New Lab Will Develop Standards for Continuous Manufacturing

The United States Pharmacopeia (USP) and Phlow Corp. have collaborated to build a new laboratory that will develop test methods and standards for continuous manufacturing. This work aims to aid product development, tech transfer, and drug application filings using continuous manufacturing to foster wider adoption of continuous manufacturing by generic-drug and other pharmaceutical manufacturers.

Operated by USP, the lab will be located in the Virginia Biotechnology Research Park, which currently houses Phlow’s R&D Laboratories and Virginia Commonwealth University (VCU)’s Medicines for All Institute (M4ALL). USP, which will also use labs at its headquarters in Rockville, MD for some analytical and testing projects, is hiring scientists for the new lab in Virginia, which will be started up as soon as possible.

“Pharmaceutical Continuous Manufacturing poses several advantages over traditional batch manufacturing, especially during supply disruptions. These include the availability and use of real-time data to accelerate manufacturing scale-up and help improve medicine quality, enabling more efficient and nimble production of essential medicines and strengthening the overall supply chain,” noted Ronald T. Piervincenzi, CEO of USP, in a Feb. 22, 2021 press release (1) . “We hope that USP’s work with Phlow will help pave the way for the pharmaceutical industry to apply continuous manufacturing more broadly for the generic medicines so many patients rely upon.”

The lab is being funded in part by Phlow, as part of a four-year, $354-million contract it signed with the US Department of Health and Human Services’ Biomedical Advanced Research and Development Authority (BARDA) in May 2020. Phlow is leading a group of partners, including AMPAC Fine Chemicals, Civica Rx, and M4ALL, to manufacture essential medicines that are at risk of shortage in the US, including drugs for those hospitalized with COVID-19 (2). The USP lab will initially focus on continuous API manufacturing.

“Phlow’s partnership with the USP, working alongside the Virginia Commonwealth University’s Medicines for All team represents another key resource in our efforts to strengthen our supply chain for essential medicines,” said Frank Gupton, co-founder of Phlow, chair of VCU’s department of Chemical and Life Science Engineering, and CEO of the Medicines for All Institute, in a press release (1).

Early adopters have done the work necessary for good manufacturing practice (GMP)-scale continuous manufacturing of their own products, but standards could help facilitate broader use of continuous manufacturing, suggests Piervincenzi. Standards, for example, could describe what parameters to measure and how to do so. “In some cases, what you need to measure for continuous manufacturing is quite different than what needs to be measured for batch manufacturing. For example, for both batch and continuous processes, you need to check your excipients for purity and strength, but in a continuous solid-dosage drug manufacturing you also need to measure powder flow characteristics,” he explains.

USP has been working with the Center for Structured Organic Particulate Systems (C-SOPS) research group at Rutgers, the State University of New Jersey, on test methods for continuous solid-dosage manufacturing processes, such as methods for characterizing residence time distribution (RTD). Researchers are currently conducting a round robin for transferring RTD test methods from one site to another.

Another area where continuous processing differs from batch manufacturing is in how and when quality tests are performed, says Piervincenzi. In continuous manufacturing, tests will need to be performed in real-time while the process is running. In the new lab, researchers will develop new on-line, in-line, or at-line analytical methods and will compare these to conventional lab methods.

USP’s research efforts will not change the organization’s current practice of drawing upon industry experts to set standards, says Piervincenzi. For now, USP researchers are being advised by an expert panel on a less formal basis but, after test methods have been more fully developed, USP will convene expert committees to create standards.

USP is an advocate for quality standards for continuous manufacturing so that questions about quality will not prove to be a barrier to adoption of the technology, says Piervincenzi. The organization is also working to remove the potential barrier of workforce capability. USP and Rutgers have developed an interactive training course so that technical personnel can gain an in-depth understanding of the skills that are needed for continuous manufacturing for solid-dosage drugs. USP sees potential in the future for similar training programs on the VCU campus. “We’re looking at expanding capability building more broadly for industry and for regulators, both in and outside of the US,” says Piervincenzi. As he notes, getting regulators throughout the world more comfortable with advanced manufacturing technologies will be another key to eliminating current barriers to the technologies’ adoption in the industry.

References

1. USP, “Phlow Corp. and USP Announce Strategic Alliance Focused on Pharmaceutical Continuous Manufacturing to Increase Supply of Essential Medicines for US Patients,” Press Release, Feb. 22, 2021.

2. HHS, “HHS, Industry Partners Expand US-Based Pharmaceutical Manufacturing for COVID-19 Response,” Press Release, May 19, 2020.