Driving Innovation in Pharma FDA’s AMT Designation Through the RAQAB Lens

During its January 2025 monthly meeting, the PDA Regulatory Affairs and Quality Advisory Board (RAQAB) discussed the U.S. Food and Drug Administration (FDA) Guidance for Industry: Advanced Manufacturing Technologies Designation Program (AMT), published in December 2024. This approach included our first ever “RAQAB Working Group,” which occurred during our January 2025 monthly RAQAB meeting. This article summarizes the key points of this discussion including the opportunities and risks it presents to the industry.

Overview of the AMT Designation Program

The AMT Designation Program is designed to encourage the adoption of advanced manufacturing technologies to enhance drug quality and reliability by supporting a robust supply of drugs that are life-supporting, life-sustaining, of critical importance to providing health care and/or in shortage. This program highlights novel and innovative applications of existing manufacturing methods to improve robustness, reduce development time, and ensure timely access to medicines. Stakeholders involved in the program include applicants, contract manufacturers, technology developers, and marketing authorization holders (MAH) or sponsors.

Eligibility Criteria and Submission Process

To be eligible for AMT designation, the technology must incorporate a novel or innovative use of existing technology and demonstrate substantially improved manufacturing efficiency while maintaining equivalent or superior drug quality. The focus is placed on reducing development time either by using the analytical method and/or process or by increasing or maintaining the supply of a drug that is life-supporting, life-sustaining, of critical importance or included on the drug shortage list. The AMT guidance noted that sufficient data and information must be available, including demonstrated technology consistency and reliability. The submission process involves developing data to demonstrate the benefits of the AMT, submitting the data electronically to the FDA with context of use details and receiving a response from the FDA within 180 days. Key outcomes of the program include early FDA interaction during drug development and expedited application assessments for drugs using AMTs. A request for an AMT designation can be submitted independently; therefore, requests can be submitted to FDA at any stage.

Benefits of AMT Designation

The benefits of AMT designation are categorized into three areas: Technology Development, Application Assessment and Broader Impact. In terms of technology development, the program facilitates early engagement with the FDA to discuss AMT integration, to address questions applicants may have and to provide collaborative support to optimize development time and regulatory submissions. For application assessment, the program offers streamlined reviews, leveraging prior AMT-related knowledge and prioritizing applications addressing critical health needs. Providing context of use is key to ensuring the eligibility criteria have been met. The broader impact of the program includes facilitated communication, strengthened regulatory predictability and encouragement of continuous innovation in pharmaceutical manufacturing, by encouraging adoption of novel technologies. This approach can also facilitate applicants as they work on their chemistry, manufacturing, and control (CMC) documentation, with the AMT designation posing no obstacle to the review cycles.

RAQAB Discussion Summary

During the RAQAB Working Group meeting, several discussion areas were explored to deepen our knowledge about the FDA guidance on AMT designation:

• Opportunities and Advantages: The guidance offers significant opportunities for the industry, particularly for contract manufacturing organizations (CMOs) and contract development and manufacturing organizations (CDMOs). It allows these organizations to have FDA review a novel technology without having to work through a sponsor submission. The guidance also has the potential to help respond to future crises like pandemics by ensuring speed in review processes.
• Clarifications Needed: Participants sought clarifications on the impact of the guidance on existing regulatory mechanisms, prioritization of requests, and alignment with other global regulators. Questions were raised about whether any change, such as a novel process improvement, analytical tool changes, or equipment usage, qualifies as AMT and how the program connects with the existing emerging technology offices.
• Concerns and Barriers: Members expressed the need for stronger evidence to support new technologies within a specific context of use and the necessity for better harmonization with global regulators. Participants also questioned the accountability of CMOs/CDMOs for advanced technologies and how these guidelines apply to different sectors. Additionally, a potential challenge in aligning regulatory approval for a CDMO with the sponsor/MAH’s filing and approval process exists.
• Additional Information Needed: Members expressed the need for further education on good practices and work between CMOs/CDMOs and sponsors, particularly regarding a sponsor’s legal responsibility for CMO/CDMO/third-party-site manufacturing problems. PDA now provides workshops for building and maintaining a transparent and sustainable relationship between the CMO/CDMO and the MAHs.

Next Steps

The RAQAB encourages open dialogue and discussion points with regards to AMT among its members, industry and the FDA. Integrating this topic into an interest group could serve as a platform for addressing members’ questions, while providing opportunities for further discussions. Insights gathered could then be communicated to the FDA. To begin discussions to increase clarity and industry understanding on the practical implementation of the new AMT guidance, the RAQAB has developed the following key points:

• Alignment with Existing Regulatory Pathways
  FDA has established valuable mechanisms for industry engagement, including CDER’s Emerging Technology Team, CBER’s Advanced Technologies Team, pre-Biologics License Application, pre-New Drug Application, and most recently, pre-Abbreviated New Drug Application meetings. These forums provide opportunities to discuss CMC technologies, identify potential regulatory concerns, and clarify submission expectations along with any requirements or information to be provided. Given the introduction of this new guidance, RAQAB is interested in learning how to incorporate it into the existing pathways to achieve enhanced efficiencies such as modifications to existing pathways, flexible approaches that applicants can use through parallel workstreams and prioritization of existing pathways with the AMT designation program.
• Novel Technology Definition
  As currently written, the guidance suggests that any technological advancement may qualify for AMT designation provided it meets criteria and is explicit in the context of use. Could this interpretation be confirmed with FDA’s intent? Could examples related to process improvements and analytical advances be examined against existing pathways for change control within the CMC regulatory strategic framework for a drug?
• CMC Impact
  While industry supports new elements that can streamline the submission and approval process, it is currently unclear whether AMT designation will introduce additional or modified documentation expectations and product approval acceptance criteria.
• Modalities
  Could an AMT pathway be used with any drug product modality for which it is applicable, whether active pharmaceutical ingredient or finished drug product? What type of data would be accepted for the AMT designation that would allow for universal use? For instance, should the AMT be required to provide data on products across different modalities or would the AMT approval be defined strictly for uses on certain classes of drug manufacture?
• MAH/Sponsor Impact
  Currently, there is no formal mechanism to hold the MAH accountable for compliance issues occurring at CMOs/CDMOs in which existing quality and/or contractual agreements may fall short of enabling effective information-sharing and promoting transparency between CMOs/CDMOs and their clients. Therefore, it would be helpful to understand how the MAH can fully utilize the required information related to CMC sections of a regulatory filing in assessing the impact to the product using the technology.
• Drug Shortages
  With a heightened focus on drug shortage prevention, examples to demonstrate circumstances under which AMT designation may be used and/or streamlined to address such shortages would be helpful.
• Global Impact
  What opportunity will the AMT designation program allow for greater harmonization with other global regulatory bodies, including harmonization of key elements of CMC submissions.

Future Dialogue

PDA recognizes and appreciates the FDA’s continuing commitment to industry to foster innovation and advance the technologies used in manufacturing, packaging and testing operations. In review, RAQAB found areas of clarification for the opportunities this new guidance presents beyond existing programs as industry continues to explore and implement these advancements. This article is intended to encourage additional dialogue, which PDA is happy to facilitate to ensure shared understanding.

As such, the RAQAB recommends engaging in discussions with the FDA to consider publishing responses or articles to address the concerns raised. Members were encouraged to provide feedback on good practices between CMOs/CDMOs and sponsors regarding sponsors’ legal responsibilities and third-party-site manufacturing problems.

To summarize, the FDA guidance on AMT designation presents a promising framework for advancing innovative manufacturing technologies in the pharmaceutical industry. Addressing the clarifications, opportunities, concerns and recommended actions discussed during the RAQAB Working Group will allow stakeholders to navigate the complexities of AMT implementation and contribute to the continuous improvement of drug quality and supply reliability.

We appreciate the Agency’s continued commitment to advancing pharmaceutical innovation and look forward to furthering discussions on these important topics.