REGULATORY AFFAIRS ( IP-2 / UNIT 3 )

REGULATORY AFFAIRS

1. Regulatory Affairs

2. Contents Introduction Historical overview of RA Responsibilities of RA Regulatory Authorities Role of RA department

3. Introduction Pharmaceutical & Clinical Research Industry most regulated among all the industries. Every drug before getting market approval must undergo clinical trials to ensure its Safety, Efficacy & Quality. Standards are set by regulatory authorities. RA department acts as a crucial link between company, products & regulatory authorities.

4. What is DRA Unique mix of science and management to achieve a commercially important goal. It touches everything relating to drugs from the development manufacture and marketing. RA takes care of Design = Development Plan Co -ordination = Writing/ reviewing, supervising Construction = Assembling& Submission management

5. It is a dynamic and challenging field in the pharmaceutical industry. It is an link between the competent authority and an applicant (company) to manage life cycle of the products. In present regulatory scenario, company requires experts in regulatory activities to manage the product life cycle. RA experts are qualified professionals to provide right solution to the technical problems under the light of laws

6. Historical overview of RA : The drug industry in India was at very primitive stage till 20 th century . Most of the drugs Were imported from foreign countries. (a)1900 -1960: Government passed the Poisons Act, 1919 to check and hold the control on cheap drugs available in market . This Act helps in the administered possession of substance or sale of substances as specified as poison. It also stated the safe and protected custody of the poisons, packaging and labeling of poisons, maximum quantity to be sold and inspection as well as examination of the poison sold by vendor during the year.

7. The Poisons Act was followed by The Dangerous Drugs Act, 1930 which includes the regulation of cultivation, manufacturing, possession and trade of opium. In1985, Dangerous Drugs Act, 1930 and Opium Act, 1878 was revoked by passing of the Narcotics and Psychotropic Substances Act.

8. Following acts and rules were passed during this era: Drugs and Cosmetics Act, 1940: This act regulates the manufacturing, distribution, import and sale of allopathic, homeopathic, unani and siddha drugs. Drugs and Cosmetics Rules, 1945: This act regulates manufacture of Ayurvedic drugs for sale only, and not for consumption and use or possession. Pharmacy Act, 1948: This law was amended in 1986 and it generally controls and regulates the profession of pharmacy in India.

9. Drugs and Magic Remedies (Objectionable Advertisements) Rule, 1955: This rule regulates the advertisement of drugs in India. Drugs Prices Control Order, 1955 (DPCO) (under the essential commodities Act): DPCO was further amended in 1995. As per this rule, government has a jurisdiction to review and fix maximum sale price for bulk drugs as well as formulation. ( b) 1960-1970: The Indian Pharmaceutical industry was not mature enough and major market share was dominated by MNC and very few Indian manufacturers were in competition.

10. Focus on pure research and development was very little because of deficiency of patent protection. The low availability and high drug price is because majority shares depend upon the high drug import. ( c) 1970-1980: Government took control for the medicines regulation and issued few acts and rules. Indian Patent Act 1970 (which came in force on 20 April 1972 and replaced Indian Patents and Designs Act of 1911): It serves as the basis for patent protection in India.

11. Under this Act product patent was not allowed but the process and method of manufacturing of Drug substance was allowed to get the patent Drug prices capped: Drug Prices Control Order (DPCO) was introduced to control the high price against consumers. ( d) 1980-1990: The Indian industry has started investing in process development of API and created production infrastructure for the same. ( e) 1990-2000 : A rapid expansion in domestic market has observed in pharmaceutical industry. The companies have started entering into Research and Development.

12. (f) 2000-2010: This period is considered to be the Innovation and Research era. During these years, innovative research activity, patenting of the drugs formula, process, indication as well as merger of companies was started. Patent Amendment Act 2005: Indian Government brought out the Patents (Amendment) Ordinance, 2004 to address the issues relating to the patent in the country which was later replaced by the Indian Patent (Amendment) Act, 2005. The new Act brought some crucial changes on the legal regime of patent protection so as to address patent issues in technology, chemicals and pharmaceuticals sectors

13. Compulsory Licenses: Such l icenses can be granted for manufacture and export of the drug products "to any country having insufficient or no manufacturing capacity, for the said product, to address public health problems”. Few names are given below: Drugs and Cosmetics (First Amendment) Rules. 2011: It mandates registration of Clinical Research Organization (CRO) for conducting Clinical Trials (CT).

14. Clinical Trial Registry-India (CTRI): It has been set up by the ICMR's (Indian Council of Medical Research) National Institute of Medical Statistics (NIMS). Pharmacovigilance Program of India (PvPI): The Central Drugs Standard Control Organization (CDSCO) has launched Pharmacovigilance programme to assure drugs safety to Indian patients

15. Scope Lifecycle management ranges from Drug Discovery post-marketing stage of the process. From Drug development to commercialization, each step is regulated.

16. Responsibilities of RA professional Keep up-to-date about international legislation, guidelines and customer practices. Update with company's product range. Compliance of company's product with current regulations Impart training to R&D, Pilot plant, ADL on current regulatory requirements Formulate regulatory submission strategies. Prepare IMPD, DMF, ANDA, MAA, Dossiers amendments & supplements etc. as per regional guidelines, submit them to regulatory authorities in a specified time frame

17. Responsibilities of RA professional cont... Monitor progress of all registration submissions Respond to queries as they arise and ensure that registration/approvals are granted without delay. Handle regulatory and customer inspections, review audit reports and compliance Arranges consultations and meetings between the firm and government regulatory agencies

18. Importance of RA Company success depends on reduction of time taken for a drug to reach market. Inadequate reporting of data may prevent a timely positive evaluation of a marketing application Proper conduct of RA activities is therefore of considerable economic importance for the company. No DMF/Dossier No Registration No Sale

19. Regulatory Agencies

20. Country Name of Regulatory Authority Website USA Food and Drug Administration (FDA) www.fda.gov Europe Europe Directorate for the Quality of Medicines and Healthcare (EDQM) European Medicines Agency (EMA) Heads of Agencies for the European Union www.edqm.eu www.ema.europa.eu http://www.hma.eu/ Japan Ministry of Health, Labour and Welfare(MHLW) Pharmaceuticals and Medical Devices Agency (PMDA) www.mhlw.go.jp/english www.pmda.go.jp/english/ UK Medicines and Healthcare products Regulatory Agency (MHRA) www.mhra.gov.uk INDIA Central Drugs Standard Control Organization www.cdsco.nic.in

21. How to Keep Up With the Constantly Changing Regulatory Landscape ? Monitor Agency’s websites Subscribe to relevant journals, newsletters Get daily e-mails from regulatory websites, commercial information provider websites Attend relevant conferences/ advisory meetings Talk to colleagues and consultants Employ a regulatory information database In-house or Paid Joining information blogs

22. Roles of Regulatory Affairs Experts Regulatory Affairs plays a crucial role in the pharmaceutical industry and is involved in all stages of drug development and also after drug approval and marketing. Pharmaceutical companies use all the data accumulated during discovery and development stages in order to register the drug and thus market the drug. Through out the development stages, pharmaceutical companies have to abide by an array of strict rules and guidelines in order to ensure safety and efficacy of the drug in humans

23. In this highly regulated environment, regulatory affairs plays a critical role not only as the interface with health agencies and as a link between different departments in the company but also as the leading department to provide strategic advice on extremely difficult decisions through the life of a drug. Regulatory professionals keep working with the authorities and different departments within the company in order to meet regulatory commitments with the health authorities. Regulatory experts also ensures the maintenance of the marketing license and leads life cycle extension activities such as broadening the indication of the drug, change of formulation , changes in the dosage etc..

24. DRA Domestic Regulatory Affairs (DRA) Country of Origin International Regulatory Affairs(IRA) other than country of origin GLOBAL MARKRT Regulated Market Semi-regulated Market US,EU (UK, Germany, France, Ireland, Sweden etc.), Japan, Canada, Australia, New Zealand, South Africa Asia ( Sri Lanka, India, Bangladesh )ASEN: 10 countries group Pillippines,Vietnam,Singapore,Malaysia,Thailand,Indonesia,Laos,Cambodia,Brunei,Darussalam,Mayanmar African Countries (Algeria, Zambia, Ethiopia, Ghana, Kenya, Malawi, Mozambique, Namibia, Nigeria, Sierra Leone, T anzania, Zimbabwe, etc.) Middle East Countries( Gulf Co-operation Council countries i.e. Bahram, Kuwait, Oman, Qatar, Saudi Arabia , UAE ) Latin America (Mexico, Brazil, Panama, Peru, Guatemala, Argentina, Chile, Dominican Republic ) CIS ( Common Wealth of Independent states): Russia, Ukraine, OFSUs( Armenia, Azerbaijan, Belarus, Georgia, Kazakhstan, Kirghizstan, M oldova, Tajikistan, Turkmenistan, Uzbekistan, etc.

25. Thank you