Innovation Gets Regulatory Backing

The FDA is working to facilitate the uptake of emerging manufacturing technologies

By By Sau (Larry) Lee, Ph.D. and Ahmed Zidan, Ph.D., Office of Pharmaceutical Quality, CDER

The emergence of advanced manufacturing technologies offers positive changes for the pharmaceutical industry. The FDA’s Center for Drug Evaluation and Research (CDER) is taking steps to facilitate the uptake of emerging technologies to improve product quality, address many underlying causes of drug shortages and recalls, and support accelerated clinical development.

Continuous Manufacturing

We recognize that a transition to continuous manufacturing may seem daunting. However, economic analyses have shown potential significant long-term savings. For small molecule drugs, the FDA has approved applications for drugs made by continuous processes. For other types of drugs, such as biological products, technology is being developed to produce them continuously, but these efforts are still in their infancy. Research is underway at CDER’s Office of Testing and Research (OTR) to address challenges, including any regulatory uncertainties that may delay product approval if an emerging technology is used.

OTR is developing continuous manufacturing platforms (e.g., continuous crystallization, loss-in-weight feeding, continuous wet granulation) that are integrated with advanced control strategy approaches such as process analytical technology, and feedback and feedforward controls. These platforms allow the FDA to investigate the impact of material and process disturbances and system dynamics on product quality, and to identify methods for validating advanced control strategy approaches.

The FDA also is providing resources to help facilitate the transition to continuous manufacturing. For example, the agency has partnered with the Biomedical Advanced Research and Development Authority, another program within the U.S. Department of Health and Human Services, to help fund and support research. We are also training our application assessment staff and conducting internal research on risk areas associated with continuous manufacturing, so we can better assess related technologies.

3d printer

3D Printing

3D printing of drugs allows for the manufacture of solid drug products in various shapes, geometric designs, strengths and spatial distributions of the active and inactive ingredients. The release profile of the active ingredients can be tailored to meet the needs of specific patients or groups with special requirements — a tantalizing step toward more personalized medicines. 3D printing could also be used to produce complex dosage forms with characteristics that cannot be achieved in conventional dosage forms, such as instantaneous disintegration of an active ingredient or other complex drug release profiles.

OTR is working to understand the effects of material and process parameters on the performance of 3D-printed drugs. OTR is also studying roles and functions of common inactive ingredients in 3D-printed products because the functions of these ingredients may not be applicable for 3D printing processes. We’re looking to better understand these differences, and developing a “risk map” that can describe how variations in material attributes and how they are processed may impact a drug’s quality, safety and efficacy.

This research will enable the FDA to answer key regulatory questions, such as, what are the critical parameters affecting the printability of different materials into drug products? How can we best assess the performance of 3D-printed drug products? In what situations might a certain 3D geometric design not perform as it should? We are working with our colleagues at FDA’s Center for Devices and Radiological Health to determine the best ways to approach these questions.

Emerging Technology Assistance

Our Emerging Technology Program is engaging with industry early in the process of developing new technology, and discussing any anticipated regulatory or scientific issues that may be part of a future application. Read the Advancement of Emerging Technology Applications to Modernize the Pharmaceutical Manufacturing Base Guidance for Industry on the FDA website to get more information and advice about how to work with the agency early in the development process.

Sau (Larry) Lee is the Deputy Director of the Office of Testing and Research, and Chair of the Emerging Technology Team, Office of Pharmaceutical Quality, CDER; and Ahmed Zidan, Ph.D., is a senior staff fellow at the Division of Product Quality Research, Office of Testing and Research, Office of Pharmaceutical Quality, CDER

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