Schering Implementing Four-Phase Proposal For Proventil Batch Release

Schering-Plough is implementing a four-phase proposal for Proventil (albuterol) batch release after receiving a warning letter from FDA July 21.

The proposal outlines the actions the company will take "in order to continue distribution of this product," the warning letter states. The steps Schering must follow include developing and validating a new in-process heat tunnel canister stress test.

The data must be submitted as a prior approval supplement. Schering "must strictly adhere to that proposal in order to continue distributing Proventil inhalers," the letter states.

The company has implemented the plan in response to an FDA inspection conducted between April 12 and May 28 at Schering's Kenilworth and Union, N.J. facilities that found deficiencies in Proventil stress testing. Particle size deviations were also found in the production of Vanceril (beclomethasone).

In response to investigator findings, Schering briefly stopped Proventil production. The voluntary hold lasted from May 26 to June 11, although the company noted no shortage of supply to its wholesalers. "We are also aware of the potentially serious threat to the public health that might have resulted from a market shortage of this product," FDA remarked.

FDA noted Schering's failure to follow written procedure for nine batches of Vanceril. The batches were re-sampled, re-tested and released.

An October 1998 warning letter stated, "Reprocessing may be performed, provided certain criteria are met according to written procedures. The practice of partial releases, no matter how stringent the re-sampling, raises doubt as to safety and efficacy of the product being released. It is not acceptable to substitute testing over adequate control of a process." Schering received three good manufacturing practices warning letters in 1998 (¹ (Also see "Schering's Three GMP Warning Letters In 1998 Counter Industry Decline" - Pink Sheet, 8 Mar, 1999.)).

Schering submitted a response to the warning letter on Aug. 9. Members of the firm met with FDA representatives on June 17 and the four-phase proposal was presented by the agency in a June 25 letter. The agency will issue comments at a later date regarding concerns over adverse drug experience reporting.