On 22 November 2017, the European Commission adopted new guidelines on Good Manufacturing Practice (GMP) specific to Advanced Therapy Medicinal Products (ATMPs). ATMP manufacturers must ensure compliance with these guidelines no later than 22 May 2018.
The guidelines seek to reflect the rapid technological and medical advancements being made in the field of ATMPs (i.e. gene therapies, somatic cell therapies and tissue engineered products), such as decentralised manufacturing for autologous products, automated production, outsourced reconstitution, and gene editing technologies such as CRISPR and immunomodulators. Currently, these new technologies must comply with the general GMP guidelines set out in Volume 4 of The rules governing medicinal products in the European Union. However, these products are often developed in an academic or hospital setting under quality systems different to those typically required for the manufacture of conventional medicinal products.
The guidelines prescribe a risk-based approach which requires manufacturers to design organisational, technical and structural measures appropriate to the specific risks of the product and the manufacturing processes used. The evaluation of these risks and effectiveness of these processes, including the controls and mitigation measures, should be based on current scientific knowledge and the manufacturer’s accumulated experience.
The guidelines specify a number of precautions and checks which aim to improve the integrity of the finished product, and enhance the detection of contaminants when manufacturing using inherently variable starting materials such as human tissues and cell lines. For example, ATMP manufacturers should establish specifications for the starting materials which should be agreed with the suppliers. These specifications should cover aspects of the production, testing and control, storage, and other aspects of handling and distribution as appropriate. Further, the risk of contamination of the starting materials as they move through the supply chain must be assessed.
The guidelines also require ATMP manufacturers to comply with more familiar GMP principles such as having an adequate number of personnel with appropriate qualifications and adequate practical experience relevant to the intended operations, and ensuring that their premises are designed to minimise the opportunity for cross-contamination, the risk of errors and adverse effects on the quality of products. Equipment must be fit for purpose and documentation systems must be designed to control, monitor and record all activities which may affect the quality of the medicinal products. Further, consistent with Article 15 of the ATMP Regulation, traceability records must be kept for a minimum of 30 years after the expiry date of the product.
The guidelines are not intended to place any restraint on the development of new technologies. Whilst they do include some additional obligations for ATMP manufacturers, such as the establishment of starting material specifications, by providing a risk-based approach they also provide autonomy and flexibility in how to ensure compliance in rapidly developing fields.