Definition of Generic Drugs

According to the World Health Organization (WHO) and CDSCO,

a generic drug is a pharmaceutical product that is bioequivalent to an innovator (reference) drug in terms of dosage form, strength, route of administration, quality, performance characteristics, and intended use. Generic drugs contain the same active pharmaceutical ingredient (API) and demonstrate comparable bioavailability.

Regulatory Authorities Involved

The regulatory oversight of generic drug approval in India is managed by:

1. Central Drugs Standard Control Organization (CDSCO)

• Apex regulatory authority for drug approval
• Functions under the Ministry of Health and Family Welfare
• Responsible for approval of new drugs, clinical trials, and import/export of drugs

2. Drug Controller General of India (DCGI)

• Head of CDSCO

• Grants final approval for new and generic drugs

• Issues guidelines on bioequivalence, GMP, and safety.

3. State Licensing Authorities (SLAs)

• Responsible for granting manufacturing and distribution licenses post CDSCO approval

Regulatory Framework

The approval of generic drugs is governed by:

• Drugs and Cosmetics Act, 1940

• Drugs and Cosmetics Rules, 1945

• Schedule Y (specifies data requirements for new drug applications including bioequivalence)

Other applicable regulatory references include:

• Indian Pharmacopoeia (IP)

• ICH Guidelines (for international harmonization)

• Bioavailability and Bioequivalence Guidance (CDSCO).

Eligibility for Filing Generic Drug Application

A drug is eligible to be registered as a generic drug when:

• The patent of the innovator drug has expired
• There are no data exclusivity barriers
• The active ingredient is well-established with known safety and efficacy profile.

Types of Applications for Generic Drug Approval

• Form 44: For seeking permission to manufacture a generic drug formulation

• Form CT-21: For bioequivalence study permission

• Form 10 & Form 41: For import of generics manufactured outside India.

Step-by-Step Approval Process for Generic Drugs in India

Step 1: Product Development and Pre-Formulation Studies

The manufacturer develops a generic version of the reference product using the same API, with the aim to match the innovator drug’s pharmacokinetic and pharmacodynamic profile. This includes:

• Pre-formulation characterization of the API

• Selection of excipients

• Stability studies (as per ICH Q1A guidelines)

• Validation of manufacturing process (Process Validation as per WHO-GMP).

Step 2: Submission of Application

The manufacturer files the application using Form 44 with the following documentation:

• Covering letter and undertaking

• Drug Master File (DMF) and Common Technical Document (CTD)

• Complete Chemistry, Manufacturing, and Controls (CMC) data

• Stability data (zone-specific as per ICH Q1A)

• Labeling, packaging and patient information leaflet

• Preclinical and clinical data (if applicable)

• Proposed product information (PI) and prescribing details

• Good Manufacturing Practices (GMP) certificate.

Step 3: Bioequivalence (BE) Study Requirement

The generic drug must demonstrate bioequivalence to the reference innovator product. CDSCO requires a BE study to establish pharmaceutical equivalence and comparable bioavailability.

Key Features of BE Studies:

• Conducted in healthy adult volunteers

• Randomized, open-label, two-treatment, two-period, two-sequence crossover design

• Measurements include:

  • Cmax (peak plasma concentration)

  • Tmax (time to reach Cmax)

  • AUC0-t / AUC0-∞ (area under the plasma concentration-time curve)

• Acceptance criteria: 90% confidence interval for log-transformed ratios of test/reference products must fall within 80–125%

BE Study Protocol Submission:

• Filed through Form CT-21

• Requires Ethics Committee approval

• Must comply with Good Clinical Practices (GCP).

Step 4: Review and Evaluation by CDSCO

The New Drug Division (NDD) and Bioequivalence Section of CDSCO evaluate:

• BE study data and statistical analysis report

• Quality attributes: purity, dissolution profile, assay, impurities

• GMP compliance of the manufacturing site

• Labeling and packaging compliance

If deficiencies are observed, CDSCO issues a clarification or query letter (deficiency letter) and waits for the applicant’s response.

Step 5: Grant of Marketing Authorization

Once the data is found satisfactory, the CDSCO grants the permission to manufacture and market the generic formulation in India. The manufacturer can then approach the State Licensing Authority (SLA) for obtaining the final manufacturing license under Form 25/28 (depending on the formulation type).

Import of Generic Drugs

If the generic drug is manufactured outside India, the following are required:

• Form 41: Registration Certificate for the foreign manufacturer

• Form 10: Import License application

• Documents needed:

  • WHO-GMP certification

  • Certificate of Pharmaceutical Product (CoPP)

  • Site Master File

  • Product Dossier

  • Bioequivalence data and BE waiver (if applicable)

Timelines for Approval

• BE study approval: ~3–4 months

• Evaluation of dossier and granting of marketing authorization: 6–12 months (depending on query resolution)

• Total time (domestic generic): ~9–15 months

• Imported generics: May take longer (~12–18 months).

Post-Approval Obligations

After approval, the manufacturer must ensure:

• Compliance with PvPI (Pharmacovigilance Programme of India)

• Submission of Periodic Safety Update Reports (PSURs) every 6 months for the first 2 years, then annually for 2 more years

• Label updates, if safety information changes

• Site inspections for GMP and pharmacovigilance audits.

Challenges in Generic Drug Approval

• Delays in BE study protocol approval

• Inconsistent interpretation of dossier requirements by reviewers

• Patent litigation risks (Section 107A of Indian Patent Act allows early submission of data before patent expiry)

• Regulatory bottlenecks due to under-resourced review teams.

Conclusion

The approval process for generic drugs in India is technically rigorous, aimed at ensuring therapeutic equivalence, product quality, and patient safety. It balances the need for affordable medications with robust scientific standards. For regulatory affairs professionals, understanding the regulatory pathway, bioequivalence protocols, and CDSCO procedures is crucial for successful generic product registration in India.

Frequently Asked Questions (FAQs)

Q1. Is clinical trial mandatory for generic drug approval in India?
No. Only bioequivalence studies are required unless the drug falls under special categories or there is no reference product.

Q2. Who is responsible for approving generic drugs in India?
The CDSCO under the authority of the DCGI.

Q3. Can a generic drug be approved without a BE study?
Yes, in certain cases such as topical preparations, oral solutions, and parenteral products where BE may be waived based on biowaiver principles.

📌 Also Read: Master Cosmetic Manufacturing License & Regulation in India – Complete Guide (2025)