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Summary of the EMA draft guideline on safety & efficacy follow-up and risk management of ATMPs

In January 2018 the EMA released for consultation the Guideline on safety and efficacy follow-up and risk management of Advanced Therapy Medicinal Products (Rev.1). This guideline is still in draft but is broadly taken as reference.

The guideline covers to the experience gained with the authorization of ATMPs and to define their risks and risk minimisations measures. This guideline also provides guidance on methodology in order to design post-authorisation S&E follow-up studies.

Two documents from the Marketing Authorisation Holder (MAH) are directly impacted by this guideline:

  • Pharmacovigilance System Master File (PSMF).
  • Risk Management Plan (RMP).

Safety and efficacy concerns for ATMPs

  • Risks to patients in relation to quality characteristics, storage and distribution of the product:
    • Transmission of diseases: viral, bacterial, etc. depending on the origin of cells/tissues.
    • Tumorigenicity: manufacturing process may affect the differentiation capacity of the cells.
    • Treatment failure: Risk related to the storage, transport…, this could impact on the activity of the ATMP.
  • Risks related to patient associated disease, or interactions with other medicinal products:
    • Immunogenicity (including anaphylaxis, graft rejection, hypersensitivity reactions, etc.).
    • Early and late consequences of homing, grafting, differentiation, migration and proliferation.
    • Infection with vectors used in gene therapy medicinal products.
    • Immunosuppression (clinical follow-up).
  • Risks to patients related to:
    • Reconstitution procedures: dosing errors.
    • Administration and re-administration procedures.
    • Persistence of the product in the patient.
  • Risks to healthcare professionals, care givers, and other close contacts and its risks to the environment.

Pharmacovigilance activities

For ATMPs, additional pharmacovigilance activities may be introduced to identify, characterise or quantify a safety hazard to measure the effectiveness of risk-management measures or to investigate missing information. The performance of pharmacovigilance activities include use of traceability data for surveillance purposes in the case of ATMPs that contain tissues and/or cells.

Risk minimization measures

For ATMPs the following additional risk minimisation measures could be needed:

  • The use of a controlled access programme by selecting accredited centres and adequately trained and experienced physicians might be necessary.
  • Educational programmes based on targeted communication could be developed to supplement the information in the SmPC and PL.

In addition, the risk minimization activity can be accompanied by specific tools to measure the effectiveness of risk minimization activities.

Efficacy and safety follow -up

ATMP developers should ensure that the patients enrolled in clinical trials (starting at phase I) or in compassionate use are appropriately followed-up to allow generation of long-term S&E data. The use of disease registries or other data sources for collecting long-term S&E data should be considered early in the development process so that appropriate plans are in place by the time the MA is granted.

Given the nature of some ATMPs and the characteristics of certain diseases being targeted by ATMPs, only limited efficacy data may be available at the time of the marketing authorisation application (e.g., slow dynamics of the disease and effects of the treatment, rare diseases, etc). Comprehensive evidence of efficacy, including for example maintenance of clinical benefit, evidence of benefit on long-term clinical outcomes and evidence of a cure may need several years of follow-up.

The guideline describes the objectives for long term follow-up for efficacy and safety based on the different types of ATMPs.

This is some of the information you need to know if you are interested in procedures for ATMPs. Nevertheless, we have launched a dedicated webpage to bring you the latest updates, guidance and developments. You can also follow us on LinkedIn.

We hope you find this useful and of interest. If you would like to discuss any of these updates with the team at REVIO, please get in touch.

If you want to know more, check out the guideline HERE!