Industry Seeks Clarification on New EU GMP Mandates

Drugmakers are asking the European Commission to clarify new requirements for equipment used in the manufacturing process, including when it’s okay to test such equipment at the factory instead of on site.

The drugmakers’ 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 that would allow companies to perform certain tests on equipment as it is being manufactured without having to repeat tests once it’s delivered if they can show the items won’t be impaired by transportation or installation.

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.

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

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

Design Qualification

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

Instead, a risk-based approach including complexity and/or criticality of the system could be applied, LEEM says.

ISPE notes that current best practice for equipment qualification is to use the data obtained from FAT and SAT. Because of constraints at manufacturers’ sites, the SAT functional testing usually offers the greatest opportunity to support the qualification effort, the group says. Additionally, the draft annex understates the significance of SAT in industry best practices.

EFPIA urges 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 Parenteral Drug Association wants the Annex 15 to include definitions for validation and qualification — similar to those used in ICH Q7 — in an effort 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.

Transportation

Gilead Sciences criticizes 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 product’s outer packaging, Gilead notes. Regulators consistently emphasize the labeled storage conditions and disregard the limits that may be included in the products’ marketing authorization, the drugmaker adds.

Public Workshop Urged

EFPIA and the European Generic Medicines Association want 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 is adopting Annex 15, meaning retrospective validation will no longer be accepted by regulators in PIC/S member countries as well.

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