Broadening the Baseline April 2013

When the editors of BPI asked us at BPSA to put together a content-rich article for the single-use supplement, we were happy to do so. Our challenge was how to bring in multiple viewpoints about the growing business of single-use that would be a “quick read” for the BPI audience. The answer: an expert colloquy (a “conversational exchange or topical dialogue”). Represented here are several of the most qualified industry spokespersons in single-use — all are members of BPSA and speak as directors of the alliance. Their message: Single-use adoption is growing. BPSA has enabled significant educational initiatives responding to many technical concerns with plastic-based systems. And there is still much to be done as the end users of single-use systems begin to assay how to implement these innovative, flexible manufacturing platforms for drug and vaccine production. It’s been said that the transition between old and new is never elegant or seamless. But in the case of single-use, BPSA serves to smooth that transition with help from the experts that populate our Alliance, featured below. Enjoy the conversation! — Kevin Ott, executive director, Bio-Process Systems Alliance

Interview Participants

Moderators: Anne Montgomery (editor in Chief) and Brian Caine (publisher), BPI Representatives of BPSA’s 2013 board of directors:

Kevin Ott, BPSA executive director

Jerold Martin, BPSA chair, Pall Corporation

John Boehm, BPSA first vice-chair, Colder Products Company

Bill Hartzel, Catalent Pharma Solutions

Paul Priebe, Sartorius Stedim Biotech

John Stover, NewAge Industries Inc.

David Radspinner, Thermo Fisher Scientific, Inc.

Facilitating Adoption of Single-Use Systems

Montgomery: What are your current priorities?

Martin: BPSA’s overriding goal is to facilitate adoption of single-use technologies for improving drug product safety and the economics of drug manufacturing. If we broaden that a bit, our priority has been to expand our membership both among suppliers and end users. We’ve had a significant increase in the number of end users both as members and as representatives on our board of directors. So our focus has expanded beyond being a trade association of suppliers to include all the stakeholders in single-use technologies.

Finally, our priorities this year have focused on refreshing our matrices guide on reference component quality test methods (www.bpsalliance.org/guides.html). We are also working on am industry consensus template for quality agreements, something that our members have asked for. We’re discussing standardization in various areas, including for extractables testing, and also looking at ways to ensure that particulate quality meets the highest standards for final filling of injectables.

Montgomery: Have there been many key changes in the documents specific to connectors, fittings, and valves?

Boehm: A cross section of suppliers and end users on the task force are looking at connectors, fittings, and valves. We’re reviewing the individual tests that we outlined previously determining appropriate updates. This will include changes to existing tests as well as adding new test areas.

Beyond identifying consensus tests for fittings, connectors, and tubings were recommendations on test frequency. So we are looking at those again: What exactly were we testing? Are we testing the material, or are we testing an end product? So we are working to bring greater clarity and understanding about what those tests are and when they should occur. In this area, having end users involved in the subcommittee has really helped open up the discussion. Most suppliers have shared a common language, whereas end users are introducing different interpretations.

So I think that’s going to allow us as a collective to publish an updated document that brings a clearer understanding to end users about what kind of tests they should consider during their component evaluation and qualification.

Montgomery: Given the many industry publications on the topic since its publication, are you planning to update your original recommendations about extractables and leachables testing?

Martin: Our first piece came out in 2008 and the second one in 2010. Current discussions are ongoing about the value of standardizing generic extraction conditions among suppliers. A number of organizations are also looking at what type of generic information the agency is looking for that would help the end users work with generic data from the suppliers.

Stover: I want to comment that as we grow globally, one of the most mentioned documents among end users are those BPSA articles on extractables and leachables, both publications. It seems to have served as a baseline for which many end users are starting to analyze extractables and proscribes an approach that regulatory agencies have adopted in their expectations. So one update may be to recommend how end users can compare extraction conditions and test results from different suppliers. In this respect, we may try to achieve some standardization where none exists yet today. There are general statements about what you should be testing for and how to conduct extraction testing and analyses, but no consensus on the conditions and assays that are used to produce the results. That’s an emerging issue. Another up-and-coming hot-button topic that’s going to be addressed by BPSA is particulate control in final aseptic filling systems. It’s being called for loudly by end users, particularly vaccine manufacturers.

Hartzel: One key guide that people are looking for is the baselining of data, which starts with test methods and methodologies associated with testing of single-use products. That baseline education then facilitates evaluation of different data sets from your suppliers and vendors. That will give you the basis and background associated with the test methods that allow you to make an educated decision about how to compare the data.

And I think that is what’s fundamental to what the BPSA provides to the market: that baseline education needed for making decisions about different components and assemblies that you are using in your process.

End-User Participation Expands

Montgomery: How large is your representation of user groups?

Ott: We presently have six end-user companies: Sanofi, Biogen Idec, Merck, Catalent, GSK Bio, and JHP Pharma. They all are a bit different in terms of product lines — vaccines, therapeutic drugs, and fill-finish, and contract manufacturing. So it is a diversified subset of end users. They are represented on our board of directors now. We have three end-user seats filled on our 14-member board. Those six companies still represent only about 15% of BPSA’s total corporate membership, but it’s a start.

Radspinner: These first few are indicative of what is to come. I think that by default we will see more end-user members come into the fold simply, if nothing else, for the opportunity to learn from the supplier base. And I hope we can be the consensus group between suppliers and users about how to push forward the adoption of single-use in drug manufacturing.

Martin: End users are increasingly becoming aware that the BPSA as the only organization that’s focused exclusively on single-use as a major focus of activities rather than as a part of the overall pharmaceutical manufacturing world. We’re a critical partner with other organizations, primarily to provide a stimulus and source of information that can be incorporated into broader standards and guides.

Stover: Although the end-user membership might be just 15% of the total corporate membership, when we work in these committees as suppliers, we are also bringin
g in the voices of end users. We all talk to end users extensively in the field. We’re not creating the information as suppliers; we’re incorporating the information that comes to us from end users into the meetings.

Martin: The end-user companies that are members of BPSA are among the largest users of single use. So while it might seem like a small number, if you measured it by actual usage of single use, the biggest players are well-represented within BPSA already.

Priebe: They don’t need to be convinced to use single-use. They want to make it easier to implement because they’re fully convinced that disposables are enabling technologies to help them meet their goals.

Radspinner: And end users recognize that through BPSA, they themselves need to partner with their suppliers. But they can see that some suppliers are all partnering with each other because we all have to work together to make single-use a success. There is no one supplier that makes every component in a single-use system. So BPSA is enabling suppliers to work together and partner with end-users.

Boehm: One point to highlight is that membership in BPSA — unlike the other organizations working on single-use issues — is not an individual membership. We’re a company membership organization. As a result, one large pharma company’s involvement brings in individuals from multiple disciplines within that company to participate in all our different committees. So BPSA is made up of different people injecting their knowledge and goals into our various subgroups.

Priebe: We’re also seeing many more individuals participating from supplier memberships.

Caine: As the market continues to evolve and we get into more specifics, how is BPSA distinguishing itself from some of these other organizations that are working on single-use guidelines?

Martin: A few years ago, I cowrote an article with representatives from ISPE, PDA, and ASME called “Organizing the Organizations for Single Use” (www.bioprocessintl.com/journal/supplements/2009/April/Organizing-the-Organizations-of-Single-Use-Manufacturing-183699). That article is still applicable today. We looked at how to facilitate, not dominate, implementation of single use. Each of those groups has its certain strength. So, for example, PDA has a lot of strength in final filling, quality, and regulatory issues. Its single-use task force is publishing a guide that focuses on application of quality by design principles and other regulatory initiatives for single use. That’s their strength, and that’s what they are doing. ASME is combining its own publications with those of BPSA to develop more formal standards where needed. BPSA has liaisons working with these other organizations to maintain consensus among the groups.

ISPE has focused an initiative on looking at standardizing extractables activities. And so we’re interfacing with them as well. We support each other in a common approach because we all recognize that if different organizations go off in different directions and make different recommendations, that’s going to be very confusing for the industry. It’s going to be very confusing for the regulators also — something we all want to prevent.

Stover: BPSA is the only group whose vision and focus is solely on single-use. All the other agencies tackle many, many different issues and, therefore, their members and committees are stretched to a much larger degree than we are.

Educational Forums

Boehm: I’d like to return to the benefits of bringing end users into the BPSA and the value that they are receiving. We recently held an educational forum at Catalent’s new biologics facility in Madison, WI. That is one example of how end-user members are realizing the level of expertise and the value of interactions among the supply base. They can appreciate the value of bringing the BPSA supplier base in to educate their employees in single-use implementation, in topics ranging from sterilization and test methods to supply-chain assurance and disposal.

Ott: And that’s once again, to the earlier question about how BPSA is different from other groups. We are a nonprofit, consensus-based 501 C6 based in Washington, DC. We are about education — at our core. We incorporate views of suppliers and end-users as well as engineering houses, ancillary laboratories, and system houses. It is everything single-use under one umbrella group.

The Catalent forum was our second road show. It is an example of how competitors can come together with the common goal of advancing single-use technologies. These ongoing collaborations underscore our combined focus toward advancing product and process development in an increasingly global manufacturing arena. Through these combined efforts, we all are working to help us live longer and better lives.

Looking Ahead

Our conversation continued with discussion of adoption and implementation rates, technical challenges, user requests, expansion into other classes of products, and supply-chain issues. Part 2, in BPI’s May issue, will conclude with these points and take an early look the 2013 BPSA International Single-Use Summit, 15–17 July 2013 (Washington, DC).

About the Author

Author Details
BPSA’s key contacts are Kevin Ott, executive director, [email protected]; and Jeanette McCool, senior associate, [email protected]. S. Anne Montgomery is cofounder and editor in chief of BioProcess International.