Abstract
This database and paper provide a comprehensive review and list of potential problematic HCPs that could impact the safety, efficacy, and quality aspects of CHO-produced biologics during their development and manufacturing. They provide a reference on the best practice and control strategy for “high-risk” HCPs” in the biopharmaceutical industry.
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To understand industry approaches for developing high-concentration formulations, BioPhorum Development Group Formulation workstream conducted an inter-company collaborative exercise which included several surveys. This collaboration provided an industry perspective, experience, and insight into the practicalities for developing high-concentration biologics.
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Key messages emerging following analysis of the survey are that bridging approaches differ between companies and there is lack of a harmonized approach outside a commercial setting. The Workstream are examining if a guidance paper would be beneficial.
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This 'Members Only' survey examines company approaches to USP129. In total it covers the responses from 11 companies and also covers how they approach equivalence and deal with different products.
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A benchmarking survey looking at what assays that have been automated including which steps, equipment used and validation strategy.
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Biological activity is a critical quality attribute for biopharmaceuticals, which is accurately measured using an appropriate relative potency bioassay. Developing a bioassay is a complex, rigorous undertaking that needs to address several challenges including modelling all of the mechanisms of action associated with the biotherapeutic. Bioassay development is also an exciting and fast evolving field, not only from a scientific, medical and technological point of view, but also in terms of statistical approaches and regulatory expectations. This paper discusses how bioassays are developed, challenges current thinking and discusses the benefits of different practices, and details a very practical industry-wide approach to the best practices for developing, implementing and maintaining cell-based assays.
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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.
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Climate change and global warming resulting from greenhouse gas emissions are widely recognized as the biggest threats to global health. The healthcare sector is responsible for 4–5% of global emissions, more than 70% of which are driven by supply chains.
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BioPhorum’s in-depth feedback includes 70 line-by-line, detailed comments, including the rationale for the points and any proposed changes/recommendations that are deemed necessary by the team to ensure a harmonized implementation across industry and regulatory agencies.
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Benchmarking survey exploring which mechanism of action assays are automated and the main concerns when automating bioassays.
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A presentation at Well Characterized Biologicals and Bioassays conference entitled Industry approaches to automation of cell based bioassay.
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A BioPhorum member survey to gather preliminary information from across the biopharmaceutical industry on the characterization and risk assessment of HCP using mass spectrometry.
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A BioPhorum member only survey gathering feedback on initial submission Biologics License Applications (BLA) / Marketing Authorization Application (MAA) supplement/variation, etc.) and the outcome of health authority review and approval of the submission.
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This article looks at the role of technology in the workplace and specifically how the Senior BioPhorum Connect group is addressing issues such as the use of remote working technologies, cyber security and digitizing the cGMP space.
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The measurement of contract development and manufacturing organization (CDMO) performance and relationship management is complex and challenging. This 'members only' balanced scorecard (BSC) tool is based on the experience and inputs of Merck Inc, Pfizer, Roche and Sanofi and provides a spreadsheet-based tool that subject matter expert can customize as required for use within their own organization.
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A BioPhorum member only survey to share knowledge into how, why and when enzymatic activity assays are performed.
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This poster summarizes thoughts of the CMC Considerations for Expedited Development Point Share team on opportunities and challenges of CMC development under accelerated registration pathways and includes some proposes for unconventional approaches for accelerated development. With a focus on breakthrough therapy and based on a benchmarking survey, discussions around the tiered requirements for CMC sections by eCTD subchapters, as well as risks associated with the acceleration options. The results of this industry collaboration reveal several key common approaches such as risk-based approach and leveraging platform knowledge.
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This presentation details the benchmark survey conducted by the member companies of the CMC Considerations for Expedited Development Point Share . The purpose of the survey was to help members understand how companies are defining and using Prior Knowledge (PK) to support marketing approval (eg BLA) filings in accelerated settings. The survey was completed by 16 companies and covers 11 key questions including, types of data considered as PK, how PK is obtained and used, the form of PK, and perceived and real benefits
Abstract
Forced degradation studies (FDSs) are often used in biotherapeutic development to assess criticality of quality attributes and in comparability studies to ensure product manufacturing process consistency. To gain an understanding of current industry approaches for FDS, the BioPhorum Development Group–Forced Degradation Point Share group conducted an intercompany collaboration exercise, which included a benchmarking survey and group discussions around FDS of monoclonal antibodies. The results of this industry collaboration provide insights into the practicalities of these characterization studies and how they are being used to support the product lifecycle from innovation to marketed products. The survey requested feedback on the intended purpose, materials, conditions, number and length of time points used, and analytical techniques carried out to give a complete picture of the range of common industry practices. This article discusses the results of this global benchmarking survey across 12 companies and presents these as a guide to a common approach to FDS across the industry which can be used to guide the design of FDS based on chemistry and manufacturing control product life-cycle and biomolecule needs.
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A BioPhorum member only benchmarking survey looking at approaches on the use of forced degradation studies for drug product (lyo to liquid formulation swap).
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The outcomes of several discussions on a survey conducted on forced degradation studies oxidation studies is available in this BioPhorum member only document.
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A benchmarking survey looking at the Forced Degradation Study (FDS) correlation to long term degradation. It demonstrates the challenges in the area experienced by member companies.
Abstract
BioPhorum Formulation Workstream has identified the increased use of closed system drug-transfer devices (CSTDs) with biologics, without an associated compatibility assessment, to be of significant concern. The use of CSTDs has increased significantly in recent years due to the recommendations by NIOSH and USP that they be used during preparation and administration of hazardous drugs. While CSTDs are valuable in the healthcare setting to reduce occupational exposure to hazardous compounds, these devices may present particular risks that must be adequately assessed prior to use to ensure their compatibility with specific types of drug products, such as biologic drugs, which may be sensitive. The responsibility of ensuring quality of biologic products through preparation and administration to the patient lies with the drug product sponsor. Due to the significant number of marketed CSTD systems, and the large variety of components offered for each system, a strategic, risk-based approach to assessing compatibility is recommended herein. In addition to traditional material compatibility, assessment of CSTD compatibility with biologics should consider additional parameters to address specific CSTD-related risks. In this paper published in the Journal of Pharmaceutical Sciences the Workstream has proposed a systematic risk-based evaluation approach as well as a mitigation strategy for establishing suitability of CSTDs for use.
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Survey examining the types of testing conducted and included in filing and research looking at companies' approaches to setting and using acceptance criteria.
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The second member only survey from the Cell Line Development workstream gathering information on the genetic characteristic and stability of cell lines.
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This 'Members Only' benchmark was used by BioPhorum to initiate discussions with USP to create a common direction on the creation of valuable ‘performance standards' to identify and quantify host cell proteins (HCPs) using mass spectrometry. As such it provides a valuable survey of the use of mass spectrometry in this domain and the shared priorities in the industry.
Abstract
Host cell protein (HCP) constitutes a significant class of process-related impurities in biological drugs. The complexity and diversity of residual HCP composition in biologics and the incomplete understanding of their potential impact also pose unknown risks besides some of the well-known risks from certain problematic HCPs. This can make the HCP risk assessment and management an industry-wide challenge. Although attempts have been made to address these challenges in the biopharmaceutical industry, gaps still remain in terms of how to manage the risks associated with HCP during bioprocess development. To this end, a BioPhorum Development Group (BPDG) HCP working team consisting of several companies initiated a collaboration among its members to align industry best practices and generated a generic risk assessment tool to manage HCP-related risks identified during biologics development from both an assay development and process development perspective. Distinct from individual HCP identity-based safety risk assessment, this tool focuses on the manufacturing process through process development. The tool will help companies to tackle the risks associated with HCP within the development lifecycle. The intent the tool is to provide a template in order to guide process development teams using a scientific knowledge-based risk control strategy, where process or assay changes may be deemed necessary to reduce the risks caused by inadequate removal of HCP upon experimental studies to assess impact of HCPs on product safety, efficacy, and stability. Companies implementing this risk management model can apply their own unique set of circumstances, products and experience to perform a more comprehensive and robust assessment of risk, identify the priority in which risk reduction steps should be applied.
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A presentation on cross-company collaborative work and learnings produced from an industry perspective on host cell protein risk assessment. The presentation included a history of the HCP workstream, previous publications, planned future work and publication plans.
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A BioPhorum member only benchmarking survey looking at the converting the implementation of PAT for Raman and flow VPE technologies
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The purpose of this BioPhorum member only survey is to assess the use and control strategy for ready to use (RtU) cells used in bioassays.
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This poster recently presented at CASSS Bioassay and BEPA describes selected results of an industry collaboration to encourage discussion on common approaches to ready to use (RtU) for bioassays cell manufacturing, testing and implementation across the industry.
Abstract
Small-scale models (SSMs) are widely used in the biopharmaceutical industry. These models are used for process development and optimization, scale-up, technology transfer, process characterization, process validation, virus clearance studies, and resolution of deviations encountered during manufacturing throughout a product’s lifecycle. SSMs are also referred to as ‘scale-down models’ or ‘scaled-down models’. Demonstration that an SSM is representative of the large-scale manufacturing system is called ‘small-scale model qualification’ (SSMQ), which is sometimes also referred to as ‘assessment’, ‘evaluation’, or ‘verification’. The demonstration is an important task that supports process validation and is required by regulatory authorities. However, design, execution and analysis of SSMQ studies can be challenging due to the lack of clear guidance on current best practices. This white paper provides options and tools for design, execution, and data analysis of SSMQs together with illustrative case studies.
Abstract
The management of knowledge in biopharmaceutical organizations has been recognized as an important challenge over recent years. Defining the pain points and designing successful knowledge management (KM) solutions have proven difficult. To address this challenge, BioPhorum Technology Roadmapping applied a KM best practice methodology to capture a process-based knowledge map for a major business process; this was performed by companies who develop and commercialize new therapies. The resulting assessment of knowledge flows revealed that there are significant challenges to both explicit and tacit knowledge flow across the control strategy and method development / technology transfer processes. Some generalized solutions have been proposed. As part of this work, a detailed spreadsheet tool was developed so that organizations can repeat this work on their business processes to understand their knowledge–flow issues and develop fit-for-purpose solutions. The knowledge mapping tool is available here. Detailed instructions are available within the tool itself. The data in the sheet reflects that used in the illustrative example documented in the companion paper. The data is intended to be removed and replaced with end users data in support of their own KM efforts.
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A benchmarking survey on the experiences in applying prior knowledge and modular claims to health authority regulatory submission for clinical programs and licensure applications.
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Historically, the biopharmaceutical industry has relied on traditional pharmaceutical manufacturing practices to make and release products. This publication examines the future of biopharmaceutical manufacturing by presenting the vision of fully implemented in-line monitoring (ILM) and real-time release. This aspirational vision includes full ILM, predictive analytics and advanced process controls (APC) enabling release of product in real time, with concomitant predictive and preventative alerts and resolution of process, equipment and other production issues.
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A BioPhorum member only benchmarking survey looking at the similarities and differences between strategies of member companies on the qualification and validation of bioassays.
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A benchmarking survey prompted by an increase in regulatory questions regarding polysorbate.
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Abstract
Delivered at BioProcess East, Boston, September 2019, this presentation details the conclusions from a survey and discussions about this topic. Designed, completed and discussed by 14 leading biopharmaceutical companies of the CMC Regulatory subteam, the purpose of the survey was to determine companies' approaches to S.4.2 section content. More specifically what content different companies providing within each subsection of S.4.2 for non-compendial methods, understand to what extent the level of information provided in core dossiers can be aligned between countries, to minimize the need for global document lifecycle management and if specific feedback from any countries been provided to indicate what content is required? This document is reserved for the use of BioPhorum Members only
Abstract
A comprehensive benchmarking survey aimed at collating data on the technical practices involved in therapeutic protein production and evaluation of if/how this has changed in response to the COVID-19 pandemic.
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A BioPhorum member only survey that aims to tackle questions around the types of PAT software for chemometrics and PAT infrastructure used, ease of instalment, its advantages and limitations
Abstract
To evaluate the application of PAT tools to the development and commercialization of a bioprocess, BioPhorum conducted a benchmarking survey of biopharmaceutical companies and published the results in Biotechnology and Bioengineering journal. Investigators assessed fifteen companies receiving seventeen responses from them and evaluated more than 20 different types of PAT tools in manufacturing using an industry-wide assessment to identify and rank the tools based on technological attributes such as technology maturity, ability to enable process control, and ease of implementation, as well as their business value such as simplicity of implementation, lead time, and cost reduction.
Abstract
In order to evaluate the application of PAT tools to the development and commercialization of a bioprocess, BioPhorum conducted a benchmarking survey of biopharmaceutical companies and published the results in Biotechnology and Bioengineering journal. The results obtained in the survey can guide scientists and new manufacturers in terms of quality product development and all the stakeholders including funding agencies to assess the business value of tools and techniques employed during biologics manufacturing. This article published in Medicine Innovates is a synopsis of the paper
Abstract
The interplay, engagement and interactions between Sponsor and C(D)MO are frequently considered, presented and discussed at the BioPhorum Development Group, a gathering of more than 20 global biopharmaceutical companies, representing both Sponsor and C(D)MO organizations, with a focus on chemistry, manufacturing and controls (CMC)-related clinical biopharmaceutical development, testing and manufacture. This self-survey was aimed at understanding outsourcing approaches and governance and focused on analytical development and testing, process development and manufacturing, project management and governance and quality system and regulatory support. From the aggregate survey responses in each area, key trends were identified, providing insights to potential best practices
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This member only survey covers the challenges of working with ultra-high concentration formulations, including; low dose volume products, viscosity aspects related to manufacturing and delivery, manufacturing and filling, automated screening, analytical challenges, osmolality considerations (hyper and hypo), syringeability, acceptable injection forces.
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This benchmarking survey from the BioPhorum Forced Degradation team has conduced a benchmarking survey for formal comparability assessments.
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For the last three years, the BioPhorum Viral Clearance team have completed a short survey on their published papers to understand how they have been used and the response of regulators if used to support filings. This is the report for 2022
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A benchmarking survey looking at worse-case conditions, which is contributing to a paper that the team are currently writing.
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Poster presentation at BPI East based on analysis of the Viral Clearance worst-case conditions benchmarking survey.
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This member only resource developed by the BioPhorum Development Group Viral Clearance team is based on their analysis of the worst-case conditions benchmarking survey and was presented at the PDA Viral Clearance conference in Brussels in June 2022.
Abstract
This paper sets out a retrospective analysis of industry data, comparing virus clearance in new and repeatedly cycled resins for two of the most commonly used chromatography steps in biopharmaceutical manufacturing: protein A and anion exchange. The vast data, collected over several decades from 12 member companies, was analyzed by the authors with the support of a statistician. The result is a coherent data set in an accessible, collated format. The compelling conclusion of the paper is that viral clearance capability is not negatively impacted by resin cycling. This supports the view that viral clearance studies for repeatedly cycled resins are not necessary if appropriate cleaning methods are applied. Companies will be able to compare their own product-specific data with the collated data in the paper to provide an evidence-based rationale for health authorities and regulators for their own manufacturing processes.
