GENERIC DRUGS FILING REQUIREMENTS - US VS EUROPE

GENERIC DRUG FILING REQUIREMENTS – US VS EUROPE

A generic drug is identical--or bioequivalent--to a brand name drug in dosage form, safety, strength, route of administration, quality, performance characteristics and intended use.  Although generic drugs are chemically identical to their branded counterparts, they are typically sold at substantial discounts from the branded price. 

Generic Drugs are approved under ANDA (Abbreviated New Drug Application) in USA and MAA (Marketing Authorization Application) in Europe.

Abbreviated New Drug Application - USA

New drugs, like other new products, are developed under patent protection.  The patent protects the investment in the drug's development by giving the company the sole right to sell the drug while the patent is in effect.  When patents or other periods of exclusivity expire, manufacturers can apply to the FDA to sell generic versions.  The ANDA process does not require the drug sponsor to repeat costly animal and clinical research on ingredients or dosage forms already approved for safety and effectiveness.  

An abbreviated new drug application contains data, which when submitted to FDA’s ‘Center for Drug evaluation and research’ (CDER), office of generic drugs, provides for review and ultimate approval of a generic product. Once approved, the applicant may manufacture and market generic drug product to provide a safe, effective, low cost alternative to American public.

Marketing Authorization Application (Europe)

In Europe drug approval process is regulated by European Agency for evaluation of medicinal products (EMEA),this agency gives Marketing authorization in European union.

Pharmaceutical companies can use 4 approval procedures to market their pharmaceuticals.

·       A centralized or

·       Decentralized or

·       Mutual Recognition

·       National Procedure

Centralized Procedure: The centralised procedure allows the marketing of a medicine on the basis of a single EU-wide assessment and marketing authorisation which is valid throughout the EU. Pharmaceutical companies submit a single authorisation application to EMA. The Agency’s Committee for Medicinal Products for Human Use (CHMP) or Committee for Medicinal Products for Veterinary Use (CVMP) then carries out a scientific assessment of the application and gives a recommendation to the European Commission on whether or not to grant a marketing authorisation. Once granted by the European Commission, the centralised marketing authorisation is valid in all EU Member States.It Allows a pharmaceutical company to market its pharmaceutical products in all 30 EEA countries (27 EU Member States plus Iceland, Liechtenstein and Norway) (Applicant need not to obtain separate approvals for each member state).

The use of the centrally authorised procedure is compulsory for most innovative medicines, including medicines for rare diseases.

National Procedure: The national procedure only one member state is involved. The documents submitted to an authority are very specific to that particular authority and evaluation of the application is carried out by the same member state. The evaluation time for an application for a national marketing authorization is 210 days from the receipt of the application.

When a company wants to authorise a medicine in several Member States, it can use one of the following procedures:

Decentralised procedure: Where companies can apply for the simultaneous authorisation of a medicine in more than one EU Member State if it has not yet been authorised in any EU country and does not fall within the scope of the centralised procedure.

 Mutual-recognition procedure: Where companies that have a medicine authorised in one EU Member States can apply for this authorisation to be recognised in other EU countries. This process allows Member States to rely on each other’s scientific assessments.

COMPARISON OF REGULATORY REQUIREMENT BETWEEN US AND EUROPE

Particulars	US	Europe
General Information
Regulatory Agency	USFDA	EMA National Agencies
Application	IND NDA ANDA BLA	MAA [Article 8(3) Full Application, Article 10(1) Generic, Article 10(3)Hybrid(mixed)Application, Article 10(4) Biosimilars, Article 10(a) well established use, Article 10(b) Fixed combination products, Article 10(c) Informed consent/Duplicate]
Registration Process	One Registration Process	Multiple Registration Process Ø Centralized Procedure (European Community) Ø Decentralized Procedure (Atleast 2 member states) Ø Mutual Recognition Procedure (Atleast 2 member states) Ø National Procedure (1 member states)
Approval Timeline	10 Months (Standard review)	210 Days –CHMP opinion Centralized procedure 210+67(EC Decision: Granting/Refusing)=277 days CHMP Opinion (Ensure that medicinal  products have a positive risk - benefit balance in favour of patients/users) EC Decision – Granting/Refusing
Administrative Part
Debarment Certification	Applicable	Not Applicable
Agent letter of appointment	Applicable	Not Applicable
Environmental  Assessment Report	Applicable	Applicable
Pharmacovigilance	Not Applicable	Applicable
Specifying Medicinal product name in Braille format	Not Applicable	Applicable
Quality
Number of batches	3 batches	3 batches
Container closure  DMF Requirements	Applicable	Not applicable
API DMF Requirements	DMF (Type II)	ASMF/CEP
Number of API lots for Submission batches	A minimum of two lots of the drug substance should be used to prepare the three primary batches of drug product.	No specific requirements
Executed BMR	Applicable (Part of Dossier Filing)	Not part of Dossier filing
Blank (Commercial ) BMR	Applicable (Part of Dossier Filing)	Not part of Dossier filing
Stability Data Requirements	Minimum 6 Month data – Accelerated, Long term & Intermediate (if applicable)	Minimum 6 Month data – Accelerated, Long term & Intermediate (if applicable)
Container orientation For primary batches of liquids, solutions, semi-solids, and suspensions	Product should be place in worst case and non-worst case scenarios (Up right/Inverted or Vertical/Horrizontal)	No such requirements
Antimicrobial Effectiveness testing (AET) Requirements	Applicable (One Batch)	Applicable (One Batch)
Special stability studies conducted to confirm the quality of the constituted drug products (for example, parenterals and/or powders reconstituted with diluents and/or drug admixtures)	Applicable (One Batch)	Applicable (One Batch)
API DMF requirements	Type – II DMF	CEP ASMF
Miscellaneous
Initial Screening	Applicable (60 Days)	Screening will be done only for administrative part
Fee Requirements	Applicable	Applicable
Faster Approval Pathways	Accelerated Approval Priority Review Fast Track Break through Therapy	Accelerated Approval Conditional Marketing Authorization
Goal Date	Applicable	Not applicable
Time Slot booking Requirements for dossier filing	Not Applicable	Applicable
Types of Queries	IR/DRL/CRL	Day 50/Day 100/Day 120/Day 180

Key Words eCTD requirements for US and EU filings/Dossier, ANDA, MAA, EU, Mutual Recognition, Centralized procedure, Decentralized procedure, National Procedure

This post is last updated on 6th April 2020)