Flexible manufacturing Single-use A story of love and hate

By Matthew Pillar, Editor-in-Chief, BioProcess Online

bioreactor in the bio lab-iStock-486734678

Brian Winstead, PMP was a fan of flexible manufacturing before it was cool. The senior director of facilities and engineering at Sarepta Therapeutics, Winstead, defines the term somewhat esoteric in broad strokes before detailing a few concrete examples. “Flexible manufacturing is the design of a facility that allows multiple products to be manufactured in a single space without too much change or modification in that space,” he says.

This is a very different paradigm than the traditional purpose-built manufacturing space, where suites are designed and equipment purchased to make Product “X” and Product “X” only. This approach may have worked for large, deep bio-pockets, but when programs fail as they so often do, it could spell the end of a clinical-stage biopharmaceutical company with limited shots on target. But while flexible manufacturing makes optionality easier, Winstead admits it’s a love / hate relationship.

Love: speed to market, low investment

Brian Winstead, PMP, Senior Director, Facilities and Engineering, Sarepta Therapeutics

Beyond agility to change, flexible manufacturing environments facilitate speed to market. They are “picked up” faster than factories with fixed infrastructure. It takes less effort and expense to change them. And that’s important, says Winstead, in an advanced therapy manufacturing space in which speed to market is critically important to both patients and investors. Where it takes five years or more to build a traditional facility, develop a drug and get it approved, even in a fast-track setting, Winstead says the lead time can be cut in half or better when using pods and pods. prefabricated installations. “When you go to your board or other financial stakeholders with the proposal to build a flexible facility, you tell them you can build it faster, which ultimately puts your drug on the shelf. market faster, which means you’re on a faster path to both incomes and meeting patient needs, ”he says.

Financially, Winstead says flexible manufacturing facilities are generally not as expensive as stick-built facilities. “I can walk into an existing warehouse with the space and utilities I need, slip in single-use pods and tech, and I didn’t have to invest in a brand new property, dig the floor and build from the bottom up. ”Single-use technologies, he says, also reduce or eliminate the cost and time of cleaning-in-place (CIP) and personnel associated with stainless steel pipes, tanks , filters and fittings These ongoing costs include consumable chemicals and disposal of highly regulated waste.

The redeveloped warehouse scenario suggested by Winstead also offers scaling benefits. These properties can be purchased at a fraction of the cost of new construction, which justifies purchasing more square footage than needed for a clinical staging as part of a longer term marketing strategy. As more product manufacturing is guaranteed to support larger clinical studies and eventually commercialization, pods can be added to meet clinical or epidemiological needs without the excessive capital, time and resource requirements associated with the additions. and physical constructions. Conceptually, flexible manufacturing facilities allow rooms and walls to be replaced with “pods” comprising equipment that requires a considerably smaller footprint. Pulling panels to accommodate growth, says Winstead, is much more effective than building walls to accommodate growth.

At Sarepta, the flexible manufacturing approach has also supported the company’s flexible approach to strategic planning. “We were buying parts, long lead time items such as fillers, tangential flow filtration equipment and bioreactors before we even selected a property,” he says. “We started integrating clean rooms into the equipment even before we had selected a site. Then we were able to make sure that the site we chose was large enough, had loading docks, lighting, ceiling heights, utilities, etc. And when we found this site, we were able to connect it quickly.

Hate: personalization issues and breakage

There are qualifiers, of course. The value of flexible manufacturing is limited if the expectation is infinite flexibility. “If I design a flexible cell and gene therapy facility, it should be able to do whatever our cell and gene therapy developers want it to do with little modification. It won’t be able to produce over-the-counter tablets, ”says Winstead. Additionally, while modular and “podular” options have come a long way, highly customized constructions may justify more traditional installations. And, of course, single-use consumables are subject to the constraints of a highly stressed supply chain. Winstead says developing relationships with qualified secondary and tertiary suppliers is a prerequisite, as is stocking what you can. But even then, maintaining the supply is a full-time job.

Finally, if modular and single-use technologies are new to your business, be prepared for things to turn as badly as you might expect. It takes time to understand and factor in the nuances of single-use consumables, and during that time, ruptures, nonconformities and the following CAPAs are to be expected. Winstead offers examples. “Instead of buying a tank with an agitator, you buy a bag with an agitator,” he says. “When you’re done with it, you dispose of it in the proper way. It sounds simple enough, but you need specialized training for operators who need to understand that the impeller inside the bag should be removed so as not to cut the bag. If he cuts the bag, you’ve lost product on the floor and the safety protocol that goes with it. The same can be said of the tubes if they are not properly welded, and when they are removed from the platform, they start to leak. Sometimes you get faulty bags from the manufacturer. If you have a product worth a million dollars in that bag, how are you going to manage the risk of contamination? “

Winstead says it’s a love / hate relationship with one-time supplies. “It’s great when it works. It’s terrible when it doesn’t work. There is no middle ground, “he says. But despite these risks, he remains adept at flexible manufacturing.” The faster we can go and the more flexible we can be, the more people we can save. this is, this is really what attracted me to this market. We are curing the disease or preventing it from continuing, and that is the important thing. If there is an opportunity to make these manufacturing facilities more flexible and do it faster, then that’s what we should be doing.

Learn more about Sarepta Therapeutics and its flexible manufacturing approach in Episode 69 of the Business of Biotech podcast.


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