Drug Approval Process in India

The Drug and Cosmetic Act 1940 and Rules 1945 were passed by India's parliament to regulate the import, manufacture, distribution, and sale of drugs and cosmetics. The Central Drugs Standard Control Organization (CDSCO), and the office of its leader, the Drugs Controller General (India) [DCGI] was established. In 1988, the Indian government added Schedule Y to the Drug and Cosmetics Rules 1945. Schedule Y provides the guidelines and requirements for clinical trials, which was further revised in 2005 to bring it to par with internationally accepted procedures.

When a company in India wants to manufacture/ import a new drug it has to apply to seek permission from the licensing authority (DCGI) by filing Form 44 and also submitting the data as given in Schedule Y of the Drugs and Cosmetics Act 1940 and Rules 1945. In order to prove its efficacy and safety in the Indian population it has to conduct clinical trials in accordance with the guidelines specified in Schedule Y and submit the report of such clinical trials in a specified format.

1. Rule- 122A of the Drug and Cosmetics Act says that clinical trials may be waived in the case of new drugs which are approved and being used for several years in other countries.
2. Section 2.4 (a) of Schedule Y of the Drugs and Cosmetics Act 1940 and Rules 1945 says for those drug substances that are discovered in India all phases of clinical trials are required.
3. Section 2.4 (b) of Schedule Y of the Drugs and Cosmetics Act 1940 and Rules 1945 says that for those drug substances which are discovered in countries other than India; the applicant should submit the data available from other countries and the licensing authority may require him to repeat all the studies or permit him to proceed from Phase III clinical trials.

• Demonstration of the safety and efficacy of the drug product for use in humans is essential before the drug product can be approved for import or manufacturing of new drug by the applicant by Central Drugs Standard Control Organization (CDSCO). The regulations under the Drugs and Cosmetics Act 1940 and its rules 1945, 122A, 122B, and 122D and further Appendix I, IA, and VI of Schedule Y, describe the information required for approval of an application to import or manufacture of a new drug for marketing.
• The changes in the Drugs And Cosmetics Act include establishing definitions for Phase I-IV trials and clear responsibilities for investigators and sponsors. The clinical trials were further divided into two categories in 2006. In one category (category A) clinical trials can be conducted in other markets with competent and mature regulatory systems whereas the remaining ones fall into another category (category B) Other than A. 
• Clinical trials of category A (approved in the U.S., Britain, Switzerland, Australia, Canada, Germany, South Africa, Japan and the European Union) are eligible for fast-tracking in India. They are likely to be approved within eight weeks. The clinical trials of category B are under more scrutiny and approved within 16 to 18 weeks.
• An application to conduct clinical trials in India should be submitted along with the data of chemistry, manufacturing, control and animal studies to DCGI. The date regarding the trial protocol, investigator's brochures, and informed consent documents should also be attached. A copy of the application must be submitted to the ethical committee and the clinical trials are conducted only after approval of DCGI and the ethical committee.
• To determine the maximum tolerated dose in humans, adverse reactions, etc. on healthy human volunteers, Phase I clinical trials are conducted. The therapeutic uses and effective dose ranges are determined in Phase II trials in 10-12 patients at each dose level. The confirmatory trials (Phase III) are conducted to generate data regarding the efficacy and safety of the drug in ~ 100 patients (in 3-4 centers) to confirm efficacy and safety claims. Phase III trials should be conducted on a minimum of 500 patients spread across 10-15 centers, If the new drug substance is not marketed in any other country.

• The new drug registration (using form # 44 along with full pre-clinical and clinical testing information) is applied after the completion of clinical trials. Comprehensive information on the marketing status of the drug in other countries is also required other than information on safety and efficacy. The information regarding the prescription, samples and testing protocols, product monograph, labels, and cartons must also be submitted.

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• The application can be reviewed in a range of about 12-18 months. The below image represents the new drug approval process in India. After the NDA approval, when a company is allowed to distribute and market the product, it is considered to be in Phase IV trials, in which new uses or new populations, long-term effects, etc. are explored. 

The drug approval process in INDIA

• Through the International Conference on Harmonization (ICH) process, the Common Technical Document (CTD) guidance has been developed for Japan, the European Union, and the United States.
• Most countries have adopted the CTD format. Hence, CDSCO has also decided to adopt the CTD format for technical requirements for the registration of pharmaceutical products for human use.

• Stages of approval:

1. Submission of Clinical Trial application for evaluating safety and efficacy.
2. Requirements for permission of new drugs approval.
3. Post-approval changes in biological products: quality, safety and efficacy documents.
4. Preparation of the quality information for drug submission for new drug approval.

• The drug approval process varies from one country to another. In some countries, only a single body regulates the drugs and is responsible for all regulatory tasks such as approval of new drugs, providing licenses for manufacturing, and inspection of manufacturing plants e.g. in the USA, the FDA performs all the functions. 
• However in some countries, all tasks are not performed by a single regulatory authority, such as in India, this responsibility is divided between Centralised and State authorities. Some countries have two review processes a normal review process and an accelerated review process as in the USA, China, etc. and others have only a single review process as in India. 
• Similarly, the format used for the presentation of the dossier submitted for approval of the drug is also different. In some countries like as in USA, EU, and Japan, it is mandatory that the dossier be prepared in CTD format, however, in some countries it is optional such as in India.

Conclusion

India's drug approval process, regulated by the CDSCO and DCGI, follows a well-defined framework outlined in the Drugs and Cosmetics Act and its rules. The process includes the submission of clinical trial applications, rigorous evaluation of safety and efficacy, and subsequent registration and approval procedures. By aligning with international standards, India ensures the quality and safety of pharmaceutical products available to its population while fostering innovation and research in the healthcare sector.

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