How to obtain a license for a Drug manufacturing firm (pharmaceuticals) in India (Manufacturing License/Test License/Product License)

How to obtain a license for a Drug manufacturing firm (pharmaceuticals) in India (Manufacturing License/Test License/Product License)

 In India a drug substance (API) or a drug product (formulation) can manufactured and marketed only after obtaining a valid manufacturing license and a product license. Manufacturing license is issued for a facility and is subjected for periodic renewal, where as product license is product specific, which are required to manufacture any product under a valid manufacturing license. 

The Central Drugs Standard Control Organization (CDSCO) under Ministry of Health & Family Welfare is the National Regulatory Authority (NRA) for pharmaceuticals (API, Formulations & Biologics) and medical devices in India. CDSCO is headed by the drug controller general of India (DCGI). 

Manufacturing, sale and distribution of drug in India is regulated under Drugs and Cosmetics Act 1940 and Drugs and Cosmetic Rules 1945. Currently, bulk drug (Active Pharmaceutical Ingredients) and finished dosage formulations (FDF) are regulated under the said Act.  

Drug and cosmetic act is a federal act, enforced by both central and state governments of India. Under the Drugs and Cosmetics Act, CDSCO is responsible for approval of Drugs, Conduct of Clinical Trials, laying down the standards for Drugs, control over the quality of imported Drugs in the country and coordination of the activities of State Drug Control Organizations by providing expert advice with a view of bring about the uniformity in the enforcement of the Drugs and Cosmetics Act (Central Drugs Standard Control Organization (CDSCO) is the national level regulator, where as State Drug Regulatory Authorities (SDRAs) are the state level regulators. Powers are shared between the center and states). Sate drug controller (SDC) heads the SDRA.   

Who grants drug manufacturing License in India

Respective State Drug Regulatory Authority (Local FDA) is responsible for inspecting new manufacturing facility and granting manufacturing license as per the provisions of Drugs and Cosmetic Act -1940.  

When/How to apply manufacturing License for a new facility?

To obtain a manufacturing license, applicant should have a manufacturing facility in India which is registered under company act or work as a firm.

A company can register as

    One Person Company

   Private limited company

   Limited liability company

   Public Company

Documents required for company registration includes DSC (Digital signature certificate),DIN (Director Identification Number),Pan card (Permanent account number),TAN (Tax deduction and collection number),identity proof, Photo, address proof etc. Applicant shall also apply for GSTIN (Goods and service tax identification number)

Before applying for manufacturing license, new firm’s production and quality control area should be qualified with required equipment's/instruments and must have competent technical staff to perform production/quality control activities (Production area should meet schedule M requirements and Quality control lab should meet schedule L1 requirements of Drug and cosmetic act,1940 & rules 1945).

Application for manufacturing license for the new firm shall be submitted to the relevant State Drug Regulatory Authority/local FDA. After submission of the application and required documents, the application will be scrutinized and will be forwarded to senior drugs control officer of the concerned zone for facility inspection. Premises will be inspected by the senior drugs control officer of the concerned zone and report will be submitted to state drugs control with recommendation for approval or rejection of firm (Drug authority reserves the right to approve or reject the application based on the evaluation of the statutory requirements and GMP compliance of the firm).

 

Documents required for fresh Manufacturing License application of a Pharmaceutical firm in India

Introductory Cover letter specifying name and address of the plant and administrative office

Application at prescribed form and format Ø Application on Form 24 for Non-biological drugs manufacturing license. Ø Application on Form 27 for manufacturing of Biological drugs

Prescribed fee receipt.

Details of constitution of the firm, partnership or company.

Documents related to ownership of the premises, rent or lease agreement.

Identity proof of all authorized persons, proprietor, partners and or directors.

Blue print of Plant and Lay out of premises specifying installation of equipment and instruments.

Design and layout of HVAC system.

SMF (Site Master File).

Fire NOC.

NOC from Pollution Board.

Proof of electricity load sanction.

Full particulars of the competent technical staff /registered persons along with copies of their educational qualification, experience and registration certificates.

Non-conviction affidavit of approved technical staff as per required which should also finds mention the defaults of his/her academic qualification & approval.

List of Equipments used for manufacturing (Production Equipments).

List of Instruments used for testing (QC instruments).

A fresh manufacturing license and product license can be applied simultaneously or product license can be applied after obtaining a valid manufacturing license. Each product manufactured and commercialized by the firm must have a product license.

R&D development and trail manufacturing of any new product shall be carried out under a test license which is issued by the drug licensing authority.

Test License

Test license is issued for the purpose of examination, test or analysis of a drug in small quantities which is otherwise prohibited under section 10 of the Drugs and Cosmetics Act and Rules, 1945. This license is issued in form 11 and form 29.

Test licence or form 11 licence is issued for the import of small quantities of drugs, for the purpose of examination, test or analysis.Import of new drugs including biological products and medical devices for the purpose of clinical trials,the test license is granted by CDSCO HQ. 

The Form 29 is a license to manufacture drugs for the purpose of examination testing and analysis.

A test license is valid for a period of 3 years and can be renewable if required. Test license cannot be used for manufacturing commercial batches, for which, a valid commercial license to be obtained from drugs control department.  

 

 

Schedules under Drug and Cosmetic Act, 1940 & Rules 1945

Schedules under Drug and Cosmetic Act, 1940 & Rules 1945

D&C Act

In India drugs and medical devices are controlled by “Central Drugs Standard Control Organization(CDSCO)".

India's GMP standards for drugs and medical devices are covered in Drugs and Cosmetics Act (DCA). Followings are the different schedules in the drugs and cosmetics Act. 

Schedules	Description
Schedule A:	Performa for applications for the Licenses, issue and renewal of licenses, for sending memoranda under the act.
Schedule B&B1:	Schedule B describes fees for test or analysis by the Central Drug Laboratories or State Drugs Laboratories. Schedule B1 describes fees for the test or analysis by the pharmacopoeial laboratory for Indian medicine (plim) or the government analyst.
Schedule C &C1:	Schedule C describes list of Biological and special products (injectable) applicable to special provisions. Schedule C1 describes list of Biological and special products (non parentral) applicable to special provisions.
Schedule D,D1,D2,D3:	Exemption of drugs from provision of import. Schedule D1 describes the Information and undertaking required to be submitted by the manufacturer or his authorized agent with the Application Form for a Registration Certificate. The format shall be properly filled in for each application in Form 40. The detailed information, secret in nature, may be furnished on a Computer Floppy. Schedule D2 describes the Information required to be submitted by the manufacturer or his authorized agent with the Application Form for the registration of a bulk drug/formulation/special product for its import into India. The format shall be properly filled in and the detailed information, secret in nature, may be furnished on a Computer Floppy. Schedule D3 describes the information and undertaking required to be submitted by the manufacturer or his authorised importer/distributor/agent with the application form for a registration certificate.
Schedule E&E1:	Schedule E has been omitted. Schedule E1 describes list of poisonous substances under the Ayurvedic, Siddha and Unani systems.
Schedule F,F1,F2,F3,FF:	Schedule F part I to Part XIIA were omitted Part XII B describes the requirements for the functioning and operation of a blood bank and / or for preparation of blood components. Part XIID describes the requirements for collection; processing, testing, storage, banking and release of umbilical cord blood derived stem cells. Schedule F1 is divided into parts. Part 1 describes about vaccines. Part 2 describes the antisera. Part 3- Diagnostic antigens which describes the Provisions Applicable to the Manufacture and Standardization of Diagnostic Agents (Bacterial Origin). Part 4 – General Schedule F2 describes the standards for surgical dressings. Schedule F3 describes the standards for umbilical tapes. Schedule FF describes the Standards for ophthalmic preparations.
Schedule G:	Describes the list of drugs which are mostly in hormonal in nature.
Schedule H&H1:	Schedule H describes list of substances (prescription) that should be sold by retail only on prescriptions of a registered medical practitioner. Schedule H1 describes the drugs which can be sold out in retail against prescription of registered medical practitioner only. This schedule contains mostly antibiotics and habit forming drugs.
Schedule I:	Schedule I has been omitted.
Schedule J:	Diseases and ailments which a drug may not purport to prevent or cure or make claims to prevent or cure. Disease under this schedule are AIDS, Angina Pectoris,Diabetes,Cancer,Blindness,Deafness,Fairness of skin, Improvement in height of children’s/adults, Obesity etc.
Schedule K:	The class of drugs and extent & condition of exemption from provisions of Drug and Cosmetic Act, 1940 & Rules 1945.
Schedule L&L1:	Schedule L has been omitted and Schedule L1 describes the good laboratory practices and requirements of premises and equipment's.
Schedule M:	The good manufacturing practices and requirements of premises, plant and equipment for pharmaceutical products. Part 1: Good manufacturing practices for premises and materials. Part 1A: Specific requirements for manufacture of sterile products, parenteral preparations (small volume injectables and large volume parenterals) and sterile ophthalmic preparations. Part 1B: Specific requirements for manufacture of oral solid dosage forms (tablets and capsules). Part 1C: Specific requirements for manufacture of oral liquids (syrups, elixirs, emulsions and suspensions). Part 1D: Specific requirements for manufacture of topical products , i.e. external preparations (creams, ointments, pastes, emulsions, lotions, solutions, dusting powders and identical products). Part 1E: Specific requirements for manufacture of metered-dose-inhalers (MDI). Part 1F: Specific requirements of premises, plant and materials for manufacture of active pharmaceutial ingredients (bulk drugs). Part 2: Requirements of plant and equipment Schedule M1 describes the good manufacturing practices and requirements of premises, plant and equipment for homoeopathic medicines. Schedule M2 describes the requirements of factory premises for manufacture of cosmetics. Schedule M3 describes the quality management system –for notified medical devices and in-vitro diagnostics.
Schedule N:	The list of minimum equipment for the efficient running of a pharmacy.
Schedule O:	Describes the standard for disinfectant fluids. Part 1: Provision applicable to black fluids and white fluids Part 2: Provisions applicable to other disinfectant fluids.
Schedule P&P1:	Schedule P describes the life period of drugs. Schedule P1 describes the pack size of drugs.
Schedule Q:	Describes the list of dye, colour and pigments. Part 1: List of dyes, colours and pigments permitted to be used in cosmetics and soaps. Part 2: List of colours permitted to be used in soaps.
Schedule R&R1:	Schedule R describes the standards for condoms made of rubber latex intended for single use and other mechanical contraceptives. Schedule R1 describes the Indian Standards laid down from time to time by the Bureau of Indian Standards for medical devices.
Schedule S:	Describes the standards for Cosmetics Standards laid down from time to time by the Bureau of Indian Standards.
Schedule T:	Describes the good manufacturing practices for Ayurvedic, Siddha and Unani medicines.
Schedule U&U1:	Schedule U describes the particulars shown in manufacturing records of drugs. Schedule U1 describes the particulars shown in manufacturing record of cosmetics.
Schedule V:	Describes the standards for patent or proprietary medicines.
Schedule X:	Describes the list of habit forming and narcotic drugs.
Schedule Y:	Describes the requirements and guidelines for permission to import and / or manufacture of new drugs for sale or to undertake clinical trials.
Schedule Z:	Proposed.

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Emergency use authorizations (EUAs)

EMERGENCY USE AUTHORIZATIONS (EUAs)

Emergency use authorizations (EUAs) are one of several tools USFDA is using to make important medical products available quickly on a public health emergency.

 Under section 564 of the Federal Food, Drug, and Cosmetic Act (FD&C Act), the FDA commissioner may allow unapproved medical products or unapproved uses of approved medical products to be used in an emergency to diagnose, treat or prevent serious or life-threatening diseases or conditions caused by CBRN threat agents when there are no adequate, approved and available alternatives.

EUA process is different than full approval procedure, because in some emergency situation, agency cannot wait for all the evidence need for new drug approval. Instead the FDA evaluates the options very quickly using the evidence that is available and carefully balances any known or potential risks these unproven products with any known or potential benefits to the public of making them available during the emergency.

Abbreviations

CBRN - 'CBRN' is the abbreviation commonly used to describe the malicious use of Chemical, Biological, Radiological and Nuclear materials or weapons with the intentions to cause significant harm or disruption.

Suitability Petitions for ANDAs

An ANDA suitability petition is a petition (request) to FDA to permit the filing of an ANDA for a drug that differs from the RLD.  Certain differences between a reference listed drug (RLD) and a proposed generic drug product may be permitted in an abbreviated new drug application (ANDA) if these differences are the subject of an approved suitability petition submitted under section 505(j)(2)(C) of the Federal Food, Drug, and Cosmetic Act, and pursuant to 21 CFR 314.93.  An applicant may submit a suitability petition to the FDA requesting permission to submit an ANDA for a generic drug product that differs from an RLD in its: route of administration, dosage form  (e.g., change from tablet to capsule),  strength, (Congress permitted this type of change but, since the passage of Hatch-Waxman and the advent of the petition process, FDA has not approved this type of change to date because it almost always raises some question of safety or efficacy.) or if it has one different active ingredient in a fixed-combination drug product. An ANDA citing a suitability petition that has not been approved will not be received for review because the application lacks a legal basis for the submission. A generic applicant cannot submit an ANDA for such a product until FDA has approved the related petition. The grounds for FDA approval of such a petition are set out in 21 CFR 314.93(e). The determination that an ANDA will be approved is not made until the ANDA itself is submitted and is reviewed by the Agency. The Food and Drug Administration (FDA) will approve a suitability petition unless, among other reasons, one of the following occurs: 1.            FDA determines that the safety and effectiveness of the proposed change from the reference listed drug (RLD) cannot be adequately evaluated without data from investigations that would be beyond the scope of what may be required for an ANDA. 2.         A drug product is approved in a new drug application for the change requested in the suitability petition. 3.      The suitability petition requests changes to a drug product that trigger the need for pediatric studies under the Pediatric Research Equity Act (Public Law 108-155) to assess the safety and efficacy of that drug product in a relevant pediatric subpopulation that would not be waived by FDA, which renders the proposed product ineligible for approval in an ANDA. 1 FDA will refuse to receive an ANDA citing to a pending suitability petition (or to a suitability petition that was denied) because that ANDA would lack a legal basis for submission. FDA’s office of generic drugs (OGD) is responsible for review of suitability petition requests. FDA’s will approve or deny an ANDA suitability petition no later than 90 days after its submission.

Key Words

ANDA Suitability Petitions/ Petitioned ANDA