The FDA has issued final guidance for biopharmas seeking to incorporate what the agency deems “promising emerging and novel technologies” in their drug manufacturing processes.
The final guidance, titled “Advancement of Emerging Technology Applications for Pharmaceutical Innovation and Modernization,” offers recommendations to companies that are interested in participating in the FDA’s Emerging Technology Program.
Through the program, biopharmas begin and maintain a dialog with the FDA before filing regulatory submissions related to new drugs when their manufacturing process incorporates what the agency calls “innovative and novel technologies that have the potential to improve drug product safety, identity, strength, quality, and purity.”
Dialog occurs as biopharma representatives submit questions and proposals to officials on the FDA’s Emerging Technology Team (ETT), with the goals of discussing, identifying, and resolving potential concerns regarding the development and implementation of novel technologies in advance of regulatory submissions.
“We’re at an inflection point in the practice of medicine, not only in terms of novel therapies, but also when it comes to the advanced technology being used to manufacture these products,” FDA Commission Scott Gottlieb, M.D., said in a statement. “The FDA is committed to continuing to foster advances in innovative pharmaceutical manufacturing, which ultimately has the potential to improve drug quality and safety.”
Michael Kopcha, Ph.D., R.Ph., wrote in a September 11 post on the agency’s blog FDA Voice that two biopharmas have engaged with the ETT before implementing continuous manufacturing (CM) processes. One is Janssen Therapeutics, which last year won FDA approval to change its manufacturing process for from HIV-1 treatment Prezista® (darunavir) from batch to CM. The other company, Vertex Pharmaceuticals, has used CM for its cystic fibrosis drug Orkambi® (lumacaftor/ivacaftor) since it was approved by the agency in July 2015.
The final guidance came a week after the agency’s September 21 deadline for public-docket submissions about issues related to the science, technology, and best practices of CM. “FDA’s goal is to provide a framework of principles that clarify our expectations, while still encouraging companies to innovate and implement CM,” Dr. Kopcha stated.
In issuing its final guidance yesterday, the FDA also offered several examples of emerging technologies it would potentially consider, which fall under three categories:
- Small molecules: Includes CM of drug substance; CM of drug product; model-based control strategy for CM; continuous aseptic spray drying; 3D printing manufacturing; and ultra-long-acting oral formulation.
- Biological molecules: Includes controlled ice nucleation for lyophilization processes; advanced process control, such as predictive modeling for process monitoring and closed-loop bioreactor control; multiattribute method; next-generation sequencing; CM for an upstream process; and “pharmacy on demand,” a small-manufacturing platform for continuous bioprocesses.
- Multiple products: Includes closed aseptic filling system; isolator and robotic arm for aseptic filling; novel container and closure systems for injectable products
“Emerging technology should be novel in the context of the pharmaceutical and related industries and it should have the potential to modernize the pharmaceutical manufacturing body of knowledge related to product quality,” according to a footnote within the guidance. “Emerging technology will be new to FDA in the context of pharmaceutical quality, with limited prior experience and knowledge.”
The FDA envisions interested biopharmas participating in the Emerging Technology Program before a wide range of submissions reviewed by the agency’s Center for Drug Evaluation and Research (CDER). These include beyond Investigational New Drug applications (IND), original or supplemental New Drug Applications (NDA), Abbreviated New Drug Applications (ANDA), Biologic License Applications (BLA), or application-associated Drug Master Files (DMF). DMFs were not included in the draft version of the guidance, issued by the FDA in 2015.
“Based on experience gained during the program, FDA intends to develop guidance and standards, as necessary, on emerging technologies and approaches to encourage and facilitate the innovation and modernization in pharmaceutical industry,” the final guidance states.