Ethylene oxide (EtO) is one of the most widely used sterilization methodologies in the biopharmaceutical industry. However, the US Environment Protection Agency (EPA) has issued proposals for a five-year timeline for cycle redesign and compliance to reduce EtO used in existing products to ≤500mg/L and two years for new products to market. The biopharmaceutical industry understands the rationale for the proposed changes but thinks the...
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The BioPhorum Closed Systems in CNC space team have collated a terms relevant to closed systems and closed processing derived from multiple sources, including the FDA, EU EudraLex Volume 4, various WHO documents, ICH Documentation, ISPE documents and ASME.
This chapter focuses on current regulations and guidelines mentioning and supporting the implementation of closed systems as a contamination control measure in the product protection strategy.
Oct 2023 | Deliverable, Deliverables Report, Digital Plant Maturity Model, Drug Substance, Information Technology, POI - Information Technology, Publication, Supply Partner, Sustainability, Technology Strategy
The tools within this resource portal introduce the BioPhorum Digital Plant Maturity Model (DPMM) and provide guidance for undertaking manufacturing plant assessments using both a quick and a detailed assessment method. The DPMM is a structured and straightforward way to assess the digital maturity of your plants and set a target maturity level aligned with your company’s digital strategy. It can be used for internal and external benchmarking, IT roadmap development, influencing software suppliers, transformation planning, investment justification, and dependency mapping.
The BioPhorum supplemental response to the Annex XV report on the proposal for universal PFAS restrictions, following the original submission in May 2023
This paper summarizes some of the approaches taken by the biopharmaceutical industry to optimize and/or minimize the number of post-approval regulatory notifications and/ or the variation categories associated with product lifecycle changes. It offers a summary of the systematic approach used in the industry for the demonstration of product and process knowledge and the definition of the appropriate process controls that will also
allow future flexibility. This approach can mitigate supply issues that are prevalent in the industry by allowing easier transfers between sites, leading to significant benefits for the patients. There are no novel approaches described in the paper, instead this is a summary of current industry practice. It is intended that this paper is used to review current regulatory practices in existing organizations, and as a reference for new regulatory
professionals and organizations.
A risk-based approach to filter integrity testing requirements for biologics drug substance manufacturers
Annex 1 of the EudraLex includes recommendations for filter integrity testing (FIT) of filters used for sterile filtration of sterile drug products. Manufacturers of low bioburden drug substances (DS) are seeking guidance on
the appropriate strategy for integrity testing of filters used in bioprocessing. The BioPhorum Closed Systems in CNC Spaces workstream developed a risk-based (and value-driven) approach for FIT testing of sterilizing grade filters used in the manufacture of low bioburden drug substances. This study yielded key criteria which served as the basis of a decision tree model for when and where FIT should be implemented to mitigate the risk of contamination. The findings of the study and the decision tree model were compared to current industry practice. Strong alignment was evident, suggesting the model could be used by DS manufacturers to develop a robust strategy for FIT which is congruent with regulatory guidance – specifically EudraLex Annexes 1 and 2. The risk-based approach is recommended to avoid dilution of effort on unnecessary FIT controls and target critical FIT use-cases that increase process reliability and patient safety outcomes.
This guidance document and the accompanying XI risk evaluation tool define the BioPhorum approach to risk evaluation of X-ray irradiation for sterilization of single-use systems (SUS) and is a flexible resource for incorporation of supporting tools into end-user quality system documents. End-users are responsible for critically reviewing this content prior to application and selecting the aspects that are most aligned with internal procedures, as well as making refinements as needed to meet local requirements.
This paper describes the tools, steps, and documents required to assess risk and qualify biomanufacturing facilities that use closed-system technologies. It sets the scene for closed systems and discusses the right approach, tools, and methods of implementing them in appropriately operated and non-classified zones. This is the first chapter in a series to be published over Q4 2023 and throughout 2024. Subsequent chapters will include the general philosophy of closed systems, standard terminology, and how to apply the risk assessment model.
BioPhorum comments on proposed national emission standards for hazardous air pollutants ethylene oxide emissions standards for sterilization facilities residual risk and technology review
Jul 2023 | Cell & Gene Therapy, Deliverable, Deliverables Report, Development Group, Drug Substance, Feedback to agency, Fill Finish, POI - Supply Partner, Publication, Regulatory, Supply Chain to Patient, Supply Partner, Sustainability
This group supports the Environmental Protection Agency’s (EPA) efforts to protect public health and the environment through the Residual Risk and Technology Review (RTR) process and recognizes the
need to develop stringent emissions standards to mitigate any potential hazards posed by Ethylene Oxide (EtO) emissions. However, they are also cautious of the impact these changes may have on the availability and timely delivery of biotherapeutics to patients who rely on them. Biotherapeutics, including vaccines, therapeutics, and other life-saving medications, play a crucial role in improving patient health outcomes and saving lives. For the biopharmaceutical industry, EtO sterilization is a critical process used to ensure product safety and efficacy. The EtO Response team raised several concerns regarding the potential impact of the proposed rule changes on the biotherapeutics market. This document discusses the concerns.