Considerations for FDA’s New Advanced Pharmaceutical Manufacturing Programs

Introduction

A persistent drug shortage crisis in the U.S. is associated with higher mortality rates, medication errors, medication rationing, delays in life-saving cancer treatment and other critical medical procedures, and significant financial costs to the health care system.

The leading cause of drug shortages is manufacturing quality issues, especially for older generic drugs that are complex to manufacture. Factors such as the use of outdated, less reliable manufacturing technologies and a lack of mature quality management practices contribute to these quality issues. Additionally, incentives exist for manufacturers of low-cost generic drugs to outsource manufacturing to a concentrated group of foreign countries. Globalized supply chains introduce efficiencies and provide access to global talent and manufacturing capabilities but also come with exposure to geopolitical risks, such as military conflict and trade constraints.

Advanced manufacturing technologies (AMTs), such as continuous manufacturing, real-time process monitoring and release, novel container-closure systems, and many other technology types, can help to address some of these risks by increasing quality assurance and reducing manufacturing downtime when quality issues are detected. The U.S. has significant expertise in AMTs—more than 80 percent of drugs currently made using AMTs are produced in the U.S. After initial investment, AMTs can reduce per-unit production costs, thus enabling domestic pharmaceutical manufacturing to be more cost-competitive.

Despite this strong potential, the vast majority of recent new drug applications still use traditional manufacturing techniques. For example, the U.S. Food and Drug Administration’s (FDA) Center for Drug Evaluation and Research only approved 19 new drug applications using AMTs from 2015 through April 2023. Adoption of AMTs in the production of generic drugs has been lower than for branded drugs. As generics drugs represent 90 percent of all prescriptions dispensed in the U.S. and more frequently experience shortages, increasing adoption of AMTs in generic drug manufacturing is critical. However, generic manufacturers frequently cite barriers to implementing AMTs, such as prohibitively high upfront investment costs and regulatory barriers.

The Consolidated Appropriations Act of 2023 directed the FDA to designate National Centers of Excellence in Advanced and Continuous Manufacturing (CoEs) and implement an Advanced Manufacturing Technologies Designation Program (AMTDP). These programs have a strong potential to increase adoption of AMTs, especially among new innovative drugs. If thoughtfully implemented, these programs could also have a positive impact on AMT adoption among generic drugs. Other policy steps to increase AMT adoption to appropriate levels among generic manufacturers, such as providing direct financial support to help cover upfront implementation costs, are likely needed as well; however, these other steps are outside of the scope of this issue brief. This issue brief discusses considerations for FDA, academia, manufacturers, and other stakeholders as the new CoEs and AMTDP are designed and implemented.

Read the full brief.