Regulatory Focus™ > News Articles > 'Questionable' Documentation Practices Lead FDA to Issue Form 483 to Biogen Idec

'Questionable' Documentation Practices Lead FDA to Issue Form 483 to Biogen Idec

Posted 09 December 2013 | By Alexander Gaffney, RAC

The US Food and Drug Administration (FDA) has released the text of a Form 483 sent to biopharmaceutical manufacturer Biogen Idec, outlining a series of alleged deficiencies affecting the manufacture of two of the company's multiple sclerosis drugs, Tysabri (natalizumab) and Avonex (Interferon Beta 1a).

FDA issues Form 483s if, during the course of an inspection of a manufacturing facility, its inspectors find deficiencies in need of addressing. If the issues are serious enough, the 483 may later become the basis of a Warning Letter from FDA threatening enforcement action unless actions are taken to immediately resolve the agency's concerns.

Certificates of Analysis

FDA's 483 to Biogen Idec refers to a five-day inspection starting on 29 July 2013 at the company's North Carolina manufacturing facility, where it makes the active pharmaceutical ingredients for Tysabri and Avonex.

The inspection ultimately yielded two major observations. In the first observation, FDA said it was unable to find evidence that the company always challenged the validity of all testing results provided by its suppliers. While certificates of analysis were noted as being present with the materials as required, "These results have never been challenged and/or verified by the firm," FDA stated.

The company, FDA added, would have no way of determining if the products were truly sterile and endotoxin-free, as the suppliers had claimed.

Documentation Troubles

The second major observation made by FDA also regarded documentation procedures, which FDA said had in at least one case resulted in "questionable" information. Such documentation is meant to provide a record of when certain activities, such as cleaning, took place and the circumstances of the activity.

FDA pointed to logbooks used by Biogen during the cleaning and sanitization of biosafety hoods used in the manufacture of Avonex and Tysabri, and said it could find no details about the cleaning materials used or the adequacy of the cleaning procedures.

Similar violations were found in four other cases, with FDA pointing to a lack of documentation about the buffers used to standardize pH-measuring probes, the purification of Tysabri, and a lack of assurance "that entries in the logbook are always made when the operations documented actually occur."

The Form 483 was issued on the final day of the inspection, 2 August 2013. The facility had been subject to three inspections since 2009, with one of those inspections resulting in a "voluntary action indicated" to remain in compliance.

Update: In a statement made available to Regulatory Focus, Biogen public affairs official Steven Goldsmith said the company is "committed to and are providing only the highest-quality medicines to patients.

"This FDA inspection of our RTP manufacturing facility was a routine biennial inspection covering multiple quality systems, processes and products. The two observations noted on the FD-483 are not uncommon, had no impact on our products, and the inspectors conveyed an overall positive impression of the quality systems and processes at this site. We welcome these inspections and the opportunity to make continual improvements. We have responded to these two observations with robust corrective actions, which are currently in progress. We believe the outcome of this inspection, as well as other FDA inspections at all of our sites, are a testament to the operational excellence and robust compliance of the Biogen Idec culture of caring deeply."

FDA's 483 to Biogen

Tags: Form 483, 483

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