FDA and EU Inspectors Draw Insight at Contract Manufacturers Into GMP Enforcement/Drug Shortage Crosscurrents

U.S. and European health agency inspectors are drawing more insight during their inspections of contract manufacturers into the complexities of balancing GMP enforcement with drug shortage prevention.

Among the issues involved is determining how the relationship between the sponsor and the contract manufacturer is impacting the compliance concerns.  Identifying what medicines are critical and deciding a course of action that ensures their availability are other pieces of the challenging puzzle.

At a mid-March supply chain conference in Cincinnati, Ohio cosponsored by Xavier University and FDA, MHRA Expert GMP Inspector David Churchward and FDA Cincinnati District Field Investigator and Drug Preapproval Manager Kathleen Culver provided recent case studies they were involved in that highlight the web of concerns surrounding contract manufacturing regulatory compliance and drug shortages (see box below).

Churchward shared the difficulties that MHRA faced recently when a sterile product found to be manufactured under non-compliant conditions that would normally trigger a recall was determined to be a medically-necessary drug with no therapeutic alternative in a handful of EU member states.

He explained the decision-making and communication processes his agency used to ensure that the drug – licensed under a central authorization and thereby available to be marketed in any EU country – remained available where it was necessary and taken off the market where it was not.

Culver discussed the cases of a domestic and a foreign contract manufacturer with which she was closely involved that she said are indicative of a “turning tide” in drug sponsor/contractor relationships.  The cases involve “legitimate contract manufacturers” pushing back when sponsor demands are unreasonable or have the potential to impact the reputation of the contract firm.

In Culver’s first example, the firm was listed as the manufacturer on an ANDA for a drug in short supply but was unwilling to submit to a preapproval inspection because it did not have a signed contract with the sponsor.

She also provided an update on a case she had reported on last fall where a contract manufacturer received a 483 due to the sponsor’s unwillingness to provide it with application information (IPQ “The News in Depth” December 20, 2012).

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See related IPQ stories:

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FDA and ISPE Seek Stakeholder Input to Improve Drug Shortage Prevention and Mitigation Strategies

CDER Officials Shed Light on Forces Impacting Generic Injectable GMP Compliance and Drug Shortages

Sponsor/CMO Communication Gaps Will Have Negative Inspection Fallout, FDA Field Investigator Cautions