The European Medicines Agency (EMA) has recently issued a Q&A guidance document detailing how the principles of good manufacturing practice (GMP) should be applied to the manufacture of starting materials of biological origin for advanced therapy medicinal products (ATMPs).
The guidance defines ATMP starting materials as “all the materials from which the active substance is manufactured or extracted”. Since there are no GMP requirements for ATMP starting materials, only for ATMP active substances and finished products, the Q&A is not intended to set out new GMP requirements but rather to guide manufacturers on what GMP principles (from Part IV of the European Union’s GMP Guidelines) apply to ATMP starting materials and how to implement them.
Where vectors, plasmid and linear DNA templates are used as starting materials, the manufacturer should employ a risk-based approach (RBA) to identify the applicable sections of Part IV of the GMP. This also applies to the QC testing site.
The document includes a non-exhaustive list of risk factors to consider when employing an RBA:
- Transmissible spongiform encephalopathy
- Potential for viral contamination and cross contamination with other vectors or other genetic material
- Replication competent virus (in case of replication-deficient viral vector). It should be demonstrated the absence of formation of replication competent virus at the level of the viral production system used
- Potential for microbiological (e.g. Mycoplasma) or endotoxin/pyrogen contamination
- Potential, in general, for any impurity originating from the raw materials, or generated as part of the process and carried over
- Sterility assurance for materials claimed to be sterile
- Potential for any impurities carried over from other processes, in absence of dedicated equipment and/or facilities (for instance residual DNA (antibiotic resistance gene, residual DNA from potentially tumorigenic cell lines etc.), substance of animal origin, antibiotic etc.)
- Environmental control and storage/transportation conditions including cold chain management if appropriate
- Supply chain complexity and integrity of packages.
Click here to view the guidance in full.