PHARMA REGULATORY AFFAIRS 1.

.Introduction Need of regulatory affairs in Clinical research To discover a New drug Treatment Diagnosis Device which is Safe & Effective for human beings Regulatory affairs in Pharmaceutical industry--------------- Aim - Protection of human health Ensures - Safety, efficacy, quality of drugs, Accurate drug information Regulates Production, import, export, storage, distribution, sale, supply of drugs Applied National, international level Effective in few developed countries Needs support government, professional associations, consumer groups, other public interest groups Need of harmonization--------------------- Prevents the compromisation in the standards of safety and effectiveness of drug. Helps in optimizing the quality of domestic and international markets while facilitating the expansion of international market Prevents in market circulation of sub-standard drugs History---------------- Countries like Egypt, Europe, UK faced the problems of drug adulterations in medieval period and in first century A.D. which lead to death of humans This lead to raise of drug control and many countries introduced laws Next came the need of new drug development Drugs with serious side effects started appearing in international market eg., Thalidomide tragedy Outcomes from the history--------------- Countries began to make a stringent demands for substantial evidence of safety and efficacy For new drugs, results of animal tests & research protocols for human tests had to be now provided before any test on humans could be initiated. Medicines Act------------------------ 1971, UK, medicines act came into force leading the pharmaceutical companies to acquire license from the licensing authority. This further ensured safety, efficacy, quality of medicines The act also gave the country the legislative power to monitor adverse events, control promotion and advertising, and inspect pharmaceutical manufacturing facilities WHO------------------------ After the establishment of WHO in 1948, the pharmaceutical trade concern received international recognition. WHO taken part in improving quality of drugs in its member states It also promoted global mechanisms for regulating the quality of pharmaceutical products in international market

Initiatives taken by WHO----------------------- Selection of international proprietary names for pharmaceutical products Publication of international pharmacopoeia Establishment of WHO GMP guidelines for pharmaceuticals Creation of WHO certificate scheme to ensure the quality of pharmaceutical products sold on international market Creation of national & regional quality control laboratories Guidelines dealing with regulatory & QA issues were developed and made available to countries Provided support in setting up & strengthening of drug regulatory & QA issues Helped around 70 countries to enact either new drug legislation, or to amend existing drug legislation Efforts were made to have common system of regulations for all countries thereby having a better hold over regulatory requirements of the drugs This was first put into practice by European union (EU) COMMON TECHNICAL DOCUMENT---------------------- The Common Technical Document (CTD) is a set of specification for application dossier for the registration of Medicines and designed to be used across Europe, Japan & US. It was developed by the European Medicines Agency (EMEA, Europe), the Food and Drug Administration (FDA, U.S) and the Ministry of Health, Labour & Welfare (MHW, Japan). The CTD is maintained by the International conference on harmonization of technical requirements for the registration of pharmaceuticals for human use (ICH) The Common Technical Document is divided into five modules: Administrative and prescribing information Overview and summary of modules 3 to 5 Quality (pharmaceutical documentation) Safety (toxicology studies) Efficacy (clinical studies) The contents of Module 1 and certain subheadings of other Modules will differ, based on national requirements. After the United States, European Union and Japan, the CTD has been adopted by several other countries including Canada and Switzerland. DRUG REGULATORY AUTHORITY NETWORKS---------------------- The creation of drug regulatory authority networks, such as International conference of drug regulatory agencies African drug regulatory Agencies conference African drug regulatory authorities network helped in promoting cooperation between national drug regulatory authorities to discuss issues of mutual interest and to facilitate timely exchange of technical information Geopolitical groups in Asia, Europe, Latin America have promoted Harmonization & mutual recognition of drug regulation at regional, subregional, global level facilitating trade in pharmaceuticals

NEED FOR DRUG REGULATIONS----------------------- Importance of drug in human life made the drug regulations mandatory. Other reasons, which favor the need for regulation of drugs are Presence of third parties like researchers, manufacturers, distributors, promoters, dispensers etc in between Prescriber and Patient. Good relation between physician and pharmaceutical industries or sales representatives which attracts the physician to gifts offered rather than having interest on prescribing good medicines to patient If a physician acts both as prescriber and dispenser the potential conflict arises between financial gain to be made from sale of more drugs and professional obligation to advice what is best for patient Misuse of drugs & drug shortages can have serious effects on health of individual patients Pharmaceutical products have limited shelf life even when stored under specific storage conditions. Thus if they are stored under adverse or improper conditions they can deteriorate very rapidly, losing their therapeutic value. PRESENT SCENERIO OF DRUG REGULATION------------------------- Since early 1960s, there has been an increasing in public & government interest in safety and efficacy of pharmaceutical products and medical devices. This increase in regulatory requirements for pharmaceutical products has dictated that companies in these industries establish a distinct department, staffed with professionals to assure in meeting regulatory requirements. These individuals are known as Regulatory Affairs Professionals Medicines exported from industrialized countries are not regulated to the same level as those domestically consumed Relabelling of products to mask details of their origin is also known to occur. The problem of distributing of drugs via internet also increased. Hence the major concern here would be how to protect consumers from substandard & dangerous drugs moving on international markets According to recent working group sponsored by World Bank & attended by representatives of WHO, United Nations childrens fund & other organizations, the main barriers to effective drug regulation are Absence of policy, regulation Lack of political support Lack of finance Corruption Insufficient human resources Absence of priorities Weak professional association etc HOW TO MAKE DRUG REGULATION MORE EFFECTIVE?-------------------------- The scope, nature & practice of drug regulation including priorities, standards, resources available vary from country to country. But, the main goal is promotion & protection of public health by ensuring safety, efficacy & quality of drugs. A drug regulatory body should Base its decisions on scientific evidences

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Provide efficient & timely services Apply sound management principles Reach its objectives Operate to safeguard against corruption Countries desiring to make their drug regulation effective need to take measures described below Assess Drug Regulation Performance Identify & Develop Priority Functions Provide a Clear Mission & Purpose Create a Supportive environment Formulate Adequate Drug Legislation Create Appropriate Organizational Structure Allocate Adequate Human & Financial Resources Minimize Corruption Assess Drug Regulation Performance Poor drug regulation leads to prevalence of substandard, harmful, ineffective drugs on national & international market resulting in serious harm to health of consumers. Therefore countries must strengthen their drug regulatory authority to ensure safety, efficacy, quality of drugs & accurate product information. Countries must assess their drug regulation performance, using indicators that focus on structures & inputs, processes & outcomes They must identify strengths & weaknesses of their regulatory system & reason for them Consider alternative options & make the most appropriate & practicable choices

Identify & develop priority functions The development of regulatory capacity occurs in phases Developing countries will need to start with limited priority activities Attempt made to introduce all regulatory measures & processes at once will lead to failure Government have to set priorities For setting priorities, a regulatory agency must first decide what exactly it wants to regulate, what activities it wants regulatees to perform, & how it can ensure they perform them 3.Provide clear mission & purpose A clear written mission, based on priorities & functions, should be provided for drug regulation, indicating what it intends to achieve & methodology to achieve it. The core mission of drug regulation for all countries is to promote public health by ensuring the quality, safety & efficacy of dugs, & accurate product information, the mission may also include Ensuring timely availability of drugs Encouraging domestic production of drug products 4. Create a supportive environment

 Effective drug regulation is promoted if political system assures basic democratic rights by allowing professional associations, consumer unions, public interest groups etc Countries with strong consumer unions, public interest groups generally have stronger consumer protection The history of drug regulation in developed countries shows that improvements in quality of drug regulation have often occurred in response to a drug incidents & resulting pressure exerted by public groups 5. Formulate adequate drug legislation Drug legislation forms the basis of drug regulation Drug legislation must Define areas & activities to be regulated State the roles, responsibilities, rights & functions of all parties involved with drug regulation Create administrative bodies necessary for the implementation of drug regulation, and define their structural & functional relationships Set the qualifications & standards for those handling drugs Establish the administrative measures & legal sanctions that will apply when provisions of drug legislations are violated 6. Create appropriate organizational structure In almost all countries, the responsibility for regulating drugs belongs to government However depending on national circumstances, the government may delegate certain regulatory activities to the private sectors like consumer groups, professional associations etc Care should be taken to ensure appropriate distribution of duties, responsibilities, functions between different bodies There should be well written terms of reference that describe the linkages between the various bodies 7. Allocate adequate human & financial resources Governments must employ people with specialized knowledge & skills if they wish to promote effective drug regulation. Moreover, they must employ individuals of great integrity & pay them well, particularly since drug regulation involves various stakeholders with commercial interests who will often apply pressure to secure favourable decisions. In promoting effective drug regulation, adequate budgeting is essential 8. Minimize corruption Corruption is often seen at the intersection of public & private sectors Some approaches to minimize corruption Making rules Punishing those who take or offer bribes etc THE DRUG REGULATORY SYSTEM IN INDIA-----------------------

 In India approval or ban of drugs are taken care by CDSCO It also acts as CLAA (central license approving authority) for Drugs CDSCO officers are participating in 3 areas of work with state Drug Regulatory Authorities officers. They are Inspection of CLAA category units Drawing samples for analysis Inspection of manufacturing units for issuing WHO GMP certificates Role of state drug regulatory authority There are 3 aspects which are observed by state DRA Regulate the manufacture of drugs in their area to meet the specifications & guidelines laid down by Drugs & Cosmetics Act, 1940 & Rules, 1945 To regulate the standards of drugs in the inter & intra state levels To prevent, control & take steps to punish the offenders Disposal of detected cases Suspension/cancellation of license if offence is detected There are state amendments in Act, which differentiate same crime from 1 state to another leading to disposal of offence The suggested modifications There should be one Act for entire country to control quality of drugs The act & rules should be implemented by 1 organization Upgrading all state drugs testing laboratories & setting up electronic network for effective functioning under the control of CDL (central drugs laboratories) Designated courts in each region of state may be established Central drug authority (CDA) Looks after the overall control of drugs moving in the country & directly reports to PM or President of India Their decisions affect the health of Nation CDA approves new drugs & directly supervises the ADR reported They should submit annual report of the quality of drugs moving into the Indian market Zonal drug authority (ZDA) Reports to CDA They also acts as licensing authority State drug authority Directly reports to NDA under intimation to RDA They are the licensing authority for manufacture of drugs in their state State vigilance officer S.P in CBI with support staff & facilities to carry criminal investigations

District drug authority I.Ph.S (Indian pharmaceutical services) or assistant director Supervises the performance of the drug officers working in his area Directly reports to SDA Licensing authority of all distribution outlets of drugs in the area Officer of drugs/ drugs officer In charge of the area allocated & responsible for the affairs of that area He can register FIR in all criminal cases arising out of the implementation of acts on drugs in the concerned police station 2. DRUG REGULATORY AUTHORITIES The Role of Drug Regulatory Authorities---------------- Before new medicines reach the prescription pad, the appropriate regulatory authorities, who assess their safety & efficacy, must approve them first Because of following incidents GMP Guidelines came into existence and became mandatory Elixir of Sulfanilamide Tragedy (1937) Thalidomide Tragedy (1961) Devonport Hospital Tragedy (1972, 5 people died at Devonport hospital because a batch of infusion solution had not been fully sterilized by the producer, due to poor GMP) GMP guidelines were 1st given by statutory authority in USA, 1962 & in UK, 1971 Now EU Guide received statutory authority, through an EU directive, in 1991 It defines GMP as that part of quality assurance which ensures that products are consistently produced & controlled to the quality standards appropriate to their intended use & as required by their marketing authorization or product specification It contains 9 chapters, designed to be applicable to all pharmaceutical manufacturing The 9 chapters are 1. Quality management 2. Personnel premises & equipment 3. Documentation 4. Production 5. Quality control 6. Contract manufacture & analysis 7. Complaints 8. Product recall 9. Self inspection Some Drug Regulatory Authorities World Wide--------------------Agencies of United States of America-----------------------------1. The World Health Organization WHO is the United Nations specialized agency for Health established on 7 th April, 1948 WHO main objective attain highest possible level of Health.

 WHOs constitution defined Health as a state of complete physical, mental & social wellbeing & not merely the absence of disease Quality assurance & safety of medicines (QSM) team is responsible for development, harmonization & promotion of international standards, & for the exchange of information The drug regulatory program supports Member states in their regulatory work with WHO guidelines All European countries face new regulatory changes that require international collaboration Drug regulation in countries of EU is covered under the CADREAC (collaboration agreement of drug regulatory authorities in European Union associated countries) agreement to discuss progressive harmonization with European union Regulation 2. Food and Drug Administration (FDA) Oldest & most respected consumer protection agencies Aim- to promote & protect public health by allowing only safe & effective products reach the market It monitors the products for continued safety even after they have been brought into use It helps the public to get accurate, scientific information needed to improve their health FDA protects the public from unnecessary exposure to radiation from electronic products (microwave ovens, cell phones, x-ray equipment, lasers etc) FDA regulates drugs & devices used for animals Manufacturers can market animal drugs after getting approval from FDA by providing proof of their safety & effectiveness 3. The PAN American Health Organization (PAHO) International public agency with 100 yrs of experience Work to improve health & living standards of Americans Serves as specialized organization for health of Inter-American system Serves as regional office for American WHO Agencies of U.K----------------------------1. National institute for biological standards & control (NIBSC) Multi-disciplinary scientific establishment Purpose is to safeguard & enhance public health by standardizing & controlling biological substances used in medicine International role in preparing, evaluating, distributing international biological standards It is also a WHO international laboratory for biological standards 2. Medicines & healthcare products regulatory agency (MHRA) Executive agency of department of health Protects & promotes public health & patient safety by ensuring that medicines, healthcare products & medical equipment meet appropriate standards of safety, quality, performance & effectiveness & are used safely Main objectives Minimize the cost of regulation Provide authoritative & accessible information

 Make an effective contribution to public health Support industry & scientific innovation Influence international regulation Australian Regulatory Agencies Therapeutic Goods Administration (TGA) Unit of Australian Government Department of Health Performs assessment & monitoring activities to ensure therapeutic goods available in Australia are of an acceptable standard Objective of TGA, 1989 is to provide national framework for regulation of therapeutic goods in Australia & ensure their quality, safety & efficacy Any product for which therapeutic claims are made must be entered in the Australian register of Therapeutic goods (ARTG) before the product can be supplied in Australia TGA regulations are on a number of factors including advertising, labeling, product appearance & appeal Pre-market assessment Products assessed as having higher/lower level of risk are evaluated for safety, efficacy, quality Once approved for marketing, products are included in ARTG as registered products & are identified by AUST R/L number Licensing of manufacturers Australian manufacturers of therapeutic goods must be licensed Their manufacturing processes must comply with GMP principles Post marketing vigilance Includes investigating reports of problems, laboratory testing of products, monitoring to ensure compliance with legislation Irish policies Irish Medicines Board (IMB) To ensure current medical & scientific knowledge, quality, safety, efficacy of medicines available in Ireland IMB provides the approval for use of medicine, monitors the type & frequency of any reported side effects IMB monitors the quality of medicines by conducting inspections at sites of manufacture & distribution of medicines In case of veterinary medicines also there must be assurance of quality, safety, efficacy IMB carries out the following services within Ireland Licensing of medicinal products for human use Licensing of veterinary products Licensing of manufacturers of human & veterinary medicines Pharmacovigilance & drug safety monitoring Clinical trial licensing Inspection of wholesale & manufacturing sites Regulatory Authority in Japan Pharmaceuticals & medical devices evaluation center Established in 1997 to strengthen governments evaluation capacity for securing safety & preventing harmful side effects of pharmaceuticals

 Evaluates quality, safety, efficacy of each prescription drugs & medical devices as well as proprietary drugs, cosmetics that are purchased directly by public Process for the approval of newly developed drug Applicant must apply to ministry of health, labour & welfare (MHW) with the data MHW leaves the data reliability survey to external institution after evaluation by different officials with different back ground The report is submitted to pharmaceutical affairs & food sanction council (PAFSC), which is a consultative body of minister Based on this report the ministry finalizes the whether they should approve the drug or not. Regulatory Authority in Republic of Latvia Non profit state joint stock company state agency of medicines ( SAM ) Founded on 9th Oct, 1996 SAM acts in accordance with Pharmacy law Law of joint stock companies Law of non profit organizations Other regulatories Regulatory Authority in Canada Health Products & Food Branch (HPFB) Integrated approach to the management of risks & benefits related to health products & food by Minimizing health risk factors to Canadians while maximizing the safety Promoting conditions that enable Canadians to make healthy choices & providing information so that they can make informed decisions about their health HPFB inspectorate is responsible for management of inspection, investigation, monitoring activities related to fabrication, packing, labeling, testing, import, distribution of regulated health products for human & animal use Marketed Health Products Directorate (MHPD) Responsible for coordination of consistency of post approval surveillance & assessment of safety trends concerning all marketed health products Works in collaboration with other directorates in Health Products & Food Branch & with other involved branches MHPD Activities Monitors & collects ADR data Conducts risks / benefit assessment Communicates product related risks to healthcare professionals & public Conducts active surveillance & drug effective projects Natural Health Products SEQ of Health products Office of Nutrition policy & planning promotion & protection of activities related to nutrition

 Office of Assistant Deputy Minister to improve efficiency & effectiveness of functions Regional operations HPFB activities are carried out through offices in the national capital region & regional offices (Atlantic region, Quebec, etc) Regulatory Agency in Slovakia State institute for drug control (SIDC) In Bratislava Is the institution of Ministry of Health of Slovak republic responsible for ensuring surveillance of quality, efficacy, safety of medicinal products for human use SIDC Responsibilities Controls, standardizes, evaluates the process of assessing Q,E,S of drugs Performs inspections of GMP, GLP, GCP, Good Pharmacy practice Keeps database of registered drugs & medical devices Performs vigilance in the field of medical devices Acts in field of training & education Status of Drug Regulation in some Countries-------------------------WHO African Region A survey conducted during 1992-93 using a questionnaire to assess existence of QA systems in WHO African Region found that Out of 26 countries 11 has QA system (including QC lab)but it was not functioning well 9 had some kind QA system without QC lab 6 did not have any QA system 19 countries mentioned illegal importation as a serious problem Of 21 countries with domestic pharmaceutical manufacturing, 6 did not have QC lab & 4 are without an inspectorate Lao peoples democratic republic Before 1988 all drugs were distributed by public sector At present, there are 6 manufacturing plants, 32 private importers & 2018 private pharmacists Food & Drug Department (FDD) is responsible for registration of drugs, inspection & licensing of manufacturers It is also responsible for public sector drug supply, control of narcotic drugs & psychotropic substances Food & Drug Quality Control Center (FDQCC), 1995. undertakes chemical analysis of drugs Kenya Kenya has 1 public sector drug procurement agency, 135 private importers & wholesalers, 40 pharmaceutical companies The legal instructions for regulating drugs are Pharmacy & Poisons Act,1957 Pharmacy & Poisons Rules, 1981 apply to registration of Drugs Pharmacy & Poisons Board established under Pharmacy & Medicines Act, is responsible for registration of pharmacy professionals, market authorization of drugs, issuing licenses to manufacturer, wholesaler, retail pharmacies

 A national drug control laboratory was established in 1995 under pharmacy & poisons Board. It carries out limited pre & post marketing QC of drugs The inspectorate, under the director of medical services/ ministry of health, undertakes surveillance of wholesale & retail outlets Drugs are being smuggled into country WHO certificate scheme is not applied as recommended by WHO when assessing status of drugs Kenya exports drugs to other African countries by issuing free sale certificates even though it has no inspectorate to assess GMP compliance Myanmar 3 authorities are responsible for drug regulation 1. The Myanmar Food & Drug Board Authority 2. Food & Drug Supervisory Committee (FDSC) 3. FDA FDSC issues licenses & inspects drug wholesalers, retailers FDA issues marketing authorization, inspects manufacturing plants & tests the quality of drugs Drug Advisory Committee (DAC)- applications are reviewed for market authorization, post marketing surveillance Vietnam Vietnams Ministry of Health Acts as Drug regulatory authority and manages state owned Drug manufactures, imports & exports FDA responsible for formulation, drug legislation, registering drugs, issuing licenses etc Drugs are being smuggled in & out of vietnam Colombia Colombias Drug Regulatory Agency (DRA) Responsibilities Controlling quality & safety of medicines, biological products, foods, cosmetics, medical devices Issuing licenses concerning manufacture of medicines Issuing marketing authorizations Pakistan Pakistans drug act, 1976 Licensing of manufacturing plants, importing & exporting & registration of medicines to federal government At federal level, Central licensing & registration body consists of Federal director general Drug controller provincial director general of health Central board of revenue & justice division, medical & pharmaceutical experts All are responsible for regulating, manufacturing, registering, imports, exports of drugs 3.REGULATIONS ON ALTERNATIVE SYSTEM OF MEDICINE

NEED FOR REGULATIONS ON ALTERNATIVE SYSTEM OF MEDICINE------------- India is a land of different origin for a number of systems of medicine like Ayurveda & Unani As there are no special rules enforced on manufacture of Ayurveda medicines, it resulted in spoiling the quality of medicines Drugs & Cosmetics Act, 1940 was valid only to Allopathic medicines But later in 1976 Ayurvedic medicines were also included With the announcement of GMP norms for alternative medicine, the Ayurvedic medicines manufacturers are now liable to follow QC measures which were intended only for Allopathic medicines till now INDIAN MEDICINE CENTRAL COUNCIL ACT, 1970-------------- To provide for the establishment of a Central Council of Indian Medicine Maintenance of a Central Register of Indian Medicine Indian Medicine the system of Indian medicine commonly known as Ashtang Ayurveda, Siddha or Unani Tibb 1. The central council & its committees :Members not exceeding 5 from each state. President, vice president elected among them selves. Meets at least once per year. Holds office for a term of 5 yrs. Decisions regarding Ayurveda, siddha, unani system of medicines. 2. Recognition of medical qualification :Medical qualifications granted by any university etc are recognized. Medical qualifications granted by institutions outside India are also recognized. Acquires information about university etc which provides medical qualification. Appoints visitors for inspection of medical colleges, hospitals etc. council withdraws recognition if the institute does not meet standards. 3. Central register of Indian medicine :Practitioners Register maintained by central council in separate parts for each system of medicine. It contains names of candidates enrolled in state register of Indian medicine. Registrar of central council maintains the central registrar & updates it by receiving copies of state register of Indian medicine. Persons who are enrolled on central register of Indian medicine are eligible to practice medicine in any part of India Regulations in regard to Indian medicine central council Act, 1970----------------- Manner of election of president, vice-president, their powers; resignation of members Appointment, powers, duties & procedures of inspectors & visitors Standards of staff, equipment, accommodation, training & other facilities for education in Indian medicine Conduct of professional examination, qualifications of examiners etc Particulars to be stated & proof of qualifications to be given in applications for registration Fees to be paid on applications & appeals GMP FOR AYURVEDA, SIDDHA, UNANI MEDICINE----------------------- GMP are prescribed to ensure that Raw materials used in manufacture of drugs are authentic of prescribed quality. Free from contamination Manufacturing process is as prescribed, to maintain standards

 Adequate QC measures are adopted Manufactured drug, which is released for sale, is of acceptable quality GMP (schedule- M)----------------------- FACTORY PREMISES The manufacturing plant should have adequate space for Receiving raw material Storing raw material Manufacturing process area QC section Finished goods store Rejected goods/ drugs store office General requirements------------------------ Location & surroundings avoid contamination from open sewage, drain etc which produces disagreeable odor, fumes, smoke etc Buildings premises used for manufacturing, processing, packaging, labeling will be in conformity with provisions of Factory Act Water supply pure water must be used. Disposal of waste waste water & residues are disposed off after suitable treatment as per guidelines of pollution control authorities to render them harmless Containers cleaning adequate arrangements separated from manufacturing operations for washing, cleaning, drying of containers Stores adequate space for storage of different types of material, such as raw material, packaging material & finished products Raw materials care must be taken to handle different kinds of raw materials. Each container used for raw material storage shall be properly identified with label clearly stating the status (approved. Under test, rejected). Raw materials shall be sampled & tested either by in house or laboratories by government. Records of receipt, testing, approval, rejection shall be maintained Packaging materials containers, closures shall be cleaned & dried before packing products Finished goods stores finished goods are stored within an area marked quarantine. Only approved finished goods after QC tests will be dispatched. Distribution records shall be maintained. Working space adequate place to facilitate easy& safe working and to minimize risk of mix-up, cross contamination etc Health, clothing, sanitation & hygiene of workers Medical services adequate facilities for first aid. Medical examination of workers periodically Equipment based on size of operation, nature of product manufactured suitable equipment shall be made available. SOP for cleaning, maintaining etc of machine shall be laid down Batch manufacturing records (BMR) the licensee shall maintain BMR to provide an account of list of raw materials, quantities obtained, chemical tests performed etc. it is essential to maintain records for each & every process

 Distribution of records records of sale & distribution of drugs shall be maintained in order to facilitate prompt & complete recall of batch Record of market complaints once in 6 months manufacturer shall submit record of complaints to licensing authority. The register shall also be available for inspection. Adverse reactions reported on the product shall also be recoded The quality control section shall carry out the following functions The section should be provided with an area of 150 sq. feet Samples should be maintained for identification of raw drugs & for reference Manufacturing record should be maintained for the various processes carried out during manufacturing Supervise & monitor adequacy of conditions under which raw materials, semi finished products & finished products are stored Keep records of shelf life &storage requirements for drugs All raw materials will be monitored for fungal, bacterial contamination with a view to minimize such contamination The standards for identity, purity & strength as given in respective pharmacopoeias of Ayurveda, Siddha & Unani systems of medicines published by government of India shall be complied Requirement for sterile products-------------------1. Manufacturing area For manufacture of sterile ayurvedic, siddha, unani drugs separate enclosed area (dust free, properly ventilated) shall be provided. HEPA filters are to be used. Manufacturing areas shall be restricted to minimum number of authorized personnel 2. Precautions against contamination and mix Provide a suitable exhaust system Carry out manufacturing operations in a separate block of adequately isolated building Expert technical staff approved by licensing authority shall check the yield Room relative humidity, volume filled, leakage & clarity should be checked & recorded THE GLOBAL AYURVEDIC PRODUCT MARKET----- The global Ayurvedic market is booming. The reported growth rate is 9-10 % per annum The herbal drugs in India is presently estimated to be around 2,300 crores with a 15% growth/annum Since, the rise of Ayurvedic medicines Kerala is fast becoming a unique selling proposition (USP) to earn for exchange for the country An Indian system of Medicine & Homeopathy drug policy is currently establishing A medicinal plant board & GMP authority is reportedly being constituted to implement good manufacturing practices Regulation relating to Homeopathic medicine------------------- Since early 1990s, number of changes in status of homeopathic remedies have taken place.

 Numerous remedies that were once sold as OTC drugs have been moved into prescription status This is due to publication of FDA, Homeopathic pharmacopoeias of United states (HPUS) The Homeopathy central council act,1973 Maintenance of a central register of Homeopathy The central council & its committees Recognition of medical qualifications Central register of Homeopathy The central council & its committees : Members not exceeding 5 from each state. President, vice president elected among them selves. Meets at least once per year. Holds office for a term of 5 yrs. Decisions regarding Homeopathic system of medicines. Recognition of medical qualification : Qualifications granted by any university etc are recognized. Qualifications granted by institutions outside India are also recognized. Acquires information about university etc which provides medical qualification. Appoints visitors for inspection of medical colleges, hospitals etc. council withdraws recognition if the institute does not meet standards. Central register of Homeopathy: Practitioners Register maintained by central council for Homeopathic system It contains names of candidates enrolled in state register of Indian medicine. Registrar of central council maintains the central registrar & updates it by receiving copies of state register of Indian medicine. Persons who are enrolled on central register of Indian medicine are eligible to practice medicine in any part of India 4.DRUG POLICY IN INDIA Main objectives of Drug Policy, 1986--------------------- To ensure abundant availability, at reasonable prices of essential & life saving medicines of good quality To strengthen the system of quality control over drug production & promoting rational use of drugs in country To create an environment for new investment into pharmaceutical industry To encourage cost effective production & to introduce new technologies & new drugs To strengthen the production of drugs The policy was implemented through Industries act and Drugs price control order Implementation of the drug policy provisions has been through Industries(development & regulation) act [I(D&R)Act] on industrial licensing aspects & through Drugs price control order (DPCO) act

 Enforcement of quality & standards in medicines is done through the provisions contained in Drugs & Cosmetics Act, which is administered by Ministry of Health & Family Welfare, Government of India The drug policy has also given the policy framework with regard to Quality Control & rational use of drugs Present status & approach adopted Over last 7 yrs, policy have been directed towards promoting growth of industry. As on date there 250 large units & 8000 small units in operation, which form the core of the country These units produce the complete range of formulations i.e., medicines ready for consumption by patients, 350 bulk drugs etc It is estimated that 70% of demand for bulk drugs & almost the entire demand for formulations are being met through domestic production In India, during the last decade the production of bulk drugs has grown from Rs.240 crores in 1980-81 to Rs.1320 crores in 1993-94 & correspondence increase in production of formulations i.e., Rs 1200 crores to Rs6900 crores Since 1986, the drug industry has grown significantly, in terms of production of bulk drugs & formulations It is estimated that in case of bulk drug production the contribution of small scale is approximately 30% of the total production in India Industrial licensing Import & economic policies have undergone major changes like pruning of negative list for imports, doing away with the Actual user condition & full convertibility of Rupee on trade market In this changed scenario, it is felt that there is no need to be more restrictive than before in granting industrial approvals, provided the 2 main concerns i.e., Achieving basic stage manufacturing Discouraging undue imports It is also felt that, like in other sectors of economy, production would get necessary importance to meet any future demands as well as of ensuring adequate availability of drugs at reasonable prices with more liberalization in granting industrial approval R & D, Investment & Pricing----------------- The drug industry is highly R & D oriented which needs to ensure that technologies used in country are cost effective & efficient. Investment is necessary in order to update the existing technologies Basic research in drug sector has assumed greater importance In order to meet the growing needs of country, to promote exports, it is proposed to treat entire drugs & pharmaceutical sector as a high priority industry for the purpose of permitting foreign investment in terms of New Industry Policy. The high turn over of a drug is an index of its extent of usage To encourage the production & availability of the drugs, it is considered to allow a uniform MAPE (Maximum allowable post-manufacturing expenses) in all cases of drugs

 The government has set up an independent body of experts, called National Pharmaceutical Pricing Authority, to do the work of price fixation for drugs. This body would also monitor the prices of decontrolled drugs & formulations & oversee the implementation of provisions of Drugs Price Control Order Government will keep a close watch on prices of medicines, which are taken out of price control. In case, the prices of the medicines rise unreasonably, the government would take necessary actions Quality control & rational use of drug--------------- Quality control & rational use of drugs are important aspects of pharmaceutical industry Steps have been taken in strengthening the Drug Control Organization by establishing Sub-Zonal offices at Hyderabad, Ahmedabad, Patna. The Bio-Laboratory at Madras has been upgraded to level of National Laboratory Central Drugs Laboratory Mumbai Regional Laboratories Guwahati, Chandigarh, Hyderabad For certain Drugs like Large volume Parenterals Sera & vaccines Whole human blood & Blood products Which has found to caused Adverse effects due to lack of drug control in or other state, the central government has taken upon itself the responsibility of granting license GMP has made mandatory Screening of irrational & harmful drugs are done Definition of new drugs has been widened & guidelines issued on clinical trials Adverse Drug Reaction Monitoring Centers Leading hospitals at Pondicherry, Chandigarh, New Delhi, Bombay, Lucknow National Drug Authority responsibilities Develop & define basic standards relating to Manufacture, Import, Supply & Use of drugs To approve & register pharmaceutical products for use in the country only if It meets real medical need It is therapeutically effective It is acceptable safe To enforce effectively appropriate quality standards of medicines & GMP throughout the country To monitor The standard practices in drug promotion The prescribing practices To ensure that appropriate information about registered pharmaceuticals is made available for the guidance of consumers in regard to Adverse consequences of non-complaince by patients particularly in case of antibiotics, steroids etc Dangers of self-medication

 Need to involve consumers as full partners in the healthcare system & to publish national formularies for the guidance of consumers & doctors Functions Special focus on examining the technology of bulk drugs Assessing suitability of manpower for bulk drug production Developing testing labs for cosmetics, diagnostics & devices Laying down standards for veterinary drugs Quality control of herbal medicines Updating new drug approval process Formation of expert committees for examination of new drugs Examination of labels In addition, Screening promotional literature Monitoring ongoing clinical trials through IRB Unearthing substandard & spurious drugs with the help of legal cum intelligence cells Centralizing all manufacturing licensees Updating GMPs Setting up of new analytical testing labs etc were also performed by National Drug Authority There is an imperative need to undertake up gradation of drug testing facilities under the central & state organizations Therefore, there is a need for establishing more Zonal & Sub-zonal offices under CDSCO as well as regional testing laboratories A coordination committee consisting of secretaries of ministries/ departments of commerce, revenue, health, biotechnology, industrial development & chairman, bureau of industrial costs & prices is been set up under the chairmanship of secretary (chemicals & petro chemicals) for monitoring the key concerns on time & for taking timely action Foreign Investment------------------- Foreign investment up to 51% is permitted in the case of all Bulk drugs, their intermediates & formulations Investment of above 51% will be considered on a case by case basis in areas where investment is otherwise not forthcoming, particularly in the manufacturing of bulk drugs Automatic approval for foreign technology agreements are also given in the case of all bulk drugs, their intermediates & formulations except those produced by the recombinant DNA technology 4. REGULATORY AFFAIRS PROFESSION The pharmaceutical industry is the most highly regulated industry demanding a high level of information be submitted to government before a pharmaceutical product is being brought to the market place Regulatory affairs is responsible for obtaining & maintaining licenses to market medicinal products in as many countries as necessary According to the present laws all organizations involved in the development & marketing of medicinal products is legally required to have some form of regulatory support

Many people move into Regulatory Affairs from laboratory research, clinical research, regulatory compliance, QC, QA or drug safety

Qualification required Minimum a life science or pharmacy degree Many technical companies require post-graduate qualification, pharmacy, chemistry, biology degrees Experience 1-2 yrs of exp in pharmaceutical industry in a related area Regulatory affairs professionals have opportunities to work scientifically or commercially, nationally or internationally & many regulatory professionals will at sometime or another experience travel in their role Roles & responsibilities of regulatory affairs professionals vary depending on the company Some of the opportunities in Regulatory affairs are Task specialist specializes in 1 area of regulatory affairs Eg ; document management, product labeling etc Regulatory specialist works as pharmacist or chemist with specialization in preparing & managing a specific element of product registration Project manager the professional manages all the regulatory aspects of a product development & maintenance Therapeutic specialist manages regulatory affairs for products in specific therapeutic area from formulation stage to license maintenance Eg ; oncology, cardio vascular Line manager professional moves into managing power Service provider work with different companies on numerous projects Graduates may enter into a role as Regulatory affairs officer or scientist or executive This could be in any number of areas like clinical research, manufacturing, sales, marketing Regulatory affairs profession provides in an depth overview of full spectrum of drug development, from clinical trials, marketing to post-approval activities As members of the drug development team, regulatory affairs professionals play a very important role in new drug approvals Development of the profession Regulatory affairs is a new profession which is developed from the desire of government to protect public health, by controlling the safety & efficacy of products The regulatory affairs profession developed in almost all countries of the world Governments have responded to public concern over public health & product safety in a number of area by placing requirements on manufacturers to confirm to stringent safety testing procedures & obtain marketing authorizations before placing a product in the market The companies responsible for discovery, testing, manufacture of the products also want to ensure that they supply products that are safe The Regulatory Affairs professionals job is to keep track of the ever changing legislation in all regions in which the company wishes to distribute its products

In order for a regulatory authority to issue a marketing authorization, it must carryout a close scrutiny of all reports generated during development of product, review the manufacturing methods, QC procedures, clinical safety & efficacy This activity is known as assessment Regulatory affairs profession is becoming increasingly influential in the overall drug development process & increasingly populated by highly trained scientists & medical professionals Responsibilities of Regulatory Affairs Professionals The regulatory affairs department is the first point of contact between government authorities & company Regulatory affairs professionals helps to ensure that the product development, manufacturing & marketing practices meet or exceed government requirements Regulatory affairs program provides graduates with the specialized knowledge required to help biotechnology, medical device, pharmaceutical & food companies manage regulatory processes Students will gain knowledge of international healthcare system, healthcare legislation, procedures & practices for regulating the development, manufacture, QA & manufacturing of healthcare products Regulatory affairs program have an international focus for the following reasons Most companies develop products for an international market Current regulatory processes in most countries are based on international guidelines Regulatory affairs professionals must ensure that the product information submitted to the authorities is as complete as possible & in the correct form They are also responsible for subsequent contacts with the regulatory authorities Since authorizations are issued for a specified time, & have to be renewed before expiry, a very important part of regulatory affairs function is maintenance & updating of authorizations Regulatory professionals will critically review all the scientific evidence presented by the company to establish the products quality, safety, efficacy Regulatory affairs executive has the responsibility to communicate with all people within the pharmaceutical company, external communicants, medics who have an input to all the data that is put together for the regulatory authorities The regulatory affairs professionals will then communicate this information to the government regulatory authorities worldwide in the for of Dossiers Regulatory affairs professionals should be involved at initial synthesis stages, preclinical stages, clinical stages & all the way through drug development lifecycle & beyond into product marketing cycle The whole process of drug discovery & ultimate release into market may take up to 15yrs & many problems may arise during this period of scientific development It is the job of the regulatory affairs professional to help the company avoid deficiencies in their data, which may create difficulties in the registration of the product

In

Regulatory affairs executive has to collect all the documented data, keep the documents in the correct & specified order, summarize where necessary, check the validity & make sure there are no conflicts among the data supplied Regulatory authorities will generally seek clarification & ask specific scientific questions from regulatory professionals on the areas of Quality, Safety, Efficacy & they will require prompt & accurate answer for giving license to product After the company got license to manufacture & sell new pharmaceutical product in the chosen market there is a need to maintain & renew the license which is the duty of regulatory affairs professional Skills, which regulatory affairs professional must have are Key negotiation skills Project management skills Information technology skills Management skills Interpersonal skills All these skills are set against a background of ever changing pharmaceutical regulations world wide clinical trials, Regulatory affairs professionals have the following role to play Provide strategic leadership for the development & execution of regulatory plans to support a global drug development plan Provide the company with regulatory intelligence & expertise in translating regulatory requirements into practical, workable plans Manage the daily activities of personnel responsible for regulatory submissions, train, mentor & coach regulatory personnel Ensure timely preparation of organized & scientifically valid submissions of IND etc Represent regulatory affairs to other departments & provide guidance on adherence to regulatory guidelines for effective submissions Assure adherence & compliance with all applicable FDA/ICH guidelines & with current GLP,GMP & GCP guidelines Set objectives for training sessions, standard practices, SOPS & departmental policies Responsible for supporting the GCP compliance program by conducting comprehension audits of clinical investigator sites Presentation of GCP training to other staff Provide support to internal & external GCP compliance program Planning, scheduling, conducting, coordinating investigator sites according to SOP, applicable regulatory requirements Assisting in performing internal systems audits, reviewing clinical documents As a product goes through the review process, regulatory affairs professionals are looking at requirements for manufacturing, packaging & advertising Manufacturing is related with QA, QC Packaging, labeling & advertising will also interfere with manufacturing There are stringent regulations everywhere that govern these spheres Regulatory affairs personnel work with distribution & make sure the processes meet regulatory requirements

Once the product is in use, regulatory affairs professional is also involved in reporting any adverse effects of a drug to FDA QUALIFICATIONS, SKILLS & ABILITIES OF REGULATORY AFFAIRS PROFESSIONAL Minimum requirement for an individual to enter into regulatory affairs profession is to have a scientific background in order to have the knowledge to ask the scientists the right questions in the light of a vast quantity of product data, pharmaceutical legislation & guidelines Having some working knowledge of the industry is always preferable The usual requirement is a degree in life science, pharmacy or medical degree with some experience in pharmaceutical /biotech industry Skills Required Good Written Skills Verbal communication skills Problem solving abilities Critical/analytical thinking skills Ability to plan & manage multiple projects Meeting deadlines Accommodate changing priorities Assignments Proficiency in computer applications Interpersonal skills to interact with other departments effectively In the pharmaceutical industry, regulatory affairs professionals should have expertise in the legal & regulatory environments, as well as in clinical research protocols They are the primary interpreters of the laws & regulations for other members of the company like R & D, manufacturing etc Regulatory affairs professionals must have a thorough understanding of the complex set of regulations Keeping up to date on regulations is essential in regulatory affairs; changes in regulations can affect the clinical trials process, regulatory strategy, what kinds of decisions are needed on trials etc According to some critics the field of regulatory affairs has become increasingly more science & issue based As the speed of pharmaceutical & biologics development has increased science has become more complex A regulatory professional now spend more time on substantive scientific & medical issues & planning for experiments & clinical studies to achieve approval A regulatory affairs professional has to be able to provide expert opinions on technical & legal matters associated with registration of products Regulatory professionals must always exercise considerable integrity & judgment in the practice of their role THE RELATIONSHIP OF REGULATORY AFFAIRS PROFESSIONS TO OTHER PROFESSIONS Regulatory affairs professional must have capacity to draw upon the information provided by specialists (pharmacologists, toxicologists, chemists, pharmacists, doctors etc) & must be able to synthesize the knowledge & use it to impart information & make aware of staff about current regulatory guidelines

As regulatory processes increase in complexity & scope, globalization occurs within this field, there will be continuing industry demand for people with a strong foundation in regulatory affairs Communication & organizational skills are also extremely important in dealing with government agencies Advantages of certification Regulatory affairs certification enhances employment prospects Many companies, both large & small are now beginning to indicate that Regulatory Affairs certificate is a desirable qualification Certified professionals will earn 5-15% more salary than others