Extractables: New streamlined protocol and industry portal

newsApr 30, 2020 | Extractables & Leachables | News

AKTA Ready Bag Kart Hollow Fiber 700

Extractables: New streamlined protocol and industry portal

The BioPhorum Extractables Workstream has made great strides in the world of extractables and is excited to announce an updated, streamlined protocol and a fantastic new web portal.

The protocol, Extractables Testing of Polymeric Single-use Components used in Biopharmaceutical Manufacturing, is based on an extensive scientific review and will reduce costs and focus people on the important data points, while the BioPhorum Extractables Portal will take users directly to the extractables data they need.

The Extractables Protocol

The protocol gives 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. In these cases, the key is to provide details of what changed, why this is scientifically valid and how it meets the overall objectives of extractables testing.

The new protocol includes significant changes to the 2014 version, including:

  • Removal of 5M sodium chloride and 1% Polysorbate 80 as extraction solvents, as these had low unique extraction capabilities
  • Elimination of the time-point zero interval, as compounds observed at this time-point were present at higher concentrations at later time-points
  • Elimination of elemental analysis of 50% Ethanol extracts.

The protocol represents the combined opinion of the biopharmaceutical manufacturers and, crucially, the supply chain. Its main achievements build on the standardization provided by the original paper and include:

  1. Suppliers have generated lots of high-quality data sets in the same format and using the same testing, which allowed the workstream to review the testing protocol using actual data. This review provides a fantastic resource for discussions, e.g. with regulators
  2. The overall quantity of testing performed is reduced by 30–50%. This makes testing more affordable, means that non-essential costs are not added to manufacturing equipment and lowers the barrier for entry to smaller suppliers and innovators
  3. An ‘extractables ecosystem’ has been agreed, which provides guidance on how to share data throughout the supply chain and, ultimately, to the end-user – overcoming historical challenges posed by needing three-way confidential disclosure agreements in many cases
  4. The protocol was developed by a combined team of biomanufacturers and suppliers. It demonstrates how expertise can come together to not only agree on what testing should be performed, but also how to share information effectively to enhance patient safety.

The Extractables Portal

The portal helps users of single-use systems by taking them directly to the extractables data pages of five leading global suppliers and integrators of biopharmaceutical manufacturing single-use systems, and we expect to add many other suppliers very soon. Users can then download extractables data on bags, tubes, valves, etc. These companies form a single-use ecosystem that will help users assess the extractables data of any system they are considering for their product stream.

If you are a BioPhorum Supply Partner and wish to connect your extractables landing page to the BioPhorum Portal, full guidance can be found here about becoming more integrated into the extractables ecosystem. If your company is not a member of BioPhorum and you want to understand more about the benefits of becoming part of the collaboration and how you can join the ecosystem, then contact us here.

Industry influence

Sara Ullsten, R&D Section Manager at Cytiva, said the revised extractables protocol is the outcome of a close collaboration between end-users and suppliers. “By working together as one team, the test protocol could be downsized while still maintaining relevant test conditions to ensure the generation of value-adding data. The downsizing is welcomed by suppliers, as the high cost of testing was preventing the wide adoption of the original BioPhorum protocol among suppliers, especially component manufacturers.”

Using the new protocol addresses many risks – the main one being to patient safety if the final product contains impurities. But there is also a real focus on resolving inflexibility in the supply chain and reducing the significant amount of work involved in extractables/leachables testing. The protocol provides certainty on regulatory inspections and filings and applies a common industry approach, which makes it much easier to discuss and justify decisions taken on extractables testing.

The project has already made a significant impact on the industry – many biomanufacturers have been generating data sets using the original protocol and are now using the new data sets. It has also paved the way for defining user requirements and change notification practices using a collaborative model.

Ken Wong, Deputy Director at Sanofi, said that the revised protocol represents a huge improvement in many areas, “such as simplification of recommended testing, refinement of extraction requirements of broader component types, greater understanding of the risks associated with deleted test solvents, and consistency of test reports with predefined extractable data summary report templates.

“Such accomplishments were built on a strong collaborative spirit of the joint team of end-users and suppliers,” Wong added. “The highly valuable and broad sets of extractable data contributed by the suppliers were critical for our scientific analysis-driven and decision-making processes. Going forward, the supplier base will have a clearer understanding of BioPhorum’s extractable recommendations to follow in their own implementation. I’d like to take this opportunity to thank all suppliers and their representatives for their invaluable contributions.”

Protocol history

Until 2014, biomanufacturers and suppliers couldn’t agree on the conditions for extractables studies or what analytical methods to use. This made it almost impossible for manufacturers to perform valid leachables assessments without resorting to separate testing by each company. This was expensive across the industry, created uncertainty of the testing that regulators might request and added an extra barrier to flexibility in the supply chain.

BioPhorum then published a standardized extractables protocol in 2014, which became a key element of its disposables plan to accelerate the understanding and uptake of SUS.

“The extractables protocol provides a comprehensive, peer-reviewed standard approach regarding extractables testing for the pharmaceutical industry,” said Bill Scott, Scientist II at Biogen Manufacturing Science. “Before its publication, the lack of standards for testing and reporting of extractables caused a great deal of confusion and rework by both raw materials suppliers and end-users. Biogen has been one of the early adopters of the protocol and it has become the backbone of our extractables/leachables platform. The excellent track record that Biogen has enjoyed with regulatory agencies on extractables/leachables testing has, in large part, been due to our adoption of the protocol.”

Follow BioPhorum

Related tags

Recent releases


Submit a Comment

Your email address will not be published. Required fields are marked *

Cell & Gene Therapy

Maximizing the impact of the many advanced therapies under development requires that the industry comes together to improve understanding of how to develop, control and manufacture these life changing therapies.

We connect strategic thinkers in drug development and contract manufacturing organizations with the aim of ensuring harmonization and alignment around issues such as potency assays, phase-appropriate guidance for critical quality attributes, operator safety, regulatory guidelines, and C&GT-specific validation issues, as well as working toward resolving the current challenges to commercializing C&GT products. Discover more and learn about the outputs here.

Development Group

The ever-increasing need to reduce product development lead times and the opportunities to exploit innovative technologies in development are two key industry themes that remain at the forefront of our work. The Phorum successfully connects process development organizations and provides a space where subject matter experts can work on issues such as quality by design and process characterization, cell line technologies, and molecule selection. Read some of the outputs and discover how you could benefit by getting involved.

Drug Substance

Accelerating improvement, exploiting opportunities offered by innovation, and identifying best practice approaches across all aspects of the manufacturing process – these are the essential objectives

Data and digital capabilities are at the core of many of these industry challenges. Work in BioPhorum Drug Substance is informed by BioPhorum Technology Strategy, which has summarized our industry’s market drivers and trends. Capacity, flexibility, sustainability and pace all feature as requirements to succeed in a rapidly changing environment.

Find out more about what our members are currently discussing and learn about some of the successful implementations of our output.

Fill Finish

Quality and demonstrating compliance are two priorities of BioPhorum Fill Finish. Representatives of the world’s top sterile filling operations come together to develop solutions to some of the most intractable technical and regulatory challenges.To address these challenges in drug product aseptic filling (‘fill’) and secondary packaging (‘finish’) operations, our community of industry experts is working relentlessly to continually improve the pharmaceutical quality system (PQS). Together they continue to strive towards developing and implementing safe, predictable, lean, and agile processes in drug product operations. Find out more about the Phorum output here. 

Information Technology

IT and digital advances are crucial in responding to the pharmaceutical industry’s challenges around speed, cost, quality, flexibility, and sustainability. Unlocking and realizing the value in the industry’s IT opportunities is the core mission of the IT Phorum. 

The digital manufacturing facility of the future needs to consider technology advances alongside organizational perspectives while maintaining foundational security requirements. All elements must be considered in the long term to deliver systemic change toward the digital factory vision. Our members collaborate in a format that stimulates and supports industry innovation and implementation. 


BioPhorum Regulatory CMC is affording professionals the opportunity to shape their own collaboration program focused on challenges and opportunities across strategy, science, operations, submissions and compliance. Following a discovery program of work with Heads of Regulatory CMC, in which we identified some key topics of collaboration, we are giving you the opportunity to participate and help us to shape the final collaboration program. This will focus on, Filing and Review, Interactions with Health Authorities, and Harmonization. Our mission is not just to discuss, but to deliver applicable outputs and publications that will have an impact – learn more about how you can get involved.

Supply Chain to Patient

The pharmaceutical outbound supply chain was built on a blockbuster model and doesn’t fit the needs of the changing pipeline and new modalities currently being developed. The geopolitical challenges of recent years have shown that the outbound supply chain needs to evolve to become more agile, and resilient, and address a more expectant end-user bying on patient-centricity. Industry collaboration can accelerate improvements and transform performance in a way not possible when working independently. This Phorum is founded on the belief that learning from each other and challenging current thinking to re-imagine the supply chain can reduce costs and increase efficiency.

Supply Partner

BioPhorum SP members want the inbound supply chain for the biomanufacturing industry to be recognized as one of the best-understood and managed global supply chains. They intend to be not only a trusted advisory group but also the engine that drives change for the industry. Working together, we aim to achieve supply chain transformation that provides:

  • an enhanced robustness and resilience
  • accelerated capability and capacity to effect technology adoption
  • reduced cost of quality, and
  • industry-wide alignment on operational implementation

There’s an extensive list of Phorum successes and tangible benefits that have been delivered to define industry best practise.


The BioPhorum Sustainability program is jointly designed, governed, and delivered by a membership drawn from licence holders, contract manufacturers, major suppliers and niche suppliers. This dynamic partnership means that we can quickly focus on the areas that have the greatest industry impact, and we can leverage learning from each other and other sectors – the chemical industry and the built environment for example.

BioPhorum’s unique ability to build a strong coalition for change for an entire industry is now being applied to the greatest challenge of our generation. Driven by evident industry needs, Phorum members are working to develop agreed industry benchmarks, establish the ROI of sustainability investments and to increase the efficacy of implementation of members’ sustainability strategies.

Technology Strategy

With a mission to define strategies to accelerate technology transformation and support the adoption of innovative technologies, BioPhorum Technology Strategy evolved from BioPhorum Technology Roadmapping, strives to realize the technology roadmap vision 2.0.

This is being achieved through a multi-stakeholder team of member companies with collective capability and influence who are committed to driving forth industry goals associated with: Speed to market, Quality, Value, Agility and On-Demand Supply and Sustainability.

Building on industry feedback to standardize plasmid release specifications

Plasmids release specifications are critical to the manufacture of many cell and gene therapy (CGT) products, but current regulatory... read more

How to predict, optimize and analyze high-concentration biologic therapeutic formulations

Developing high-dose biologic drugs for subcutaneous injection often requires high-concentration formulations. It also needs to optimize... read more

A media fingerprinting toolbox that comes with a host of benefits

Cell culture media raw materials can contain many chemical substances, each with its own properties. While simple substances can be... read more

Why 100% visual inspection does not mean 100% defect detection

There is a common misunderstanding that 100% visual inspection (VI) of biopharmaceutical products should mean 100% detection of defects.... read more

How to bridge the data integration gap between sponsors and contract organizations

Bringing BioPhorum’s unique perspective to continuous manufacturing in biologics

Continuous manufacturing (CM) has been a goal for the pharmaceutical industry for several years. While small molecule drug substances and... read more

Supply Chain to Patient has launched!

Have your outbound supply chain costs increased? Do you want to leverage data and digital technologies more effectively to reduce... read more

Electronic data exchange – the foundation for an efficient, resilient inbound supply chain

The COVID-19 pandemic, geopolitical unrest, and military action across the world have fundamentally disrupted the assumption and practice... read more

How are you improving your environmental sustainability performance?

Climate change and global warming resulting from greenhouse gas emissions are widely recognized as the biggest threats to global health.... read more

Adding value for analytical instrument partners

Analytical instrument vendors have been integral to developing and publishing our technology roadmaps and developing product... read more

Introducing MediPhorum

The medical technology (MedTech) industry is a critical and complex sector. As highlighted during the Covid-19 pandemic, the MedTech industry provides a wide array of products and technologies that are vital to the safe and effective provision of care to many. Also, as seen over recent years, there is often the requirement for flexibility in supply, rapid development, and the introduction of new products to keep pace with global public health demands.

Advanced Wound Care and Wound Management

Advanced wound care (AWC) is the medical treatment for wounds that have not healed properly using conventional wound care products such as gauze, bandages, plasters, and wadding.

AWC involves treating chronic or complex wounds using products that are not as easily obtained over the counter. AWC can be divided into three main categories: wound healing, infection prevention, and restoration.

Drug Delivery

Drug delivery products are therapeutic and diagnostic products combining drugs, devices, and/or biological products, which enable safer and more efficient treatment due to careful and precise drug targeting, local administration, and tailored treatment.

Introducing the new MediPhorum

MediPhorum by BioPhorum has been launched to bring together senior business leaders and subject matter experts across multiple MedTech... read more

Introducing the new MediPhorum

MediPhorum by BioPhorum has been launched to bring together senior business leaders and subject matter experts across multiple MedTech... read more

Introducing the new MediPhorum

MediPhorum by BioPhorum has been launched to bring together senior business leaders and subject matter experts across multiple MedTech... read more
BioPhorum Deliverables Report
BioPhorum brings you the latest Deliverables Report, an informative and inspiring consolidation of the benchmarks, position papers, guidance documents, assessment tools, industry user requirements, study results, and roadmaps produced in the last twelve months.
BioPhorum Downloads
Access a variety of free tools and papers and other resources designed to provide you with up-to-date information and insights to help you make informed decisions and maximize your success. Access our resources today and start making improving and streamlining your business processes.
Case Studies
Welcome to the BioPhorum case studies page, where you can learn how our clients have used our service to discover innovative solutions and save money. Here you can read real-life stories of how various organizations have used our unique data-driven approach to streamline their processes and make the most of their resources. Whether you're looking for inspiration or want to learn more about the potential benefits of our service, you'll find it here.
Webinars and podcasts
Welcome to BioPhorum Connect, the podcast series that keeps you up to date with the latest news and trends in the biopharmaceutical industry. From experienced professionals to thought leaders, this podcast brings you the insights and perspectives of experts from around the world. We'll discuss all aspects of the biopharmaceutical industry, from digitization and knowledge management to raw materials, supply chain, sustainability and more. So, join us on our journey as we explore the world of biopharmaceuticals and learn from the perspectives of those at the forefront of the industry.
Share This