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Impact Story: Regulatory Science is Strengthening U.S. Drug Product Manufacturing

Impact Story: Regulatory Science is Strengthening U.S. Drug Product Manufacturing

Regulatory Science Impact Story

Back to Regulatory Science In Action

Continuous manufacturing provides a quicker, more reliable way to make pharmaceuticals. FDA is helping bring this method into widespread use.

The stunning technological advances in recent decades have transformed our lives in ways many of us would not have imagined. In contrast, many pharmaceutical manufacturing processes have remained largely unchanged.

To address this issue, CDER is supporting the pharmaceutical industry's transition to continuous manufacturing - a more technically advanced and automated manufacturing method. Continuous manufacturing has the potential to make U.S. manufacturing faster and more reliable. In doing so, it can help reduce drug shortages and recalls related to problems with product or facility quality.

Continuous Manufacturing: Improving Speed and Quality in Drug Production

A bench-scale continuous process for biotechnology products. This model perfusion bioreactor was developed with MIT students hosted by the Office of Pharmaceutical Quality in 2016.A bench-scale continuous process for biotechnology products. This model perfusion bioreactor was developed with MIT students hosted by the Office of Pharmaceutical Quality in 2016.

Since the 1960s, most drugs have been manufactured using a “batch” process that involves a series of manufacturing steps with many stops and starts. At the end of the process, the product is collected and analyzed for release testing. Each step can introduce problems that may cause inefficiency and delay and increase the possibility of defects and errors.

Continuous manufacturing involves an uninterrupted process that has a number of important benefits. Continuous manufacturing is reliable - there are no breaks between steps, so there are fewer opportunities for human error. Further, online monitoring means quality assurance testing can take place during the manufacturing process.

Continuous manufacturing can also significantly decrease the time it takes to make a product. In some cases, manufacturing that takes a month with batch technology might take only a day with continuous manufacturing.

Advantages of Continuous Manufacturing

  • Eliminates manual handling and human error
  • Increases quality assurance through online monitoring and control
  • Reduces manufacturing time and increases efficiency
  • Reduces capital costs by using smaller equipment and less manufacturing space
  • Responds more nimbly in the event of a drug shortage
  • Allows manufacturers to tailor drug production to fit the needs of precision medicine

Advancing the Science of Continuous Manufacturing

Sponsored Research

CDER supports the implementation of continuous manufacturing by sponsoring research in this area.

CDER funded research by Rutgers University and Purdue University to advance the understanding of how raw material attributes and the manufacturing processes affect the quality of the final drug products.

CDER also funded research by CONTINUUS Pharmaceuticals to better understand process monitoring and control approaches in an end-to-end continuous manufacturing process, from the synthesis of the active pharmaceutical ingredient (API) through to the final tablet.

Additionally, CDER is developing manufacturing platforms at the laboratory scale to help address specific policy and quality control questions raised by continuous manufacturing. These platforms incorporate advanced process analytics, automation, and modeling. They are designed to address some key areas of drug manufacturing:

  • Continuous manufacturing of API
  • Continuous manufacturing of small-molecule drug products
  • Continuous upstream and downstream processing of biotechnology drug products

Partnerships

CDER partners with stakeholders to promote the development and use of continuous manufacturing and to address the challenges drug manufacturers face in implementation. For example, in an initiative with the Biomedical Advanced Research and Development Authority (BARDA) of the Department of Health and Human Services, FDA is using continuous manufacturing research to help build a U.S. manufacturing infrastructure that can rapidly produce vaccines and other biologics against emerging threats.

Taking Steps to Transition to Continuous Manufacturing

Transitioning to an emerging technology can be challenging for a variety of reasons, including the high upfront cost of changing machinery and determining the steps a company must take to meet regulatory requirements.

To help facilitate implementation of novel pharmaceutical technologies, including continuous manufacturing, FDA has created an Emerging Technology Team (ETT). The ETT responds to pre-submission questions and proposals about advanced pharmaceutical manufacturing technologies, as explained in the guidance to industry “Advancement of Emerging Technology Applications to Modernize the Pharmaceutical Manufacturing Base.”

The ETT helped support FDA's approval of the first new drug product made using continuous manufacturing and the first switch from a batch process to a continuous process for a previously approved product.

The ETT has used process modeling to better understand continuous manufacturing processes. Process modeling can help scientists determine how changes in process parameters affect drug quality.

Process Simulation for Continuous Manufacturing of Tablets

This model was developed with MIT students hosted by CDER’s Office of Pharmaceutical Quality in 2016. As the residence time distribution (E) varies along the length (L) of a process unit (e.g., inline blender), the known feed rates (Cin) of incoming materials can be used to predict the outgoing concentration (Cout) over time (t).

Spotlight on CDER Science

Read more about how the transition to continuous manufacturing is modernizing the way drugs are made in a Spotlight on CDER Science article by Sau (Larry) Lee, Ph.D., Deputy Director of the Office of Testing and Research, and Chair of the Emerging Technology Team, Office of Pharmaceutical Quality, CDER.

For more information, please visit the Office of Pharmaceutical Quality.

Related Publications

Related Guidance

Advancement of Emerging Technology Applications to Modernize the Pharmaceutical Manufacturing Base: Guidance for Industry (PDF - 63.4 KB)

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