Managing Microbiological Out of Specification (OOS) and Out of Trend (OOT) Results in Sterile and Non-Sterile Production FDA & ICH Expectations and Guidance

Why Should You Attend:

Microbiological Out of Specifications (OOS) may occur with the production of both non-sterile and sterile products. They may occur as early in the process as with Incoming Raw Materials and extend throughout In-process and Active Pharmaceutical Ingredient (API) phases to the final product.

With the advent of the revised USP<61> Microbial Examination of Nonsterile Products: Microbial Enumeration Test, a new latitude in result interpretation has come to the fore; however, one needs to understand how to utilize this inherent variation of USP<61> with Out of Trend (OOT) and Out Of Specification (OOS).

Microbial data deviations or non-conformances periodically may occur as well as OOT, OOS and Corrective and Preventive Actions (CAPA). However, unlike chemical analytical deviations, all microbial non-conformances to include OOS and CAPA investigations may require as many as six months to complete these studies based on their degree of difficulty and additional laboratory tests that may be required.

Sterility testing practices (USP<71> Sterility Tests) comprise the historical "gold standard" for releasing pharmaceutical and biotechnology products as sterile. Because extensive contamination is often required before a sterility test fails, regulatory agencies require initial and then periodic media fills as well as smoke studies, observation of technicians, and extensive environmental studies to add additional confirmation to sterility assurance prior to the commencement of aseptic filling. Therefore, OOS may not only directly examine sterility, but all of the results that indirectly impact it.

Areas Covered in the Webinar:

• Review of the new latitude within USP <61> and how it may impact OOT and OOS.
• Review issues that may occur within the Incoming Raw Materials, In-Process and API phases.
• How developing a comprehensive validation of the facilities, the aseptic processing area and gowning qualification can minimize non-conformances.
• How to manage when a failure still occurs.
• How and when to bridge the "gap" between deviations, OOS and CAPAs.
• How the use of metrics may provide a “roadmap” for corrective action.
• Where Risk Management applies to deviations, OOS and CAPAs.
• Review Guidance for Industry Investigating Out-of-Specification (OOS) Test Results for Pharmaceutical Production.
• Phase I and Phase II of an Out of Specification Investigation.
• Examine the new FDA “attitude” that is being taken with non-sterile product.
• Identify the OOT and OOS regulatory concerns in a cGMP environment.
• Review the microbiological issues that may occur within Incoming Raw Materials, In-Process and API phases.
• Discuss key issues in manufacturing non-sterile products.
• Identify gaps within current regulatory and industry expectations.
• Explore Form FDA 483s and Warning Letters that have recently been issued.

Who Will Benefit:

• Quality Assurance
• Regulatory Compliance
• Quality Control
• Research & Development
• Regulatory Affairs Professionals
• Validation
• Metrology
• Auditors
• Project Managers

Barry A. Friedman
Consultant in Biotechnology, Regulatory Compliance and Aseptic Processing Arena

Barry A. Friedman, Ph.D., is a Senior Consultant in the Biotechnology, Regulatory Compliance, Microbiology and Aseptic Processing arena. Dr. Friedman has over 30 years of industrial managerial experience in various aspects of biopharmaceuticals and medical devices to include regulatory compliance, expert witness assistance, quality control, sterility assurance, microbiological/analytical validations and fermentation technology.

From 2000 to 2007, Dr. Friedman was associated with Cambrex Bio Science Baltimore, a contract manufacturer of GMP bulk biopharmaceuticals located in Baltimore, MD. In that capacity as the Director, Quality Control, he managed a multi-shift Department of thirty one individuals involved in Client management, the receipt and testing of raw materials, environmental monitoring and microbiology, analytical chemistry and QC compliance for the production of Phase 1, 2, 3 and commercial products manufactured from bacteria, yeast and mammalian cells. In this capacity Dr Friedman enjoyed many client and regulatory compliance interactions.

In addition to the associations listed above, other associations have included Chesapeake Biological Laboratories, W.R. Grace, Sigma Chemical Co., Sherwood Medical, Becton Dickinson, American Cyanamid and Union Carbide.

Dr. Friedman is a frequent seminar and webinar speaker and specializes in the areas of regulatory compliance, internal auditing, aseptic processing for sterile drug products, USP and Warning Letter “dissection”, multi-departmental interactions, validations and the requirements for the manufacture of Phase 1, 2 and 3 clinical trial materials. He has recently given presentations for the FDA, PDA, PTi, TungstenShield (PharmaWebinars), IPA (Canada), Executive Conference Corp, Compliance On-Line and Pharmig (UK).

Dr. Friedman maintains an active Blog (www.barryafriedmanphdllc.com) that contains over 200 Blogs that address various Warning Letter and FDA 483 issues as well as over 1,500 “Search” terms to assist with finding the appropriate Warning Letter and FDA 483. He is a member of ASM, PDA and RAPs. He served as a Captain in the Medical Service Corps, U.S. Army and is the past President and current Treasurer of the Capital Area Chapter, PDA. He recently received the James Agalloco award from PDA which is awarded to a PDA faculty member who exemplifies outstanding performance in education.

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