U.S. FDA Publishes Final Guidance and Incentive Designations for Pharmaceutical Manufacturers Using Advanced Manufacturing Technologies

In December 2024, the U.S. Food and Drug Administration (FDA) released its finalized guidance on the Advanced Manufacturing Technologies (AMT) Designation Program, marking a significant milestone in the agency’s efforts to modernize pharmaceutical manufacturing. This program is designed to facilitate the adoption of innovative manufacturing technologies that can enhance drug quality, ensure a robust supply chain, and expedite the development and availability of critical medications.

This guidance finalizes the draft guidance of the same title issued on December 13, 2023. FDA considered comments received on the draft guidance and in response made changes to the final guidance including clarifying the following:

• the process of submitting a request for AMT designation to FDA
• description of eligibility criteria to receive AMT designation
• information that should be included in AMT designation requests, including when and how FDA will assess the requests
• roles and responsibilities of various entities that might be involved in the development and use of designated AMTs
• relationship between the Advanced Manufacturing Technologies Designation Program and other FDA programs addressing emerging or advanced technologies

Background and Purpose

Advanced manufacturing encompasses innovative technologies that improve the reliability and robustness of pharmaceutical production processes. Recognizing the potential of these technologies to address challenges such as drug shortages and quality issues, FDA established the AMT Designation Program to encourage their integration into drug development and manufacturing. The program aims to provide a clear regulatory pathway for the adoption of novel manufacturing methods, thereby reducing uncertainties and fostering innovation within the industry.

Key Features of the AMT Designation Program

1. Eligibility Criteria: The AMT designation applies to manufacturing methods that incorporate a novel technology or use an established technique in a novel way that substantially improves the manufacturing process for a drug while maintaining or enhancing drug quality. This includes technologies that reduce development time or increase the supply of drugs that are life supporting, life sustaining, or critical to healthcare. The guidance states that the technology meets the eligibility criteria if it is as described in Section 506L(b) of the Federal Food, Drug, and Cosmetic Act, the requestor has sufficient data and information to demonstrate eligibility, and the technology is mature enough to consistently and reliably manufacture product in the context of use described in the AMT request.
2. Application Process: Entities such as drug and biological product sponsors, contract manufacturers, and technology developers can request the AMT designation. FDA recommends early engagement with its Emerging Technology Team or the Center for Biologics Evaluation and Research (CBER) Advanced Technologies Team to discuss potential designations. Requests can be submitted independently of application submissions, allowing flexibility in timing.
3. Benefits of Designation: An AMT designation allows for early and frequent interaction with FDA through written correspondence and meetings. The agency prioritizes interactions intended to discuss the use of a designated AMT in drug development or commercial manufacturing, especially for technologies that can significantly improve product quality or address known quality issues.
4. Scope of Technologies: It is noted in this guidance that both Center for Drug Evaluation and Research and CBER products can apply to receive AMT designation. Examples of potential platform technologies include lipid nanoparticle platforms for mRNA vaccines or gene therapies, monoclonal antibody platform technologies, and platforms using chemically defined targeting moieties in conjugation with well-characterized synthetic small interfering RNA.

Implications for the Pharmaceutical Industry

The AMT Designation Program is expected to have several significant effects on the pharmaceutical industry.

• Enhanced Drug Quality: By promoting the adoption of advanced manufacturing technologies, the program aims to improve the consistency and quality of pharmaceutical products, reducing the likelihood of defects and recalls.
• Supply Chain Resilience: Innovative manufacturing methods can increase the flexibility and responsiveness of production processes, helping to prevent drug shortages and ensuring a steady supply of essential medications.
• Regulatory Clarity: The program provides a structured pathway for the adoption of new technologies, reducing regulatory uncertainties and encouraging investment in advanced manufacturing solutions.
• Competitive Advantage: Companies that successfully integrate advanced manufacturing technologies may achieve faster development timelines and more efficient production processes, offering a competitive edge in the market.

Stakeholder Engagement and Feedback

The FDA has actively sought input from industry stakeholders throughout development of the AMT Designation Program. In February 2024, the agency extended the comment period for the draft guidance to March 13, 2024. This collaborative approach has been instrumental in shaping a program that addresses the needs and concerns of both the FDA and the pharmaceutical industry.

The FDA’s Advanced Manufacturing Technologies Designation Program represents a proactive effort to modernize pharmaceutical manufacturing and enhance public health outcomes. By providing a clear regulatory framework and encouraging the adoption of innovative technologies, the program seeks to improve drug quality, strengthen the supply chain, and expedite the availability of critical medications. As the pharmaceutical industry continues to evolve, initiatives like the AMT Designation Program will play a crucial role in fostering innovation and ensuring the safety and efficacy of medical products.