Advanced Therapies (ATMPs)

ATMP classification is a non-binding, optional procedure offered by the EMA to confirm whether a product falls within the scope of Advanced Therapy Medicinal Products under Regulation (EC) No 1394/2007, Article 17. The classification determines whether the product is:

GTMP -  gene therapy medicinal product (GTMP),

sCTMP - somatic cell therapy medicinal product (sCTMP),

TEP -  tissue-engineered product, or

A combined ATMP.

Key Points:

Submit a classification request before scientific advice or MAA preparation.

CAT issues an opinion within 60 days.

Helps clarify regulatory pathway and dossier expectations early.

Following Regulation EC No. 726/2004, Scientific advice gives the opportunity to developers to align their development plans with EU expectations, particularly for complex or novel therapies like ATMPs. 

Key Points:

Optional but highly encouraged for ATMPs, especially SMEs and early-stage developers.

Covers quality (CMC), non-clinical, clinical, and regulatory strategy.

For products with orphan designation, protocol assistance is free or reduced-fee.

According to Regulation (EC) No 1901/2006, all MAAs for new medicinal products must include an agreed PIP or a waiver. This is especially relevant for ATMPs intended for rare genetic diseases, many of which affect paediatric populations.

Key Points: 

Submit PIP early (ideally at the end of the preclinical phase).

EMA’s Paediatric Committee (PDCO) assesses and issues decisions.

Waivers may apply if the condition does not occur in children.

 Timeline: ~120 days (may involve clock stop)

Manufacturing of ATMPs must comply with EU Good Manufacturing Practice ( GMP) standards, specifically: EudraLex Volume 4, Annex 2 (Biological and ATMP-specific GMP) & EudraLex Volume 4, Part IV (Guidelines for GMP for ATMPs).

GMP compliance is verified through inspections by EU competent authorities, typically before or during the MAA process.

The application must follow the Common Technical Document (CTD) format, as defined in Commission Directive 2003/63/EC and Annex I of Directive 2001/83/EC, and must be submitted in eCTD format. Compiling Modules 1–5, including data on: Quality (CMC, GMP certification), Non-clinical (pharmacology/toxicology), and Clinical (safety/efficacy, GCP compliance).

Key Points:

Environmental Risk Assessment (ERA) for gene therapies (per Directive 2001/18/EC)

Risk Management Plan (RMP)

Long-term follow-up plan (especially for GTMPs)

CAT classification opinion (if obtained)

After submission, EMA performs validation to confirm the application is complete.

Missing or incorrect documents result in a clock stop. Validation phase: typically 30 days.

The scientific evaluation is a 210-day clock (excluding clock stops for questions). It involves:

CAT (Committee for Advanced Therapies) drafts a scientific recommendation specific to the ATMP.

CHMP (Committee for Medicinal Products for Human Use) adopts a final opinion, which may follow or diverge from CAT’s recommendation.

Two major List  of Questions (LoQs) are typically issued during the review:

1. Day 80 (major objections)
2. Day 120 (minor objections)

The applicant may be invited to give an oral explanation to CAT/CHMP to clarify responses to critical objections.  Often used for innovative or borderline products.

CHMP issues a final opinion, followed by a European Commission decision within ~67 days.

Approval results in a single marketing authorisation valid in all EU/EEA Member States.

For ATMPs, post-marketing activities are critical due to the potential for long-term or delayed adverse events, especially in gene therapies.

Long-term safety follow-up (e.g., 5–15 years) may be required.

Implementation of Risk Management Plan (RMP) and Post-Authorisation Safety Studies (PASS).

Real-world evidence (RWE) is often required as a condition of approval.