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Pharmacopoeial Microbiology Update – USP and EP Developments

8 November 2017

Objectives

This conference will be focused on the last pharmacopoeial changes and revisions in the chapter with a microbiological relevance. Speakers from industry, pharmacopoeial expert groups and authority will present the most important revisions and discuss the impact of the work of microbiological QA, QC and testing for marketing authorisation.

Background

During the session 2016/2015, the USP – Microbiology Expert Committee has focused a lot of interesting topics:

  • Proposal for New Endotoxins Control Material: The EC discussed a proposal for a new endotoxins control material (secondary standard) prepared from a cell wall extract of a well characterized Gram-negative bacterial species. The proposal will be posted on USP.org for public comment.
  • Modern Microbiological Methods Expert Panel: This Expert Panel is developing a list of user requirements and will recommend candidate - Rapid Sterility Test technologies for the EC’s consideration.
  • <1111> Microbiological Examination of Nonsterile Products: Acceptance Criteria for Pharmaceutical Preparations and Substances for Pharmaceutical Use: The EC discussed potential revisions to this General Chapter in closed session.
  • Microbiological Specifications in Monographs for Nonsterile Drug Substances and Products: USP staff and U.S. Food and Drug Administration staff will discuss the potential modernization of microbiological specifications in monographs for nonsterile products.

Additionally, several USP chapters were revised, e.g. the chapters <1115> Bioburden Control on Non-sterile Drug Substances and Products, <1223> Validation of Alternative Microbiological Methods, <1211> Sterility Assurance, <1228> Depyrogenation, <1229> Sterilization as well as the chapters <55> Biological Indicators and <1207> Package Integrity Evaluation.

In the same time, several chapters of the European Pharmacopoeia were revised and published between 2016-2017, relating to the fact, that the fast development of science as well as of modern medicinal products necessitate an ongoing development of the regulatory requirements:

  • Revision of 5.1.6 ”Alternative Methods for Control of Microbiological Quality” was published in 2016. This takes account of the latest technological developments in this field (e.g the use of rapid microbiological methods (RMM) for process analytical technology and their evolution in the molecular field). Moreover, further guidance on how to develop and validate a RMM has been added in order to facilitate their adoption and approval.
  • “Methods of preparation of sterile products (5.1.1)” and “Biological Indicators in the Preparation of Sterile Products (5.1.2)” (formerly "Biological Indicators of Sterilisation") have been updated to reflect the state of the art within the different sterilisation processes, to give guidance on how biological indicators are used for the development of the sterilisation process and on the different types of BI available and their characteristics.
  • The chapters “Monocyte-activation test (2.6.30)” and “Guidelines for using the test for bacterial endotoxins (5.1.10)” were updated in addition to guidance given on how to choose the appropriate pyrogenic tests and MAT is now considered as a replacement for the rabbit pyrogen test.
  • Finally, a new chapter entitled “Determination of bactericidal, fungicidal or yeasticidal activity of antiseptic medicinal products (5.1.11)” dealing with a test that can be used for the determination of antimicrobial activity in antiseptic medicinal products that are miscible with water and intended for administration by direct contact with the skin or mucous membranes, was recently published in 2017.

Target Audience

This conference is of interest to professionals from

  • Biotechnological & Biopharmaceutical Companies
  • Contract Service Laboratories
  • Academic Research Institutions and Organizations
  • Government Agencies
  • Supplier Detection Systems

with responsibilities in

  • Manufacturing
  • Quality Assurance
  • Quality Control
  • Regulatory Affairs
  • Research & Development
  • Process Development
  • Validation

Programme

Overview of Current USP Activities
Radhakrishna Tirumalai, USP

  • Role of USP and the Standrad setting process
  • USP Microbiology Chapters
  • Recent and Current Activities of USP in Microbiology and Sterility assurance

Overview of different revised microbiology-related European Pharmacopoeia chapters
Dr Sébastien Jouette, EDQM

  • Sterilisation/BI
  • Endotoxin/MAT
  • Determination of bactericidal, fungicidal or yeasticidal activity of antiseptic medicinal products (5.1.11)

<1229.x> Series of Sterilization Chapters
Don Singer, GSK / USP

  • Need for separation of content on Sterilization , Depyrogenation and Sterility Assurance
  • Greater and new or updated content on bioburden monitoring, biological indicators, and sterilization processes including filtration of liquids and gases
  • Biological Indicator is only a measurement tool and emphasis on material being sterilized
  • Need for a balance between the lethality of the sterilization process to the product bioburden and for a safe, stable and efficacious product

Revisions to <1211.x> and <1222.x> Sterility Assurance and Parametric Release
Don Singer, GSK / USP

  • Revised <1211> to focus only on Sterility Assurance
  • Greater and updated content on Sterility Assurance
  • Sterility is achieved through the implementation of interrelated controls that in combination provide confidence of sterility
  • The process design objective should be minimization of microbial ingress
  • It is the controls that provide the assurance rather than the results of any in-process or finished goods testing
  • Revised <1222> on Parametric Release as it applies to terminally sterilized products
  • Processing parameters, critical processing parameters, and operational ranges assuring the requisite microbial destruction should be understood, defined, measured and controlled to support parametric release.

The revised European Pharmacopoeia chapter 5.1.6 related to alternative methods for control of microbiological quality
Dr Sébastien Jouette, EDQM

  • Background and Reasons
  • Important Changes

Current USP Perspectives on a Rapid Sterility Test
Dr David Roesti, Novartis/USP

  • Current growth-based Sterility Tests with at least a 14-day incubation is not suitable for short-lived products
  • Most critical user requirements specifications for candidate rapid sterility tests established
  • Based on these URS recommendations on appropriate modern/rapid technologies available from multiple vendors have been made

Current USP perspectives on Objectionable Organisms
Dr Radhakrishna Tirumalai, USP

  • Specified Organisms vs Objectionable Organisms
  • Risk analysis
  • Not possible to test for every potential microbial contaminant and analyze risk
  • Prevention of Objectionable Conditions is a prudent approach

Implementation of USP <1115> in the Non-Sterile Pharma Manufacturing Environment
Dr Rick Jakober, Perritt Laboratories Inc.

  • Discuss compendial differences in non-sterile vs. aseptic manufacturing and rationale in developing USP <1115>. Review USP <1115> risk-based approach to non-sterile manufacturing taking into account patient safety.
  • Review environmental monitoring strategies for non-sterile manufacturing
  • Microbial monitoring of the non-sterile environment
  • Microbial points to consider during development and manufacturing of drug products

Moderator

Dr. Marcel Goverde, MGP, Switzerland
Member of EP Microbiology Expert Group

Speakers

Rick Jakober, Perritt Laboratories, Inc., USA
Vice President Laboratory Services. Over 35 years experience in pharmaceutical microbiology, specializing in non-sterile products.

Sébastien Jouette, PH.D., EDQM, Strasbourg, France
Scientific programme officer in the Biological Division of the European Pharmacopoeia department.

David Roesti, PH.D., Novartis Pharma Stein/USP, Schwitzerland
Head of the RMM team and the Novartis Pharma expert network in microbiology.

Donald C. Singer,GSK/USP, USA
GSK Senior Fellow / Biopharmaceutical GMP Ops at GSK. Vice-Chair of the USP Microbiology Committee of Experts

Radhakrishna Tirumalai, PH.D., USP, USA
Principal Scientific Liaison-General Chapters in the Science Division. Liaison to the USP Expert Committee on Microbiology.