A reliable supply of life-saving drugs requires understanding and mitigating any variability to support consistent supplies. However, the crucial timelines for making a drug product available to patients can be heavily impacted when variability is introduced through raw materials such as cell culture media (CCM) and reagents. Investigating a failure in production is costly and time-consuming and can delay product supply to the market – so a...
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Trace element variation for chemically defined cell culture media: biopharmaceutical industry requirements and cross-company collaboration to mitigate risks
Mar 2022 | Deliverable, Deliverables Report, Drug Substance, POI - Drug Substance, Publication, Raw Materials Program
A proactive risk-based approach to understanding key factors that can introduce product variability is necessary to avoid delays. One such factor identified is elemental impurity variability introduced by cell culture media. Though the impact of the variability will differ, it is important
that both manufacturers and supply partners understand the sources of elemental impurities and perform risk assessments to identify mitigation strategies. Such assessments will allow an understanding of the level of risk, and what steps may be taken to dissipate it. This paper is an effort to drive regulatory bodies, drug manufacturers, supply partners and N-1 suppliers toward a common understanding of the problem and possible solutions that can be taken towards risk mitigation. Though there may not be a single or ideal solution for this issue, a common rational approach can be taken by all parties to understand the impact on their processes and products, to drive identification of mitigation strategies.
The four steps for registering innovative and complex raw materials
Feb 2022 | Drug Substance, News, Regulatory
The Covid-19 pandemic has put extra strain on an already stretched biopharmaceutical supply chain. As industry has grown exponentially over the last couple of years, there has been an increased demand for materials and many existing products share these with the new Covid-19 vaccines, testing kits and therapies. As a result, these materials have been diverted to this high-priority use. The pandemic has therefore demonstrated that reliance on...
An industry reflection on the application of the Russian Pharmacopeia to the registration of biologics
Sep 2021 | Deliverable, Drug Substance, POI - Regulatory, Post Approval Strategies, Publication, Regulatory
In this paper, a BioPhorum member team of experts in biologics and vaccines have summarized the current challenges linked to the registration of global products in Russian Federation. This paper describes some of the challenges faced by the industry in relation to current pharmacopoeial requirements for biologics and vaccines and presents a framework of options and activities that would lead to greater alignment with the ICH and the expectations of other regulatory agencies.
Raw Materials: Supplier change notifications: change areas and requirements
Jun 2021 | Deliverable, Drug Substance, POI - Drug Substance, Publication, Raw materials, Raw Materials Program, Supply Partner
This guidance document identifies the relevant change areas, and for each area, exemplifies the type of changes which the biopharmaceutical industry needs to be informed about. It also lists the required information, in terms of supporting data and documentation, to support notification of changes. This guidance is relevant to all raw materials used to produce biopharmaceutical products, including but not limited to cell culture media, fermentation broth components, column resin, buffers, solvents, and excipients. By highlighting the changes biopharmaceutical industry end-users need to know about and specifying the information required, the intention of this industry-aligned guidance is to reduce the quantity of rework required and the time taken to process change requests. In turn, this will reduce variability in demand patterns as end-users refrain from building extensive inventories to mitigate against the perceived risks which arise from proposed changes. While complete alignment and standardization on the information which should be provided for changes is not possible, a more robust alignment on the typical information required, as set on in this guidance, will significantly improve the current state.
Deviation Management (DMS): Guide to implementing a risk based deviation management system
Sep 2020 | COVID 19, Drug Substance, POI - Drug Substance
BioPhorum has developed a risk-based deviation management system (DMS). 13 member companies have implemented this approach, and summary data from these companies shows improved quality performance plus an average time saving of 22,200 work hours per site per year, which is equivalent to a $888k cost saving.
This guide outlines the work of the BioPhorum DMS Workstream in defining and creating a simplified and effective risk-based deviation management system with advanced RCA methodologies, and a track-and-trending process of low-risk events. It includes everything required to build a risk-based approach to DMS, including the business case for change, the new process, risk-based tools, and a detailed sharing of post-implementation benefit.
Shared clean-in-place systems: to share or not to share
Jul 2020 | Drug Substance
This paper discusses design challenges such as how biomanufacturers often use extreme measures to segregate a post-nanofiltration operation from a cell-culture operation – but use a common glass washer or clean-in-place (CIP) skid for cleaning and sanitizing components from the two operations. The article looks at this apparent contradiction by using a mathematical model to evaluate the potential carryover/crossover risk.It aims to simplify production facilities so that a manufacturer doesn’t have multiple systems performing the same task. This means lower costs and complexity and facilities that are quicker to build and operate.
Microbial control: Disinfectant Efficacy: Understanding the Expectations and How to Design Effective Studies That Include Leveraging Multi-Site Data to Drive an Efficient Program
May 2020 | Drug Substance
This paper provides general guidance on how to perform disinfectant efficacy validation and implementation. It includes how to ensure the concepts of disinfectant efficacy are understood, how to interpret facility data and use it to demonstrate control awareness for your facilities, and how to leverage the data to reduce redundancies in validation or verification. It also details an efficient way to qualify disinfectants without impacting the quality of the study. The recommended program could be more robust than any individual approach developed in any one site.
As regulators now require thorough validation studies, the paper is not about why you need to do disinfectant efficacy, but how you do it so you can meet that regulatory challenge for study data and will help build a business case for change.
Disposables: Extractables testing of polymeric single-use components used in biopharmaceutical manufacturing
Apr 2020 | COVID 19, Drug Substance, Extractables & Leachables, POI - Drug Substance, Supply Partner
This revised extractables protocol for polymeric single-use components in biopharmaceutical manufacturing is based on an extensive scientific review and represents the combined opinion of the biopharmaceutical manufacturers and, crucially, the supply chain. It will reduce costs and focus people on the important data points. The protocol provides guidance on the suggested methods for extractables studies, including sample preparation, extraction conditions, recording test-article sampling conditions, and reporting data from the analysis of extracts. Flexibility is built-in, allowing suppliers to alter many study parameters due to restrictions based on the use of SUS, physical form factor, chemical compatibilities, etc.
The new protocol includes significant changes to the 2014 version, including the removal of 5M sodium chloride and 1% Polysorbate 80 as extraction solvents, the elimination of the time-point zero interval, and the elimination of elemental analysis of 50% Ethanol extracts.
Microbial control: Risk assessment of traditional culture-based microbiological tests requiring contemporaneous verification
Mar 2020 | Drug Substance, POI - Drug Substance
Unlike most analytical chemistry tests relying on validated automatic instrument systems from which the test is automatically performed, data are electronically recorded and archived; traditional microbiological tests are performed manually, and the results are generally obtained by visual examination and transcribed by hand. Ensuring data integrity in microbiological test data is fundamental and significant to drug product quality and patient safety. The soundness of traditional culture-based microbiological test data is largely determined by multiple factors including effective sampling, valid testing and appropriate result reading and interpretation. In this paper, the fundamentals ensuring microbiological test data integrity are discussed and qualitative risk assessment is performed for the traditional culture-based quality control (QC) microbiological tests requiring contemporaneous verification by the second person.