Abstract
This blinded "Members Only' survey, developed and completed by 14 companies in the the BioPhorum Development Group, Analytics Team, considers the state of MAM in the industry. More specifically the survey covers 30 questions and several sub-points covering such topics as, the purposes companies have used MAM for, the state of company implementation, preparation of samples, use of CQAs, the approach to validation, dealing with equipment variations, implementation and challenges in QC, data analysis and software automation and regulatory feedback. Abstract
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. Abstract
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. Abstract
This is a companion presentation to the paper Best practices in bioassay development to support registration of biopharmaceuticals has been written by members of BioPhorum Development Group Bioassay workstream and published online in BioTechniques in September 2019. Available on to members of the phorum only was presented at USP's 8th Bioassay workshop and at the PEGS Summit program at BioProcess International. Boston MA, Sept 2020. Abstract
This blinded 'Members Only' survey designed and completed by 15 leading pharmaceutical companies, compares and draws conclusions on 62 different aspects on bioassay qualification and validation. The survey questions cover matters such as, guidelines do you use for your validation experimental design, qualification parameters and levels used, acceptance criteria, personal and functions involved, provision and preparation of samples, potency levels and linearity considered, use of DoE and QbD and how these change in development phases, specification ranges and re-validation. Abstract
The FDA's positions is that “Clinically relevant specifications can be defined as a set of criteria and acceptance ranges to which drug products should conform in order to deliver the therapeutic benefit indicated in the label.” and that “Clinically relevant specifications increase flexibility within the pharmaceutical manufacturing sector while maintaining quality by establishing acceptance criteria based on clinical relevance, instead of process capability or manufacturing process control.” The professionals in the BioPhorum CMC Regulatory team are aligned on the concept, but still have practical questions about what is expected. To address this they considered a case study concerning an mAb-X product and then survey the experience and discussed the positions of twenty four biopharma companies. This 'Members Only' document captures the details of the case study and points of discussion between the companies. No views are attributable to any individual company. Abstract
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.
Abstract
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. Abstract
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. Abstract
To gain a better understanding of current industry approaches for establishing biopharmaceutical drug product (DP) robustness, the BPDG-Formulation Workstream conducted an intercompany collaboration exercise, which included a benchmarking survey and extensive group discussions around the scope, design, and execution of robustness studies. The results of this industry collaboration revealed several key common themes: (1) overall DP robustness is defined by both the formulation and the manufacturing process robustness; (2) robustness integrates the principles of quality by design (QbD); (3) DP robustness is an important factor in setting critical quality attribute control strategies and commercial specifications; (4) most companies employ robustness studies, along with prior knowledge, risk assessments, and statistics, to develop the DP design space; (5) studies are tailored to commercial development needs and the practices of each company. Three case studies further illustrate how a robustness study design for a biopharmaceutical DP balances experimental complexity, statistical power, scientific understanding, and risk assessment to provide the desired product and process knowledge. The team discusses identified industry challenges with regard to biopharmaceutical DP robustness and presents some recommendations for best practices. Abstract
As a companion to the paper 'An inter-company perspective on biopharmaceutical drug product robustness studies', you can find here a poster and presentation that have been presented at five conferences between August 2017 and September 2019. Abstract
High concentration formulations can be challenging to develop and there was interest in the Formulations workstream in the comparative approaches taken towards stability testing, syringability testing, the approach to subvisible particles, how solubility, aggregation, and particle formation issues are studied, the challenges associated with high viscosity formulations in PFS, the use of needle-free delivery systems or large volume injectors, concentration-driven formulation challenges, approach to unstable biopharmaceuticals, how acceptable opalescence is defined, how Gibbs-Donnan and excluded volume effects for excipients are accounted for, among other more detailed questions Abstract
This blinded survey was devised and completed by 11 companies, compares and explores the use of surfactants in biologic formulations. In total the responsants covered 59 different questions in such areas as, general use of surfactants, polysorbate raw material, polysorbate handling for GMP manufacture, polysorbate degradation, specifications, poloxamer and health authorities interactions. Abstract
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
This presentation compliments the papers and risk manage tool. The goal of the Host Cell Protein (HCP) Workstream is to deliver for industry alignment; building a common understanding of agency requirements for HCPs through benchmarking and gap analysis of guidance. To widen understanding of the risks associated with HCPs and what can be done to mitigate these risks during process development. This poster available to 'Members Only' discusses, Industry benchmarking, understanding of what companies are doing in order to understand HCP risk through the stages of development, risk assessment methodology and risk scoring tool to perform qualitative and semi-quantitative assessment of risk when dealing with HCPs, case studies and next steps.
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. 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. Abstract
In the manufacture of biologics produced in mammalian cells, one recommendation by regulatory agencies to help ensure product consistency, safety, and efficacy is to produce the material from a monoclonal cell line derived from a single, progenitor cell. The process by which monoclonality is assured can be supplemented with single-well plate images of the progenitor cell. In this paper the BioPhorum Monoclonality team highlight the utility of that imaging technology, describe approaches to verify the validity of those images, and discuss how to analyze that information to support a biologic filing application. This approach serves as an industry perspective to increased regulatory interest within the scope of monoclonality for mammalian cell culture–derived biologics Abstract
Members can find here a companion presentation to the paper entitled 'Implementation of plate imaging for demonstration of monoclonality in biologics manufacturing development'. This presentation has been made at, BioProcess International West Conference, San Francisco, March 2018, Cell Line Development and Engineering, San Francisco - KNect365, June 2018 and BioProduction 2018 - Cell Line Development and Engineering Symposium, October 2018. 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
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. Abstract
Members can download presentations that complement the paper 'Retrospective evaluation of cycled resin viral clearance studies - A multiple company collaboration'. These materials have been presented at twuce between Oct 2018 and May 2019. Abstract
Considerable resources are spent within the biopharmaceutical industry to perform viral clearance studies, which are conducted for widely used unit operations that are known to have robust and effective retrovirus clearance capability. The collaborative analysis from the members of the BioPhorum Development Group Viral Clearance Working Team considers two common virus reduction steps in biopharmaceutical processes: low-pH viral inactivation and viral filtration. Analysis included eight parameters for viral inactivation and nine for viral filtration. The extensive data set presented in this paper provides the industry with a reference point for establishing robust processes in addition to other protocols available in the literature (e.g., ASTM Std. E2888-12 for low-pH inactivation). In addition, it identifies points of weakness in the existing data set and instructs the design and interpretation of future studies. Included is an abundance of data that would have been difficult to generate individually but collectively will help support modular viral clearance claims. 