This document outlines standard operating procedures for regulatory affairs in the pharmaceutical industry in India. It discusses maintaining proper documentation for clinical trials, including investigator files, informed consent forms, and regulatory forms like the FDA Form 1572. It provides the order that documents should be filed and stored. It also describes the regulatory approval process and requirements for medical devices in India through the Central Drugs Standard Control Organisation.

1. Standard Operating Procedures R E G U L A T O R Y A F F A I R S BII INDUSTRY PROGRAME IN PHARMA REGULATORY AFFAIRS

2. INDEX 1 Introduction 2 Standard Operating Procedures 3 Order Of Documents 4.CDSCO Regulatory Status

3. Introduction A standard operating procedure is a set of instructions having the force of directive, covering those features of operations that lend themselves to a definite or standardized procedure without loss of effectiveness. Standard Operating Policies and Procedures can be effective catalysts to drive performance improvement and improving organizational results. This standard operating procedure (SOP) describes the policy and procedure in the performance of the study review portion of the investigator regulatory files. It is required that all principal investigators maintain complete regulatory documentation since these documents permit evaluation by the proper regulatory authorities for the conduct of the research study as well as the quality of the data produced. The regulatory documents serve to demonstrate compliance of the investigatory and/or sponsor with the standards of Good Clinical Practice (GCP) and other applicable requirementsThe Office of Human Research Protection (OHRP) strongly recommends that all supportive study documentation for individual studies be maintained in an easily accessible and organized file systemsuch as a three-ringed binder labeled with the appropriate tabs

4. The Indian Council of Medical Research (ICMR), New Delhi, the apex body in India for the formulation, coordination and promotion of biomedical research, is one of the oldest medical research bodies in the world. In 1911, the Government of India set up the Indian Research Fund Association (IRFA) with the specific objective of sponsoring and coordinating medical research in the country. After independence, several important changes were made in the organisation and the activities of the IRFA. It was redesignated the Indian Council of Medical Research (ICMR) in 1949, with considerably expanded scope of functions. The ICMR is funded by the Government of India through the Ministry of Health & Family Welfare

5. A.IRB submission B. VA submission C. Informed consent: D. IRB approval E. Clinical regulatory documents 1. Statement of the Investigator (Form 1572) is the form that is required by the FDA. 2. Curriculum Vitae 3. Medical License 4. Local Conflict of Interest Document 5. Sponsor Conflict of Interest Document 6. Local Laboratory Documentation 7. Request for Taxpayer Identification Number and Certification F. Amendments Regulatory Affairs SOPs

6. G. Completing FDA Form 1572: H. IND submission-Initial submission-Sponsor or investigator I. IND submission-Investigator Initiated J. Completing FDA Form 1571 1.Name of sponsor: . 2.Date of submission: 3. Address 4. Telephone number 5. Name(s) of drug 6. IND number 7. Indication(s): 8. Phase(s) of clinical investigation to be conducted 9 List numbers of all INDs, NDAs, DMFs, and PLAs referenced to in this application 10. IND submission should be consecutively numbered

7. 11. This submission contains the following 12. Contents of application 13. Contract research organization information 14-15. Monitoring and safety evaluation information 16-17. Name and signature of sponsor 18-19. Address and phone number: 20. Date K. Reporting SAE's from other sites

8. The order of the documentation is as follows: A.Company Protocol/Protocol B. Investigational Drug Brochure C. Amendments D. IRB Submission E. VA Submission (if required) F. IRB Correspondence G. IRB Approval H. Annual IRB Re-approval for Phase III studies I. Company Correspondence

9. J. Signed Protocol K. Confidentiality Agreement L. Final Approved (Informed Consent) M. Indemnification Statement N. Clinical Study Agreement (Investigator's Agreement) O. Advertisement P. 1572 Q. CV's R. Laboratory Reference Range and Certification

10. CDSCO- Regulatory Status The Central Drugs Standard Control Organisation (CDSCO), headed by the Drugs Controller General (India) (DCGI) discharges the functions allocated to Central Government. The CDSCO is attached to the office of the Director General of Health Services in the Ministry of Health and Family Welfare. The DCGI is a statutory authority under the Act and has port offices, zonal offices with drug inspectors and drug testing laboratories functioning under him. The CDSCO is the authority, which lays down rules, standards and approves import and manufacturing of drugs, diagnostics, devices, and cosmetics. Currently, CDSCO’s functions are to establish the standards and regulations for drugs, blood and blood products, intravenous fluids, and vaccines. With added responsibility of regulating the medical devices industry, CDSCO will be the approving authority for import, manufacture and sale of medical devices in India. The regulatory procedure will be clear only after the government notifies the regulations and the CDSCO provides the import guidelines. But as we understand it, subsequent to the government’s notification, foreign and India companies will have to apply for permission to import, and sell medical devices in India.

11. Both the manufacturer and the importer will have to register with CDSCO. The Indian importer will have to obtain a “no objection” certificate to import and sell in India. Approval of the product from any other regulatory agency (Separate evidence for the approval from the each agency) US FDA clearance/approval. EU medical device directive (CE Certificate). Australia/Canada/Japan approval. Approval in any other country. List of countries where the device is being sold. List of countries where device is withdrawn from sale with reasons, if any. Copy of ISO/EN Certification if any for the manufacturing facility. Normally, the FDA and CE approved products are preferred because of their betterquality and performance. But, India being a price sensitive market, low priced medical devices find a big market.

12. To ensure the quality of healthcare service, the Government of India is in the process of developing regulations for medical devices. According to industry contacts and the Ministry of Health officials, a notification is expected that would bring a select group of medical devices under the regulatory framework The authority regulating medical devices will be the Central Drug Standard Control Organization (CDSCO) in the Ministry of Health.. However, it is expected that for products that are approved by the FDA and/or CE, the registration process to obtain an approval to sell will be a trouble-free. To register a new medical device or non FDA/CE approved devices in India, an application will have to be submitted to the regulatory authority along with documents such as details of the regulatory status in other countries; restrictions of use in approved countries; a free sale certificate from the country of origin.

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