Generics & Biologics

Regulatory Strategy: Biotech products must go through the Centralized Procedure (CP) as mandatory under Regulation (EC) No 726/2004.

Classification Check: Biotechnology products are defined under Annex of Regulation (EC) No 726/2004.

CP eligibility request: Mandatory - regardless of CP scope, mandatory, or optional.

Paediatric Investigation Plan (PIP): Mandatory — and can be complex for biotech products, with early engagement strongly advised.

CP Pre-submission meeting: Highly recommended — and can be invaluable for biotech products.

Scientific Advice: Highly Recommended - It is almost standard for biotech, especially if it's first-in-class.

EU GMP Certification: For both drug substance and drug product sites.

Cell Bank Certification: Master and Working Cell Banks must be fully characterized and tested for adventitious agents.

Process Changes Control: Biotech products require stringent change management — even small changes can affect the product.

Module 1: Standard, also, ensure Orphan Designation documents are included if applicable.

Module 2: Emphasize the comparability exercise if you are developing biosimilars.

Module 3 (Major Attention):

Extensive Characterization (physicochemical, biological activity, immunochemical properties).

Process Description and Validation are extremely critical — biotech processes are highly sensitive (cell culture, fermentation, purification, etc.).

Viral Safety Studies mandatory (Adventitious agents testing, viral clearance studies).

Module 4: Often includes immunogenicity studies in animals.

Module 5: Clinical focus on immunogenicity, PK/PD bridging studies, and comparative studies for biosimilars.

Mandatory Centralized Procedure for all biotechnology-derived products.

Advanced Therapies: If your product is a Gene Therapy, Somatic Cell Therapy, or Tissue-Engineered Product, you must apply via EMA's CAT (Committee for Advanced Therapies) evaluation.

Additional EMA Committees:

CHMP leads the biologic/biosimilar evaluation.

COMP (Committee for Orphan Medicinal Products) assesses orphan status.

Immunogenicity Assessment: EMA pays special attention to immune responses (antibody development against biologics).

The Commission Decision applies to the entire EU.

Orphan Status Confirmation at marketing authorization if applicable.

Pharmacovigilance: Biologics usually require specific additional monitoring.

Risk Management Plan (RMP): Must cover immunogenicity risks, loss of efficacy, and rare but severe side effects.

PSURs/PBRERs: It may be more frequent initially.

Post-Authorization Safety Studies (PASS) or Post-Authorization Efficacy Studies (PAES):
It can be imposed especially for advanced therapies.

Regulatory References: Article 28 of Directive 2001/83/EC & CMDh Best Practice Guides (BPGs)

Check eligibility: The Product must BE authorised in any EU/EEA Member State.

Choose a Reference Member State (RMS): The RMS will lead the scientific assessment. All other participating Member States are Concerned Member States (CMSs).

Pre-submission meetings with RMS and CMSs: Discuss regulatory strategy, procedural timelines, and specific data requirements.

Compile a full dossier in CTD format: Module 1 is region-specific and must include national-specific info (e.g., administrative data, translations, packaging mock-ups).

Modules 2–5 must be harmonized for all RMS and CMSs.

Submit the application simultaneously to all selected Member States in scope.

Each authority validates the application (typically 14 calendar days).

Missing documents may lead to a clock stop during validation.

RMS shares the Assessment Report (AR) and authorized product information to CMSs.

CMSs begin their review and may raise questions or concerns.

Day 50: CMSs provide comments to the RMS and the Applicant.

1. If CMSs raise objections, a clock stop is triggered by Day 50, and the Applicant must respond to all CMSs via the RMS. RMS may update the Assessment Report as needed.

By Day 90, CMSs must either accept the RMS's assessment and proceed to the MA grant.

Or refer to the CMDh if serious objections remain.

Applicant submits Final product information  translations and national administrative forms.

National MA is granted (within 30 days of the Agreement).