This TR serves as a resource on controlled environments test methods, focusing primarily on microbiological control for sterile product manufacturing. (Some nonviable particulate information is also included.) This second revision reflects substantial revision to regulatory guidelines, international standards, and scientific advances in environmental monitoring procedures and equipment.

This revised TR takes a thorough look at the aseptic processing technology, including the continuing changes that have occurred in within the global industry over the last 15 years. Contributions to this topic by organizations, regulators, compendia, and individuals in this area are considered. Guidance is offered regarding where risk-based approaches may be applied.

The systematic elements essential to assuring compliant cleaning and disinfection programs for aseptic- and bioburden-controlled manufacturing facilities and classified environments are identified in this TR. Focusing on controlled and non-controlled environments, microbial contamination control and corrective actions for loss of control for viable excursions contamination, this TR provides comprehensive information, suggested best practices, and appropriate references to support such guidance.

This TR presents the current scientific understanding of the causes 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.

Methods and approaches for control and evaluation of aseptic processing operations for drug/medicinal products that use all or partially manual procedures are outlined in this TR. It has value for hospital and formulation pharmacies where manual aseptic processing may occur, and may be applicable to the following select operations: vaccine preparation, cell culture, gene therapy, Investigational New Drug/IMP manufacturing, clinical and commercial manufacturing, and pharmacy formulation and dispensing.

This TR provides guidance in the design, development, controls, procedures, validation, regulatory submission, and implementation of reprocessing procedures for biopharmaceutical manufacturing. It focuses on recombinant biopharmaceutical products, including proteins and polypeptides produced via recombinant and non-recombinant cell-culture expression systems. Two case studies are presented to illustrate how the general principles may be applied.

Timely, real-world guidance for the application of a lifecycle approach to process validation is presented in this TR. It reviews requirements for process validation studies across the three-stage approach defined by the U.S. FDA and discusses best practices for integration with supporting quality systems.

This TR provides an overview of the knowledge and skills used during a successful technology transfer project (TTP), along with references to consult, if necessary. It includes practical examples of technology transfer activities.

This TR is intended to provide guidance for the successful evaluation, validation, and implementation of alternative and rapid microbiological methods needed to by the pharmaceutical, biotechnology, and medical device industries to ensure product quality. It 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.

Practical and strategic guidance to efficiently use historical data and knowledge to design suitable risk-based AMV studies and to set appropriate protocol acceptance criteria are provided in this TR. An illustrated map of the typical method lifecycle steps prior to, during, and beyond the AMV studies is included to help users visualize their AMV program. Users will benefit from risk-based guidance for the validating methods following their development or qualification and other, related method lifecycle step, such as analytical method transfer.

This TR offers detailed guidance for the application and implementation of quality risk management (QRM) principles throughout the product lifecycle. Intended to align with ICH Q9 and present information that can be helpful to the reader on how to implement QRM, this TR emphasizes QRM application during commercial manufacturing and integrating QRM into the pharmaceutical quality system.

Gain practical, risk-based guidance for the development and qualification portions of the analytical method lifecycle for biotechnology products in this TR. Guidance for analytical method development and analytical method qualification studies, such as risk-based strategies and priorities, analytical target profile and quality-by-design concepts, target performance criteria, and modern quality expectations are also included in this TR.