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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.

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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.

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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.

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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.

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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.

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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.

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Shared clean-in-place systems: to share or not to share

Shared clean-in-place systems: to share or not to share

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.

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Microbial control: Disinfectant Efficacy: Understanding the Expectations and How to Design Effective Studies That Include Leveraging Multi-Site Data to Drive an Efficient Program

Microbial control: Disinfectant Efficacy: Understanding the Expectations and How to Design Effective Studies That Include Leveraging Multi-Site Data to Drive an Efficient Program

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.

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Extractables testing of polymeric single-use components used in biopharmaceutical manufacturing

Extractables testing of polymeric single-use components used in biopharmaceutical manufacturing

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.

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