Drug Approval Process in India
Approval Procedures for New Drug
There is no requirement for any registration of a drug in India. However, there is need for approval from the Drug Controller of India (DCI) to import, market, or manufacture a “new drug.” All new drugs (drugs not previously used in India or in use for less than four years) proposed to be introduced must be approved for import or manufacture in India by the DCI. The application for permission to import or manufacture must be accompanied by the appropriate dossier as follows.
The full set of data to be submitted consists of:
• Introduction: description of drug and therapeutic class
• Clinical and pharmaceutical information
• Animal pharmacology
• Animal toxicology
• Human/ clinical pharmacology (Phase I)
• Exploratory clinical trials (Phase II)
• Confirmatory clinical trials (Phase III)
• Special studies
• Regulatory status in other countries
• Marketing information
All items above may not be required for all drugs. In case the drug is already approved and marketed abroad, then only Phase III trials may be required in India. Further, such trials would need to be conducted on at least 100 persons spread over 3-4 locations in the country. However, the DCI may agree to dispense with the need for local clinical trials, if it is in the public interest and if it can use the data of trials carried out in other countries. Similarly, the submission of data related to animal toxicology, reproduction studies, teratogenic studies, perinatal studies, mutagenicity and carcinogenicity may be relaxed or modified in case the drugs are in use overseas for several years and there is adequate published evidence regarding the safety of the drug.
Permission from the DCI has to be obtained to import samples for clinical trials and to carry out the clinical trials in India.
In case the new drug is a fixed dose combination (FDC) of existing approved active ingredients, and these are merely being combined for convenience and provision of a stable acceptable dosage form and the ingredients are unlikely to have significant interaction of a pharmacodynamic or pharmacokinetic nature, then no additional animal or human data are generally required and marketing permission may be granted if the FDC has an acceptable rationale. However, if the combination is being done for the first time, and a claim is being made, and/or the combination is likely to result in a significant interaction of a pharmacodynamic or pharmacokinetic nature, then it is treated in the same way as any other new drug.
The period taken to give approval to a new drug largely depends on whether clinical trials will be required by the Drug Controller. It is not possible to estimate the time, and the law lays down no time limit. However, it can be assumed that after the submission of the full (final) dossier, it may take around three months, though this is only an estimate. The actual time taken depends on the amount and effectiveness of follow-up that is done by the local agent with the concerned authorities.
Most pharmaceuticals are freely importable under the foreign trade law. Certain drugs may not, however, be imported except under a license given by the Drug Controller of India. Such products cannot be imported after the date shown on the label as being that on which the potency would reduce or toxicity would increase beyond the standard permitted.
The foreign manufacturer would have to appoint an Indian agent to apply for the import license. The agent would be responsible for fulfilling all the terms of the license. An agent has to be an entity (individual, partnership or company) registered in India. A license is valid for a year, up to December 31st of the year following the year in which the license was granted, and has to renew thereafter. The importer must have a license to stock and sell drugs. In case there is any repacking or labeling to be done, then the importer must also have a drug manufacturing license. A single license may be applied to all drugs imported from one manufacturer, provided that the drugs are manufactured at one factory or more than one factory functioning conjointly as a single unit. If the drugs are made in two separate factories, a separate license is required for drugs manufactured by each such factory.
In case the drug being imported is a “new” drug, i.e. not so far used in India or used for less than 4 years, it has to be approved by the Drug Controller of India(DCI) for sale or clinical trials in India before he will give an import license.
The license holder has several responsibilities including: maintaining detailed records of sales, permitting inspectors to enter his premises to take samples, to
furnish samples to the DCI for examination when required, not selling any item of a batch until the sample is cleared (if so directed by the DCI), withdrawing or recalling sold items if the batch from which the sample is drawn does not meet the prescribed standards.
All license applications from the importer/agent have to be accompanied by an undertaking from the foreign manufacturer stating that the applicant is the authorized agent of the manufacturer, the date since when the manufacturer has been making drugs at the relevant factory premises, an undertaking that any change of location of manufacturing will be informed to the DCI, an undertaking that the drugs imported will comply with the Indian standards and other undertakings as to compliance with the DCA and the conditions of license.
The Different Fees charged by the Drug regulatory authority in India is
•Import ff/ Mfg ff/ Import bulk + Mfg ff = Rs. 50,000/-
of new drug
Application by same applicant, = Rs.15, 000/-
for modified dosage form or with new claim
Secondary applicants after 1 = Rs. 15,000/-
year of approval
Import / Mfg FDC = Rs. 15,000/-
Conduct Clinical trial with ND/IND
–Phase I = Rs. 50,000/-
–Phase II = Rs. 25,000/-
–Phase III = Rs. 25,000/-
–No separate fee to be paid along with application for import / mfg based on successful completion
Data submitted along with the application
A. Permission to market new drug
1. Chemical and Pharmaceutical information
2. Animal Pharmacology
3. Animal Toxicology
4. Human / Clinical Pharmacology
5. Exploratory Clinical Trials
6. Confirmatory Clinical Trials
7. Bioavailability / dissolution and stability data
8 Regulatory status in other countries
9. Marketing information:
(a) Proposed product monograph
(b) Drafts of labels and cartons
10. Application for test license :
B. Subsequent approval / permission for manufacture of already approved new drug
Bioavailability / bioequivalence
Name of the investigator / centre
Source of raw material and stability
b) Raw Material
QC parameters, specs, stability
C. Approval / permission for FDC
•P’cokinetic / P’codynamic data
•Any other data
D. .Subsequent approval or approval for new indication – new dosage form:
•Number and date of Approval already granted
•Data on safety, efficacy and quality