Dr. A. Ramkishan M.Pharm , PhD. FIPS, FTASc , FIPA. Deputy Drugs Controller (India)

1. Regulatory Tools ensuring transparency of Registration and Inspection Procedures for entering into the Indian Market Dr. A. Ramkishan M.Pharm, PhD. FIPS, FTASc, FIPA. Deputy Drugs Controller (India) Central Drugs Standard Control Organization (CDSCO), Ministry of Health & Family Welfare, East Zone, Government of India, Kolkata-700020, India

3. Evolution of Indian Drug Legislation Preamble To regulate manufacture, sale, distribution and import of drugs, cosmetics, Biologicals, medical devices and other products. Objective The Objective of Drugs & Cosmetics Act is to ensure that public are supplied with safety, efficacy and quality of drugs (Sec. 3b). Basic Philosophy The basic philosophy of Drugs & Cosmetics Act is that the manufacturer is responsible for the quality of drugs manufactured by them and the Government/Regulatory Agencies will monitor the quality of drugs by periodic inspections of the manufacturing and sales premises for confirmation to the provisions of Drugs & Cosmetics Act and monitoring the quality of drugs moving in the market by carrying out post market surveillance.

4. Regulatory provision for Import and Registration of drugs in India • Import of drugs are regulated under the Drugs and Cosmetics Act, 1940 and the Drugs and Cosmetics Rules, 1945 made there under. • Bulk drugs (Active Pharmaceutical Ingredients) and Finished formulations are regulated under the said Act. Any substance falling within the definition of Drug (Section 3b of the Act) is required to be registered before import into the country. • Not only the drug but the manufacturing site also needs to be registered for import • Chapter III of Drugs & Cosmetics Act 1940, governs the import of Drugs & Cosmetics into India • The provision for grant of Import Registration Certificate and Import Licenses are prescribed under Part IV of the Drugs & Cosmetics Rules 1945.

5. Documents to be submitted for grant of Registration Certificate • Application in Form 40 • Power of Attorney ( POA) • GMP certificate / COPP (as per WHO format) or WC issued by their NRA or certificate equivalent to WHO GMP guidelines issued by NRA of USA or Japan or Australia or Canada or the European Union for the purpose of marketing of the drugs in their country • Countries where marketing authorization or import permission is granted (122A Permission) • Countries where marketing authorization or import permission is cancelled/ withdrawn • Schedule D (I): Information and undertaking required to be submitted by the manufacturer or his authorized agent with the application form for a registration certificate • Plant Master File • Plant Layout, HVAC system, Water system, etc., • List of Major equipment's in Production and QC. • List of key personals with qualification, experience and responsibilities. • Distribution, Complaints & products recall SOP, List of Contract Manufacturing/analysis

6. Documents to be submitted for grant of Registration Certificate • Schedule D(II) : Information and undertaking required to be submitted by the manufacturer or his authorized agent with the application form for the registration of bulk drugs/formulations/special products for its import into India • Drug Master File • General: Name of the drug/formulation and its therapeutic class • Regulatory status of the drug. Free Sale Certificate / COPP/GMP issued by NRA of the country of origin. Free sale approval from other major countries. • Chemical and pharmaceutical information of drugs. • Chemical name, dosage, composition, source of API ; Biological and biopharmaceutical information of drugs • Pharmacological and toxicological information of drugs.; Clinical documentation • For new drug, permission to market in India (Form-45/45A), brief summary and clinical documentation. • Labelling and packaging information of drugs. Original Labels • Whole-sale license; Specific information required for the special Products.

7. Registration Fees: • Manufacturing premises - 10000 USD (or its equivalent to Indian Rupees), • Drug - 5000 USD (or its equivalent to Indian Rupees) / per drug if manufacturing site remains the same. • Inspection - 25000 USD (or its equivalent to Indian Rupees) in case of inspection of the manufacturing site. • Timelines: • Form 41 (Registration Certificate): 270 days from date of application. • Form 10 (Import License): 45 days from date of application. • Import License • Import License is required for import of drugs (Bulk Drugs and Finished Formulations) into India, under rule 23 and 27 of the Drugs and Cosmetics Rules; • Requirements: • Application in Form 8; A copy of Registration Certificate authenticated by Indian Agent. • Undertaking in form 9 from the authorized agent or from manufacturer duly verified by the Indian Embassy where the manufacturer is located; Copy of sale license or manufacturing license . • Fees of Rs.10000/- for the first drug and Rs.1000/- for each additional drug.

8. Exemptions for Registration • In case of emergencies the licensing authority may with the approval of Central Government, issue an import license in Form-10 or 10-A as the case may be, without the issuance of Registration Certificate • Import of drugs required for personal use for any patient. • Government hospitals can import drugs for their own patient. • Drugs imported for clinical trials. • Drugs imported for products/formulations development and data generation. • Drugs not yet approved and marketed in the country and meant for export only. • Control Measures • Drug complies with the standard set out in the Second Schedule of the Drugs and Cosmetics Act are imported. • No drug, which is misbranded, adulterated or spurious, or which makes false or misleading claims about its true nature is permitted to be imported. • Drug whose import has been banned is not permitted to be imported.

9. New Drugs and Clinical Trial Rules, 2019 • The New Drugs and Clinical Trial Rules, 2019 GSR 227 (E) dated 19.03.2019 have been notified with an aim to promote clinical research in the Country. The New Rules will change the regulatory landscape for the approval of New Drugs and the conduct of Clinical Trials in the country. • The new rules are structured around 13 chapters (including 107 Rules) and 8 schedules and applicable all new drugs, IND, Clinical Trials, BA/BE studies and Ethics Committee. • The new regulations cover provisions for promoting clinical research as well as complex topics like Orphan Drugs, Post trial access, pre and post submission meetings, waiver of local clinical trials, deemed approval, Validity of CT permission for 3 years and accelerated approval.

10. e-Governance • The e-Governance portal (SUGAM) has been set up to provide a single window for multiple stakeholders (Pharma Industry, Regulators, Citizens) involved in the processes of CDSCO. • SUGAM enables online submission of applications, their tracking, processing and grant of approvals through online mainly for Drugs, Clinical Trials, Ethics Committee, Biological Products, Cosmetics and Medical Devices. • The SUGAM portal set up at the Central Drugs Regulatory Authority is being linked to the State Drugs Regulatory Authorities. • The software (SUGAM) providing a common platform for online submission and processing of applications for grant of various licenses by all SLAs across the country (India-one software) • New GSR 19(E) dated 10.01.2019 (Rule 84AB) published to have comprehensive database of the licenses and drug products is being created to upload the information in SUGAM portal (The information should be uploaded on www.cdscoonline.gov.in)

11. INDIAN PHARMACEUTICAL EXPORTS • Export Performance of Indian Medicines • 08 out of top 20 Global generic companies are from India. • 55% India’s exports are to highly regulated markets(USA is the largest exporting partner of India). • India contributes 50% of Africa’s generic market ( Value of 6000 Million USD) • Indian exports are covering to 201 countries. • India produces 65% of WHO demand for DPT& BCG and 90% of Measles vaccines.

12. Indian Pharma exports

13. Region wise Indian Pharma exportsNorth America – 32% Africa -18% EU – 16% Asean Countries- 7% LAC – 7% Middle East - 5% South Asia -4% CIS Countries -4% Asia (Excluding Middle East)-4% Other European Countries- 1% INDIAN PHARMACEUTICAL INDUSTRY Total number of Manufacturing units -10,000 (Approx.) No. of Units registered with Pharmaceutical Export Council (Pharmexcil) set up by Ministry of Commerce & Industry, Govt. of India- 4474 a. Large Scale Manufacturers : 357 b. Small Scale Manufacturers : 1852 c. Merchant Exporters : 2265 Number of units engaged in Exports : 2209

14. What are the markets to focus by SMEs for Exports? Africa region (18% Exp.-South Africa, Nigeria, Kenya, Uganda & Tanzania) The Southern African Development Community (SADC) comprising of 16 countries has formed a pooled procurement arrangement for Pharma products for which medical store department (MSD) of Tanzania is identified as the Nodal agency. Asian 7% exports- (Vietnam, Philippines, Myanmar, Thailand ). Asia (excludes Middle East) : (4% Export-Nepal Sri- Lanka, Bangladesh) CIS- (4%)-Russia LAC (7%)- Brazil, Mexico Middle East (5%)- UAE, Iran, Turkey For CARICOM countries : Caribbean regulatory system (CRS) is the centralized regulatory agency.