By Gail Dutton, Contributing Writer
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Inviting FDA scientists into your manufacturing facility or laboratory for one or two days may feel unsettling, but it can be rewarding when the visits are designed to bring FDA scientists up to speed on real-world issues and new technologies.
Drug developers can learn the extent of that potential benefit in 2017 when CDER launches the Staff Experiential Learning Site Visit Program. The educational program focuses on 17 areas of scientific interest, ranging from drug/device combo products to continuous manufacturing, nanotech, and APIs. It is expected to start during the first half of 2017, once CDER receives and approves appropriate applications from pharmas to host FDA scientists for one- to two-day learning visits.
WHAT CAN THE FDA GAIN?
The scientists and engineers at CDER’s product quality office generally have industry experience and access to cutting edge equipment and techniques. “They’re pretty savvy, so we have to wonder what they would gain from a site visit,” says Darryl Sampey, president and CEO of BioFactura, a developer of biodefense countermeasures and high-value biosimilars.
The answer is “insight into new technologies and commercial-scale operations.” At BioFactura, the key learning opportunity probably would involve its continuous manufacturing operations for bioprocessing. That is a relatively new approach to biomanufacturing and is garnering a lot of industry interest. As companies begin to adopt this linked method of biomanufacturing, it’s only natural that the FDA also wants to learn the practical realities and what it takes to implement continuous manufacturing successfully.
EDUCATIONAL VISITS OR COVERT INSPECTIONS?
“People get stressed having regulators on site because they associate visits with audits,” says Yaky Yanay, president and COO of Pluristem Therapeutics, an Israeli developer of stem cell therapies. “FDA site visits help make regulators more familiar with an industry that is changing rapidly. Therefore, there are a lot of advantages in having the FDA involved in learning and understanding the challenges in the technologies. Learning programs and site visits will only be beneficial.” That’s because regulators who thoroughly understand the processes, technologies, and issues involved in a product’s development and scale-up are better qualified to review subsequent FDA submissions.
There’s another benefit, too. By sharing knowledge with regulators, scientists on both sides of the regulatory milieu have had an opportunity to discuss any issues of concern. Therefore, companies can use new technologies more confidently.
“The focus of the visits is for staff in the Office of Pharmaceutical Quality to further develop their understanding of current industry practices, processes, and procedures,” emphasizes Tralisa Colby of the CDER Trade Press. During the one-to-two-day visits, program hosts are expected to provide “experiential, first-hand learning opportunities” for visiting FDA staff rather than merely lectures or discussions. The goal is to improve FDA reviewers’ understanding of the industry and its operations, including issues that affect drug development and a product’s commercial life cycle. A facilities tour is integral to this experience.
To ensure confidentiality, CDER staff will be trained to handle information properly. Colby stresses the visits do not replace regulatory inspections.
This program is similar to others in the FDA. The Center for Devices and Radiological Health (CDRH), for example, began an experiential learning program in 2012 to close the knowledge gap between emerging and innovative technology and the premarket review of medical devices. “Since 2012, 1,557 premarket reviewers have gone on 130 site visits,” Colby says. CDER also has a site visit program for regulatory project managers that was renewed in 2016.
Such on-site learning programs are very helpful to FDA scientists, stresses David Rosen, J.D, former regulatory counsel and special assistant to the director of CDER. Rosen currently is FDA practice group leader and co-chair of life sciences industry team at Foley & Lardner LLP. He says, “Looking at things that are difficult to formulate or manufacture helps FDA reviewers understand critical parameters. This helps them ask the right questions during the application review process.”
CDRH reviewers say the visits expedite the application review probes by improving their understanding of how medical devices are developed, clinically tested, manufactured, and used. Biopharma executives expect CDER’s new site visit program to extend similar benefits to drug development reviews.
ARE NEUTRAL SITES BETTER?
Any time a regulator visits a site, there is some degree of concern that something will be spotted that triggers an official site inspection. Rosen says, “If FDA reviewers do spot something during a site visit, one would hope they would inform the company and have a scientific discussion without triggering an inspection.” He characterizes the risk that a learning site visit would trigger an official FDA inspection as extremely minimal. Nonetheless, there may be some concerns.
“As an investor, I think FDA site visits would raise a red flag,” says Jeff Hausfeld, director of the board and chief medical officer of BioFactura. That said, “I support transparent communication between companies and regulators as long as we’re all on the same page.”
These site visits aren’t the only way to provide learning opportunities for regulators. Interactions may be more productive when public entities serve as the interface, Sampey points out. He recommends meetings with reviewers, academics, and enterprises at neutral locations. For example, in 2016, the University of Maryland and the National Institute of Standards and Technology hosted the FDA, BioFactura, and other companies to discuss capabilities and commercial concerns. “It was very comfortable for the government and private sector to open this dialog on neutral ground. It was a very productive interaction,” Sampey says.
Even in a neutral environment, industry can provide valuable insights into scale-up and commercialization that put real-world challenges into perspective. Neutral locations can’t provide the full picture, however. “Meetings in neutral locations can be useful, but they can’t replace visits to real companies to understand large-scale, commercialization concerns and practices,” Yanay counters.
IF YOU PARTICIPATE…
If you decide to participate in CDER’s new site visitation program, have a specific focus in mind that meets the FDA’s learning objectives. As you craft a proposal as a learning-site host, involve your company’s leadership and development executives to ensure your program is beneficial for everyone involved.
Yanay advises beginning the learning experience in a conference room to set expectations for the visit. This is a good place in which to provide an overview of the company as well as the technology or process that regulators are on-site to explore. Be sure to discuss how this process affects upstream and downstream processes and, if applicable, other areas of operations. For example, a discussion of APIs may involve supply chain risks and geopolitics if ingredients are sourced from a single site or even a single country, as well as the standard safety and purity concerns.
A PowerPoint presentation may help explain the equipment, critical process parameters and controls, and some of the actual issues your company has had to address during implementation or scale-up. Once regulators have a general understanding of the situation, they can tour the labs or manufacturing facility to see real-life operations.
Before touring the facility and talking with scientists and operators, Rosen cautions, alert your staff that guests will be coming through the facility. “Ensure that staff understand what’s going on and what’s expected of them, and be sure that the facility is clean and organized.”
Rosen also warns against allowing visitors access to files. If an FDA scientist asks a staff member for information, it may be temping for that person to open a seemingly innocuous file and show it to the visitor. Instead, caution staff members to relay such requests to a designated individual who can provide the information without inadvertently sharing confidential data.
Details of this new program are listed in the Federal Register. When CDER requested hosts for its Regulatory Project Management Site Tours and Regulatory Interaction Program, only one company volunteered to host the program. The agency subsequently sent a request for additional participants. Therefore, although the deadline has passed to apply to host the Staff Experiential Learning Site Visit Program, companies may still have opportunities to participate.