Pharma Inspection Co-operation Scheme Criticizes Plan to Lower GMP Requirements for ATMPs

The regulatory group known as the Pharmaceutical Inspection Co-operation Scheme (PIC/S) said in a letter released this week that it is “unanimously concerned” about the public health and safety impact of a new European Commission guideline that would lower good manufacturing practice (GMP) requirements for advanced therapy medicinal products (ATMPs).

"By lowering the GMP requirements for ATMPs, the European Commission is not only exposing patients to an increased risk to their health; it is also engaging its individual and collective responsibility for any health incident (and related court action) that lower ATMP standards may occasion. We would like you to duly ponder this aspect," the letter sent on 24 February says.

The PIC/S Committee, which is comprised of regulators including the US Food and Drug Administration, Health Canada, Swissmedic and dozens of others, is also concerned that due to the European Commission’s proposal, which stopped accepting comments in September 2016, the PIC/S GMP Guide and the EU GMP guideline will no longer be equivalent.

"Your decision to amend Annex 2 and repeal Annex 13 of the EU GMP Guide is a serious setback in terms of co-operation between the EU and PIC/S. It is very unfortunate that under your leadership the process of GMP harmonisation between the EU and PIC/S GMP Guides has resulted in a divergence that may be difficult to reconcile in the future," notes the letter signed by PIC/S Chairman Paul Hargreaves of the UK’s Medicines and Healthcare Regulatory Agency and Deputy Chairman Boon Meow Hoe of Singapore’s HSA.

With its focus on continued harmonization of GMP requirements across its members’ borders, the letter notes that in addition to patient health risks with a lower bar, there are liabilities that the commission may be newly exposed to if it finalizes its draft guideline.

Other Comments

In terms of the 53 others weighing in on the ATMP GMP consultation, the commission said in a summary of the comments that the approach described “was supported by the majority of the respondents.”

However, a “significant number” of comments also called for further changes, particularly on:

• “Premises: The principle of dedicated production areas for ATMPs was deemed too stringent. Additional guidance/clarification was requested regarding the use of closed systems and biosafety cabinets, as well as regarding the handling of infected materials. A number of stakeholders also considered that it should be possible that closed systems are used in a non-classified environment.
• Aseptic manufacturing: The requirements on aseptic process validation (so-called ‘media fill test’) was the topic that received most comments. Demands for adaptation to the specific characteristics of ATMPs were shared by academia, SMEs and industry. It was generally perceived that the standard requirements for parenteral products are not fit for ATMPs, in particular in cases where each unit is subject to sterility testing prior to the administration to the patient. Various proposals for adaptation were made.
• Requirements of the on-going stability program in Section 12: It was considered that a pragmatic approach similar to the principles outlined for process validation should apply also to the on-going stability program.
• Certification by the Qualified Person (‘QP’): considering that – for many ATMPs– each unit constitutes a separate batch and taking into account the new manufacturing models that are emerging, additional flexibilities were asked regarding the role of the QP.”

PIC/S Letter to European Commission