are defined by their ability to keep dividing and renewing
their population and thus are not exhausted. In contrast some of the differentiated
Page 58 of 87
specialized cells often do not divide and once damaged are depleted. Potential of
stem cells to renew and differentiate offers exciting possibilities to reverse tissue
and organ damages caused by metabolic and degenerative diseases and aging.
Where are Stem Cells found? Gametes/ blastocysts/ fetal tissues/ placenta/umbilical
cord cells/ adult tissues serve as sources of stem cells. Classification of Stem Cells
according to their Differentiation Potential Totipotent stem cells: These are stem
cells with absolute developmental plasticity which can give rise to all cell types that
are found in an embryo, fetus or developed organism including the trophoblast and
the placenta. The zygote and the cells of the very early stage (i.e. the 2-cell stage)
are totipotent. Pluripotent stem cells: as the zygote undergoes further mitotic
divisions a mass of cells develops. This mass consists of unspecialized cells that can
give rise to most, but not all, the tissues necessary for fetal development. Further
specialization gives rise to multipotent cells that are committed to give rise to cells
that have a particular function (e.g. multipotent cells committed to giving rise to the
red cells, white cells and platelets). Unipotent stem cells These self renew as well as
give rise to a single mature cell type; e.g., spermatogenic stem cells. They can
proceed only along one developmental pathway. Induced Pluripotent Stem Cells
(iPS): A recently developed technique has made it possible to develop multipotent
stem cells from adult skin cells by genetic reprogramming (Yamanaka, 2006). The
iPS resemble embryonic stem cells in their ability to differentiate into myriad of cells
that constitute tissues and organs of the body and offer the advantage that they
can be developed and put back in the same individual from whom they were
derived. They therefore escape immune surveillance. 4 Sources of Stem cells are as
follows: There are many sources of stem cells and appendix 1 details some of the
issues related to stem cell research. i) Adult Stem Cells: Derived from peripheral
blood, tissue or bone marrow ii) Cord Blood Cells: Derived from placenta iii)
Embryonic Stem Cells: Derived either from blastocysts or foetal tissues I. Adult stem
cells: Adult bone marrow cells have been used for more than a decade. Stem cells in
adult tissue are often multi-potent and can produce many, but not all cell types.
These cells can be multiplied but do not have an unlimited capacity for renewal like
embryonic stem cells. Adult stem cell therapy (ASCT) by qualified and experienced
staff using appropriate validated technology, has become well established in certain
hematological disorders such as very severe aplastic anemia, chronic granulocytic
leukemia and thalassaemia major (well chelated, Pessaro category 1). ASCT has also
been used for other hematological conditions such as relapsed childhood acute
lymphoblastic leukemia and acute myeloid leukemia, but its use is not established
as standard of care. Research is ongoing to determine whether these adult stem
cells can also be made to differentiate into other tissues but in contrast to ASCT in
hematological disorders, the use of such cells for nonhematological indications is
experimental. The same applies to emerging techniques of modification of adult
stem cells such as retro-differentiation, which are experimental at this stage. II. Cord
Blood Cells: Cord blood stem cells (CSC) are also obtained from aborted fetal tissue
and umbilical cord blood and have shown to be successful in reconstitution of bone
marrow in children in many disease conditions. These stem cells and those from the
adults are pluripotent in nature. They can be multiplied and maintained in culture
and do not have unlimited capacity for renewal like the embryonic stem cells.
Research is ongoing to determine whether these cells can also be made to
differentiate into other tissues. Use of fetal stem cells will reduce the amount of
foetal tissue used for various therapies. TERMINATION OF PREGNANCY FOR
Page 59 of 87
OBTAINING FOETUS FOR STEM CELLS research or for transplantation will not be
permitted. III. Embryonal Stem cells: These are pluripotent and have the capacity to
develop into any cell of the body. These are obtained from the very early stages of
the embryonic development probably up to 2-4 cell stage in humans i.e. within 5-7
days of conception. While scientists believe that these cells can be directed in the
laboratory to differentiate into any cell or tissue to treat many diseases affecting
various tissues and organs, these applications are still experimental. The main
source of embryonic stem cells is currently IVF clinics dealing with infertility
treatment, where SPARE OR SUPERNUMERARY embryos (at a very early stage) may
be available for these purposes. However no embryo should be CREATED for the
sole purpose of obtaining stem cells. 5 Stem Cells at the Center Stage of Biology
and Medicine The journey of a stem cell as it traverses the trajectory of its life
reveals the molecular and genetic events underlying growth, differentiation and
development from a single fertilized egg to a complex multicellular organism. It also
provides understanding of disease, aging and death. Stem cells have generated a
new medical paradigm known as stem cell therapies. Some of these such as bone
marrow transplant (BMT) using adult hematopoietic stem cells are well established.
Certain cell based treatments for ophthalmologic and musculoskeletal conditions
are also being used. Geron Corporation, one of the leading stem cell companies is
awaiting FDA clearance for the first ever trial of treatment for spinal cord injury. But
treatment modalities for other diseases such as Parkinsons and Alzeimers ,
immunogenetic conditions and stroke and cardiac repair are still at the stage of
animal studies and are unlikely to develop into routine bed side therapies in
foreseeable future. Promise and Problems: on the one hand there is no doubt that
the yet far from fully realized potential of stem cells holds great promise for many
life threatening and debilitating diseases and on the other they have been hyped as
magic bullets for rejuvenating aged human skins. Claims abound as to the
effectiveness of skin treatment with stem cells without proof of the principle. There
is a need to regulate the diverse aspects of stem cell research and therapy where
the immense power to cure and rejuvenate is harnessed and possible harm is
avoided. 6 THE NEED FOR NATIONAL REGULATORY AUTHORITY AND INSTITUTIONAL
OVERSIGHT AND MONITORING COMMITTEES Stem cell research and its applications
pose serious ethical, social, legal and safety concerns and call for exceptional care
and vigilance particularly when it comes to human embryonic stem cells (hES)
derived from embryos. Research and therapy with adult stem cells is not embroiled
in serious controversies but unrelenting watchfulness is indicated. Detailed National
and institutional guidelines should be formulated to protect patients and donors
from possible harm. It is extremely important that persons drafting guidelines are
professionals with adequate understanding of scientific, ethical, legal and social
aspects of SCRT and that all stakeholders are represented. As the field is new and
rapidly advancing it is equally important that once the guidelines are developed
they are reviewed at appropriate intervals. It is imperative to develop mechanisms
for implementing guidelines/Regulatory Frame Work and to invest the Implementing
Authority with adequate powers to punish violations. Human Organ Transplant
Authority (HOTA) for cell based research & therapy: The guidelines have to be in
accordance with religious sensitivities and cultural norms of our people. PMRC
should remain the main Regulatory Authority in the area of stem cell and related
medical research. HOTA will set up an advisory subcommittee of the National
Bioethics Committee in Research (NBCR) for cell based Research & Therapy. Given
Page 60 of 87
the wider application of such technologies by sector other than the Ministry of
Health such as educational and research institutions and Ministry of Science &
Technology, the HOTA Sub-Committee will have additional representation from these
sectors. The membership of this HOTA Sub-Committee will be derived from the
membership of the National Bioethics Committee for Research and shall also consist
of additional co-opted members representing the fields of reproductive health,
hematology and representatives of all organ transplant societies/ institutions. All
centers performing stem cell research and therapy should be registered with the
HOTA for accreditation, on the basis of their technical competence (in stem cell
collection procedures, enumeration, cryopreservation, stem cell viability studies)
and ethical review and oversight procedures. All proposals involving stem cells of
any source for research or non-approved therapy (see Appendix 1 for approved
therapeutic indications), should be cleared by Human Organ Transplant Authority
(HOTA) Sub-Committee, through the National Bioethics Committee. Scope: The
HOTA will have the responsibility to examine the scientific, technical, ethical, legal
and social issues in the area of cell based research and therapy. 7
Scientific/Technical Issues: All proposals, from public or private sector, for research
or non-approved stem cell therapy (SCT) should be placed before the HOTA Sub-
Committee for approval after due clearance through appropriate institutional ethical
review committee and scientific peer review process. Ethical, legal and social
issues: Institutional Ethics Committees should keep in view the ethical, legal and
social issues and should adhere to the ethical guidelines as per the Pakistan
National Guidelines for Human Research (2006), the Helsinki Declaration (2000), the
CIOMS guidelines (2002) as well as the WHO publication on Genomics and Global
Health (2003) 8 GUIDELINES Adult stem cells: While the approved use of specific
adult stem cells does not pose major ethical problems at present their use must be
considered experimental except for specific hematological indications. As indicated
above, all centers doing stem cell treatment and research should register with
HOTA. Bone marrow, peripheral, blood, skin, limbal cells are some of the tissues in
use for procuring adult stem cells. No commercial sale or transaction for stem cell
use or research will permitted All clinical use or therapeutic trails of stem cell must
be conducted by institutions and qualified specialists who must be registered with
HOTA. Proper informed consent procedures are to be followed as given in
international ethical guidelines. Standard Operating Procedures, as outlined in the
Appendix I, should be followed for procurement, cataloguing, source identification,
storage and preservation. In vivo Studies: Experimental work on stimulation of
adult stem cells also has tremendous future. However, approval from HOTA must be
sought for carrying out all such experiments. Cord Blood stem cells: For using
umbilical cord blood from a live fetus or a neonate it must be ensured that no harm
should occur to the fetus or the neonate. Since the exact timing of the clamping of
the umbilical cord has a significant impact on the neonate and early clamping may
cause an abrupt surge in arterial pressure resulting in cerebral intraventricular
haemorrhage, particularly in premature neonates, normal clamping protocol
(Appendix II) will be followed when collecting foetal blood for transplantation. There
is a risk that the neonate donor may need his or her own cord blood later in life.
Parents will be informed of the risks of donation and a written consent will be
obtained from them on behalf of the fetus. Cord blood stem cells are generally used
for hematopoietic stem cell transplantation. For any other form of therapy detailed
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protocol has to be submitted for approval. The following points should be
specifically considered while collecting umbilical cord blood for banking: No harm
should occur to the fetus or the neonate. Exact timing of the clamping of umbilical
cord should be defined. Early clamping may lead to cerebral haemorrhage. Normal
clamping protocol should always be followed. Parents should be correctly informed
regarding risks and benefits involved. Free informed consent should be obtained
from both parents. If there is disagreement between the parents, the mothers wish
shall prevail. ID card should be issued for voluntary donation to enable
access/benefit in future in case required for self/relatives. Cord blood stem cell
banking is permissible. However, all Cord Blood Banks should be registered as per
guidelines applicable to the blood banks. Commercial exploitation of 9 stored blood
should be regulated strictly. Special care must be taken in collection, processing and
storage of umbilical cord stem cells to avoid transmission of infections. Maternal
screening should be carried out for transmissible infections. Purpose of banking
should be clearly explained to couples interested in storing cord blood. The ideal
use of these cells at present is for allogenic hematopoietic stem cell transplantation.
Expansion of umbilical cord stem cells for transplantation in adult and use for non-
hematopoietic indications is still in exploratory phase. When it comes to registries
and banking, the commercial aspects pose additional problems. The advertisement
related to collection of samples should be carefully looked into with respect to
conflict of interest, utility of samples, accessibility and affordability Fetal stem
cells/tissue: These can be processed from spontaneously aborted fetus or from
fetuses obtained from hospitals. International guidelines for fetal tissue
transplantation should be followed. DNA fingerprinting of the cell line should be
preserved and it is advised to keep it in cell repository. Generally fetal stem cell use
is presently experimental. Any therapeutic fetal cell transplantation will not be
permitted at present and this possibility will be examined at an appropriate time
later. Termination of pregnancy should not be sought with a view to donate fetal
tissue in return for possible financial or therapeutic benefits. Informed consent to
have a termination of pregnancy and the donation of fetal material for purpose of
research or therapy should be taken separately. The wishes of the mother will
prevail in case of any difference of opinion. Embryonic stem cells (ES Cells): No
Embryo should be generated for the sole purpose of obtaining stem cells. Only
surplus or spare or supernumerary embryos (under 16 weeks gestation), can be
used with the permission of the couple from IVF clinics. Cell lines generated should
be registered. At present only research program relating to in vitro induction of
differentiation into various cell lines will be cleared by the NRC on case to case
basis. Any therapeutic trial will be examined in detail before approval. Reproductive
cloning will not be permitted on ethical grounds. Human cloning is not permitted for
the purpose of creating a new individual. Monitoring Mechanism: The HOTA will be
authorized to make site visits as required and receive annual reports of cleared
projects. These annual reports should be submitted in appropriate format for further
continuation of the project by the 10th month of commencement of the project
decision and review should be communicated in 4-6 weeks. Any violation of
guidelines would be strictly dealt with and procedures will be established to enforce
such regulations and penalties in the event of violation through the PMDC and the
Ministry of Health. Commercialization and Patent issues: Established stem cell lines
can have considerable commercial value as wide ranging potential benefits for large
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number of patients is possible. Patent issues need wider discussions and public
debates should be held on who should be the beneficiary and what 10 type of
patents can be taken. Exploitation of Pakistani biological material by foreign
commercial interests is not permitted. IPR protection should be accorded to
commercially utilizable materials and procedures. Benefits of commercialization
should be extended to community including patients, researchers and institutions
engaged in research and applications. Regulation of stem cell lines: All cell lines
should be registered with HOTA. All proposals for therapeutic trial should be cleared
by this committee before submitting to national or international funding bodies.
International collaboration: National guidelines of respective countries should be
followed and all research protocols for sponsored research must be cleared with
appropriate ethical review committees in the sponsoring country. Collaboration will
be permitted only after the joint proposal with appropriate MOU is approved by the
National Research ethics Committee following clearance by the HOTA. No export of
cell lines per se will be permitted. Generation of embryonic stem cells from non-
human sources: Embryonic stem cells for experimental purposes cal also be
obtained from sources such as rodents. Primates, domestic animals, farm animals
etc. Research in these areas should be encouraged but is strictly experimental and
must undergo similar ethical review and clearance. Check list to be submitted to the
Human Organ Transplant Authority (HOTA) for any proposal 1. Title of the proposal.
2. Institution concerned. 3. Investigators name with brief bio-data and relevant
publications. 4. Source of funding. 5. An assurance signed by the responsible
institutional head that the pluripotent stem cells were derived from human embryos
in accordance with the guidelines. 6. Informed consent document duly signed by
appropriate individuals. 7. Brief summary of the proposed work. 8. IRB/IEC clearance
(if sponsored, ethical review and clearance from appropriate ethical review
committees in the sponsoring countries). 9. Certificate that no undue inducements/
incentive is provided for donation of embryo. 10.Separate consent for infertility
treatment and donation of embryos to be taken. 11.Certificate that only spare
embryos are being used. Private sector involved in such research should also come
under the purview of this committee and it should comply with due safeguards and
standards and submit all proposals for clearance. 11 Permissible Research on Stem
Cells 1. Use of human stem cell lines derived from hES, hEG, hSS or fetal/adult stem
cells is permitted for in vitro investigations. 2. In vivo studies of human cell lines
and their differentiated derivatives are allowed in small non-primate animals at
various stages of development (embryonic, fetal, postnatal, adult). The animals
derived from these experiments shall not be allowed to breed especially when there
is a possibility that human cells could significantly contribute to development of
gonads and/brain. 3. Animal studies for pre-clinical evaluation of efficacy and safety
of human stem cell lines is also allowed as per above mentioned criteria. 4.
Informed consent from donors is required for: in- vivo animal studies when using
stem cells from donors of bone marrow, peripheral blood, umbilical cord blood, skin,
limbal cells, dental cells, bone cells, cartilage cells or any other organ (including
placenta) Establishment of fetal/adult hSS and new hES cell lines from spare,
supernumerary embryos. Establishment of Umbilical Cord Stem Cell banks Clinical
Grade Stem Cells for Biomedical Research and Therapy Clinical grade stem cells
are classified as therapeutics and are required to be produced under international
GMP/GTP conditions. The cells should be well characterized about their stemness

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and safety. Prohibited Research Creation of a zygote by IVF, SCNT or any other
method with the specific aim of deriving a hES cell line for any purpose.
Introduction of hESCs into non-human primate blastocysts in vitro culture of any
intact human embryo for longer than 14 days or until formation of the primitive
streak begins, whichever occurs first Breeding of animals that have had hESCs
introduced into the germ line Germ line genetic engineering or reproductive
cloning. Transfer of human blastocysts generated by SCNT or parthenogenetic or
androgenetic techniques into a human or non-human uterus. Animals in which any
of human stem cells have been introduced at any stage of development should not
be allowed to breed. Research involving directed non- autologous donation of any
stem cells to a particular individual is also prohibited. Any research involving
implantation of human embryo into uterus after in vitro manipulation, at any stage
of development, in humans or primates. Ref: Ethical Guidelines for Biomedical
Research in human Subjects. 2000, 2006 ICMR 12 Application of blood and marrow
transplantation (BMT) Introduction: The clinical use of progenitor cell transplantation
technology has been instrumental in the treatment and cure of thousands of
patients with haematological and non haematological malignant disorders.
However, the procedure still carries significant morbidity and mortality. It is also at
risk of commercial exploitation and unethical practices. The setting up of centres for
BMT must be strictly regulated and their working should be periodically and
objectively monitored. The following guidelines are for the infrastructure of these
centres: BMT Centre This centre must be located in a tertiary care hospital which
will provide a wide range of support and patient care services including critical care
management, haemodialysis, advanced imaging facilities, cardiac support facilities,
infection surveillance and management facilities. Dedicated areas, according to
workload will be earmarked for BMT patients in these hospitals. The BMT Centre will
have A clinic to perform pre-donation physical examination and specialized tests
(X-ray, ECG, Echo etc) Indoor facilities which must have dedicated operation
theatres and isolation rooms with state-of-art ventilation facilities. The BMT Centre
must have harvesting facilities for bone marrow and progenitor cells. There should
be atleast two cell-separators, facilities for quantitative and qualitative evaluation of
harvested progenitor cells and facilities for cryo preservation and storage of
progenitor cells. The Centre must have direct access to the following accredited
facilities. HLA Typing Laboratory Microbiology Laboratory Biochemistry
Laboratory Blood Transfusion Laboratory Histopathology Laboratory I. Essential
Personal a. Medical Director The centre must be under the control of a medical
doctor who has accredited postgraduate qualification in haematology, a minimum of
15 years experience in laboratory and clinical haematology and demonstrable
knowledge and interest of BMT. 13 b. Transplant Physician At least two transplant
physicians should be full time employees of the centre. They must be medical
graduates and have accredited post-graduate qualification in haematology. They
must have 10 years experience of clinical haematology, have worked under the
supervision of a transplant physician for atleast 2-years at a centre doing a
minimum of 10 BMT per year. They should have exposure to atleast 10 bone marrow
harvesting procedures. c. Program Coordinator Master in Social Sciences, having
working knowledge of statistics, computers and record keeping. II. Support Medical
Faculty 1. Anesthetist 2. Pulmonologist 3. Gastroenterologist 4. Nephrologist 5.
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Cardiologist 6. Neurologist 7. Infection Disease Physician II. Support Services 1.
Pharmacy 2. CSSD 3. Nutritionist 4. Social Worker III. Monitoring of Services The
services of the centre must be supervised by a regulatory body which will include;
1. Medical Director 2. Program Coordinator 3. Legal Expert 4. Financial Advisor 5.
Ethical Service Advisor 6. Social Service Advisor 7. Womens Representative 8.
Donor Representative IV. Accreditation of the Centre It should be mandatory for all
BMT centres to allow access to inspectors for the purpose of accreditation. The
inspection team, to be constituted by HOTA, must ensure that the centre is located
in an institution at a fixed physical site, is equipped and staffed as per regulation,
and is not involved in unethical commercial practices. The centre must maintain a
record of donors of blood, aphaeresis progenitor cells and bone marrow. It should be
carrying out management activities including education, counseling, rehabilitation
of patients and should be capable of dealing with medical screening and
confidentiality issues. 14 Appendix I GUIDELINES FOR THE COLLECTION,
PROCESSING AND STORAGE OF HUMAN BONE MARROW, PERIPHERAL STEM CELLS
FOR TRANSPLANTATION General principles: Each stem cell transplant unit shall
establish, document and maintain an effective and economical quality system to
ensure and demonstrate that adequate and appropriate standards of work are
maintained. Procedural step Related to Bone Marrow Harvest: Donor suitability must
be ensured. The donation may be an autograft or an allograft from a related or
unrelated donor. The allogenic donor should be counseled and a full medical
examination carried out to establish that the donor is fit for anesthesia. Routine
haematological, biochemical and virological parameters are checked. A chest X-ray
and ECG should be performed. Written informed consent must be obtained from the
donor before the recipient commences pretransplant conditioning. It is a cardinal
principle that unrelated donors should be anonymous, unpaid and not pregnant. The
donor is admitted, night before harvest to the transplant centre or hospital
experienced in marrow harvests. The donor receives a unique donor identification
number (DIN) and this must be assigned to the marrow, both primary and
secondary collection packs and all the sample tubes used. Marrow Collection: Before
the start of harvest the identity of the donor must be checked. Collection of marrow
should be by aseptic technique into pyrogen-free containers with sufficient
anticoagulant for the quantity of marrow to be collected and appropriate for the
subsequent processing. The container label should state the amount of
anticoagulant and the maximum amount of marrow that can be collected and
required storage temperature. The marrow should be anticoagulated with ACD-A
unless preservative free heparin is requested by the transplant centre. In the latter
case marrow should be returned to the patient within 12 h. The anticoagulant
solution must be clear, free from deposit. Harvest should only be undertaken by
trained medical staff. Personnel required are an anesthetist; operators to harvest
marrow, haematological scrub nurse and theatre staff. Harvest lists should be
dedicated or at the beginning of the operating list. The volume of marrow withdrawn
from the donor must be controlled. The volume taken should be such that a target
cell count appropriate to transplant is reached. Records: A record of the total
volume of marrow removed from the donor must be documented in the patients
notes. The most efficient way of measuring the volume in plastic bags is by weight
of 1 ml. Of marrow is 1.06g; a unit containing 405-495 ml should therefore weigh
430-522 g plus the weight of the container and its anticoagulant. 15 Operating
procedure: The anaesthetized patient is positioned on the operating table with
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pelvis supported to make the iliac crest prominent. The choice of harvest needle is
one of personal preference and can very from conventional needles for diagnostic
aspiration from iliac crests through to designed harvest needles with holes along the
lateral aspect of the shafts (e.g. (Islam). No more than 5 ml of bone marrow should
be collected into a 20 ml syringe containing preservative free heparin and the
needle then repositioned after each aspiration. It is usually possible to take marrow
at several different depths from one site. The needle is then withdrawn and resited,
samples being taken as widely as possible along the posterior iliac crest. If an
inadequate cell count is obtained from both posterior iliac crests the patient should
be turned over and further aspirates taken from the anterior iliac crests and the
sternum. Marrow Processing: A closed system is preferred in which the syringe is
emptied directly into 500ml or 1L bags containing anticoagulant. Marrow should be
filtered in accordance with the harvest centers routine practice to remove fat,
aggregates, clots or bone spicules if it is not processed further by centrifuge or
sedimentation. During and after harvesting samples of marrow can be obtained
from the bag and nucleated cell count carried out to ascertain the anticipated
volume needed to produce engraftment. Estimation of Marrow dose at harvest: The
present recommended dose of nucleated cells is expressed per kilogram of
recipient body weight. 1. Autografts: minimum dose 1.5 x 108 cells /kg. 2. HLA
identical sibling allografts for aplastic anaemia: minimum dose 3 x 108 cells /Kg
(Storb et al, 1977). 3. HLA identical sibling for leukemia haemoglobinopathies and
inborn errors of metabolism: minimum dose 1.5-2 x 108 cells/kg 4. Unrelated donor
allograft: minimum dose 2-3 x 108 nucleated cells/Kg A minimum number of
marrows (nucleated cells) per kilogram recipient body weight should be stated by
each transplant unit to permit engraftment. The weight of the recipient must be
ascertained. Post-Harvest Marrow Processing: In allogeneic transplantation the
completed barrow bag is rendered airtight, labeled and its contents may then be
infused intravenously into the recipient where both donor and recipient are ABO
compatible or cryopreserved. If volume reduction is required buffy coat cells can be
separated and transferred to a second sterile pack. When there is no major blood
group incompatibility between donor and recipient then a cell fraction known to
contain the repopulating stem cells and low in haematocrit should be obtained by
density separation. If removal of T cells is required to prevent graft versus host
disease the volume of the donation is reduced before incubation with monoclonal
antibodies. An appropriate method 16 is to use blood cell washer or cell separator.
Processing also may be modified to collect donor red cells for autologous reinfusion.
Autologous marrow can be similarly separated to leave a buffy coat or further
processed to a mononuclear cell fraction which may be purged before storage.
Purging involves incubation of the marrow with most commonly the
cyclophosphamide antimetabolite, 4 hydoxy-per-oxy-cyclophosphamide (4 H-C;
Kaizer et al., 198) or with monoclonal antibodies. Monoclonal antibodies may also
be used for positive selection of putative progenitor stem cells (e.g. anti-CD34
antibodies). The purged / unpurged marrow is then cryopreserved (see below).
Biological methods of purging such as long-term bone marrow culture are still
experimental. Peripheral Blood Stem Cell Collection: Haemopoietic cells are present
at low concentration in steady-state blood. Such cells can be mobilized from the
bone marrow into peripheral blood during the recovery phase from
myelosuppressive chemotherapy or following administration of haemopoietic
growth factors or by a combination of the two. They are collected by leukapheresis
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on a blood cell separator set to obtain sufficient mononuclear cells for engraftment.
A suggested value is 7x 108mononuclear cells/kg but this will vary according to the
centre and whether myeloablative treatment is given. Some centers use lower
values of 2 x 108 mononuclear cells /kg. Mobilized blood progenitor autografts are
usually associated with very rapid haemopoietic reconstitution. Timing of the
leukapheresis may be guided by the appearance of CD34 positive cells is the blood,
or by surrogate markers such as white blood cell and platelet counts. During
recovery from myelosuppressive therapy a white count greater than 1 x 109 /1 and
platelets greater than 70 x 109 /l are generally taken as the time to initiate
leukapheresis but absolute counts will very with the chemotherapy regime and
whether or not growth factors are employed. Mobilized blood stem cells collections
are usually assessed by their CD34 positive cells or CFU-GM. Threshold doses need
to be determined by each centre by the recommended minimum number of CFU-GM
and is usually in the range 5-20 x 104 /kg (Craig et al., 1992). It is usual that the
donor is an autograft recipient and that the material is stored by cryopreservation.
Nucleated cell collection: The technique for procurement of the nucleated cell layer
rich in stem cells depends on the cell separator machine used. The aim is to collect
the buffy coat interface between plasma and red cell. The total nucleated cell
volume collected is determined from the total blood volume of the donor
ascertained from their height/ weight prior to apheresis. It is recommended that in
adults 7-15 /l is processed. Where the nucleated cell yield is greater than 100 x
109 /l dilutions in plasma are needed to prevent aggregation during the process of
freezing (see Storage). When the collection is complete the residual volume of blood
is returned to the donor. 17 Appendix II GENERAL SPECIFICATION FOR
IDENTIFICATION, STORAGE AND TRANSPORTATION OF BONE MARROW AND
PERIPHERAL BLOOD STEM CELLS Identification: The unit containing stem cells must
be labeled with the name of the product, the donors name and hospital number,
unique donation number, date of collection, the presence and type of anticoagulant
and additive media if any, ABO and Rh D group and the volume of the product.
Storage (Rowley & Davis.1990; Reiman & Sacher, 1991) An SOP should be written to
include the following: a designated storage area: a procedure for quarantine of bone
marrow and peripheral blood stem cells: a procedure for validating the conditions of
storage achieved in any given storage area. This should include temperature control
and preventation of microbiological contamination. If, as a result of microbiological
screening, the donor is positive for any of the mandatory microbiological marker
(table 1) then that unit should be stored in isolation to avoid cross contamination of
other units. Storage unfrozen. Unmanipulated bone marrow and peripheral blood
stem cells may be stored unfrozen for up to 72 h at 4 + 2C. The anticoagulant
conventionally used in ACD. Heparin is unsuitable. Storage at 4C will, however,
reduce leukocyte viability and cellular aggregation may occur. Preparation of frozen
marrow and peripheral blood haemopoietic cells Haemopoietic cells in bone marrow
are enriched and concentrated by differential centrifugation into a buffy coat.
Further enrichment using a density gradient may be required. Peripheral blood cells
are not normally concentrated. The cell concentration frozen should be less than
100 *109 /1 (see above Nucleated Cell Collection). The above products are
cryopreserved using one of the established cryoprotectants, for example 10 or 15%
v/v dimethyl sulphoxide (DMSO) or 5% v/v DMSO plus 6% w/v hydroxyethyl starch
(HES). DMSO should be added slowly to its diluents to avoid a rise in temperature
since desired final concentration of DMSO is isotonic in molar terms. This requires
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the addition of albumin solution (HAS) is used additional salts or a suitable
impermeable sugar are necessary (Pagg. 1984). The diluent is then cooled on ice to
0-4C, DMSO added and the cryoprotectant mixed with an equal volume of
haemopoietic cells. The freezing process: A feedback-controlled cooling machine
(controlled rate freezer) will provide reproducible, standardized cooling conditions.
The cooling program should be one that has been shown to be effective (e.g. 2 C/
min to -30C, followed by 4C/min to -70C with adequate control of freezing
plateau: Gorin, 1986). Passive cooling methods may also be effective providing that
they produce acceptable cooling profiles (Makino et al., 1991). The bags in which
the marrow is cooled should be made from plates ton produce a 18 thickness of
about 3 min to facilitate heat transfer. Temperature should be recorded in a control
bag and the data kept with the processing records. Peripheral blood cells may be
cryopreserved by the same methods. Once below -70C the bone marrow and
peripheral blood stem cells should be transferred for storage. Such deep frozen is
fragile and container bags may fracture. Thawing of frozen bone marrow/peripheral
blood cells: 1. Contamination of the marrow/peripheral blood bag with water bath
fluid is to be avoided and it is essential that double bags are used. 2. Thaw in a
water bath at 37-40C with gentle agitation. Observe carefully for rapid expansion
of the bag during thawing which will suggest that liquid nitrogen has leaked into the
bag during storage. If this occurs release the pressure immediately by puncturing
the bag with a sterile needle. 3. DMSO toxicity is temperature dependent ( Goring
1986). It is therefore important to remove the bags from the waterbath soon as the
last ice has melted and not to allow the marrow to reach the waterbath
temperature. Keep the thawed marrow cool until administration and infuse within 5
min of complete thawing. Current practive is not to remove the DMSO before
injection into the patient (Rowley & Anderson, 1993). Premedication of the patient
with steroid/ antihistamine is recommended. 4. Any thawing incidents should be
documented and reported to the clinician in charge of the recipient who will decide
whether action is required. Testing: Testing of frozen products may be performed
utilizing 1-or 2-ml aliquots of material frozen at the same time under conditions that
are as close as possible to the bulk product. It should be noted that small ampoules
will not cool at the same rate as large bags. Assay may be performed to determine
short-term progenitor growth post-cryopreservation. Specific Laboratory Procedures
Related to Provision of Haemopoietic Cells for Engraftment Serology: The ABO and
RhD blood groups of all donors should be performed as set out in the Guidelines for
Compatibility Testing in Hospital Blood Banks (Boulton et al, 1987). Cell Counting:
The minimum information required is the total nucleated cell count obtained at
stem cell harvest. If counts are corrected for peripheral blood dilutions, this should
be clearly indicated to avoid confusion with uncorrected nucleated counts. Such
counts should be performed on a cell counting machine by validated methods or
performed manually. The volume of bone marrow or peripheral blood harvest is best
calculated by weight. 19 Cell Viability The quality of frozen cells can be assessed by
the trypan blue exclusion test or automated techniques using a flow cytometer and
propidium iodide. These results do not correlate with in vitro growth, but given
indication of consistency of the technique. Red Cell Depletion: Red cell depletion of
the donor graft is strongly recommended in ABO mismatched allogenic transplant.
This can be carried by HES sedimentation or differential centrifugation (Braine et al.,
1982: Ho et al., 1984). An alternative is to plasma exchange the recipient and/or to
give A/B antigen rich secretor plasma prior to the transplant. Microbiology and
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Virology: The sterility of the bone marrow/ peripheral blood product at various
stages should be ascertained using liquid and semi-solid culture medium. This is
especially important prior to freezing and at the final stage of processing after
freezing before the product is infused into the patient. A pilot tube is thawed and
cultured. The clinician should be informed if the cultures are positive. Donor bone
marrow can transmit infectious disease and all donors should have the mandatory
tests (shown on table 1) carried out and where possible the serological tests
repeated at not less than 90 days from the first screening sample. Table-1: 1.
Mandatory HBsAg (hepatitis B surface antigen) HIV 1+2 antibody (human immune
deficiency virus) Anti-HCV (Hepatitis C virus antibody) VDRL or equivalent test for
syphilis 2. Advisable CMV antibody Toxoplasma gondii antibody 3. Desirable HSV
(herpes simplex antibody) HZV (herpes zoster antibody) HTLV-1 (Human T-
Lymphotrophic virus) 20 Appendix III PRE-REQUISITES FOR A STEM CELL
TRANSPLANTATION CENTRE Standard Operating Procedures (SOPs): Standards for
collection, processing and storage of cells for clinical use: For the consistence and
reliable results International standard procedures should be adopted. These
standards are designed to provide minimum guidelines for facilities and individuals
performing collection, processing and storage of cells for clinical use or providing
support services for such procedures. These standards are not intended to include
all procedures and practices that a facility or individual should implement if the
standard of practice in the community or governmental laws or regulations establish
additional requirements. Each facility and individual should analyze their practices
and procedures to determine whether additional standards may apply. Protocols
shall be developed, implemented, and documented for the validation or
qualification of significant products of facilities, processes, equipment, reagents,
labels, containers, packaging materials, and computer systems. For this purpose
training of the staff in renowned stem cell/transplantation centers is recommended.
There shall be procedures for biological, chemical, and radiation safety, as
appropriate, and a system for monitoring training and compliance. Personnel 1.
There shall be a Collection Facility Head / Officer in-charge an individual with a
doctoral degree, qualified by postdoctoral training or experience for the scope of
activities carried out in the facility. This individual is responsible for all technical
procedures and administrative operations of the collection facility. This individual
should participate regularly in educational activities related to the field of cell
collection and / or processing. 2. The Collection or Processing Facility Head / Officer
in-charge with a doctoral degree, n shall have at least one years experience in the
collection procedure. This individual shall have performed or supervised at least 10
collection procedures of each type that are to be carried out at the facility. 3. There
shall be a Collection Facility Medical Head/Director who is a physician licensed in the
jurisdiction in which the facility is located. This individual is directly responsible for
the pre-collection evaluation of the donor, final approval of the prospective donor
for the collection procedure, conduct of the collection / processing procedure, care
of any complications arising from collection and compliance of the collection facility
with these Standards. 4. There shall be adequate numbers of trained support
personnel available at the facility where the collection is performed. 21 5. The
training, continued education and continued competency for the performance of
operations shall be documented. Ethical issues: Informed consent from the donor
shall be obtained and documented by a licensed physician or other health care

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provider familiar with the collection procedure before the high dose therapy of the
recipient is initiated. The procedure shall be explained in terms the donor can
understand, and shall include information about the significant risks and benefits of
the procedure and tests performed to protect the health of the donor and recipient
and the rights of the donor to review the results of such tests. The donor shall
have an opportunity to ask questions and the right to refuse to donate. In the case
of a minor donor, informed consent shall be obtained from the donors parents or
legal guardian in accord with applicable law and shall be documented. Laboratory
facilities for cell processing The facility responsible for cell processing shall be of
adequate space and design for the intended procedures. The operation of the
facility shall be divided into defined areas of adequate size for each operation to
prevent improper labelling and/ or contamination of the product. The facility shall
be operated in a manner to minimize risks to the health and safety of employees,
patients, donors and visitors. The facility shall have written policies and
procedures for infection control, biosafety, chemical and radiological safety,
emergency response to worksite accidents, and waste disposal. Instructions for
action in case of exposure to communicable disease or to chemical, biological and
radiological hazards shall be included in the safety manual. Decontamination and
disposal techniques for medical waste shall be described. Human tissue shall be
disposed in such a manner as to minimize any hazard to facility personnel or the
environment in accordance with applicable governmental laws and regulations.
Eating, drinking, smoking, the application of cosmetics or the insertion or removal of
contact lenses shall not be permitted in work areas. Gloves and protective clothing
shall be worn while handling human specimens. Such protective clothing shall not
be worn outside the work area. There shall be adequate equipment for the
procedures performed at the facility. The facility shall be maintained in a clean and
orderly manner as established in SOPs. The facility shall be secure to prevent the
admittance of unauthorized personnel. Equipment Equipment used in the
processing, testing, freezing, storage, transportation, and transplantation of
products shall be maintained in a clean and orderly manner and located so as to
facilitate cleaning, calibration and maintenance. 22 Each collection facility shall be
operated in a manner to minimize risks to the health and safety of employees,
donors, volunteers, and patients. Suitable environment and equipment shall be
available to maintain safe operations. Environmental control lab facilities of
international standards are must. Equipments used in the collection of products
shall be maintained in a clean and orderly manner and located so as to facilitate
cleaning, calibration and maintenance. The equipments shall be observed,
standardized and calibrated on a regularly scheduled basis as described in the SOPs
Manual and according to the Manufacturers recommendations. Sterilization
equipments shall be designed, maintained and used to ensure the destruction of
contaminating micro-organisms. Refrigerators and freezers used for the storage of
specimens, cell products, blood products, human tissues, or reagents shall not be
used for any other purpose. Consumables Reagents used in collection of products
shall be of appropriate grade for the intended use and shall be sterile. Procedures
for production of in-house reagents shall be validated. Each supply and reagent
used in the collection of the product shall be examined visually for damage or
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evidence of contamination as it comes into inventory and this review shall be
documented. Such examination shall include inspection for breakage of seals,
abnormal colour and expiration date. All supplies and reagents used in the
collection of products shall be stored in a safe, sanitary, and orderly manner. Lot
numbers and expiration dates of reagents and disposables shall be recorded.
Supplies and reagents should be used in a manner consistent with instructions
provided by the manufacturer. Tissue processing Human tissue refers to cells
obtained from any living or cadaveric human donor or organ. The cell processing
facility shall have written policies and procedures addressing all appropriate aspects
of the operation including processing; emergency and safety procedures; donor and
patient confidentiality; quality management and improvement; errors, accidents
and adverse reactions; corrective actions; personnel training; competency
assessment; outcome analysis; audits; labelling; storage, including alternative
storage if the primary storage device fails; transportation; expiration dates; release
and exceptional release; disposal of medical and biohazard waste; equipment and
supplies; maintenance and monitoring; cleaning and sanitation; and a disaster plan.
All open cell handling procedures must be performed in class 100 environment.
More than minimal manipulation of products should only be performed in a clean-
room environment. Environmental monitoring of such rooms must be performed and
documented. There shall be a written request from the recipients physician before
processing is initiated. 23 Processing of cellular therapy products shall be
performed according to protocols defined in the facilitys SOPs. Methods for
processing shall employ aseptic technique and be validated to result in acceptable
cell viability and recovery. There shall be written documentation of an interim
assessment of donor suitability for the collection procedure by a qualified person
immediately prior to each collection procedure. For donors of peripheral blood
aphaeresis products, a complete blood count, including platelet count, shall be
performed within 72 hours prior to the first collection and within 24 hours before
each subsequent aphaeresis. For progenitor and other adult cell collection,
methods for collection shall employ aseptic technique and shall use procedures
validated to result in acceptable progenitor cell viability and recovery. The
collected cells shall be packaged in a closed sterile container / transfer packs
approved for human cells and labelled. Bone Marrow shall be filtered to remove
particulate material prior to final packaging, distribution or transplantation using
sterile filters that are non-reactive with blood. Labelling control Labelling
operations shall be conducted in a manner adequate to prevent mislabelling of
products that shall include the following quality management elements: Container
labels shall be held upon receipt from the manufacturer pending review and
proofing against a copy approved by the Collection Facility In-charge or designee to
ensure accuracy regarding identity, content, and conformity. Stocks of unused
labels representing different products shall be stored in an orderly manner to
prevent errors. Stocks of obsolete labels shall be destroyed. A system of checks in
labelling procedures shall be used to prevent errors in translating information to
container labels. All labelling shall be clear and legible and printed using moisture-
proof ink. Labels shall be affixed or attached firmly to the container. The proper
name and significant modification(s) shall be noted on the label. Products that are

Page 71 of 87
subsequently re-packaged into new containers shall be labelled with new labels as
appropriate. Records to allow tracking of products including collection or processing
facility identity, unique numeric or alphanumeric identifier, collection date and time,
product identity, donor and recipient information on the original container shall be
maintained. When the label has been affixed to the container, a sufficient area of
the container shall remain uncovered to permit inspection of the contents. The
product label shall be complete. Not applicable (NA) may be used when appropriate.
Stem cell storage and transportation facilities: Cell collections shall be handled and
discarded with precautions that recognize the potential for transmission of
infectious agents. Issues of donor health that pertain to the safety of the collection
procedure shall be communicated in writing to the collection facility staff. 24
Prospective donors shall be evaluated by medical history, physical examination by a
trained physician and laboratory testing for the risks of the collection procedure
including the possible need for central venous access and/or mobilization therapy
for collection of blood cells and anaesthesia for collection of marrow. This evaluation
shall be documented. Cryopreservation Sample aliquots of the product,
cryopreserved and stored under the same conditions as the product, should be
available for testing for 5 years. Cryopreservation procedures shall be included in
the cell processing facilitys SOPs and shall describe: The name and freezing
criteria of the cell product or aliquot. The cryoprotectant solution and its final
concentration. Cryopreservation container & acceptable range of product volume
for reproducible cryopreservation. Acceptable range of nucleated cell
concentration of the final product after cryopreservation. Cooling rate and product
temperature at endpoint of controlled cooling. The cooling rate achieved shall be
recorded, if a rate-controlling device is used. Acceptable temperature range for
storage. Storage Materials that may adversely affect cell products shall not be
stored in the same refrigerators or freezers. For products immersed in liquid
nitrogen, procedures to minimize the risk of microbial cross-contamination of
products shall be employed. Refrigerators and freezers for product storage shall
have a system to monitor the temperature continuously or at least every 8 hours.
For products fully immersed in liquid nitrogen continuous temperature monitoring is
not required. There shall be a mechanism to ensure that levels of liquid nitrogen in
liquid nitrogen freezers are maintained. Storage devices for products or reagents
for product processing shall have alarm systems that are continuously active. The
alarm systems shall have audible signals. If laboratory personnel are not always
present in the immediate area of the storage device, a remote alarm device shall be
required at a location staffed 24 hours a day. Alarms shall be set to activate at
temperatures or an unsafe level of liquid nitrogen to allow time to salvage products.
There shall be written instructions to be followed if the storage device fails. These
instructions shall be displayed in the immediate area containing the storage device.
Alarm systems shall be checked periodically for function. Additional storage
devices of appropriate temperature shall be available for product storage if the
primary storage device fails. The storage device shall be located in a secure area.
Locking capability for the device or the storage location should be used when the
area is unattended. 25 Transportation Procedures for transportation of the collected
product shall be designed to protect the integrity of the product being shipped and

Page 72 of 87
the health and safety of facility personnel. The primary product container shall be
placed in a secondary container and sealed to prevent leakage. The outer shipping
container shall be thermally insulated and shall conform to the regulations
regarding the mode of transport. Frozen or non-frozen products that leave the
facility or are transported on public roads shall be shipped in an outer shipping
container. The outer shipping container should be made of material adequate to
withstand leakage of contents, shocks, pressure changes, and other conditions
incident to ordinary handling in transportation. Cryopreserved products with an
indicated storage temperature below -80C shall be shipped in a validated liquid
nitrogen dry shipper that contains adequate absorbed liquid nitrogen to maintain
temperature at least 48 hours beyond the expected time of arrival at the receiving
facility. The product shall be shipped to the processing laboratory at a temperature
defined in the SOP Manual. The transit time should be minimized. If the intended
recipient has received high-dose therapy, the product shall be hand-carried by a
suitably informed courier in the passenger compartment. There shall be plans for
alternative transport in an emergency. The products should not be passed through
X-Ray irradiation devices designed to detect metal objects. If inspection is
necessary, the contents of the container shall be inspected by hand. 26 Appendix IV
TRANSPLANT REGISTRY FORM STEM CELL TRANSPLANT FIRST REPORT FORM-16(c)
Refer Rule 10(4) Transplant Centre Name of Physician Recipient Name Recipients
Age/Sex Recipients Fathers Name Recipients CNIC number/Form B Address
Donors name (if applicable) Donors Age/Sex Donors CNIC number/Form B Donors
Fathers name Relationship of recipient Indication for transplant Source of stem cells
i) Adult stem cells: a. Bone Marrow b. Blood c. Tissue If source is blood or tissue
please mention by what process stems are harvested. Is this harvesting procedure
experimental YES NO accepted norm YES NO ii) Cord Blood Cells: iii) Embryonal
stem cells: Derived either from blastocytes or foetal tissues Date of
Procedure_________________________ Date reported: ____________________ Signature:
___________________ Signature: ___________________________________ Head Transplant
Centre Member Evaluation Committee Name: Name: Note: In case donor/recipient is
a married woman, Name of husband as well as father will be endorsed. Fax/Mail to
Administrator, Monitoring Authority Transplantation of Human Organs& Tissues, Al-
Farabi Special Education Complex, G-8/4, Islamabad. On the day of Transplantation
followed by a copy by Courier/post. 27 REFERENCES 1. Jones, R. & Burnett, A.K.
(1992) How to harvest bone marrow for transplantation. Journal of Clinical
Pathology; 45, 1053-1057. 2. Makino, S., Harada, M., Akashi, K., Taniguchi, S.,
Shibuya, T., Inaba, S. & Nilo, Y. (1991) A simplified method for cryopreservation of
peripheral blood stem cellsat -80OC without rate-controlled freezing. Bone Marrow
Transplantation, 8, 239-244. 3. Pegg, D.E. (1984) Red Cell volume in glycerol/sodium
chloride/water mixtures. Cryobiology, 21, 234-239. 4. Braine, H.G., Sensenbrenner,
L.L., Wright, S.K., Tutschka, P.J., Sasal, R. & Santos, G. (1982) Bone marrow
transplantation with major ABO blood group incompatibility using erythrocyte
depletion of marrow prior to infusion. Blood. 60, 420-425. 5. Commission of the
European Communities (1989). Rules Governing Medical Products in the European
Community, Vol. IV, Guide to Good Manufacturing Practice for Medicinal Products.
Consumer Protection Act. (1987) Chapter 43, Part I, HMSO, London. 6. Reiman, E.M.,
& Sacher, R.A. (1991) Bone marrow processing for transplantation. Transfusion
Medicine Reviews, 5, 214-227. 7. Gorin, N.C. (1986) Collection, manipulation and
Page 73 of 87
freezing of haemopoietic stem cells. Clinics in Haematology, 15, 19-48. 8. Craig,
J.I.O., Turner, M.L. & Parkar A.C. (1992) Peripheral blood stem cell transplants. Blood
Reviews, 6, 59-67. 9. Hrowitz, M.M., Przepiorka, D., Champlin, R.E., Gale, R.P.,
Gratwohl, R.H., Prentice, G.H.,Rimm, A.A., Ringden, O. & Bortin, M.M. (1992) Should
HLA identical sibling bone marrow transplants for leukaemia be restricted to large
centres? Blood, 79, 2771- 2774. 10.Gluckman, E., Wagner, J., Hows, J., Kerman, N.,
Bradley, N., & Broxmeyer, H.E. (1993) Cord blood banking for haematopoietic stem
cell transplantation: an introductional cord blood transplant registry. Bone Marrow
Transplantation, 11, 199- 200. 11.Boulton, F.E., et al. (1987) Guidelines for
compatibility testing in hospital blood banks. Clin. lab. Haemat. 9, 331-341.
http://hota.pk/Files/Protocols-stem-cell-tx-09[1].pdf

11. Registration and functions of recognized medical institution or hospital.- (1) An

application for registration shall be made to the Monitoring Authority as specified in
Form 11. The application shall be accompanied by a processing fee of rupees two
hundred thousands to the Monitoring Authority paid into Authoritys authorized bank
account as processing fee to be used on the activities of the Authority. (2) The
Monitoring Authority shall, after holding an inquiry and after satisfying itself that the
applicant has complied with all the requirements, grant a certificate of interim
registration as specified in Form 12. After inspecting the hospital physically the
Monitoring Authority shall grant a certificate of registration in Form 13 which shall
be renewable on the payment of renewal fee of rupees one hundred thousands on
yearly basis to be paid into Authoritys authorized bank account to be used on the
activities of the Authority. (3) Every recognized institution shall maintain complete
record of all transplants undertaken including details of the donor. All such
institutions shall report to the Monitoring Authority on the follow-up of the donor
and the recipient. The record of follow-up shall be maintained in a manner as laid
down in Form 14 and Form 15. (4) Transplant Registry Form specified in Form 16,
Form 16(a), Form 16(b) and Form 16(c) in respect of each and every transplant done
by the recognized institution shall be submitted to Authority on day of operation by
electronic mail or fax, followed by a copy by post and processing fee to be fixed by
Page 74 of 87
the Authority from time to time. 12. Renewal of registration.- (1)An application for
the renewal of a certificate of registration shall be made to the Monitoring Authority
within a period of three months prior to the date of expiry of the original certificate
of registration and shall be accompanied by a fee of rupees two hundred thousands
payable to the Monitoring Authority into its bank account. (2) A renewal certificate
of registration as specified in Form 17 shall be valid for one year. (3) If, after an
inquiry including inspection of the hospital and scrutiny of its past performance and
after giving an opportunity of being heard to the applicant, the Monitoring Authority
is satisfied that the applicant, since grant of certificate of registration under sub-rule
(2) of rule 11 has not complied with the requirements of the Act and the Rules made
thereunder and conditions subject to which the certificate of registration has been
granted, shall for reasons to be recorded in writing, refuse to grant renewal of the
certificate of registration. 13. Essential Conditions for grant of certificate of
registration.- No hospital shall be granted a certificate of registration under the Act
unless it fulfils the following requirement of manpower, equipment, specialized
services and facilities etc., as laid down below,- (a) General manpower requirement,
specialized services and facilities,- (1) twenty four hours availability of medical and
surgical, (senior and junior) staff; (2) twenty four hours availability of nursing staff,
(general and specialty trained); (3) twenty four hours availability of intensive care
units with adequate equipments, staff and supports system, including specialists in
anaesthesiology, intensive care; (4) twenty four hours availability of laboratory with
multiple discipline testing facilities including but not limited to microbiology,
biochemistry, pathology and hematology and radiology departments with trained
staff; (5) twenty four hours availability of operation theatre facilities for planned and
emergency procedures with adequate staff, support system and equipments; (6)
twenty four hours availability of communication system, with power backup,
including but not limited to multiple line telephones, public telephone systems, fax,
computers and paper photo-imaging machine; and (7) experts, (other than the
experts required for the relevant transplantation) of relevant and associated
specialties including but not limited to and depending upon the requirements, the
experts in internal medicine, diabetology, gastroenterology, nephrology, neurology,
paediatrics, gynaecology, immunology and cardiology etc., should be available to
the transplantation centre; (b) Equipments.- Equipments as per current and
expected scientific requirements specific to organ being transplanted. The
transplant centre shall ensure the availability of the accessories, spare-parts and
back-up, maintenance and service support system in relation to all relevant
equipments; (c) Experts and their qualifications,- (i) For Kidney transplantation,-
FCPS or M.S. General surgery or Urology or equivalent qualification with three years
post FCPS or M.S. training in a recognized centre in Pakistan or abroad and having
attended to adequate number of renal transplantation as an active member of
team; (ii) Transplantation of liver and other abdominal organs,- FCPS or M.S. General
surgery or equivalent qualification with at least three years post FCPS or M.S.
training in an established centre with reasonable experience of performing liver
transplantation as an active member of team; (iii) Cardiac, pulmonary, cardio-
pulmonary transplantation,- FCPS or M.S Cardio-thoracic and vascular surgery or
equivalent qualification in Pakistan or abroad with at least three years experience as
an active member of the team performing an adequate number of open heart
operations per year and well-versed with coronary by-pass surgery and heart-valve
surgery; and (iv) Cornea transplantation,- FCPS or M.S. ophthalmology or equivalent
Page 75 of 87
qualification with at least one year post FCPS or M.S. training in a recognized
hospital carrying out corneal transplant operations. Form-11 [See Rule 11(1)]
APPLICATION FOR REGISTRATION / RECOGNITION OF INSTITUTION / UNIT FOR
TRANSPLANTATION Proforma to be completed and sent to Human Organ Transplant
Authority (HOTA), 36 Aga Khan Road, Super Market, F-6/4, Islamabad, Fax No.051-
9216107 Name of the
Institution______________________________________________________________ Mailing
Address____________________________________________________________________
________________________________________________________________________________ Tel
No.___________________Fax No.___________________Email__________________________
Name of the Head of the
Institution_____________________________________________________
Designation______________________________Mailing
Address____________________________
________________________________________________________________________________ Tel
No.___________________Fax No.____________________Email_________________________
Status of Institution Public Sector Private Any other____________________ Specialty
units/departments accredited with CPSP/PMDC/University__________________________
S. No Name of Specialty Accreditation Authority Name of Deptt. Heads With
postgraduate qualifications 1. Urology (Kidney Transplant) 2. Nephrology (Kidney
Transplant) 3. Gl and Hepatology (Liver & intestinal transplant) 4. Pulmonology
(Lung Transplant) 5. Cardiology (Cardiac Transplant) 6. Hematology (BMT, Stem cell
Transplant) 7. Ophthalmology (Corneal Transplant) 8. Radiology 9. Anesthesiology
10. Pathology (Please provide list of faculty in all Specialties with qualification and
experience in Transplant as Annexure) Total beds in the institution___________
Male________Female______Children__________ No. of OPDs________Attendanece/year
Male________Female______Children__________ Total beds in Transplant Unit:_________
Male________Female______Children_________ SUPPORT FACILITIES Blood bank Is the
blood bank present? Yes No If No please specify about storage
_____________________________________________ Are cross matching facilities available?
Yes No Are blood products available in house? Yes No If No. what arrangements are
in place for 24 hours availability _______________________ (Attach separate sheet if
needed) Laboratory Please supply a list of tests, which are done in the laboratory in
the following area. (Attach separate sheet if needed) Bio-
Chemistry_____________________________________________________________
Histopathology_____________________________________________________________
Microbiology_______________________________________________________________
Hematology_______________________________________________________________
Immunology_______________________________________________________________ Drug
Monitoring ___________________________________________________________ Radiology
Please furnish a list of radiological test routinely carried out in the Institution (Attach
separate Sheet if needed) Specialized diagnostic facilities: Ultrasound Yes No MRI
Yes No CT Scan Yes No Radioisotopes Yes No Doppler Yes No Portable X- Ray Yes No
Intensive Care Unit If yes No. of ICU beds with high end monitoring and ventilation
______________________ Number of Monitors____________Total ventilator
available_________________________ ABG machine in ICU Yes No Other Facilities
__________________
________________________________________________________________________ Dialysis Yes
No Availability of dialysis facility in ICU Yes NO If yes No. of Dialysis machine in
Page 76 of 87
hospital__________Number of Sessions / day _________ If the following Specialties are
not available in house please mention the arrangements for access at all time
(Attach separate sheet if needed). Cardiology
_____________________________________________________________ Pulmonology
____________________________________________________________ GI /
Hepatology_____________________________________________________ Infectious
Disease___________________________________________________
Neurology__________________________________________________________
Orthopedics________________________________________________________ Operation
Theatre and Anesthesiology Please provide List of Equipment available for
Transplant surgery as annexure. Record Keeping System of storage and retrieval of
records__________________________________
___________________________________________________________________ Do you produce
Annual Report? Yes No (If yes please furnish the copy of annual report of last year)
How are the case records maintained? [ Manual Computerized Library Yes No
Working days of the library_________________Daily working hours____________ (Please
provide the list of Textbooks of Transplant Sciences and Journals available in the
Institution Department) Research Facilities: No. of in hand projects and title of
research conducted by the faculty of the department: (Attach separate sheet if
needed) Additional Essential Activities / Facilities Nursing Adequate number and of
sufficient seniority to cover Transplant ward ICU Medical Social Officer Depending on
transplant activity minimum of 3 to (Transplant Coordinator) help put pre transplant
assessment and donor selection Isolation Facility 1 to 2 rooms for isolation of
patients when required Pharmacy Dedicated staff to respond to needs of transplant
patients specially immunosuppressant, antibiotics and other drugs Seminar Room
For daily patient related Meetings (AM and PM).Morbidity Mortality review, Clinical
Audits Other resources Computers, Video films, internet access, multimedia
Videoconferencing facilities with reference centre in future Form-12 [See Rule 10(2)]
CERTIFICATE OF INTERIM REGISTRATION In pursuance of Section 6, Sub-section (3)
of The Transplantation of Human Organs and Tissues Act, 2010 (VI of
2010)________________________Hospital has been accorded Interim Recognition for
__________________________________ transplantation. 2. Interim Recognition will NOT
be a guarantee for formal recognition, which will be subject to detailed scrutiny of
the hospital record, infrastructure, faculty and facilities available for transplant
procedures. Hospital/institutions will facilitate the Inspection Team and provide free
access to necessary information/record/data. Administrator Human Organ
Transplant Authority (HOTA) Official Seal Form-13 [See Rule 11(2)] CERTIFICATE OF
REGISTRATION In pursuance of section 6, sub-section (3) of The Transplantation of
Human Organs and Tissues Act , 2010 (VI of 2010)________________________ Hospital
has been recognized for __________________________________transplantation for a
period of one year with effect from the date of issuance of this certificate.
Notification in the Official Gazette will be published in due course. Administrator
Human Organ Transplant Authority (HOTA) Official Seal

http://hota.pk/Files/REGISTRATION_Form_%20of_Hospital_Medical_Institutions.pdf

Page 77 of 87
Page 78 of 87
 15 hospitals allowed kidneys
transplantation
Lahore

AUGUST 24, 2016 BY APP

Punjab Human Organs Transplantation Authority (PHOTA) has

allowed only 15 hospitals of Lahore and Rawalpindi to transplant
kidneys.

A mechanism will soon be evolved for action against the hospitals

which are not registered with the authority for transplantation of human
organs.

This was informed in a meeting of evaluation committee of PHOTA

presided over by Advisor to Chief Minister on Health Khawaja Salman
Rafique.

The meeting was told that regular inspection of registered hospitals for
transplantation of human organs will be conducted and it will be
compulsory for these hospitals to intimate PHOTA 48 hours before
such operations and the hospital will also prepare a calendar of
operations for this purpose.

The hospitals registered for transplantation will display the logo of

PHOTA prominently at the hospital. It was said the government is
ensuring that no hospital should undertake organ transplantation

Page 79 of 87
without proper facilities and that stern action would be taken against
those violating these instructions.

Khawaja Salman Rafique said that consultations had been made with
Secretary Law and other legal experts for amendments in the laws of
Punjab Human Organs Transplantation Authority and that legislation
would soon be undertaken. He said that action would be taken against
the donor as well as the recipient in case of illegal kidney
transplantation.
http://www.pakistantoday.com.pk/2016/08/24/15-hospitals-allowed-kidneys-
transplantation/

Human Organ Transplant Authority handed over to NHS

ministry
IKRAM JUNAIDI PUBLISHED Oct 23, 2016 06:34am

2 COMMENTS
Page 80 of 87
EMAIL

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ISLAMABAD: Prime Minister Nawaz Sharif has placed the Human Organ Transplant Authority
(HOTA) under the Ministry of National Health Services (NHS).

The authority previously worked under the Ministry of Capital Administration and Development Division
(CADD).

Talking to Dawn, NHS Secretary Ayub Sheikh said that the ministry will first get a new administrator for
HOTA. Second, we will add more experts to the monitoring authority, some amendments will be made in the
laws and it will be ensured that the authority is made effective, he said.

We are also moving HOTA records to the NHS ministry, so we know about its weaknesses and flaws and how
to address them, he added.

ADVERTISEMENT
The ministry of NHS is primarily responsible for devising policies for the regulations of institutions.

One the organs of one person can save the lives of 27 people, however, there is no trend for or awareness about
organ donation in the country. Because of the unavailability of human organs, they are sold on the black
market, in which a number of health institutions and departments are also involved.

A number of bills are being discussed in parliament for regulating human organ transplants and in July this
year, the National Assembly Standing Committee on Human Rights suggested increasing punishments for the
illegal trade in human organs and put a ban on visas acquired for medical treatment in the country.

During a meeting, a representative of the Sindh Institute of Urology and Transplantation (SIUT) Dr Mirza Naqi
Zafar said the trade in human organs is continuously increasing in the country and people from all over the
world come to Pakistan for organ transplants. According to Dr Zafar, the price for one organ is between Rs4
million and Rs10 million though the person who sells the kidney is given just a nominal amount.

He said the business was more common in Punjab, where half the residents of some villages had sold their
kidneys. He added that a number of people were also taken to China and other countries for liver transplants
and that the donors had died due to the sensitive and complicated process for donating a part of the liver. After
they had died, the victims were declared missing.

Dr Zafar said SIUT had received a number of e-mails from various countries including Canada, Australia,
Saudi Arabia and Kuwait saying that people had had organ transplants in Pakistan and had developed
complications. He had claimed that HOTA did not have a control over the issue.

A bill titled The Transplantation of Human Organs and Tissues (Amendment) Bill, 2014, tabled by MNA
Kishwar Zehra was passed in March this year by the National Assembly Standing Committee on Cabinet
Secretariat. MNA Zehra is also an organ donor.

Published in Dawn, October 23rd, 2016

https://www.dawn.com/news/1291663

Page 81 of 87
Organ Transplantation And Proposed Legislation In Pakistan

Dr. Najib ul Haq

Page 82 of 87
T
he Supreme Court while hearing the case of trade of human organs in
Pakistan on July 26th and 27th, once again directed the Federal Government
to draft and implement an ordinance on organ transplantation on priority
basis. This may not have been an issue of political interest for the
legislators but it is certainly an issue of public interest with immense ethical, social
financial and medical implications. The issue was brought to light when a television
program highlighted, that majority of poor people of a village, confirmed selling of
their kidneys for small amount of money. Most of them were apparently coerced
while making their decision and appeared unaware of the overall implications of
their act.

It appears that the Apex Court is primarily interested in banning the illegal and
immoral sale of kidneys. If this practice did not stop immediately. Then one might
see other human organs on sale on the streets of this country in near future.
Pakistan is a Heaven of this unfortunate criminal trade in the absence of any
legislation. Influential private lobbies and beneficiaries will not leave any stone un
turn to block such legislation or assure, to leave a lacunae in law, to continue their
criminal lucrative business of sale purchase of human organs.

The sale/purchase of human organs can be and should be immediately stopped.

World Health Organization (WHO) has already approved guide lines on human organ
transplantation (Executive committee meeting and World Health Assembly meeting
in 2004). The relevant articles (5 to 8) are reproduced below and can be used as
guiding principles for proposed legislation;

The human body and its parts cannot be the subject of commercial
transactions. Accordingly, giving or receiving payment (including any other
compensation or reward) for organs should be prohibited.

Advertising the need for or availability of organs, with a view to offering or

seeking payment, should be prohibited.

It should be prohibited for physicians and other health professionals to

engage in organ transplantation procedures if they have reason to believe that
the organs concerned have been the subject of commercial transactions.

It should be prohibited for any person or facility involved in organ

transplantation procedures to receive any payment that exceeds a justifiable fee
for the services rendered.

Page 83 of 87
Human organs can either be donated as free (gift) or sold by the donor. The organs
could be accepted / purchased directly by a patient / his elatives or through a third
party.

Selling of human organs has enormous ethical, sociocultural and religious

implications and is prohibited in the majority of countries of the world. It is banned
in US and most of the European countries. However comprehensive laws of
transplantation were still not invoked till recent past in four Countries in Europe
(Report steering committee on Bioethics European Health Committee Strasbourg
June 2004).

The Islamic religious scholars also disapprove this practice of selling human organs.
The organ donation is based on three Islamic principles i.e. beneficence, gift
(donation) and usefulness and sustenance of human life.

In light of the general consensuses on this part of the issue Human Organ
Transplantation, there should be little problem in prohibiting sale of human organs
through framing required legislation.

However, it should be recognized that Human organ transplantation is a complex

issue having multiple dimensions. These must be fully comprehended and analyzed
before any final legislation. A board comprising medical, religious and social
scholars of the society can formulate a draft bill / guidelines for this purpose. More
public, legislative and experts debates should be initiated for covering major
aspects of the issue. Related issue to cadaveric organ used for transplantation (e.g.
defining and declaring death and cell / tissue transplantation) must also be
addressed while making a final decision on the bill.

The major areas that need to be addressed include;

Ethical issues in organ transplantation will reported to

o Global perspective
o Islamic perspective
Prevailing Law
Types of organ used for transplantation (Non regenerative, regenerative or
partially regenerative, for example kidney, bone marrow and liver respectively)
Cell / sperm/ ova donation transplantation /
Transplantation for non-essential medical needs e.g. beautification
Laws governing definition of brain death and related issues
Transplant research (including stem cell issues)
Transplanting animal organs to humans (Xenotransplantation)

Page 84 of 87
 Import and export of Human Organs / tissues

Sources of Organs for transplantation: These can be obtained from human

source from living donors or deceased (cadavers). The possibility of obtaining
organs from animals is still an experimental but promising future tool
(Xenotransplantation) with additional ethical considerations.

Cadaver organs: There may be few issues in obtaining organs from cadavers for
transplantation. There is general consensus of opinion on the sanction of this
practice, although some religious scholars disagree even with this type of organ
donated and consider transplantation against the basic Islamic principles. The same
is true for some Non Muslim communitarian / faith groups who would not accept
even blood from a donor.

The rights of the dead body may be an important ethical and religious issue that
needs to be addressed in such cases.

Other question that would need satisfactory answers in cadaver organs use include;
Do the legal heirs have the right of substitute decision making in the absence of
anticipated decision / will of the deceased? Is the state competent to make such
decision in case of unclaimed dead bodies? Has the death been confirmed by
appropriate board / committee having no short / long term conflict of interest with
cadaver transplant services? How and who will ensure a fair distribution of required
organs from organ bank? How should decisions be made on distributing scarce
organs?

All these issues can be relatively easily address in the presence of relevant laws
with only some ethical dilemmas. However complete ban on live donors in the
absence a cadaver organ bank may raise many uncertainties in decision making.
But having said that it must also be appreciated, that in the presence of easily
available living donors a pressing need for developing cadaver organ
transplantation facility was never felt in the past. We have not moved an inch
forward to develop this very important and urgently required service.

Live Donors: The case of live donors organs for transplantations has many
more related issue. Some of these could be;

Is donating an organ the health need of the donor? If not what are the factors for
prompting him to donate organ? Is human body a commodity? Can it be bought?

Page 85 of 87
Does the person understand all the implications of his decision to donate organ?
Can parents / guardians make substitute decision making for minors and mentally
disabled persons? Can an entrepreneurial service facilitate / organize a transplant
service in the absence of sale / purchase system of organs, by the donors /
recipient? Are "non-financial" rewards / gifts equivalent to sale of organs?

Specific ethical issues that could need elaborates guidelines indeed includes selling
of organs, sustenance capacity of recipient, intellectual / physical / psychological
state of the recipient / donors, age of donor/recipient and religious / social
acceptability etc.

Additional question that will need proper redressal include.

Can a genetically non-related person donate to a patient who has a genetically
related capable donor available? Can organ be given for the second time to a
person (who had a failed previous transplant), while another patient waiting for his
first time transplantation? What is acceptable level of risk for the donor / recipient
in terms of expertise in surgical, anesthesia, post-operative care in a specific setup?
Is a better setup available for risk reduction? Is a reasonable alternate choice
acceptable to the patients (e.g. dialysis for patients with kidney failure) available,
that has been full explained for which he might willfully opt?

In addition one very important issue regrettably not given its due importance in our
society is that of informed consent Unfortunately the donors in this country (and
even the recipients) do not exactly know the over all medical, financial and social
implications of the transplant. Capacity (ability to fully understand and comprehend
the consequences of transplantation), voluntariness (the decision made is not
under duress or as a result of coercion, but free will of the person ) and disclosure
(the patient has been explained all the related issue by the concerned doctors and
its implication in detail and the patient has understood the overall issue) are all
essential components of informed consent and these are rarely fully accomplished
in true spirit.

I cant forget Mr. Amjad a young man of thirty who sold all his assets and
finally had to sell his young daughter for want of money, needed for
post kidney transplant medication, which he could otherwise not arrange.
I wish that the doctor had explained him all the post-operative cost and
care which the patient had to pay for life long that was never told to late
Amjad

All these and many other questions will need to be addressed while making a final
legislation on the Organ Transplantation Bill. The present pressing issue of sale of

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kidneys discussed in the Supreme Court stirred up, following multiple complaints
and news items of commercialization of the kidney transplantation in Pakistan.
The government should immediately put a ban on sale of human organs / tissues,
through an ordinance. A comprehensive Organ / Tissue Transplantation Bill should
only be promulgated after addressing all the related concerns of this complex
having with enormous medical, ethical and socio-cultural implications.

Note: The author is Professor of Medicine and Dean Faculty of Medicine Peshawar
Medical College
professornajib@yahoo.com

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