WHO continues to publish Inspection Report Summaries

On an on-going basis the World Health Organization (WHO) publishes summaries of GxP inspection report of manufacturers of APIs and finished products, of CROs and quality control laboratories. The report summarizes the observations and findings made during the inspection, but excludes confidential proprietary information. It indicates also the date and duration of the inspection as well as the scope of the inspection. Most recent reports are from September 2011. .As of December 2011 the report is available on the WHO website.

FDA expects Global Corrective Actions for Inspectional Observations

For companies operating in global environments FDA expects global corrective and preventive actions to avoid reoccurrence of the same or similar problems at other sites. This became obvious in Warning Letter to a global pharmaceutical company. The letter states: "We note that CGMP violations listed in this letter include multiple repeated violations from those cited in the August 2008 Warning Letter issued to COMPANY, North Carolina facility and repeated observations from previous inspections at your COMPANY Canada facility. It is apparent that COMPANY International is not implementing global and sustainable corrective actions. FDA expects COMPANY to undertake a comprehensive and global assessment of your manufacturing operations to ensure that drug products conform to FDA requirements. Finally, the Agency is concerned about the response of Novartis to this matter.". Deviations cited in the letter include: Missing procedures for media fill studies, missing failure investigation, failure to find the root cause of the problem, inadequate response to 483, investigation not extended to other batches, missing cleaning and maintenance at appropriate intervals, inadequate process validation, Field Alert Report (FAR) not submitted. The 483 can be downloaded from the Labcompliance Usersclub. Scroll down to W-262. Non members can preview excerpts. To learn everything about FDA's expectation for adequate responses to 483 obsrrvations, attend the Labcompliance audio seminar and receive 10+ best practices guide for easy implementation

PPD Publishes White Paper on Clinical Developments for Biosimilar Drugs

Because of pending expiration of numerous therapeutic monoclonal antibody patents drug companies are trying to develop biosimilar versions of innovator drugs. Opposite to small molecule based generic drugs follow-on biologic drugs require some preclinical and clinical evaluations. Pharmaceutical Product Development, Inc (PPD) has published a white paper addressing clinical investigator considerations for biosimilar development. As of December 2011 the paper is available on the PPD website. Copyright resides with the publishedr Attend the Labcompliance audio seminar to learn more about the registration process and compliance requirements for Biopharmaceutical laboratories

Inadequate SOPs for Analytical Method Validation and Transfer cited in FDA Warning Letter

An inspection of a drug manufacturer in July 2011 ended with a 483 inspectional observation. Several observations were related to inadequate method verification and transfer of analytical methods. In one instance the SOP did not require that method verifications are done at the laboratory site where the method will be utilized. No specific reason was given. Another SOP was found to be inadequate because it listed several reasons why formal transfer is not required:
1) When test procedures employing the techniques are already in use by the receiving laboratory and therefore, the method is not new., 2) When the receiving lab analysts are trained by the R&D or originating lab scientist. 3) When based on professional judgment a formal transfer study is not required but the rationale must be documented. 4) When the test procedure has built-in  control to verify the performance at each run.
While the USP draft chapter <1224> describes waivers as one possible option for method transfer, obviously the justifications given by the company have not been accepted by the inspection team. The 483 can be downloaded from the Labcompliance Usersclub. Scroll down to W-261. Non members can preview excerpts. To learn everything about FDA's expectation for validation and transfer of analytical methods, attend the Labcompliance audio seminar and receive 10+ best practices guide for easy implementation.

EU will require Certificates for API Imports from  third Countries

According to a concept paper published on December 7, 2001.  APIs will only be imported into the EU if,the active substances are accompanied by a written statement from the competent authority of the exporting third country with a  confirmation that the standards of good manufacturing practice and control of the plant are equivalent to those in the EU. The paper also describes criteria for equivalency. Most important is that the country not only must have equivalent GMPs but also equivalent inspection and efficient enforcement practices. In addition the country must regularly and rapidly provide information on non-compliant producers of APIs. The new rules of importation of APIs will apply as of July 2013. The concept paper is available for download from the EC Website. 

FDA expects an SOPs to manage Out-of-Trend (OOT) Situations

FDA Guide on Investigating Out of Specifications Test Results for Pharmaceutical Production also mentions out-of-trend situations. "Although the subject of the guidance is OOS results, much of the guidance may be useful for examining results that are out of trend (OOT)". No further details are given. What it can mean in practice became obvious during an inspection of a drug manufacturer that resulted had in several 483 observations. One of them stated: There is no standard operating procedure in place that describes the steps to be followed during an Out-of-Trend (OOT) Investigation, besides, the "OOT Investigation" performed was inadequate. The 483 can be downloaded from the Labcompliance Usersclub. Scroll down to W-241. Non members can preview excerpts. To learn everything about FDA's expectation for handling Out-of-trend situations, attend the Labcompliance audio seminar and receive 10+ best practice guides for easy implementation, including an SOP on handling OOT situations. .

Free Document of the Month

As a 'Thank You' for our visitors Labcompliance offers every month one document for free. This month's document is the Best Practice Document "Network Qualification Plan". To download your free copy, go to the Network Qualification Package website. Scroll down and click on the corresponding ICON on the left (offer expires on December 31 , 2011). Labcompliance offers more than 130 SOPs and other documents that help to comply with FDA and ISO 17025 compliance. For titles and ordering, click here.