During June of 2016 the European Commission opened a three-month consultation on proposed Good Manufacturing Practice (GMP) guidance for Advanced Therapy Medicinal Products (ATMP). The purpose of the consultation was to allow academic groups, CMOs and commercial developers of ATMPs to provide feedback on the proposed ATMP-specific manufacturing rules. Perhaps, surprisingly for the European Commission, the draft guidance document received a lukewarm reception from the industry. The commission’s aim was to develop ATMP-specific GMP standards which would expedite the access to these products by clarifying the guidelines associated with manufacturing them. However, notable responses from the Alliance for Regenerative Medicine and PIC/S (Pharmaceutical Inspection Co-operation Scheme) have questioned some of the details contained in the guidance document.

One of the starkest rebuttals of the guidance document came from PIC/S in an open letter, PIC/S is not alone with its concerns regarding the possibility of having separate GMP standards for ATMPs and non-ATMP products.  Several QPs have questioned the logic associated with this potential scenario.  Furthermore, there is discontent regarding the potential for lowering GMP standards for first into man manufacturing of ATMP products. Another key observation was the missed opportunity to develop a pan-European approach to interpretation of the EU’s directives associated with the collection and handling of blood, tissues and cells. Currently, European Union member states are allowed some discretion when interpreting and enforcing the details of the European Union directives. For example, the German interpretation of the Blood Directive requires QP certification of blood products whereas other European countries do not necessary require this as part of product release. This may seem like a minor detail, but with the current preference for centralised manufacturing strategies for autologous therapies, a single European approach to the way in which patient-specific starting materials are managed would have been welcomed by the Cell Therapy Industry.

The guidance document also addresses traceability, which is a key attribute to a successful autologous supply cycle.  Indeed, the requirements must not be overlooked for allogeneic therapies; for both autologous and allogeneic products records associated with the collection of starting materials and manufacture must be maintained for thirty years (which agrees with current EU directives), this contrasts with the FDA’s requirement for ten years’ record retention. Interestingly, the proposed new guidance allows for traceability records to be kept outside of manufacturing batch records providing that these are auditable and inextricably linked to the manufacturing records. Furthermore, and in contrast to some practices for autologous supply outside of the EU, the draft guidance details that traceability must be recorded up to delivery of the therapy to the patient; some autologous treatments in North America have only been traced to delivery at the hospital/treatment centre. TrakCel’s software platform has been used to provide full traceability throughout supply cycles of ATMP products, demonstrating both chain of identity and chain of custody from collection of starting material to the treatment of patients and facilitates long-term, compliant, data storage and controlled access to records.

The uncertainty regarding borderline ATMP products could be very challenging, if two separate GMP strategies exist, manufacturers must be sure of their product classification, in order to apply the correct GMP standards during manufacture. However, the Committee for Advanced Therapies (CAT) will be able to determine if the investigational product meets the scientific criteria which qualifies it for ATMP status.

The complexity associated with the regulatory environment could become exacerbated following the UK’s exit of the European Union, although it is unlikely that the UK would turn its back on the existing legislation framework, there are no certainties regarding QP certification by a UK-based QP being accepted by mainland-Europe QPs once the UK has waved goodbye to its membership status. Whatever the case, detailed scrutiny will be given to the outcomes of the guidance document and the protracted UK-EU Brexit negotiations.

Consultation Document Good Manufacturing Practice for Advanced Therapy Medicinal Products

Reflection paper on classification of advanced therapy medicinal products

Standards of quality and safety for the collection, testing, processing, storage and distribution of human blood and blood components

Standards of quality and safety for the donation, procurement, testing, processing, preservation, storage and distribution of human tissues and cells