Is The Single-Use Standardization Debate Slowing Down Adoption?
By Trisha Gladd, Editor, Life Science Connect
There’s a tremendous interest from the biopharmaceutical industry to establish standards around single-use, in order to simplify the approach to selection and implementation. Experts are in agreement that there is a need for best practice standardization and many industry organizations are currently making great strides in working toward this goal.
However, when it comes to equipment standardization, the conversation is still divided among users and suppliers. And while suppliers express concern that standardization could strip them of their ability to differentiate themselves in a heavily competitive market and ultimately reduce profits that fund new innovations, there is a bigger issue at hand that needs to be considered as we wait out this stalemate—without standardization, the customization required to build a single-use facility may prevent a full-scale adoption of single-use technology (SUT).
So how do we move forward? Maybe, by taking a look back.
Industrialization Through Standardization
It’s easy to argue that a lag in SUT adoption is just the result of an industry always slow to adopt new technologies, but with so many suppliers offering their own single-use equipment designs, the customization required to build a single-use facility creates a challenge for pharmaceutical manufacturers who want to make the transition. “When you’re using single-use to create flexibility in an existing clinical environment, then customization is just what you want,” says Tony White, director of the BioPharm Operations Group (BPOG). “But when you’re committing to a new technology across commercial operations, you want ‘plug and play’, interconnectability, rapidly available validation packs, and the comfort of knowing that re-supply will always be excellent. This is where standardization is key.” He says the lack of standardization has put off some companies from implementing single use, unless they have a very strong vision around where they want to go operationally and are prepared to work hand-in-hand with one or two suppliers. White adds, “For some, it’s still about relying on a platform they know—stainless steel—when push comes to shove for massive multimillion-dollar decisions.”
In a previous article on BioProcessOnline, Chris Smalley, Ph.D., director of validation compliance at Merck, says he believes the necessary change will come when someone is able to learn from history and implement the innovative thinking this issue warrants. “What the industry needs to do is think in new ways,” says Smalley. “I have told the vendors of many single-use components that someone in their industry needs to be the next Henry Ford.” Ford, often referred to as the “The Man Who Changed America,” revolutionized the automobile industry by recognizing that developing one model would allow for automobiles to be manufactured in large quantities. However, the parts were made to order from other businesses, which meant when they arrived at Ford’s factory, a team of mechanics would have to use files and hammers to make them fit each other. He realized that by standardizing the parts for his Model T, he could reduce efficiency and improve productivity. Taking a cue from other industries, he implemented the use of interchangeable parts and the result was the first moving assembly line ever used for large-scale manufacturing. This concept allowed for mass production and ultimately opened the door to consumerism.
Moreover, when Ford came up with the concept of mass production in 1903, he wasn’t enjoying the benefits of a monopolistic market. At that time, there were already over 50 automobile manufacturers in business and an additional 88 were established that year. Yet, in a market full of competition, Ford not only made standardization work but he thrived because of it. Despite this important lesson from history, champions of single-use standardization are still fighting an uphill battle. So who will be the one to change pharma?
Standardization Through Collaboration
In order for standardization to occur, it will require collaboration from both the supplier and the end user. However, for something to actually happen, some experts believe it may come down to a call for action from end users. “The industry has got to come together and do so because they’ve recognized that the costs of adoption have got to come down in the supply chain,” says White. “End users need to come together with other end users and set compelling direction for standardization and harmonization that suppliers can respond to.”
He says one way end users can start doing this now is by consolidating supply into fewer partners, to build a small team of suppliers they can work with strategically in order to standardize and manage their own product portfolios. Also, he says that while standardization is going to be a long and painful journey, it’s going to come eventually. “The dominant suppliers in the market will be ones who realize this and jump into the next phase of industrial development first, to deliver outstanding supply chain and information services, all facilitated by a bedrock of physical standards.”
Jerry Martin, senior VP of global scientific affairs and biopharmaceuticals at Pall Corporation and chairman-emeritus of the board for BioProcess Systems Alliance (BPSA), suggests that users establish a single-use group within their own company to share information across facilities and reduce the variability of what they’re selecting when it comes to single-use equipment. He references the Single-Use Network, or SUN, at Merck as what he calls “an ideal model.”
SUN was created to facilitate the adoption of SUT at Merck and evolved from a group of single-use advocates at the company who shared a common interest and passion. Smalley says he created validation packages for each of the components in the Merck catalog as a way to make selection and use easier for Merck users. While not everyone will use the same components, they will all be selected from the same group of validated components. “We’re telling people, ‘If you pick something out of the catalog, you’re good to go,’” he explains. “However, if they customize something, they’ve just created a whole world of hurt, because now they have to submit a request for it to be validated. This is something Merck is happy to share and is working together with Pfizer, Genentech, Amgen and others, who have all done significant pioneering work for single-use, to do the same because we want to support the industry in moving forward.”
While some vendors might not see it this way, standardization wouldn’t just benefit the users; it would also be an enormous benefit to the suppliers as well. Jim Robinson, VP of vaccine product & technical operations at Merck, once said, “If we build connectivity and interchangeability, there will be greater use of single-use systems,” states Robinson. “Even if there is more competition, vendors will compete in a bigger business. It’s a win-win.”
Despite Objections, Progress Is Being Made
As previously mentioned, despite objections from some of the industry about equipment standardization, industry organizations are working diligently to make progress when it comes to standardized testing. “There’s a tremendous amount of interest in somehow standardizing how equipment is to be evaluated so the test results that are generated both by different suppliers or by different testing laboratories are all done essentially the same way,” explains Martin. “Basically, that provides users with two benefits. One is that they get to do more comparison, which is difficult for them to do now as this has been done under different conditions. The other is that users are saying that the expectations they hear from the FDA reviewers and inspectors are inconsistent because there is no guidance as to what inspectors should expect to see, and standardized protocols will help with that.”
Depending on their degree of expertise, Martin says many of the expectations are reasonable, but some are less so, which can be a struggle for the user to resolve. He continues, “If we can standardize how this equipment is to be evaluated and get it up to the level of an ASTM standard or USP, which is all underway right now, that will guide the FDA on what to ask. And if the FDA is asking for the things the industry knows it needs to do, it will all become a lot easier.” Doug Ball, research fellow at Pfizer, serves as a co-chair and toxicology lead on the Product Quality Research Institute (PQRI) Leachables and Extractables Parenteral and Ophthalmic Drug Product work team. He says the regulators they are working with are pleased with the progress of the work team. Ball explains, “From a qualification standpoint, PQRI is using safety thresholds to determine the Analytical Evaluation Threshold. The regulators feel very comfortable that the PQRI Safety Concern Threshold levels not only will help to qualify the safety attributes but also will help to define the quality attributes of the materials used in the container closure and/or single-use system.”
With all of the various organizations working on standardization within the single-use industry, Ball says he is sometimes concerned that “the left hand is not always talking to the right hand.” Martin, who serves on both BPSA and as supplier representative to the USP packaging committee, who is writing new standards on extractables and leachables for single-use systems, says they most certainly are. “We are all talking with each other and we all ultimately recognize that unless these organizations align the standards they’re writing, it’s going to make matters worse. All of the standards bodies have their own incentives to write their own standards, but they recognize that these standards have to be aligned with the other groups or else they lose their value.”
The pharmaceutical industry has made significant progress over the past few years when it comes to the adoption of single-use, but there is still a long way to go. Because it requires a dramatic transformation of the system for users and vendors, it will not happen overnight. However, with support growing from big pharma and the FDA, it is imminent. And working together to facilitate this change rather than oppose it may be the best option for anyone who doesn’t want to one day find themselves on the wrong side of history.