Regulatory aspects

1. Regulatory aspects of Pharmaceuticals and Bulk drug Manufacturing, Regulation of drugs and pharmaceuticals . By K. Sampath Kumar, Y11MPH18060, I/II M.Pharm , 2 nd Semester, Pharmaceutical Analysis, Sims college of Pharmacy. Under the guidance of Sri B. Thangabalan Sir, M. Pharm ( Ph.D ) 1

2. Drugs play an important role in the health of both people and the economy of a country. Pharmaceutical drugs are available from a large number of sources . People and Governments willing to spend money on drugs for many reasons so, it must be safe, effective and good quality and used appropriately. This means, in turn, that development, production , importation , exportation and subsequent distribution of drugs must be regulated to ensure that they meet prescribed standards . Therefore , effective drug regulation is required to ensure the safety , efficacy and quality of drugs as well as accuracy and appropriateness of the drug information available to the public Introduction: 2

3. In an ideal world, the need for analysis should be driven by the desire to assure the quality of a drug product. However, in the real world the need for pharmaceutical drug analysis is driven largely by regulatory requirements. A team consisting of R&D, QC, and QA unit members develops these quality and compliance systems. It should be one of the highest priorities of top management and QA units to develop and monitor these systems to comply with the cGMP and GLP expectations. Compliance documents are needed, in addition to the regulatory and research documents, to demonstrate the integrity of the data. Compliance documents refer to those reports required by GMP and/or utilized during the course of inspection by a health authority. Regulatory requirements 3

4. Product registration (drug evaluation and authorization, and monitoring of drug efficacy and safety); Regulation of drug manufacturing, importation, and distribution; Regulation & Control of drug promotion and information. Adverse drug reaction (ADR) monitoring. Licensing of premises, persons and practices. Key function of regulatory agencies Goal of regulatory agency Main goal of drug regulation is to guarantee the safety, efficacy and quality of drugs available to public. 4

5. Drug Laws Drug Regulatory Agencies Drug Regulatory Boards Quality Control Drug Information Centres etc. The drug regulation 5

6. Drug regulatory system in India Drugs and Health is in concurrent list of Indian Constitution It is governed by both Centre and State Governments under the Drugs & Cosmetics Act, 1940. MAIN BODIES Central Drug Standard Control Organization (CDSCO) Ministry Of Health & Family Welfare (MHFW) Indian Council Of Medical Research (ICMR) Indian Pharmaceutical Association (IPA) Drug Technical Advisory Board (DTAB) Central Drug Testing Laboratory (CDTL) Indian Pharmacopoeia Commission (IPC) National Pharmaceutical Pricing Authority (NPPA) 6

7. WELL DEFINED DRUG REGULATORY SYSTEM(Govt. of India) Ministry of health and family welfare Enforcement & GMP audit Division Quality Control Division – CDTL Registration Division New Drug Division Pharmacovigilance Trainings DGHS CDSCO DCGI DTAB 7

8. Approval of Investigational New Drug (IND) IND Applicant CDSCO Examination by new drug division Recommendation to DCG (I) Approval Detailed review by IND committee 8

9. Manufacturer State licensing authority Joint inspection by state and central inspectors Examination of report License prepared by state licensing authority CLAA approval and grant of license Central licensing 9

10. Head quarters New Delhi North Zone Ghaziabad West Zone Mumbai South Zone Chennai East Zone Kolkata. Other zonal offices Ahmedabad and Hyderabad. Sub- Zonal Office 2 Port offices/Airports 7 Laboratories 6 CDSCO Central Drug Standard Control Organization 10

11. CDSCO Drug Controller General (I) Head Quarter Zonal & sub Zonal office Port Office Laboratory New Drugs CLAA Imports DTAB/DCC GMP Audits Coordinates with states Import Export Testing of drug samples Validation of Test Protocol 11

12. Functions undertaken by Central Government Statutory function: Laying down standards of drugs, cosmetics, diagnostics and devices. Laying down regulatory measures, amendments to Acts and rules. To regulate market authorization of new drugs. To regulate clinical research in India To approve licenses to manufacture certain categories of drugs as Central License Approving Authority(CLAA) i.e. for Blood Banks, Large Volume Parenterals and Vaccines & Sera. To regulate the standards of imported drugs. Work relating to the Drugs Technical Advisory Board ( DTAB ) and Drugs Consultative Committee (DCC). Testing of drugs by Central Drugs Labs. 12

13. National Institute of Health and Family Welfare NIHFW is an Apex Technical Institute, funded by Ministry of Health and Family Welfare, for promotion of health and family welfare programmers in the country through education, training, research, evaluation, consultancy and specialized services. The NIHFW was established on March 9, 1977 by a merger of the National Institute of Health Administration and Education (NIHAE) with the National Institute of Family Planning (NIFP) NIHFW 13

14. • 18 members List of Governing Body Members of NIHFW NIHFW 1 Chairman (ex-officio) 1 Vice Chairman (ex-officio) 1 Member Secretary (ex-officio) 9 Member (ex-officio) 6 Member 14

15. Measuring weight of children to assess the nutritional status. Assessment of diseases like level of anemia. Testing of food material like cooking salt for level iodine. To release fund on the advice of the Ministry. It is responsible for all governmental programs relating to family planning in India. ACTIVITIES AND RESPONSIBILITIES 15

16. Structure and organization Union Health Minister Governing body Scientific Advisory Board Task forces Scientific advisory groups Scientific advisory committee Expert groups Steering Committee ICMR 16

17. Extramural research is promoted by ICMR by establishing Centers for Advanced Research in different research areas. Open-ended research is conducted on the basis of applications for grants-in-aid received from scientists in non-ICMR Research Institutes, Medical colleges and Universities located in different parts of the country. Balancing of research efforts between different competing fields, especially when resources are severely limited, is a typical problem encountered in the management of medical research, particularly in developing countries ACTIVITIES AND RESPONSIBILITIES 17

18. The Indian Pharmaceutical Association (IPA) has demanded to amend the Drugs &Cosmetics Act and Rules 1945 to make only the pharmacy graduates eligible to become expert staffs in the pharma manufacturing units. In the resolutions passed during the just concluded IPA Convention, the IPA also urged the government to expedite action to amend the Rules in such way that all regulatory positions in the country must be an exclusive area for experienced and qualified pharmacists. Indian Pharmaceutical Association (IPA) is the premier professional association of pharmacists in India. The association has more than 10,000 members from various parts of the country and it operates in India through 17 state branches & more than 33 local branches. The association represents various facts of pharmaceutical profession and in managing several academic programmes. IPA 18

19. DRUG TECHNICAL ADVISORY BOARD The Central Government constitute a Board (to be called the Drugs Technical Advisory Board) to advise the Central Government and the State Governments on technical matters arising out of the administration of D&C, Act 1940 The Board shall consist of the following members, – 20 Members DTAB DTAB 5 Nominated Members 5 Elected Members 10 ex-officio Members 19

20. It advices matter related to Drugs. The nominated and elected members of the Board shall hold office for three years, but shall be eligible for re-nomination and re-election. The Board may, subject to the previous approval of the Central Government, regulating its own procedure. ACTIVITIES AND RESPONSIBILITIES 20

21. CENTRAL DRUG TESTING LABORATORY The central drug laboratory, Kolkata is national statutory laboratory of the government of India for quality control of drug and cosmetic and established under the D&C act ,1940. Oldest quality control laboratory of the drug control authorities in India. Function under the director general of Health Services in the Ministry of Health and Family Welfare. CDTL 21

22. Statutory Function : To Act as an Appellate authority. To function as Government Analyst for such states who do not have their own testing facilities. Analytical quality control of majority of the imported drugs. Analytical quality control of drug formulations manufactured within the country on behalf of the Central & State Drug standard control organization Other Functions: Procurement , establishment, maintenance, Storage and d istribution of I.P & International Reference standards. Preparation and standardization of I.P. reference standards against USP, BP primary standards. To undertake analytical research in standardization and methodology development of drug. FUNCTIONS UNDER TAKEN 22

23. Indian Pharmacopoeia Commission IPC General body (19 Members) CIPL lab Governing body (10members) IPC secretariat Scientific body 23 experts IPC 23

24. Development of comprehensive monographs. Accord priority to monographs of drugs included in the national Essential Drug List and their dosage forms. Preparation of monograph for products that have normally been in the market for not less than 2 years. Collaborate with pharmacopoeias like the BP, USP, JP and International Pharmacopoeia with a view to harmonizing with global standards. ACTIVITIES AND RESPONSIBILITIES 24

25. National Pharmaceutical Pricing Authority • For the purpose of implementing provisions of DPCO, powers of the Government have been vested in the National Pharmaceutical Pricing Authority (NPPA). • Drugs have been declared as essential and accordingly put under the Essential Commodities Act. • Only 74 out of 500 commonly used bulk drugs are kept under statutory price control. • However, the prices of other drugs can be regulated, if warranted in public interest. • The NPPA was established on 29th August 1997 as an independent body of experts following the Cabinet Committee’s decision in September 1994 while reviewing the Drug Policy. NPPA 25

26. The Authority, inter alia, has been entrusted with the task of fixation/revision of prices of pharmaceutical products (bulk drugs and formulations), enforcement of provisions of the Drugs (Prices Control) Order monitoring the prices of controlled and decontrolled drugs in the country. NPPA 26

27. Ceiling and Non Ceiling Prices of drugs and medicines in the controlled category regulated . Ceiling Price is the single maximum selling price fixed that is applicable throughout the country in the case of each bulk drug, which is under price control. Non-Ceiling Price fixed by NPPA are specific to a particular pack size of scheduled formulation of a particular company. Features 27

28. Good Manufacturing Pratices GMP guidelines are not prescriptive instructions on how to manufacture products. They are a series of general principles that must be observed during manufacturing. When a company is setting up its quality program and manufacturing process, there may be many ways it can fulfill GMP requirements. It is the company's responsibility to determine the most effective and efficient quality process. GMP 28

29. To ensure that their products are safe, pure, and effective. To minimize or eliminate contamination, mix up and errors. Issues including recordkeeping, personnel qualifications, sanitation, cleanliness, equipment verification, process validation, and complaint Handling. GMP is also sometimes referred to as " cGMP ”. Failure of firms to comply with GMP regulations can result in very serious consequences including recall, fines, and even imprisonment. REQUIREMENTS 29

30. WHO GUIDELINES (World Health Organization): Who is an agency of United Nations. It is a specialised agency and its primary responsibility includes international health matters so that the goal, health for all, can be achieved. The WHO GMP and the certification scheme was accepted by WHA (world health assembly) in solution no WHA 28.65, as the revised version in 1975. With appearance of ISO (International Organization For Standardization) the WHO GMP needed next revision. The revised text contains 3 parts. Part I: out lines the general concepts of quality assurance and salient components of GMP’s. Part II: outlines on actions to be taken by production & quality control personnel separately for implementing general principles of quality assurance. Part III: supporting and supplementary guidelines. 30

31. The revised text of GMP appears as annex. ANNEX I: Quality Management in the Drug Industry – Philosophy & Essential Elements Quality Assurance Good Manufacturing Practice Quality Control Sanitation & Hygiene Validation Complaints Product recalls Contract Production & Analysis Self inspection and quality audits Personnel Premises Material Documentation 31

32. ANNEX II: Good Practices – Production & Quality Control Good Practices in Production Good Practices in Quality Control ANNEX III: Supporting and Supplementary Guidelines Sterile pharmaceutical Products Good Manufacturing Practice for Active Pharmaceutical Ingredients 32

33. WHO GMP Certification Originally established in 1969 and revised in 1975. Main objectives were : To inspect drug manufacturing facilities To assess compliance of GMP This would facilitate implementation of the scheme. WHO GMP ensures the following: Avoidance of Cross- Contamination Prevention of Mix-ups Provide Traceability Accountability of actions Responsibility Product Performance Guarantee 33

34. DEFINITION The U.S. Food and drug administration is an agency of the United States Department of Health and Human services and is responsible for the safety regulation of most type of foods dietary supplements Drug Vaccines Biological medical products blood products medical devices radiation – emitting devices veterinary products and Cosmetics The agency of the U.S. Department of Health and Human Services. Established in 1927. FDA 34

35. How does ICH work? ICH operates through the ICH Steering Committee with administrative support from the ICH Secretariat and ICH Coordinators. The Steering Committee meets at least twice a year . During these meetings, new topics will be considered for adoption, reports are received on the progress of existing topics, and maintenance and implementation of the guidelines are discussed. The topics identified for harmonization by the Steering Committee are selected from Safety, Quality, Efficacy, and Multidisciplinary matters. 35

36. Before searching any person, explain him that he has a right to be searched before a gazetted officer or a magistrate. If he so requires, take him to a gazetted officer or a magistrate before whom he can be searched. (Section 50.) without giving him a chance to part with the drug, controlled substance, etc. you can search him under Section 100 of the Cr. P. C. (Section 50(5) and 50 (6)). Take down any information given by any person in writing before authorizing a search (Section 41). If the search is under Section 42, also send a copy of the information taken in writing or the grounds of belief for search within 72 hours to your immediate superior officer. Inform the arrested person, as soon as may be, the grounds of his arrest (Section 52 (1)). Your Responsibilities Under The Law 36

37. If a person is arrested or an article has been seized under a warrant issued by a magistrate, forward the person/seized article to that magistrate (Section 52 (2)). If the person has been arrested or the article has been seized otherwise than under a warrant , forward it to the nearest police station or any other officer empowered under section 53 (Section 52 (3)). If the person has been arrested or the article has been seized otherwise than under a warrant , forward it to the nearest police station or any other officer empowered under section 53 (Section 52 (3)). Whenever you arrest any person, make a full report to your superior within 48 hours ( Section 57) 37

38. Officers Officers acting in discharge of their duties in good faith under the Act are immune from suits, prosecution and other legal proceedings ( Section 69). Addicts Addicts charged with consumption of drugs (section 27) or with offences involving small quantities will be immune from prosecution if they volunteer for de addiction. This immunity may be withdrawn if the addict does not undergo complete treatment (Section 64 A ). Offenders Central or state governments can tender immunity to an offender in order to obtain his evidence in the case. This immunity is granted by the government and not by the court (Section 64). Minors All offences committed under any law by persons under the age of 18 will be covered by the Juvenile Persons (Care and protection) Act. This Act seeks to reform such juveniles rather than punish them under the respective Acts. It prevails over any other Act in respect of persons below the age of 18. IMMUNITIES IN DRUG CASES 38

39. DRUG REGULATORY AFFAIRS by sachin itkar , Dr.S.wyavahare www.fda.gov/cder/guidance/index.htm www.fda.gov/cber/cberftp.html . References 39

40. Any Queries ????????????? 40

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42. End of 2 nd semester Thank you all for your cooperation and appreciation. All the best for the exams & your future Ur’s K. Sampath Kumar 42