4 Facility Considerations for API Manufacturing
By Katie Anderson, Chief Editor, Pharmaceutical Online
Pharmaceutical manufacturers are accelerating efforts to expand production of active pharmaceutical ingredients (APIs), investing in new facilities, upgrading existing sites, and expanding current capabilities Yet building a more secure and resilient API supply chain remains a complex challenge. As Dennis Hall of the United States Pharmacopeia explains, API manufacturing differs fundamentally from finished dosage production. Success depends not only on equipment and infrastructure, but also on specialized workforce training, rigorous quality control, robust data management, and increasingly sophisticated supply chain and manufacturing technologies.
In a recent Pharmaceutical Online virtual panel, I sat down with Hall, along with Hugh Kelly (Associate Vice President and Site Head for Eli Lilly and Company) and Brian Doty (Vice President of R&D and Programs for the API Innovation Center) to discuss what to consider when adding more API manufacturing capabilities, and the below four points were highlighted.
1. A Basic Start
Whether you are building a Greenfield facility, constructing an expansion or adding API capabilities to your current facilities, the panelists recommend starting with the basics of manufacturing.
Hall emphasized the importance of what he calls the two w’s and the two p’s: water, waste, power, and people. “Getting those things right likely in that order is a significant, I won't say hurdle, but it is a significant aspect of building out new API manufacturing capabilities specifically,” noted Hall.
Kelly continued that GMP compliance must be a focus from the beginning. “You touched on both retrofitting and greenfield build, and we can maybe elaborate on some of those, but regardless of the type of investment, I think you've got to build in GMP compliant design from the start, ensuring that everything from your HVAC to segregation and controls, people flow, etc. is compliant,” explained Kelly.
2. The Right Technology
When it comes to technology, API manufacturing is certainly more bespoke than once size fits all, but selecting the right technology will always result in a better outcome.
As a champion of advanced manufacturing technologies in API manufacturing, Hall knows first-hand what benefit they can provide, one of which is a smaller footprint. “From the API perspective, we'll utilize advanced manufacturing technologies which have continuous flow chemistry associated with them. That footprint in the manufacturing space is significantly smaller than what you would see with a batch process, and adding process analytical technology to that doesn't really change that space requirement either. So you can get more bang for the buck regarding floor space and ability to make more in a smaller area. So, I'm a heavy advocate of advanced manufacturing technologies. I think it's the way that we're going to be competing against foreign manufacturers and making processes more efficient and more cost effective,” elaborated Hall.
Not only can AMTs reduce the footprint needed, but they can also reduce the carbon footprint. For example, water, waste and power can be reduced with flow chemistry.
At Lilly, technology is highly utilized for data collection, according to Kelly. “Technology and automation and sort of our backbone, ensuring that all of your systems are connected. MES limbs, your quality management system, we have a goal of being paperless from day one and really what that's enabling us is the highest levels of data integrity, which is sort of not optional in today's environment, explained Kelly.
3. Workforce
Though a well-designed facility and high-tech machinery can lend themselves to successful API production, not without highly skilled operators.
Skilled operators must be a consideration from the start, according to Kelly. “Workforce design is very important. Understanding the capabilities that you need locally and in-house are very important. We have the saying that the facility is only as capable as the people running it,” added Kelly.
He continued that workforce design starts in the design and construction phase. During that time, the operators are onboarded, trained and sent to other locations to hone their expertise. “We aim to have all of our site team embedded in the qualification process and performing all of the operational readiness activities that we need to be sort of ready from day one,” he added.
4. Allotted Space
Space considerations are largely determined by the API that you are manufacturing, according to all of the panelists. Kelly elaborated that for Lilly, a separate facility for API was needed, but that it really is dependent on the API manufactured and the amount needed.
“I think it's down to considerations of downstream. Supply chain can play a role in that as well as scale difference, right? Co-location I think makes sense when the scale of your API in terms of a number of doses matches very closely with what a drug product line would require. In many cases you can scale API more significantly, and so you can end up with a mismatch and often you need multiple drug product locations to take the supply from an API site,” added Kelly.
Lilly doesn’t favor Greenfield or Brownfield, so they believe in careful analyzation before choosing a site strategy, according to Kelly. According to him, Greenfield can take longer but may show more benefits upfront. “I think when we're talking about retrofit, often you have to stage the various different elements of modern facility build, and that requires a lot more integration over maybe a multi-year program. When you start talking about electronic systems and data connectivity, it kind of happens more in a planned fashion and carefully integrating as you're running. So again, pros and cons to both,” noted Kelly.
Hall agreed with Kelly that it depends on a lot of factors, and should be determined on a case by case basis. “We have seen it easier to retrofit than build Greenfield if that Brownfield site has already been doing some form of API manufacturing or some sort of manufacturing that uses the same basic principles, Hall explained. “But then again, if it's something completely new and how you're making the product, Greenfield could certainly be a great way of doing it.”
Bringing The Elements Together
The road to a more secure API supply chain may not be easy, but it is important. Though each of these elements (among others) must be considered, one is not more important than the other, according to Kelly. Rather, bringing all these elements together at time of operation will result in not only operational success, but quality API.