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Labcompliance News, August 2004

August 9, 2004

Reference Samples and Retention Samples: New Annex to the EU GMP Guide (Volume 4):

A proposed new annex to the EU GMP Guide provides guidance on the taking and holding of reference samples of starting materials, packaging materials and finished products as well as for retention samples of finished products. The annex provides definitions of the terms "reference sample" and "retention sample", which are often incorrectly considered as synonyms. The guidance is wide ranging in scope and includes the case of multiple manufacturing sites, the position with respect to importers and what should happen when a manufacturing site ceases to operate. Updated guidance is also given on the size of reference samples and a consequential amendment will therefore be necessary to Chapter 6 section 14 of the GMP Guide to maintain consistency. The Pharmaceutical Committee has endorsed the proposal by written procedure. The document is released for a consultation period until 15 January 2005.

August 9, 2004

Insight on FDA Inspections and Recommendations

Sybil Wellstood, Ph.D., of FDA CDRH Division of Bioresearch monitoring gave a presentation on FDA's Bioresearch and In Vitro Diagnostics. The objective was to provide an overview of the CDRH Bioresearch monitoring program (BIMO) and to discuss how the BIMO program applies to in vitro diagnostic (IVD) studies conducted under 510(k) pre-market notifications. One of the responsibilities of the Office of Compliance is to develop and issue inspection assignments to field offices, to evaluate and classify Establishment Inspection reports and to initiate follow-up regulatory actions and correspondence. In line with this responsibility Dr. Wellstood gave an insight on FDA inspections: the inspection process, whom they inspect, their expectations, type of inspections and how an inspections is conducted, concluded and followed up. An FDA 483 form report is written right after the inspection with deviations from regulations. Deviations from guidelines do not appear on the Form FDA-483, but may be included in the discussion" she said. She also recommended to respond verbally during the final discussion and/or sent a written response to District Office. The response should explain any special circumstances regarding the observations. The response should also describe specific actions taken or planned that will correct and prevent future deviations. Later on in the presentation Dr. Wellstood talked about Establishment reports (EIR's) and post inspectional regulatory activities. Labcompliance Usersclub members can download the presentation. For preview and ordering, click here. To learn more about FDA inspections click here.

August 9, 2004

21 CFR Part 11 and Risk Assessment: Adapting Fundamental Methodologies to a Current Rule

In September 2003, FDA released the 21 CFR Part 11 scope and applicability final guidance document, addressing industry concerns regarding the complexity and cost of Part 11 compliance. With this new guidance the FDA expects a firm that is subject to GxP to develop a risk evaluation of its product and to then mitigate the identified risks. Identified risks may be addressed by technical fixes that effectively eliminate the risks or reduce the likelihood of occurrence and/or severity of consequences to acceptable levels. As the guidance states FDA's intentions to take a more discretionary risk-based approach to enforcing compliance, this article describes various risk assessment methodologies with which a company can identify and address its own at-risk areas.

August 9, 2004

New FDA Warning Letter Statistics

Concept Heidelberg regularly evaluates FDA cGMP warning letters and publish statistics about most frequently found deviations. The 2003 report has just been published. As in the past year, the list is headed by § 211.100, which refers to the creation, approval and handling of written procedures. The findings referred to the fact that there were no written procedures, procedures were inadequate or procedures were not followed. Second on the list are deviations related to 211.165 - Testing of products and release for distribution and 211.25 - Responsibilities of quality control unit and 211.192 - Production record review.

August 9, 2004

New Warning Letter for Inadequate SOPs

"No adequate procedures" or "procedures not followed" are amongst the most frequently cited deviations in FDA Warning Letters and 483's. Probably all FDA regulated companies have SOP's but why is it that they are not accepted and used by their employees and by the FDA? There seems to be lack of understanding on what the regulations are, their interpretations and expectations of inspectors. SOPs are either not available for specific processes or tasks or they are not followed by employees. An example is a warning letter from May 2004. During an inspection of a GLP facility the FDA found several deviations related to SOPs. The list starts with: "The testing facility management failed to establish standard operating procedures (SOPS) adequate to ensure the quality and integrity of the data generated during the course of a study, to limit unauthorized and undocumented procedural deviations, and to establish controls to ensure accountability of SOPS." The letter continues with five examples where SOPs had been expected". A second deviation was that existing protocols have not been followed without authorization and documentation. The FDA gave the advice: "If exceptions from laboratory’s SOPS apply for the study, then those exceptions should be described in the protocol". Other deviations are related to retention of reserve samples from each batch of test and control articles from studies longer than four weeks and inadequate reporting of laboratory study results. . The warning letter can be downloaded from the Labcompliance Usersclub. Non members can preview excerpts. Click here to learn how to write SOPs that will be accepted by the FDA and by your employees.