On November 22, 2017 the European Commission published the first guideline for GMP for Advanced Therapy Medicinal Products which will come into force no later than May 22nd, 2018.
This is the first time the Commission publishes a consistent framework for GMP for ATMPs. The ATMP specific topics addressed in this guideline cover all the specific aspects of ATMPs and thus is a comprehensive guidance when preparing trials or the MAA for your product.
A broad array of topics is covered in the new guideline, e.g.:
- Production facilities
- Equipment, including validation
- Definition and testing of raw and starting materials
- Requirements for seed lots and cell banks
- Qualification and validation of production sites and equipment
- The role of the qualified person
- Quality control and Batch release
- Environmental control
How will this impact future projects?
The good news is that this is the first consistent document that connects all the aspects of GMP for the very diverse field of ATMPs. We can certainly think of products where the guidance is less practicable. However, the fact that there is a guidance out gives us insight in the way of thinking of the regulatory bodies in Europe and allows us to better prepare for inspection or submission of a CTA or an MAA. In special cases, e.g. when the guidance is less appropriate, companies still have the opportunity to discuss their individual approach to GMP for their product based on the guidance and the unique properties of the product.
Will this increase the hurdles for new ATMPs?
It certainly will raise the minimum standards as such standards have been set now and published as part of an official guidance document. On the other hand it takes out differences that we have seen so far between countries when inspecting sites or reviewing documentation. Therefore, it also levels the playing ground for the different parties and gives certainty to industry.
The principles for ATMP GMP are the same as for conventional (investigational) medicinal products. In this respect, the guideline does not introduce any new guiding principles or make market access more difficult.
Risk Based Approach
This guideline introduces the Risk Based Approach to the GMP area. With this approach the Commission wants to have a broader approach to GMP as this group of medicinal products is very diverse and the risk differ substantially between products. The responsibility for the identification of risks and the development of a mitigation strategy are with the manufacturer and should be based on an analysis of the potential implications for quality, safety and efficacy of the ATMP. The evaluation should include the complete manufacturing process from the initial starting materials until the final testing strategy and release specification. Safety should be built in the process and not be given by quality control afterwards. It must be an inherent property of the product.
Important point to consider is that this document gives guidance but also leaves the opportunity to deviate from the guidance given in those cases where it can be justified based the risk evaluation of the process and the properties of the final product.
In the detailed sections of the guideline, a lot of practical guidance is given on how to implement GMP in the manufacturing of ATMPs. This will certainly help manufacturers in improving their current site or setting up new sites. In this respect, the guideline is close to practice and good guidance for those in charge of these manufacturing facilities.
This new guidance provides a good basis for development plans for new ATMPs and helps to improve the status of those that have been approved already. This is a major step towards the future but certainly not the last one.
Frank Wierckx PhD, Exec. Director, Head Regulatory Affairs