13/14 December 2022
Especially in the field of Advanced Therapy Medicinal Products (ATMPs), developments are progressing rapidly. These have also been taken into account by the regulatory authorities in many cases, e.g. with the publication of corresponding guidelines, which are intended to provide assistance and support for development, marketing authorisation and GMP-compliant manufacturing. Nevertheless, new problems, questions and ambiguities often arise, especially in new, rapidly developing areas. Many of these questions also reach the European and national authorities.
Especially with the publication of a "stand-alone" guideline for the implementation of GMP in the field of ATMP, many questions have arisen. The EMA has now published the "Questions and answers on the principles of GMP for the manufacturing of starting materials of biological origin used to transfer genetic material for the manufacturing of ATMPs".
In its introductory sentences to this Q&A document, the EMA states that a GMP certificate is not required for manufacturing and testing sites of starting materials for ATMPs, but that the principles of GMP are certainly relevant for certain starting materials of biological origin. These include, for example, linear DNA used as a template for ex vivo transcription into mRNA, plasmids used to generate viral vectors and/or mRNA, and vectors used to transfer genetic material for the manufacture of ATMPs. While the new document does not impose any new regulatory requirements, it does provide guidance on how the requirements of the existing guidelines can be implemented in practice.
To this end, a methodology is described for identifying minimum requirements in the areas of quality management system, risk management, product development, production and quality control in order to define the principles of GMP for the respective starting materials. The assessment of the minimum requirements is carried out by the ATMP manufacturer or the marketing authorisation holder or importer into the European market. It is essential that the manufacturer has access to information on the relevant starting materials in order to determine their impact on the quality, safety and efficacy profile of the finished medicinal product. Accordingly, there should be appropriate contracts or technical agreements between the parties involved, such as the manufacturer, marketing authorisation holder, importer, distributor, etc., which define the obligations in the given process, especially with regard to the starting materials. In doing so, the EMA writes: "In defining the GMP principles applicable to starting materials, it is necessary to recognise a certain degree of flexibility for ATMP at the investigational stage based on a risk-based approach (RBA), especially in the early phases of clinical trials (Phase I and Phase I/II), due to the often incomplete knowledge of the product as well as the evolving routines."
Read more directly in the "Questions and answers on the principles of GMP for the manufacturing of starting materials of biological origin used to transfer genetic material for the manufacturing of ATMPs"