Compounders Say FDA Guidance on Interim GMPs is Subjective, Unclear

Compounding pharmacies are asking the FDA to overhaul its guidance for interim good manufacturing practices, contending the recommendations for such things as the cleanliness of air filters and presence of particulates are unclear and subjective.

Various GMPs that the FDA has proposed are confusing and lack direction, says the International Academy for Compounding Pharmacists (IACP) in recent comments to a July guidance outlining an interim GMP framework for large compounders.

The guidance notes, for instance, that compounders should not use damaged, dirty or discolored HEPA air filters. “The terms damaged, dirty or discolored are somewhat subjective and open to interpretation by FDA inspectors,” the compounding trade group said.

IACP was one of 22 organizations and individuals to offer critical comments on the guidance.

The Biotechnology Industry Organization (BIO), for instance, said certain restrictions need to be in place to prevent compounding of complex biologics. The guidance should clearly state that the GMPs only apply to small molecule products, BIO said. The group also wants the agency to place biotherapeutic products on a difficult to compound list because of their complexity.

The Generic Pharmaceutical Association argued in separate comments that rigorous GMPs are needed for large-scale compounding without a prescription.

GPhA also expressed concern that there is no distinction in the guidance between products compounded from sterile drugs and those compounded from non-sterile APIs. The safety risks differ “between these two types of products, necessitating different controls,” GpHA said.

Baxter Healthcare commented that large compounders that make preparations from non-sterile APIs should be held to the same quality standard as traditional manufacturers. Baxter provides outsourced compounding services in addition to manufacturing pharmaceuticals.

But it was the compounding pharmacists who took the most direct aim at the guidance itself. IACP, for instance, challenged a requirement to limit visible particles in sterile drug products.

“IACP does not believe there is a published norm or standard for visible particulates in a sterile product,” the comments said. “What is the amount which the agency would accept? Is 10 percent, 20 percent or more too much? Is 1 percent too stringent? This requires specificity and clarification.”

In addition, the IACP slammed requirements to check the quality of a supplier’s active pharmaceutical ingredients (APIs). The guidance notes that compounders should ensure the API meets applicable U.S. Pharmacopeia monographs and conduct identity tests to confirm the API is the one specified in the purchase order.

But the IACP interpreted these requirements to mean compounders have to audit FDA-registered suppliers, which isn’t their responsibility. “It is the agency’s responsibility to assure that those registered suppliers are only producing and distributing products which meet those standards,” the group said.

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