FDA appears willing to allow some flexibility for compounders who must adhere to Good Manufacturing Practices, allowing for potential alternatives to minimize the burden of some testing requirements.

New draft guidance on GMPs for outsourcing facilities sets interim standards for compounders registered with the agency under the Drug Quality and Security Act.

The draft was one of several compounding-related documents issued July 1 by the agency, including a proposed rule for a do-not-compound drug list and final guidance on other compounding policies (see box).

FDA issued draft guidances in December 2013 outlining how it intends to implement outsourcer registration and some other portions of its new compounding authority ([A#14131202007]).

FDA Assembles Its Compounding Regulatory Library

Below is the list of compounding-related documents released by the agency July 1.

The GMP draft guidance focuses on sterility assurance and drug safety, issues that have been raised since the agency began a push to inspect compounding facilities in late 2012 following the deadly meningitis outbreak traced to the New England Compounding Center.

But FDA indicated that the requirements are only temporary. The draft guidance is intended to bridge the gap until the agency issues “specific cGMP regulations applicable to outsourcing facilities,” according to the draft guidance.

Outsourcing facilities were not expected to have to comply with all GMPs ([A#14130509006]).

Gabrielle Cosel, manager of drug safety for The Pew Charitable Trusts, said in a July 1 interview that the interim standards are important to help operationalize the compounding law, which was enacted in 2013 along with provisions for a drug shipment tracking system.

The International Academy of Compounding Pharmacists said in an emailed statement that it was still reviewing the documents “to determine whether there is any adverse impact on the availability of customized prescription medications for patients.”

IACP has been asking for more clarity on some aspects of FDA’s compounding oversight, including rules for office stock ([A#14140519005]).

Valid DMF May Suffice For Third-Party Testing Validation

Outsourcers are required test to assure the quality of incoming drug components and outgoing products.

But FDA asked for input on potential alternative approaches that could minimize the burden the requirements.

One idea could prevent outsourcers from establishing an in-house laboratory to conduct final release testing.

Outsourcers must create product specifications and release procedures and verify that finished drug products meet them before distribution, according to the draft guidance. Some exceptions were noted.

FDA is willing to consider a system that would allow outsources to use outside labs for the work. The agency asked for comments on a method to avoid forcing outsourcers to establish their own lab and also ensure “confidence about the accuracy of testing performed by a third party,” according to the draft.

Labs that desire to conduct the testing could submit a drug master file to the agency with descriptions of testing procedures, how methods and equipment were capable of producing valid results, quality assurance activities and other information.

If the agency did not have any questions about the DMF submission, it would issue a letter indicating no further comments, which the outsourcers would have to keep and produce during an inspection.

Labs also would have to update their DMFs if procedures change significantly and agree to tell outsourcing facilities of problems such as errors in test results.

Testing problems were among those found during one FDA inspection of a drug compounder that led to a warning letter Also see "FDA Compounder Inspections May Help Set New Enforcement Standard" - Pink Sheet, 11 March, 2013..

DMF For Component Testing Also Possible

FDA also suggested a potential DMF procedure so an outsourcer could “have confidence in the quality of incoming components without periodic laboratory testing following initial qualification testing to confirm the information in the supplier’s certificate of analysis.”

The procedure could “reduce the need for duplicative testing by multiple outsourcing facilities,” according to the draft guidance.

The agency said in the draft guidance that it would not take action against outsourcers regarding additional testing to verify a supplier certificate of analysis if the supplier submits a DMF with a description of the testing performed before component release and shipment, procedures to ensure package integrity during distribution and other information.

If it passes FDA review, the DMF holder would send a copy of the agency no further comment letter to the outsourcer, which it would keep and produce during an inspection.

The outsourcer could then rely on the DMF to meet component testing requirements, according to the draft guidance.

DMF holders also would have to agree to update the submission if the testing performed is significantly modified or if quality problems arise among components that were already shipped.

Outsourcers Need Quality Control Unit

The draft guidance recommends that each outsourcer establish an independent quality control unit to oversee sterile production and ensure each batch meets release specifications.

The unit also would be responsible for investigating discrepancies and failures and developing and overseeing corrective and preventive actions related to rejected lots of finished product, stability failures, process deviations and other issues.

The draft guidance also identified facility design and control system requirements that should be followed, such as air quality standards and cleaning schedules and methods.

In addition, it identified requirements for personnel monitoring to ensure proper conditions in aseptic processing areas, such as operator glove and gown practices and equipment sterilization.

Sterility problems have been among the most common problems FDA has identified during compounder inspections. The agency said personnel in one facility were wearing inappropriate clothing and that cleaning and air supply systems were deficient ([A#14130903005]).

GMP Flexibility For Compounders Signaled In FDA Draft Guidance

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