PDA Pharmaceutical Microbiology Conference 2024 Onsite

This technical report addresses the ongoing evolution of contamination control principles to a holistic approach, where the practices are designed to work together to achieve proactive contamination control and are evaluated for their collective effectiveness. The holistic approach also demands that contamination control measures be tailored to the specific risks around each individual process. This document focuses on contamination control practices against microbial and other adventitious agents, endotoxins, and foreign particulate matter in the manufacture of sterile drugs, low bioburden drug substances, and some nonsterile drugs that are vulnerable to contamination. (single user digital version)

This Points-to-Consider document provides a summary of microbiological challenges for ATMPs and guidance on how to address these challenges based on the current state of technology, regulatory environment, and industry best practices. It addresses ATMP process technologies from cell-free production of mRNA therapeutics to viral vector-induced in-vivo gene therapies to ex-vivo engineering of human cells for autologous or allogeneic cell therapies. The control aspects covered include facility design, equipment and instrumentation design and maintenance, analyst and operator gowning and qualification, and microbiological process monitoring.

This revision of TR 13 aligns with current industry trends and regulatory expectations and provides additional guidance and focus on increased expectations concerning data management and data integrity, qualification and maintenance of controlled environments, and rapid microbiological methods (RMM). It will aid in the establishment of a robust environmental monitoring program that embraces innovation and the principles of quality risk management. Updates regarding microbiological and total airborne particulate control concepts and principles related to facilities involved in the manufacture of sterile pharmaceutical products are also included.

This technical report presents a holistic approach for performing a microbiological investigation. It provides a framework to assist with focusing on the investigational areas that may contain or contribute to the root cause of data deviations. Distinct areas where microbial data is collected and inspected for deviation investigations are the focus of this document; the roles of other contributors to deviation investigations required for effective root cause analysis are also briefly described. This TR promotes a lifecycle approach, with an emphasis on laboratory and manufacturing investigations of marketed drug products.

This technical report is a complementary addendum to PDA Technical Report No. 13 (TR 13, Revised 2014) that provides elements to consider when designing a risk-based environmental monitoring program to support the manufacture of low bioburden products using low bioburden processes. A review of regulatory requirements and the development of risk assessments based on the criticality and complexity of processes is included, along with industry examples of these risk-based approaches.

PDA Technical Report No. 69, (TR 69) Bioburden and Biofilm Management in Pharmaceutical Manufacturing Operations presents the current scientific understanding of the causes of and control strategies for bioburden in pharmaceutical production systems, with a special emphasis on biofilms in fluid-handling systems. It encompasses pharmaceutical and biopharmaceutical manufacturing processes, but does not include the final aseptic and terminal sterilization fill-finish operations.

The purpose of TR 67 is to provide guidance to the nonsterile product manufacturing industry on how to manage the microbial risks associated with manufacturing and storage as well as how to determine what isolates would be deemed an objectionable microorganism in nonsterile products.

This technical report was written to establish industry-wide criteria on what constitutes an acceptable alternative or rapid microbiology test to the compendial or classical method and how to prove it to the satisfaction of quality organizations and regulatory agencies.