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Labcompliance News, October 2004

October 17, 2004

FDA Inspection Report Advices to Upgrade HPLC Systems

During an inspection of an API manufacturer in China the FDA advised the company to upgrade a strip chart recorder based HPLC system to system with reprocesses sing capabilities. The HPLC system was used to check APIs for impurities. The recommendation reads in the Establishment Inspection Report: The firm needed to upgrade several pieces of their equipment. Principally, the old HPLC being used still was using the equivalent of a strip chart recorder. This made accurate determination of the related compounds, etc, very difficult unless additional standard and sample injections were made with the scale set a pre-determined setting. The system didn't have the capability of reprocessing data, etc.

A second recommendation was to add a time limit to the HPLC retention time so that the test can have acceptable ID, and/or use FT-IR as the principle test.

A third recommendation was to revise the SOP to perform the SST at time of use and add a system check injection after every five or so sample injections. While the 3rd recommendation made it into the 483 form the first two were just recommendations.

The observation in the 483 did read: The SOP requirement for the assay analysis of xxx was not followed in that the HPLC system suitability test was only performed weekly per firm SOP, instead of the actual time of testing". A second 483 item was related to solvent recycling: "Recovered xxx solvent used for the production bulk API xxx is not tested with a specific assay for purity".

This inspection reports are good examples to learn what the FDA is looking at during inspections, what they recommend for likely follow up during next inspections and what goes into the official 483 inspection observation form. The EIR also ahs many examples on how devioations from previous inspections have been corrected.

The complete set with the 15 page EIR and the 483 can be downloaded from the Labcompliance Users Club (44 pages). Non members can preview excerpts.

October 17, 2004

New FDA Quality System Guide for Drug GMPs

On September 29 the FDA released a the quality systems guide: Quality Systems Approach to Pharmaceutical Current Good Manufacturing Practice Regulations. This long awaited FDA guidance describes a comprehensive quality system (QS) model for manufacturing human and veterinary drugs, including biological drug products. Is intended to help implementing modern quality systems and risk management approaches and at the same time to meet cGMP requirements. It is positioned as part of FDA's pharmaceutical CGMP initiative for the 21st century where the FDA explained the agency's intent to integrate quality systems and risk management approaches into existing programs with the goal of encouraging the adoption of modern and innovative manufacturing technologies. To learn more about the objectives, scope and content of the guide, click here.


October 4, 2004

Laboratory Compliance Event of the Year: More than 1500 Professionals Had Signed up

The video web seminar on September 23 was a big hit. With more than 1500 registrations from over 50 countries and up to 50 attendees at single registrations it probably was the biggest event for laboratory compliance ever. The seminar was sponsored by Agilent Technologies, moderated by David Markovitz, president of the Institute for Effective Innovation (IEI), and presented by Dr. Ludwig Huber, international compliance expert of Agilent Technologies and editor of the Labcompliance Newsletter. The seminar was delivered into four parts:

In part one Dr. Huber explained why risk assessment is important: the FDA is asking more and more to base controls on 'justified and documented risk assessment'. The industry is paying attention to risk based compliance as a way to optimize their resources.

In the second part Dr. Huber introduced a four step approach for risk management using the ISO Standard 14971-1:1998 as model. "Currently the FDA is asking only for a risk assessment, but when you start doing this I recommend to take the next steps and include risk mitigation and on-going review and control in the process"., Dr. Huber said. He also pointed out the importance of a Risk Management Master Plan as frame work for efficient and consistent individual risk management projects. An example of such a plan is available from the Labcompliance book shop.

In part three Dr. Huber explained a concept on how to determine validation steps for different risk levels. "Look at all validation phases where you can make validation more efficient", Dr. Huber said. He also gave specific validation examples for high, medium and low risk systems.

In the last part Dr.Huber recommended to look for resources what ever possible. "One of the best resource can be the vendor, as long as they have the expertise to design the right products and services". He used the product and compliance offerings of Agilent Technologies as an example: "They not only offer products with built-in functionality for Part 11 and GxP compliance, but also offer global services to qualify all types of instruments from different vendors in a laboratory. Qualification services include equipment hardware, laboratory computer systems and and network infrastructure. And on Agilent's new Enterprise Content Management system the compliance reports can be combined with all other data collected from all types of scientific instruments and office applications and are readily available in one place for audits."

Dr. Huber answered many questions that came in from the audience through a chat box . David Markovitz did an excellent job to moderate the session and to add valuable comments based on his long-term experience with FDA regulated industries. At the end he expressed his appreciation for Agilent's unique expertise in this highly critical area. He specifically pointed out that now a single company provides compliance services for all types of laboratory instruments from multiple vendors with the same protocols used all over the world.

For a CD with the video, send an e-mail to huber@labcompliance.com .

October 4, 2004

Five New Guidance Documents from the FDA

On Sept 29, 2004, the FDA has issued several new guidances and a final report on Pharmaceutical cGMPs for the 21st Century.
Look in upcoming Labcompliance News for more details

Final Guidances

  • PAT - A Framework for Innovative Pharmaceutical Development, Manufacturing, and Quality Assurance
  • Sterile Drug Products Produced by Aseptic Processing - Current Good Manufacturing Practice

Draft Guidances

  • Computerized Systems Used in Clinical Trials: Revision 1
  • Current Good Manufacturing Practice for Combination Products
  • Quality Systems Approach to Pharmaceutical Current Good Manufacturing Practice Regulations