Drug Substance

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

The risk of viral contamination is acknowledged when developing biopharmaceutical products derived from mammalian-cell culture. And viral clearance and appropriate viral segregation are important factors in the manufacturing process and facility design. Good manufacturing practice guidelines from the US FDA and the EMA emphasize that appropriate segregation of process operations is a regulatory expectation. However, the word ‘appropriate’ is...

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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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Standards and best practices to support trace metal quantitation in cell culture chemically defined media and hydrolysates

In March, Dr Bala Ramanathan, Senior Scientist at Janssen presented the latest views, standards and best practices to Support Trace Metal Quantitation in Cell Culture Chemically Defined Media and Hydrolysates. The webcast (linked above/below) was organized by BioPhorum and USP.   What the webcast covers Many elements such as copper, manganese, zinc, and iron have significant biological relevance, and are well established as key contributors to...

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Microbial control: Risk assessment of traditional culture-based microbiological tests requiring contemporaneous verification

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.

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Human Performance: ‘Blue sky’ thinking in human performance and how to get there

In any industry, quality is the building block of everything. People are relied on to deliver the services and products customers expect and need. This is especially so in biopharmaceuticals. But what happens when things go wrong? And what makes them go wrong in the first place? The reasons are myriad but ‘human error’ is often cited as the cause of problems such as accidents, product recalls and patient safety issues. Unfortunately, a human error is not seen as an opportunity to learn, but as something that drains time, money and resources. Changing this mindset is crucial to a better understanding of how success and failure happen within an organization, and how to improve its potential to anticipate, monitor, respond and learn – the cornerstones of resilience. This paper sets out to accelerate industry’s maturity by building a greater understanding of what is desired and explaining how to get there. It provides proven guidance and a case
study of why one company’s standard approaches to root cause analysis were ineffective at reducing repeat events – both minor events but also significant ones that caused a loss of product and production time, such as contaminations. It discusses how the culture of the company changed from one of ‘it only happened once’ with weak corrective and preventive actions, to one where ‘human errors’ were only considered symptoms of wider system-level problems in the organization.

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To err is human: How to improve risk management through ‘blue-sky’ human performance

In any industry, quality is the building block of everything. People are relied on to deliver the services and products customers expect and need. This is especially so in biopharmaceuticals. But what happens when things go wrong? And what makes them go wrong in the first place? The reasons are myriad but ‘human error’ is often cited as the cause of problems such as accidents, product recalls and patient safety issues. Unfortunately, a human...

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Russia: In-country analytical testing of biopharmaceuticals, general recommendations

In 2020 the Russian agency adopted a new testing regimen for biological imports, that moves from testing all batches to testing the first imported batches and then potentially only annually. While the changes are intended to support industry and align with procedures in other regions there is concern that some parts of the approach and unintended consequences may worsen the supply of biological products to patients. This paper makes a series of proposals and recommendations to mitigate these concerns and help alignment between the Russian Federation requirements and those of other prominent agencies.

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Russian release – how to manage the risks of new analytical testing in Russia

The Russian Federal Service for Surveillance in Healthcare currently mandates in-country testing for all batches of biologicals imported into its market. However, later this year, a new regulation will change the testing regimen. This will move from testing all batches (although only tests that are deemed ‘simple’) to testing the first batches of biological products that are imported and then on an annual basis – but performing all tests in the...

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