Drug Substance

Viewing related articles

Closed systems: How much harm can a single droplet do? Considerations for a viral inactivation step

Closed systems: How much harm can a single droplet do? Considerations for a viral inactivation step

This paper discusses a systematic approach to assessing virus segregation measures, which can help biopharmaceutical developers achieve sufficient segregation for the low-pH inactivation steps in their downstream processes. It covers a process description, mathematical modeling, failure modes and the effects on viral clearance, and the importance of proper design.

read more
Post-Approval Strategies: Risk-based approach for analytical comparability and comparability protocols

Post-Approval Strategies: Risk-based approach for analytical comparability and comparability protocols

Chemistry, manufacturing, and control post approval changes are an intrinsic part of the life cycle of pharmaceutical products. In this paper, the authors examined the potential impact of such changes on the product quality, safety, and efficacy of biologics. Comparability studies and more specifically analytical comparability are introduced as one of the tools that can support both biomanufacturers and health agencies in ensuring that patient safety and product safety and efficacy is maintained through the proposed changes. Together with a scientific risk-based review approach based on product and process knowledge and the definition of acceptance criteria that will ensure that the product is “essentially similar”, what constitutes a holistic comparability study is detailed. ICH Guidelines principles and definitions are used throughout the paper to aid the reader with other appropriate references. Finally, two case studies are presented: change to the manufacturing facility of the drug substance, and change to the manufacturing process of a drug substance intermediate and manufacturing facility.

read more
Disposables: Single-use systems bag assembly leakage and defect toolkit

Disposables: Single-use systems bag assembly leakage and defect toolkit

This toolkit gives users a set of tools to respond to problems and materials to include in their communications and operator training.It will help reduce product losses, investigations, manufacturing disruptions and the number of leaks. It equips industry with tools to help standardize the vocabulary around SUS anatomy and processes and expand its understanding of SUS abnormalities.

read more
Human Performance: Investigation root cause analysis best practices

Human Performance: Investigation root cause analysis best practices

The Human Performance Workstream recognized the importance of effective investigation techniques during their collaborative work in 2016. The team conducted a survey of member companies and shared within the workstream a report with 14 recommendations, and 11 best practice company case studies. These recommendations and case studies were used to create an investigator training package for the industry, and to inform the contents of the human performance
assessment tool, which the group uses to benchmark and improve human performance.

read more
Raw Materials: Trace element variation of soy hydrolysate used in biopharmaceutical manufacturing

Raw Materials: Trace element variation of soy hydrolysate used in biopharmaceutical manufacturing

It is important for biomanufacturers to understand trace element variation within soy hydrolysates (by knowing the minimum, maximum and average concentrations), so they can determine if the degree of variation has an impact on their process. The knowledge gained through process characterization across the maximum variation found in soy hydrolysates can be evaluated to determine if it has an impact on the biomanufacturers’ process or product on a product-byproduct basis.

This is the first in a series of proposed hydrolysate white papers. The purpose is to educate users of hydrolysates of the various characteristics that they should be aware of to manage their processes. There are many parameters to consider within a hydrolysate. The intention is to start with data that can be collected on as many different hydrolysates used in the biopharmaceutical industry.

read more
TVR: Determining testing validation and release requirements for single-use systems through risk assessment

TVR: Determining testing validation and release requirements for single-use systems through risk assessment

When testing single-use items for biopharmaceutical manufacturing, when is it appropriate to leverage vendor data, and when does the end-user need to carry out testing? Is current regulatory guidance clear and sufficient in the fast-moving area of disposables? This best practice guidance has been developed as one of a suite of tools designed to assist the industry in providing a risk-based approach to testing requirements.In the rapidly evolving area of single-use systems (SUS), the industry will benefit from standardization while leveraging risk-based approaches to testing requirements to ensure compliance of parameters that are important for the process and product quality. This document establishes best practice guidance on how to use risk-assessment methodology to evaluate the level of testing needed to qualify and release SUS.

read more
Extractables: A comprehensive review of BioPhorum standardized extractables testing data – a deep dive into similarities, differences and trends across extraction solvents and time points

Extractables: A comprehensive review of BioPhorum standardized extractables testing data – a deep dive into similarities, differences and trends across extraction solvents and time points

Extractable and leachable (E&L) compounds associated with the use of polymeric single-use systems (SUS) are of primary concern due to their direct impact on product and patient safety. The 2014 Biophorum extractables protocol provided a standardized framework to conduct E&L testing and has been widely used by SUS suppliers as well as the end-user biomanufacturing companies. Since its implementation, several concerns associated with the testing methods proposed in the protocol have been raised by testing laboratories. A comprehensive review of the data generated using the 2014 BioPhorum extractables protocol was initiated by Biophorum’s Extractables and Leachables workstream to mitigate these concerns.

This document aims to summarize the findings of the data review and make scientific, data-driven recommendations to address specific concerns about extraction solvents and testing timepoints. This review established that certain extraction solvents (5M Sodium Chloride and 1% Polysorbate 80) and timepoints (Time 0) proposed in the testing matrix of the 2014 protocol added limited value to determination of the full extractables profile. Such trends were
observed for organic and elemental extractables alike. Based on these findings, specific recommendations about elimination of these solvents and timepoints are outlined in this document.

read more
Change Notification: A guide to change notification packages for single-use manufacturing systems

Change Notification: A guide to change notification packages for single-use manufacturing systems

This paper is intended to be an all-inclusive manual (a one-stop shop) on change notification best practices for single-use biomanufacturing systems. A summary of previous publications is also provided. This includes improvement updates to the decision tree and supporting table based on user feedback. This paper delineates the main attributes of an effective supplier change notification program. The team’s vision for this toolkit is to facilitate adoption of these practices by the majority of end-users and suppliers in the single-use supply chain. In time, it is hoped that these practices will become reflected in quality management practices and in formal business agreements.

read more
Deviation Management (DMS): Guide to implementing a risk based deviation management system

Deviation Management (DMS): Guide to implementing a risk based deviation management system

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.

read more