An Industrial Training Report Of

Cipla Ltd. (Pithampur)

Shri G.S. Institute of Science & Technology

Department of Applied Chemistry & Chemical
Technology

Submitted to Submitted by
Dr. Madhavi Verma Ms. Praveena Pathak
HEAD, Dept. of App. Chem. 0801MS172004
SGSITS, Indore 3rd Sem
 ACKNOWLEDGEMENT

It is my pleasure to be indebted to various people, who directly or indirectly

contributed in the development of this work and who influenced my thinking,
behaviour, and acts during the course of training.

I express my sincere gratitude to Dr. Madhavi Verma (Prof. & HoD), and Dr.
Nitish Gupta (Asst. Prof.), SGSITS, Indore for providing me an opportunity to
undergo one month training at CIPLA.

I am thankful to Mr. Ashutosh Tomar (H.R.), Ms. Pooja Tiwari (H.R), Mrs
Neelam Maurya (training Coordinator), Ms. Anita Zitshi (QC), Mr. Hemkrishna
Raghuvanshi (liq. Orals), Mr. Rajesh Rathore (stores), Mr. Sonu Kumar (FFS),
Ms. Shubham Pare (QA) and Mr. Sandeep Sharma (QA) for their support
cooperation, and motivation provided to me during the training for constant
inspiration, presence and blessings.

Lastly, I would like to thank the almighty and my parents for their moral support
and my friends with whom I shared my day-to-day experience and received lots of
suggestions that improved my quality of work.

Praveena Pathak
M.Sc. 3rd Sem
 DECLARATION

I hereby declare that the original Industrial Training carried out in Cipla, Unit I,
SEZ, Pithampur and the report submitted to Shri govindram Seksaria Institute of
Science and Technology, Indore has been truly done by me.

The matter embodied is the actual work and this work has not been submitted earlier
in part or full for the award of any other degree.

Praveena Pathak
M.Sc. 3rd sem
 Index
S. No. CONTENT PAGE No.
1. Introduction 1-4
1.1 History 2
1.2 Operations 3

2. Change Room Procedure 7

3. Departments 8

4. Store 9-11

5. Production 12-20
5.1 Section of Manufacturing 13
Area
5.2 Changeover 16
5.3 Area and Line Clearance
5.4 BMR
5.5 Products manufactured 17

6. Packaging 21-26
6.1 Types of Packaging 21
6.2 Equipment/ Instrument 23
6.3 Security Check 25
6.4 Documentation 25

7. Quality Control 27-31

8. Quality Assurance 32-36

8.1 GMP & cGMP 33
8.2 Validation 33
8.3 Audit 33
8.4 CAPA 34
8.5 Deviation 34
8.6 Change over 34
8.7 Recall and Withdrawal 34
8.8 Qualification 35
8.9 Data Integrity 35
9. Engineering 36-37
9.1 HVAC 36
9.2 AHU 36
9.3 Calibration 37
9.4 Utilities 37
10. Water System 38-39
 INTRODUCTION
Mission:
Cipla‟s mission is to be a leading global healthcare company which uses technology and
innovation to meet every day needs of all the patients.

Incorporated in : 1935
Employees : 2,00,000+
Turnover : USD 2 Billion
Founder : Dr. K.A. Hamied (1898-1972)
Non-Executive Chairman : Dr. Y.K. Hamied
Non-Executive Vice-Chairman : Mr. M.K. Hamied
MD and Global CEO : Mr. Umang Vohra

Cipla Limited is an Indian multinational pharmaceutical and biotechnology company, headquartered

in Mumbai, India, Belgium, Surrey in the European Union and Miami, Florida, and in United States.
Cipla Ltd is a public limited company established in 1935 and managed by a professional board of
directors. It manufactures and markets a wide range of Pharmaceutical Formulations and Active
Pharmaceutical Ingredients (APIs). The corporate headquarters including corporate quality
assurance (CQA) is located in Mumbai.
The company has eight manufacturing sites in India:
 1.1 HISTORY

It was founded by Dr. Khwaja Abdul Hamied as 'The Chemical, Industrial & Pharmaceutical
Laboratories' in 1935 in Mumbai. The name of the Company was changed to 'Cipla Limited' on 20
July, 1984. In the year 1985, US FDA approved the company's bulk drug manufacturing facilities.
Led by the founder’s son Yusuf Hamied, a Cambridge-educated chemist, the company became a
global icon for its role in defying Western multinational pharmaceutical companies in order to
provide generic AIDS and other drugs to treat poor people in the developing world. In 1994, Cipla
launched Deferiprone, the world’s first oral iron chelator. In 2001, Cipla offered medicines
(antiretroviral) for HIV treatment at a fractional cost (less than $350 per year per patient).

In 2012, the company slashed prices of three life-saving cancer drugs by 50-64%. As of 17
September 2014, its market capitalization was ₹517 billion (US$7.7 billion), making it India's 42nd
largest publicly traded company by market value.

1.2 Operations
Cipla has 34 manufacturing units in 8 locations across India and has presence in 170 countries.
Exports accounted for 48% 49.48 billion (US$740 million) of its revenue for FY 2013-14. Cipla
spent INR 517 cr. (5.4% of revenue) in FY 2013-14 on R&D activities. The primary focus areas for
R&D were development of new formulations, drug-delivery systems and APIs (active
pharmaceutical ingredients). Cipla also cooperates with other enterprises in areas such as consulting,
commissioning, engineering, project appraisal, quality control, know-how transfer, support, and
plant supply.

As on 31 March 2013, the company had 22,036 employees [out of which 2,455 were women
(7.30%) and 23 were employees with disabilities (0.1%)].During the FY 2013-14, the company
incurred 12.85 billion (US$190 million) on employee benefit expenses.
 Awards and Recognitions:-

In 2012, Cipla received the Thomson Reuters India Innovation Award.

Cipla won Dun & Bradstreet American Express Corporate Awards for 2006.
In 2005, Forbes included Cipla in the 200 'Best under a billion' list of best small Asian
companies.
In 1980, Cipla won Chemexcil Award for Excellence for exports.

1.2.1 Cipla Ltd. Indore SEZ

The manufacturing site of Cipla Ltd, Indore SEZ located in Pithampur, District Dhar, India, was
inspected by the WHO prequalification inspection team. Cipla Ltd, India, Indore SEZ is located on
Plot 9, 10 and 15 of the Indore SEZ Phase II, Pithampur District Dhar in Madhya Pradesh (MP),
India. The operations were commenced from April 2010. The site had four units which manufactures
following dosage forms/products:

• Unit I: Form, Filled and Sealed (FFS) Eye Drops, Liquid Orals, Respiratory solution /
suspension, Unit dose ophthalmic products.

• Unit II: Aerosol–-Metered Dose Inhalers.

• Unit III: Pre-filled syringes (PFS), Nasal Sprays, and 3 Piece Eye Drops.

• Unit IV: Coated /Uncoated tablets, effervescent tablets, hard gelatine capsules, powders
/granules and pellets.

•
According to the presentation, the site employees approximately 1583 staff, and the operations are
mainly carried out in two shifts, if required then operations are extended to third shift.

1.2.2 Affiliations

  USFDA(USA)
  WHO (Geneva)
  MHRA(UK)
 TGA (Australia
 EMA ( Europe)
  SUKL (Slovakia Republic) APUMA (Australia)
  MCC (South Africa)
  PIC ( Germany)
  AMUISA (Brazil)
  MHLW (Japan)
  IMUIMA ( Columbia)
  NDA( Uganda)
 MOH( Saudi Arabia)


 Unit 1 Production
A. RESPULES :
Respules contain a medicine called budesonide. This belongs to a group of medicines called
'corticosteroids'. It works by reducing and preventing swelling and inflammation in your lungs.
Respules are used to treat asthma. They are also used to treat croup in infants and children.

B. Eye Drops Generic name : Tetrahydrozoline

Eye drops are saline-containing drops used as an ocular route to administer. Depending on the
condition being treated, they may contain steroids, antihistamines, sympathomimetic, beta receptor
blockers, parasympathomimetics, parasympatholytics, prostaglandins, nonsteroidal anti-
inflammatory drugs (NSAIDs), antibiotics, antifungal, or topical anaesthetics.
Tetrahydrozoline is a decongestant used to relieve redness in the eyes caused by eye irritations (e.g.,
smog, swimming, dust, or smoke). It belongs to a class of drugs known as sympathomimetic amines. It
works by temporarily narrowing the blood vessels in the eye. Some brands of
tetrahydrozoline eye drops may contain lubricants. Lubricants help protect the eyes from more
irritation and dryness. Eye drops can be steroidal or antibiotic in nature. Eye drops sometimes do not
have medications in them and are only lubricating and tear-replacing solutions.
Eye drops have less of a risk of side effects than do oral medicines, and such risk can be
minimized by occluding the lacrimal punctum, (i.e. pressing on the inner corner of the eye) for a
short while after instilling drops.

C. Salbutamol Respiratory Solution/Suspension :

Salbutamol Respirator Solution is a member of the group of drugs called short-acting beta-2
agonists. This medicine is used for the relief of asthma symptoms, but it can also be used to
delay delivery in women undergoing premature labour. It is very useful for preventing asthma
symptoms due to exercise and other conditions too.

Salbutamol Respirator Solution is usually used with a nebuliser or inhaler but is also available
as an intravenous solution and a pill. Dosage is based on your age, gender, response to therapy,
medical condition, and use of certain interacting medicines.

Some of its side effects include feeling a bit shaky, headache, uneven heartbeat,
flushing, muscle cramps, irritation or dryness of the mouth and throat, low blood potassium
levels, weakness, restlessness, dizziness, bronchospasm and lactic acidosis.

Salbutamol Respirator Solution should be used with caution in those with severe asthma, heart
problems, high blood pressure, diabetes, an overactive thyroid gland, infection of the lungs,
arrhythmias, those who have intolerance to some sugars or those with low levels of potassium
in their blood.
 2. CHANGE ROOM PROCEDURE
 Entry procedure


Remove all jewelleries.


Remove street clothes and hang them on the hanger.


Remove street footwear & keep them in the locker.


Disinfect both the hands with 70% IPA solution.


Collect factory uniform from linen room.


Wear the uniform properly.


Wear the factory footwear.


Disinfect both the hands with 70% IPA solution.


Check the mirror for proper attire and enter into main corridor through air lock.


 Exit procedure during breaks



Remove footwear and keep them in the locker.


Disinfect both the hands with 70% IPA solution.


Remove uniform and hang them on the hanger.


Cross the bench.


Wear street clothes & footwear.


Disinfect both the hands with 70% IPA solution.


Leave the change room through air lock.


 Exit procedure during end of the shift



Remove footwear and keep them in the locker.


Disinfect both the hands with 70% IPA solution


Remove the uniform.


Cross the bench.


Drop the uniform in the linen drop box.


Disinfect both the hands with 70% IPA solution.


Wear street footwear & street clothes.

Leave the change room through air lock.
 3. DEPARTMENTS
The various departments of Cipla Ltd. SEZ Unit-II are as follows:-

STORES

PACKAGING

QUALITY CONTROL

QUALITY
ASSURANCE

ENGINEERING

MAN
 4. STORES
The quantity of goods for use as needed & keeping / accumulating it for future use can be termed
as stored material. It can be raw material or finished good awaiting to be dispatched. Since all the
materials imported or received are not used in manufacturing or all the finished goods are not
dispatched, therefore a separate department for inventory is required. The stores department is not
only concerned with the receipt and storage of materials but it also involves many documented
procedures, like placing of indent and making purchase orders. It also sends the required conditions
of storage to the engineering department for management of quarantine area. The area of recall or
rejected materials also comes under stores department.

Functions of stores department

  Receiving of incoming consignments (goods).

  Safe keeping of goods.
  Disposal of undesirable goods.
  Inventory management.
  Housekeeping and record maintenance.
 Balance verification and calibration.

4.1 Types of stores in Cipla Ltd. SEZ Unit I

  V & C store
  Raw material store
  Packaging material store
  Finished goods store
 Miscellaneous store

Receiving Bay: There are two types of receiving bay in unit I-

  One for raw materials and V & C stores

 Another for packing material and finished goods

4.2 Storage Areas

 De-dusting Area – Here the received material is de-dusted with the use of vacuum
 cleaners.
 Quarantine Area - After the receipt raw material is stored in this area, pending for
 GRN.
 On-area test - After sampling material is stored in this area, pending for analysis &
 testing.
 Sampling area - After sampling by QC material is kept over here, pending for GRN
from store.
  Pass area – On-test material duly tested & passed by QC is stored in this area.

 Dispensing area – In this area dispensing of pass material is done.

 D-I Area : Temperature -19-250C


 
D-II Area: Temperature -19-
250C RH: 15-35%
 Rejected Area-Where rejected materials from QA & QC are placed under lock &
key.
 
 Washing Area-Where equipment’s & accessories are washed with the help of
disinfectants such as-
  
Bacillocide (2%)
  
Cidex (2.45%)
  
Saniquad (1%)
 
Teepol (0.1%)
 
Taski R2 Sol. (3%)


 Scrap area-Here shredders are used for shredding of waste material.

4.3 Instruments/Equipment’s Used

Mobile rack
S Weighing balance
Hydraulic trolley
Vacuum cleaner
Air curtain
Label counting machine
UV light
SS Pellets
RLAF
Order picker
SS Trolley

4.4 Temperature and RH of Areas

S. No Area Temperature (in 0C) RH (in %)
1 Raw Material 15-25 15-50
2 V&C 15-25 15-55
3 Finished Goods 15-25 NA
4 Packing Material 15-25 NA
 Batch Size of Packing Material
S. No Materials Batch Size
1 Labels 10000
2 Cartons 100
3 Actuators 1000
4 Leaflets 500

Material flow in store

Purchase department
order to approved
vendor
Rejected material is
QC sampling and stored in rejected
approval / rejection area and is sent to
of material vendor or destructed
as per SOP

Material received at Passed material is

security gate and GRN sent to QC issued to
security inform to store along with COA manufacturing and
officer packing department

Document checking
against PO /indent Material is shifted to
address, customs quarantine area with
inward GRN awaiting label

Material is sent to
Dedusting, cleaning
stores and material is
of material and its
unloaded at
physical verification
receiving bay
 5. PRODUCTION
Cipla Ltd. SEZ Unit I deals with the manufacturing of respules, eye drops and oral liquids,
mainly anti-asthmatic drugs. These drugs are packed under high pressure therefore
manufacturing and packaging are considered as a single unit of production.

General Flow in Production

R. M Stores Raw Material Sampling A/L

Material Sampling
Quarantine
Release I
Booth

Dispensing Manufacturing Filling

(Stores)

F/G Dispatch Quarantine

Packing
FG Store
Manufacturing section consists of two parts, manufacturing area and filling area.

Raw Material Manufacturing Filling Area

Area (I & II)

From stores FFS

(approved by Filling Machine
QA) And liquid orals

The manufacturing of finished goods requires raw materials, supplied by the vendor, along with the
basic utilities, like water, electricity and steam. These utilities are provided by the governmental
authority AKVN (Audyogic Kendriya Vikas Nigam).

5.1 Sections of manufacturing area of Cipla Ltd. SEZ unit I:-

R.M Corridor:-

Raw material from the vendor is received through the receiving bay (located at the side of unit I).
This raw material is then sampled and after approval is sent for the further process through pass box.
This handling of R.M is done in R.M corridor which includes
 R.M stores
 V & C Corridor
 Day store I & II
 Autoclave area

Raw material is stored in RM stores. Then it is dispensed from day store I & II. This section makes
use of RLAF (Reverse Laminar Air Flow) for material and human safety.

Manufacturing Area:-
For FFS line 1, 2, 3 and 4: The raw material after dispensing is received in the manufacturing
vessels/ tanks. The FFS Filtration has 2 manufacturing tank with capacity 5000L and 1000L
respectively. Then there are 2 holding tanks with capacity 5000L and 1000L respectively.

For Liquid Orals line 3 and 4: the raw material after dispensing, is received in the
manufacturing vessels/ tanks. There are external pipes for addition of Glycerine, Propylene
Glycol, Sorbitol and Lycasin which is mixed with material according to the quantity required
by the product. Full capacity of the vessels is 6000L, and working capacity is 5000L. Temp.
maintained is 102°C. then they are passed to mixing tanks which are jacketed with capacity
800L and 1200L. there is another non-jacketed tank with capacity 5000L to hold the material.
Here, radar sensors are there to check the volume but manually by use of dip-stick volume is
 confirmed. From mixing tanks, material is passed to holding tanks, from where filling machine
operates.

Filling area:-
For FFS line 1, 3 and 4: FFS filling machine is of Weiler engg. Inc., USA. Model no. is 640.
Its capacity is 10200 Respules/hour. Here LDPE granules from stores are added to melt. Then
there is Parison head machine with 8 parison continuous extrusion sterile air flow through
parison. From here, melted granules enter mold machine. It has 3 parts – main mold, seal mold
& holding jaw that forms respules cavity card. The cavity cards are passed on to fill head which
has 40 cavity filling head sterilized, housed in grade “A” shower. And finally to the respules
card which has 40 cavity cards. Each card has 4 combi and each combi has 5 respules.

For Liquid Orals line 3 and 4: filling machine is of Merchesini group. And then there is the
sealing machine of Ambica engg. Works. Each Filling machine has 12 filling heads. The
syringe fill volume is different for filling. For line 3, fill volume is 30-450ml and for line 4, it
is 10-120ml

After filling, the Sealing machine seals the product. Each sealing machine has 9 sealing heads. For
every batch, samples are withdrawn by IPQA team for each filling and sealing head in starting, mid
and end of batch. So total 36 bottles from filling machine and 27 form sealing machine are sampled.

Quarantine:-

The finished products with in-process label are sent to the quarantine for 14 days (28 days for the
products of USFDA) in inverted position, as a check for leakage of the product. Meanwhile they are
sampled by QC department for their analysis. The report of analysis is sent to QA for approval.
These products under analysis are labelled as “under test” (yellow colour code), this is termed as in-
process label. After the approval they are labelled as “approved “(green colour code) which is then
finally dispatched as finished good. This approved label is known as status label. The left over
product as extra is kept as storage for future demand.

5.2 Changeover:-
In manufacturing, changeover is the process of converting a line or machine from running one
product to another. It is an important aspect of pharmaceutical industry. On completion of
manufacturing and packaging of a batch when next batch is manufactured, it is known as batch
changeover and when an entirely new product is manufactured then it is termed as product
changeover. Changeover is divided into 3 ups-
  Clean up: It deals with disassembly of the equipment, cleaning and sterilizing of the line
components. It requires line clearance.
 Set up: It is the process of converting the equipment. This can be achieved by adjusting the
equipment to correspond to the next product or by changing non-adjustable change parts to
accommodate the product.
 Start up: It is the time spent fine tuning the equipment after it has been started.

5.3 Area and line clearance:-

Line clearance is permission taken from the authorized QA person before starting actual production.
These procedures are mainly established to prevent mix-up of containers, products, labels and
mistakes in the documents and hence to prevent cross contamination of the product. Line clearance
includes-
Manufacturing area : It checks the following-
 All the equipment’s should be clean
 Checking all the raw materials are properly weighed or not.
 Mixing time and granulation time.
 The clean labels of equipment’s should be attached in BMR.

Filling area:
 Wash water sample is checked
 Clarity and pH
 Filled volume
 Status label
 To verify whether the previous product packaging material are removed or not.
 Under use label should be there on each equipment.

Dispensing or packaging area

5.4 BMR (Batch Manufacturing Record):-

The BMR is the necessary quality and GMP documentation for tracing the complete cycle of
manufacturing batch. It is a document that is intended to give a full and authoritative record of
manufacturing history of each batch of every product. It is basically based on master formula record.
It is created, checked, rectified and sanctioned by designated, competent and technical person/s that
is responsible for organization’s production and quality control.
It consists of following details-
Product name
Batch number
Date on which significant intermediate stages were commenced and completed.
The name of the person who is responsible for each stage of production.
Initials of both operators who carried out significant processes and the persons who checked
these.
Details such as the quantity, batch no., quality control record no. of each ingredient actually
weighed, along with the amount of any recovered material that may have been added.
Details of in process controls, their results and signature of each person who performed these.
Whenever variation that exceeds expectation is observed, batch manufacturing record in
pharmaceutical industry should make note of the theoretical yield and actual yield at every
appropriate stage of production. These should be accompanied by an explanation.
Details of authorization of any deviation, if any were made.

These batch records are preserved till 1 yr. after expiry of the product.

5.5 Products Manufactured in Unit I:

1. Ipravent respules : Ipratropium Bromide respirator Solution 500mcg.
2. Levobuterol inhalation solution, USP, 1.25mg/3ml
3. Ipratropium Bromide and Albuterol Sulfate, 0.5mg and 3mg/ml
4. Ciplox eye drop- Ciprofloxacin 0.3%
5. 9pm eye drops- latanoprost + Benzalkonium Chloride IP
6. Aerovent Respule- salbutamol Sulfate, 2.5mg/2.5ml
7. Cipcal sirop- Vit D + calcium
8. Asthavent- Salbutamol
9. Ibugesic plus suspension
10. Petcam- meloxicam
 6. PACKING
Packaging can be defined as all the activities involved in designing and producing the container or
wrapper of the product. The product after completion of quarantine period and all the QC checks
are labelled as approved. These approved labelled products are then transferred for the final packing
for dispatch to the market, and this task is completed by marketing department. Cipla Ltd. Indore
SEZ unit II has a 3 line for packing.

Functions of packaging department

 It gives protection to the product.


 It improves product dependability.

 It leads to ease of product handling

 It aids product differentiation.

 It gives separate identity to the product.

 It is responsible for packaging and convenience of public.

6.1 Types of packing material

There are mainly three types of packing materials used in pharmaceutical industries-

 Primary packing material: The packing material which is in direct contact with the drug
or the product is known as primary packing material. It includes, can and valve.

 Secondary packing material: The packing material which is in direct contact with the
secondary material and does not have any direct contact with the drug is known as secondary
packing material. It includes: leaflets, booklets, labels, cartons, etc.

 Tertiary packing material: The packing material which is in direct contact with the
secondary packing material but does not have any contact with the product is known as
tertiary packing material. It includes, shippers, BOPP wrap, tear tap, etc.
General Flow of Finished product in Packaging

Bulk Finished
Goods Batch handover to
Packing

Labelling

Spray check

Cartonating of the Top Bottom

Labelled cans Labelling

Wrapping and
Final packing Bundling

Batch transfer to
Finished goods store
6.2 Equipment’s/ Instruments used in packaging:-
For liquid orals packing:
Cleaning: the pPM i.e., Bottles and caps are cleaned. The capacity for bottle washing
machine of Make Ambica Engg. Works is 240 bottles per unit. It uses 80L of water for
washing which is changed manually in every 3-4 hours of operation. 8 levels of cleaning is
done for washing the bottles.
1st level: washing with cold purified water, inner and outer side.
2nd level: compressed air washing inner and outer of bottle
3rd level: washing with cold purified water, inner and outer side.
4th level: compressed air washing inner
5th level: washing with hot purified water, inner side.
6th level: washing with hot purified water, outer side.
7th level: compressed air washing inner
8th level: compressed air washing inner and outer of bottle

Similarly caps are also inspected in a separate room. They are made sterile and then added
to a vessel from where they are sucked through vacuum to cap hopper.
Optical Magnifying lens: it’s a lens filled with liquid that enlarges the bottle head and neck
region. Here check is performed manually to detect faulty/defect in caps, fill volume, etc.
Turn table:
It is a stainless steel table that rotates continuously over its axis. Tray with cans is unloaded
manually over the table and it provides a pathway for the cans for their entry in spray
checking machine through belt conveyor.
Label printing Machine: it is Utopia make printing machine which labels the filled bottles
and the video jet sensor checks the label which has batch no., manufacturing and expiry. If a
defect/misprint/smudge is observed, bottle is rejected. In between challenge test is performed
in every 4 hours of operation.
Visual inspection: manually bottles are checked to assure label and print quality.
Again a turn table is there to rotate and collect bottles.
Cartonator: this machine prints the 2d code on carton. It is of utopia make and the video jet
sensor checks the label quality, weight of carton.
Track and trace system: check weigher
Aggregation system: this generates the shipper, labels shipper and seals it
 For FFS Respule packing:

Deflasher machine: it removes the respules cavity cards and scrap aside. Each card has 4
combi.
Pinhole Master: it is of Nikka densok, Japan. This machine performs the leak test. If
found respules card is rejected.
Pack Leader Labelling machine: it prints top and bottom labels. If missing it rejects the
combi.
Pillow Packing: make Omori Chankong China. This machines packs the respules combi in
a silver foil.
Check Weigher: it is of Nikka densok, Japan. It weighs the card, and rejects if high or low
weight found.
Pouch labelling. Make Utopia. It is labelling machine with inspection system. It labels the
pouch card.
Track and trace system: Make Utopia, model UTOS 200. It labels the carton of respules
and checks the quality of label.
Aggregation system: this generates the shipper, labels shipper and seals it.

For FFS eye drop packing:

Pinhole Master: it is of Nikka densok, Japan. This machine performs the leak test. If
found eye drop is rejected.
Capping machine. This caps the eye drop bottle.
Pack Leader Labelling machine: it prints top and bottom labels. If missing it rejects the
combi.
Printing machine: Make Utopia. It is labelling machine with inspection system. It labels
the inner carton of eye drop.
Cartonator: this machine prints the 2d code on outer carton. It is of utopia make and the
video jet sensor checks the label quality, weight of carton.
Check Weigher: it is of Nikka densok, Japan. It weighs the carton, and rejects if high or
low weight found.
Track and trace system: Make Utopia, model UTOS 400. It labels the carton of respules
and checks the quality of label.
Aggregation system: this generates the shipper, labels shipper and seals it.
 6.3 Security Checks:-
The automatic system has relieved the work of employees and has speed up the process to many
folds but is still not completely reliable, especially in case of pharmaceutical industries. Therefore
security checks are must to minimize the faults. The machines undergo many challenging and in-
process checks. Following are some of the security checks-
Leakage
Container checkweigher
Tip sensor
Challenging without label
Pharmacode and 2D code sensor
Challenging without cap actuator
Container without leaflet challenging
Pharmacode and 2D code on cartons and leaflets sensor
Overprinting of cartons
Overprinting of labels
Without container/ carton challenging
Check of more/ less weight bundles
Weight of each shipper

6.4 Documentation
Following documents are generally concerned with the packaging department-

 BPR

 SOP

 Log Books
 SPMS

6.4.1 BPR (Batch Packing Record): It is a complete set of topics containing full details of packing
procedure and analytical documents. It contains packing procedure and list of equipment’s. It is
required for the analysis in root cause analysis. It is required to register the product in different
countries and regulatory authorities.

6.4.2 SOP (Standard Operating Procedure): It is a written procedure giving instructions for
performing operations not necessary for a given product or material. However, it gives specific
instruction like for operating, cleaning and maintenance of equipment’s, calibration of balances,
sampling procedures and carrying out stability studies.
6.4.3 Log Book: It provides information regarding activity performed in packing. Various log books
are maintained in packing to record various activities.
Types-


Area and equipment usage and cleaning log


Daily verification and full scale calibration log


Machine log

Challenging log books

6.4.4 SPMS (Standard Packing Material Specification): It is prepared according to export party’s
requirement. SPMS is a controlled document which provides detailed information of item code,
pharmacode or 2D code value and overprinting details of packing material and other information
like storage conditions, pharmacopoeia status and expiry.


 7. QUALITY CONTROL
Quality control can be defined as day to day control of quality within the company. They are
responsible for the acceptance or rejection of incoming raw material, packing components and
finished products, for the myriad of in process tests and inspections, to assure that system are been
controlled and monitored for the approval and rejections of complete dosage.
Functions of Quality Control:-

Microbial
Control
Analytical Packagin
Control g
Control

Q
.
C

QC in cipla unit I
 Analytical Methods:
General Flow of goods:

GRN (Goods
Raw Material Received Note) &
COA (Certificate
of Analysis)

LIMS(Laboratory
Information
Management Sampling
System)

Allocation of work Review and

And analysis of the Approval by QC
Samples Head

Involvement of
SAP(System, UD( Usage
Application & Decision)
Product) Preparation

Pass label by QC Raw material sent

For Production
 Instruments/Equipment’s used in SQC:
 Density meter
Make: Anton Par
Model: DMA4100M
 Viscometer 1.
Make: Brookfield
Model: Lv
 UV-Spectrophotometer 2.
Make: Shimadzu
Model: UV- 1800
 Polari meter
Make: Rudolph Research Analytical 3.
Model: Autopol v
 Digital Microscope
Make: Motic 4.
Model: B1 Series
 FTIR
Make: Bruker 6.
Model: Alpha X
 Melting Point Apparatus
8.
Make: SRS
Model: Optimelt
 Refractometer
Make: Rudolph Research Analytical 9.
Model: 1357
 Osmometer
Make: Gonotec
Model: Osmomat 030-D
10.
 Liquid Bound particle counter (LBPC)
 Potentiometer
Make: metrohm
Model: Titrando 809
 Titrator 11.
Make: metrohm
Model: Titrando 890
 HPLC
Make: Shimadzu
Model: 13.
  PACKING MATERIAL QUALITY CONTROL (PMQC)
General flow of goods:-

SAP (System,
TRF (Test Request Applications &
Sampling
Form)
Product)

Allocation of work Information

Preparation of
through WOR (Work automatically feeds
Checklist
Output Record) in LIMS

Report is sent to QC INIT (Initiated & APGR (Approval

head Approval Required) granted)

Report is sent to QA INCO (Analysis

and UD is taken Completed)

Tests performed:-
Various tests performed for packing materials (secondary and tertiary) include the following-
 Description of leaflet, container, valve, etc.
 Print testing (using positives and negatives of leaflets)
 Dimension check
 Grammage test
 User test

These tests are well defined in Standard Pack Specification (SPS). It consists of all the information
regarding container, valves, label sticker, carton, leaflet, tear tape, BOPP film, shippers, BOPP tape
and PP strap.

Various tests performed for primary packing materials include the following-
 Visual inspection
 Variation in design
 Serrated mouth edges
 Unclean containers
 Mix up with other containers
 Dents and cracks
 Scratches over the cans
 Dimensions
 Body diameter
 Rim diameter
 Rim thickness
 Overall length and height
 Neck depth and diameter
 Weight of container
 Cleanliness check
 Additional test ( Bioburden of primary packing)
 Total yeast and bacterial count

Instruments/Equipment’s used in PMQC:-

 Digital Bursting Strength Tester

Make: Mc Sparr
Model: Auto Deluxe Burst

 Precision Thickness Gauge 1.

Make: Olympus
Model: Magna-Mike 8600

 Cutter
Make: IndTech systems, pune
Model: ISO DCP
2.
  Shore Hardness meter
Model: HT-6510 A 5.

 Illuminated Magnifier
Make: optics & Allied Engg. Pvt. Ltd., Bangalore
Model: Opto MaG 7

 Pressure checker : GS Flow meter

 Label printer
Make: Zebra
Model: ZM 480

 Melt Flow Index

Make: Presto Stantest Ltd., Haryana
8.

Sections:-
There are two main sections of QC department in Cipla. These perform routine and non-routine
work.

Quality
Control

Routine Non-Routine

Analysis Calibration Qualification Training

Cipla Ltd. SEZ Unit I has following sections under QC department accounting for its phenomenal
working strategy.
 Raw material (R.M) section
 Routine
 Non-Routine
 Compliance
 In-Process check
 Finished goods section
 PMQC (Packing Material Quality Control) section
 Stability Testing
 Chromatographic section (HPLC and GC)
 Instrumental room

Thus QC can be summarized as-

QUALITY CONTROL

Central
Site QC PMQC
QC
 8. QUALITY ASSURANCE
 In developing products and services, quality assurance is any systematic process of checking
to see whether a product or service being developed is meeting specified requirement or not.
 A quality assurance system is said to increase customer confidence and a company’s
credibility, to improve work processes and efficiency, and to enable a company to compete.
with other country in a better way

Functions
of QA

Training Audit

Doccumentation CAPA

Validation QMS & Deviation

 Quality policy of Cipla SEZ Unit I:-
The quality policy of Cipla focuses mainly on improving the following parameters of a drug-
 Purity
 Quality
 Efficacy
 Safety

8.1 GMP & cGMP :-

GMP: GMP recommended by agencies that control authorization, licensing for manufacture, sale
of food, drug products, and active pharmaceutical products. These guidelines provide minimum
requirements that a pharmaceutical or a food product manufacturer must meet to assure that the
products are of Good manufacturing practices (GMP) are the practices required in order to conform
to the guidelines high quality and do not pose any risk to the consumer or public.

cGMP: cGMP refers to the Current Good Manufacturing Practice regulations enforced by the
US Food and Drug Administration (FDA). GMPs provide for systems that assure proper design,
monitoring, and control of manufacturing processes and facilities. Adherence to the cGMP
regulations assures the identity, strength, quality, and purity of drug products by requiring that
manufacturers of medications adequately control manufacturing operations. This includes
establishing strong quality management systems, obtaining appropriate quality raw materials,
establishing robust operating procedures, detecting and investigating product quality deviations, and
maintaining reliable testing laboratories. This formal system of controls at a pharmaceutical
company, if adequately put into practice, helps to prevent instances of contamination, mix-ups,
deviations, failures, and errors. This assures that drug products meet their quality standards.

8.2 Validation and its importance:-

Validation is a process of establishing documentary evidence demonstrating that a procedure,
process, or activity carried out in production or testing maintains the desired level of compliance at
all stages. In Pharma Industry it is very important apart from final testing and compliance of product
with standard that the process adapted to produce itself must assure that process will consistently
produce the expected results. Here the desired results are established in terms of specifications for
outcome of the process.
 Types of validation
 Process validation
Process Validation is the analysis of data gathered throughout the design and manufacturing
of a product in order to confirm that the process can reliably output products of a determined
standard. Regulatory authorities like EMA and FDA have published guidelines relating to
process validation. The purpose of process validation is to ensure varied inputs lead to
consistent and high quality outputs. Process validation is an ongoing process that must be
frequently adapted as manufacturing feedback is gathered. Process validation can be broken
down into 3 steps: process design, process qualification, and continued process verification.

 Cleaning validation
Cleaning validation is the methodology used to assure that a cleaning process removes
residues of the active pharmaceutical ingredients of the product manufactured in a piece of
equipment, the cleaning aids utilized in the cleaning process and the microbial attributes. All
residues are removed to predetermined levels to ensure the quality of the next product
manufactured is not compromised by waste from the previous product and the quality of
future products using the equipment, to prevent cross-contamination and as a GMP
requirement.

8.3 Audit:-
Auditing is a critical function within a pharmaceutical company. It provides management with
information about how effectively the company controls the quality of their processes and products.
Auditors must perform their jobs competently to ensure their company’s compliance with
pharmaceutical USFDA and GMP regulations and other quality standards like ICH Q10. Auditing
for GMP is specifically designed to address the challenges of GMP auditing for the pharmaceutical
industry and present the basic competencies required to effectively perform the auditor's assigned
responsibilities and contribute to the improvement of auditor performance within a regulated
industry.

Types of audits
 Internal audit - done by QA officers
 External audit - done by USFDA, WHO, FDA, etc.
8.4 CAPA (Corrective Actions & Preventive Actions) :-
CAPA is a fundamental management tool that should be used in every quality system.
 Corrective Actions: A corrective action is a term that encompasses the process of
reacting to product problems, customer complaints or other nonconformities and fixing
them. The process includes:
 Reviewing and defining the problem or nonconformity.
 Finding the cause of the problem.
 Developing an action plan to correct the problem and prevent a recurrence.
 Implementing the plan.
 Evaluating the effectiveness of the correction.

 Preventive Actions: A preventive action is a process for detecting potential problems

or non-conformances and eliminating them. The process includes:
 Identify the potential problem or non-conformance.
 Develop a plan to prevent the occurrence.
 Implement the plan
 Review the actions and the effectiveness in preventing the problem

8.5 Deviation:-
Deviations are measured differences between observed value and expected or normal value for a
process or product condition, or a departure from a documented standard or procedure.
A deviation may occur during sampling and testing, raw materials- and finished product acceptance
and manufacturing. Deviations may also be triggered by customer complaints or comments when
the customer company's standards do not meet critical attributes as delivered per certificate.

8.6 Change control:-

The change control program evaluate all changes that could affect the production and control of the
drug product, intermediate or API. It is the most critical element in the overall quality management
of pharmaceutical industry.
 8.7 Recall, withdrawal and complaints:-
Recall - Recall means removal from market of specific batch/batches of product from further scale
or use to protect public health and wellbeing.
Withdrawal - It refers to removal of a product from market from sale or use that does not violate
regulation administered by the FDA.

8.8 Qualification:-
When this approach is related to a machine or equipment, rather than Validation, this is referred as
Qualification. Qualification is part of, but not limited to, a validation process, which in turn can be
divided into Installation Qualification (IQ), Operation Qualification (OQ), or Performance
Qualification (PQ).

URS (User Required Specification)

CER (Capital Equipment Requisition)

DQ (Design Qualification)

FAT (Factory Acceptance Test)

SAT ( Site Acceptance Test)

IQ (Installation Qualification)

OQ (Operational Qualification)

PQ (Performance Qualification)

Product handover and post implementation Review

 8.9 Data Integrity:-
Data integrity refers to the complete, consistency and accuracy of data. ALCOA in data integrity is:

ALCOA

ATTRIBUTABLE
LEGIBLE

DATA INTEGRITY

ACCURATE CONTEMPORANEOUS

ORIGINAL
 9. ENGINEERING
The engineering department of the plant mainly deals with the technical and mechanical lookout of
the machines. And hence each department requires the presence of an employee of engineering
department during the start-up of machine after line clearance. The maintenance of AHU systems
and HVAC systems is also a concern of engineering department. The distribution of basic utilities
provided by government is also done by this department. Hence, the pioneer work of this department
cannot be neglected.

Engineering Department Responsibilities:-

Maintain the Facility, Equipment’s and upgrade Facility and Equipment as per CGMP
Requirements.
To Prepare and Execute Preventive Maintenance Calibration, Validation Schedule of
HVAC Systems.
To Maintain Central Utilities Equipment so that required Quality utilities can be provided
to plants.
To execute the projects in given time lines.
To Maintain the BMS for the plants as per requirements.

HVAC ( Heating, Ventilating and Air

Conditioning)

AHU ( Air Handling Unit)

Callibration

Utilities
 9.1 HVAC
It is a technology of indoor and vehicular environmental comfort. Its goal is to provide thermal
comfort and acceptable indoor air quality. Its working and management is based on principles of
thermodynamics, fluid mechanics and heat transfer. Refrigeration is also sometimes added as
HVAC&R. it is basically done to control temperature, oxygen replenishment, and removal of
moisture, odors, smoke, heat, and dust, air borne bacteria, carbon dioxide and other gases.

9.2 AHU
It is a device used to regulate and circulate air as part of a heating, ventilating and air-conditioning
system. It is usually a large metal box containing blower, heating or cooling elements, filter racks
or chambers, sound attenuators and dampers. Air handlers usually connect to a ductwork ventilation
system that distributes the conditioned air through the building and returns it to the AHU.

9.3 Calibration:
Calibration is the process of finding relationship between two quantities that are unknown (when
the measurable quantities are not given a particular value for the amount considered or found a
standard for the quantity). The purpose of calibration is for maintaining the quality of measurement
as well as to ensure proper working of the instrument.

9.4 Utilities
Utilities are the primary resources or sources which are provided to a system or machine to convert
power or secondary utility. Basic utilities of engineering department include-
Electricity
Chilled water
Warm water
Cooling water
Compressed water
Steam
 10. WATER SYSTEM
Cipla Ltd. SEZ Unit II has its water implant system, which softens and adjusts the water according
to the requirement and distributes it to the whole unit. Water is one of the utilities provided by the
government through AKVN (Audyogic Kendriya Vikas Nigam). This unit uses RO Water and its
management activities are performed by a separate individual of manufacturing department.
The water system implanted here uses ‘use and throw’ EDI system and filters to avoid contamination
of drug molecules. The RO system uses filters of 0.2 microns and 5 microns which are replaced
after every 2 months. The pH of water is adjusted around 5.5-8.0. The system is subjected to weekly
cleaning though circulation of steam. The compressed air is used for the automatic opening of valves
in case of water damping.

Water treatment plant

Water Damping Phenomenon

When the quality of water received from AKVN is below the grade or its hardness level is more
than the normal value then the filters may get blocked or deposition of salt may occur in the water
tank or EDI system. This is followed by automatic damping of this impure water out of the water
system to prevent the destruction of filters. This management phenomenon is termed as water
damping. This takes place through automatic opening of valves by the force of compressed air
circulating in the SS pipes.

The water system acts by the following three processes-

Water
Pre-treatment Water generation Water distribution
 Water treatment process is as follows-

Raw water turned into

Potable water from AKVN

Adjustment of pH through 0.5 % NaOH

And softening of water through 1% SMBS

RO (Reverse Osmosis)

Settlement of electric charge of

water Through Electo deionisation
system (EDI)

Purified water storage tank of capacity

1000 lit. (Grade: SS 316 L)

Generation tank with regulation of TOC

(NMT 500 ppm), Conductivity (1.2
Us/cm) and ORP (NMT 400 mV)

Subjection of water to UV Radiation

Distribution of water to the unit

 REFERENCES
 Manufacturing: a. liquid orals- Mr. HemKrishna Raghuvanshi
b. FFS- Mr. Kamlesh Kamdar
 Packing: a. liquid orals- Ms. Sandhya Thakur
b. FFS- Mr. Sonu Kumar
 Changing Room Procedure training: Ms. Sangeeta Meena
 cGMP Training: Mr. Dilip Gour
 Quality Control: Mr. Sandeep Mishra And Ms. Aarti Hetawal
 PMQC: Ms. Shweta Gupta
 Stores: a. RM- Mr. Rajesh Rathore
b. PM- Mr. Shamuwel Chandane
c. Miscellaneous- Ms. Vishakha Ranpise
d. F/G- Mr. Krishna Rao Deshmukh
e. pPM- Mr. Vikas Borase
 Quality Assurance: Ms. Shubham Pare, Ms. Neelam Maurya, Mr. Sachin Jain, Mr.
Dharmendra Chaturvedi, Mr. Pandurang Patil
 Microbiology: NA
 Engineering: Mr. Pankaj Holkar and Mr. Ravi Solanki
 www.cipla.com
 www.life.cipla.com
 CONCLUSION
The four weeks industrial training proved to be a golden opportunity for us in letting us understand
various operations involved in pharmaceutical industry. During our training period we came very
close to all the aspects and analysis which are carried out in the industry, from the point of
manufacturing to final packing and dispatch of the product to the other country. At the same time
we learned how to follow the rules & regulations as per cGMP and GLP and specifications of other
countries like USFDA and MCC. On the exposure to the industrial staff we found that the company
staff is really hard working, sincere and dedicated to their work & very co-operative in nature. The
company members work like family members and support each other. On the whole this training
period helped us to co-relate our theoretical knowledge with the practical experience. We are
thankful and wish the best for the welfare and letter achievement along with every worker of this
company.
