PIC/S Opens Consultations on Manufacturing ATMPs, Biological Medicinal Substances

The Pharmaceutical Inspection Co-operation Scheme (PIC/S) is seeking comments on revisions to two parts of its GMP Guide (Annex 2A and Annex 2B) that deal with the manufacture of advanced therapy medicinal products (ATMPs) and biological medicinal substances and products for human use.

PIC/S explains that draft Annex 2A accounts for international developments in the regulation of ATMPs, with particular attention to the European Commission guideline on GMP for ATMPs, while addressing concerns related to patient safety and the proportionate regulation of ATMPs.

“Although one of the objectives of this present revision was to prepare a document that would stand for several years the field is quickly changing; it is recognised that amendments may be necessary to accommodate technological change, to clarify uncertainty or to specifically recognise important alternatives,” the draft Annex 2A says.

The document is divided into two parts related to the manufacture of ATMPs, “from control over seed lots and cell banks through to finishing activities and testing,” and another part on further guidance for specific types of ATMPs and substances.

The consultation poses a number of questions, including: “Considering the length of time that some advanced therapy investigational medicinal products (ATIMP) could be in clinical trial phase; is there a need to include requirements to periodically perform a Product Quality Review proportionate to the development stage? Currently, product quality reviews are not required for medicinal products in a clinical trial phase.”

PIC/S also seeks views on working environment requirements when processing is not performed in a closed system. “Section 3.13 of Annex 2A presents a PIC/S proposal. These expectations align the same requirements expected for the manufacture of sterile medicinal products but allow for an exception-based system if authorised by the competent authority,” the consultation says.

The consultation also seeks comment on a PIC/S proposal when certain manufacturing activities must be extended into hospitals as part of decentralized or point-of-care manufacturing.

And it seeks views on the expectations specified when the release of a product batch may be in the best interest of a patient but it does not comply with specification. Novartis previously supplied some of out-of-specification doses of its CAR-T drug Kymriah. Further questions posed by PIC/S deal with equipment used in a hospital ward or theater, and the control of starting materials, among others.

PIC/S notes that part of the consultation is meant to take into consideration how harmonized international GMP standards can help to facilitate manufacturing of these products, especially in consideration of the increasing amount of manufacturing that occurs across borders and in non-traditional manufacturing settings.

The other document, Draft Annex 2B, is the revised version of Annex 2 for biologics (excluding ATMPs). This annex contains supplementary guidance on the manufacture of biological active substances and medicinal products, "from control over seed lots and cell banks through to finishing activities and testing," as well as a section on further guidance on certain types of biological active substances and medicinal products.

The consultation period ends on 20 December.

Focused stakeholders consultation on revised draft PIC/S GMP Guide Annex 2A (Manufacture of Advanced Therapy Medicinal Products for Human Use) and Annex 2B  (Manufacture of Biological Medicinal Substances and Products for Human Use)