Pre-use post-sterilization integrity testing (PUPSIT) continues to generate considerable debate in the industry. Committing to a PUPSIT strategy is no mean feat because, while it is recommended by regulatory bodies, it may compromise downstream sterility and it is expensive to mitigate these risks. To help clarify industry thinking, the Sterile Filtration Quality Risk Management (SFQRM) Consortium is sharing its knowledge and expertise on...
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Alternative and rapid micro methods (ARMM): A framework for the evaluation, validation and implementation of alternative and rapid microbiological testing methods
Jul 2020 | Fill Finish
There are now available to the biopharmaceutical industry several alternative and rapid microbiological methods (ARMMs) for the detection and enumeration of microorganisms during testing. Regulatory authorities are encouraging the biopharmaceutical industry to adopt innovative technologies. Together these methods will lead to improved monitoring and assurance of control of biopharmaceutical processes and manufacturing environments, as well as shortened cycle times in the supply chain. This paper addresses the need for a systematic and best practice approach to the evaluation, validation and deployment of these methods. The absence of such best practice has hindered the adoption of ARMMs, resulting in slow adoption. A nine-step framework and common language is described which can be applied by biopharmaceutical companies wanting to take advantage of the numerous benefits of ARMMs.
This article presents an update on the efforts of the joint PDA and BioPhorum collaboration workstreams—masking studies, historical data mining, filter manufacturing and use risk assessments and PUPSIT risk assessment and the development of a best practice guide.
This paper is one in a series of publications that are the result of the collaboration, and these should be considered together and viewed holistically in order to determine the best course of action with regard to PUPSIT. This paper examines the test process and looks at the results of potential masking of sterilizing grade filters.
SFQRM: The use of scientific data to assess and control risks associated with sterilizing filtration
This article draws conclusions from the scientific studies, workstreams, and publications delivered by the Sterile Filtration Quality Risk Management (SFQRM) consortium formed between BioPhorum and PDA. It uses those conclusions to provide guidance to industry (sterile drug manufacturers, filter suppliers, and regulators) on the use of quality risk management principles and scientific data to prevent undetected non-integral sterilizing filters.
Eudralex volume 4, Annex 1, the EU GMP for sterile products, requires that ″The integrity of the sterilised filter should be verified before use · · ·″ (1). Implicit in this requirement for a pre-use, post-sterilization integrity test (PUPSIT) is the rationale that the sterilizing filter could sustain damage during sterilization or use (i.e. subsequent to any pre-use test conducted prior to sterilization), causing a defect which would not be detected by the post-use integrity test. That is, that such a defect could be ″masked″ during filtration.
To assess whether a filter defect could be masked by partial filter plugging the Consortium evaluated the impact of bacterial retention testing on the bubble point (BP) of the test filters.
The paper concludes that filtration processes producing bubble point changes sufficient to present a risk of masking defects are not common, and detectable during the routine BCT. Thus the BP ratios observed during routine bacterial retention testing is one means to assess the potential of a given filtration process for masking of defects and can be considered when determining whether a PUPSIT should be implemented.
Container–closure integrity (CCI) is a vital patient-safety and product-efficacy aspect of parenteral biopharmaceuticals. The challenge is how to identify, qualify and maintain the appropriate methods to ensure CCI’s role in providing patient and regulatory confidence in these medicines. To describe an overarching approach to CCI and BioPhorum’s work in this area, Scott Ewan has written an article called A Holistic Approach to Container–Closure...
When testing single-use items, at what point is it appropriate to leverage vendor data, and when does an end user need to carry out testing? Is current regulatory guidance clear and sufficient in the fast moving area of disposables? And wouldn’t it be great if we had a tool that gave the industry a harmonized risk based approach to testing requirements. These are the questions that the BioPhorum Drug Substance TVR team have been...
In the second half of 2020, BioPhorum Drug Substance will publish a comprehensive set of tools and guidance to help the industry foolproof the transportation, deployment and use of single-use systems. Inspired by the work of Bayer's Berkeley facility, who over many years reduced leak rates from totally unsustainable 40% to a phenomenal 0.04%, the industry package takes the position that single-use systems are complex delicate...
Moving the site of manufacture for commercial cell banks, microbial or mammalian, the renewal of working cell banks for commercial products, or making minor changes to cell banking processes is becoming more onerous from a regulatory perspective and does not have a consistent harmonized approach even within a single regulatory body such as the FDA. In the past analytical comparability of cell banks was acceptable and this changed to requiring...