EMA Issues Regulatory Requirements for Gene Therapy Developers
The European Medicines Agency has issued draft guidance describing the types of evidence developers of gene therapies need to support marketing authorization — saying very small firms, which comprise the majority of this segment, may not be familiar with the regulatory process.
All starting materials should be proven genetically stable, with tests conducted on virus seed banks, mammalian cell banks, RNA or DNA vectors and plasmids, bacterial cell banks and complexing materials. Data should demonstrate the quality and consistency of all raw materials used in production, the May 21 draft says.
Further, tests on the product’s specifications should cover appearance, identity and integrity, quantity, potency, impurities, extraneous agents and physiochemical properties.
The manufacturing process should be set up to minimize the risks of microbiological contamination. Developers should justify their quality control strategy and critical manufacturing steps, the EMA says.
For nonclinical development, developers should evaluate the gene therapy’s effect on physiological functions, including the reproductive system, as well as its toxicity and immunogenicity.
The absence of control groups in clinical studies should be justified. If randomized controlled clinical trials are not feasible, alternatives may be accepted — for example, well documented natural history data or using patients as their own control, the EMA says.
Developers should perform conventional pharmacokinetic studies. For treatment of genetic diseases using gene correction or addition strategies, the therapeutic effects of the product on different causative gene mutations should be investigated, the EMA says.
Design of long-term studies should focus on the sample size, sample treatment, analytical methods and endpoints to maximize evidence, particularly when invasive methods are used, the agency adds. This is especially important when the gene therapy is meant to provide a life-long treatment effect.
The updated guidance will replace a 2001 version, Note for Guidance on the Quality, Preclinical and Clinical Aspects of Gene Transfer Medical Products.
Comments on the draft are due Aug. 31. Read Guideline on the Quality, Non-clinical and Clinical Aspects of Gene Therapy Medicinal Products at www.fdanews.com/5-15-EMA-GeneTherapies.pdf. — Jonathon Shacat