Stakeholders Want Elaboration on New EU GMP Annex 15 Mandates

Drugmakers are asking the European Commission to clarify new requirements for factory acceptance and site acceptance testing, including when it is okay to perform only the factory tests.

The comments, in response to a public consultation on revisions to Annex 15 of the EU’s good manufacturing practice guideline, focus largely on a provision in the annex that would allow companies to perform certain tests on equipment at the factory stage without having to repeat them on site if they can show that the items won’t be impaired by transportation or installation.

According to the European Federation of Pharmaceutical Industries and Associations, the Commission needs to clarify that FAT and SAT are not always part of the qualification process, but could be recommended preliminary or complementary steps that are leveraged as part of overall qualification.

French industry association LEEM suggested that the language be changed to state that FAT and SAT support the qualification process, but aren’t strictly a part of it.

The trade group also took issue with a requirement that design qualification be performed in all cases, noting there are cases where design qualification can be confirmed later in the validation process and, therefore, a separate design qualification should not be required.

“Since DQ should be not required for all cases, a risk-based approach including complexity and/or criticality of the system could be applied,” LEEM said.

ISPE noted that current best practice for equipment qualification is to use the data obtained from FAT and SAT to support qualification activities. Due to utility constraints at vendor sites, it’s usually the SAT functional testing that offers the greatest opportunity to support the qualification effort, the group said, adding the draft annex understates the significance of SAT in industry best practices.

EFPIA urged the Commission to clarify that Annex 15 applies to qualification of analytical equipment as well as conventional equipment, noting that both the International Society for Pharmaceutical Engineering and ASTM International describe these processes and they are widely accepted by industry.

The new requirements — which take effect Oct. 1 — call for drugmakers to use a risk-management approach to qualify and validate manufacturing processes that cover the lifecycle of their drugs or active pharmaceutical ingredients. Among the major changes, retrospective validation will no longer be accepted, but firms may use data from outside sources provided the approach was justified and controls were in place when the data was acquired.

The Parenteral Drug Association wants the Annex 15 to include definitions for validation and qualification — similar to those used in ICH Q7 — to avoid ambiguity and confusion. Under that scenario, “qualification” would apply to supporting systems and processes such as utilities and transportation, while “validation” would apply to the manufacturing process and analytical methods.  

Gilead Sciences criticized the guideline’s transportation requirements, saying a requirement that materials be transported according to conditions defined in the marketing authorization, product specification file or by the manufacturer conflicts with current good distribution practices. GDPs require that storage conditions for drugs be maintained during transportation within the limits defined by the manufacturer on the outer packaging, the drugmaker said.

Regulators consistently emphasize the labeled storage conditions and disregard the limits that may be included in the products’ marketing authorization, Gilead added.

EFPIA and the European Generic Medicines Association urged the Commission to hold a public workshop to clarify the regulatory expectations around Annex 15 before finalizing the guidance.

The Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-operation Scheme announced in April that it was adopting Annex 15, meaning retrospective validation will no longer be accepted by regulators in PIC/S member countries as well.

The full list of stakeholder comments is available at www.fdanews.com/05-19-15-Comments.pdf. — Kellen Owings