FDA finalizes advanced manufacturing technology designation guidance

The US Food and Drug Administration (FDA) has finalized a guidance to assist sponsors interested in participating in the Advanced Manufacturing Technology (AMT) designation program.

In response to feedback, FDA has revised its guidance to clarify the Advanced Manufacturing Technology (AMT) designation process, the roles of various entities involved in the program, and its application to Biologics License Applications (BLA) applicants to reference an AMT designation within their applications. (RELATED: Industry clamors for clarity on FDA’s advanced manufacturing designation program, Regulatory Focus 21 March 2024)

The guidance finalizes a draft version issued in December 2023. (RELATED: FDA guidance details new advanced manufacturing technology designation program, Regulatory Focus 14 December 2023)

The AMT program aims to facilitate the development of manufacturing methods that incorporate a novel technology or use an established technology in a unique way to produce a drug of equivalent or superior drug quality. FDA was mandated to create the program as part of Congress’ omnibus spending bill in December 2022. (RELATED: Omnibus brings new advanced manufacturing programs to FDA, Regulatory Focus 11 January 2023)

In the final guidance, FDA clarifies in the content section that AMT designation requests must contain “evidence that the proposed AMT will maintain equivalent or provide superior drug quality (e.g., quality data from studies comparing drugs manufactured using the proposed AMT and those manufactured using an established technology in the same context of use).”

The guidance also clarifies the roles of the various parties involved in the AMT programs in the question-and-answer section at the end of the guidance.

The guidance defines the requestor as “a person or organization that has developed a technology and has submitted an AMT designation request to FDA for that technology.” The term designated AMT holder is “a person or organization whose AMT designation request has been evaluated by FDA and granted designation under the program.” The applicant is “an entity that has submitted or plans to submit to FDA an NDA, ANDA, BLA, or investigational new drug application (IND).”

There is also a new question regarding how FDA will handle multiple AMT designation requests for similar technologies.

The new text states that “FDA may determine that multiple similar technologies, independently submitted by different requestors in separate AMT designation requests, are each eligible for designation. In this event, FDA will individually assess the data and information contained in each request and independently determine AMT designation, as described in section III.D of this guidance. Unless they are used in a novel way, technologies similar to AMTs that have graduated from the program or are close to graduation are likely not eligible for designation.”

The agency also agreed to industry requests to permit BLAs to reference a designated AMT through a drug master file (DMF). In the final version, new language states that “a BLA applicant can use, reference, or rely upon a designated AMT in the development or manufacturing of a biological product that is the subject of their application if they are authorized to do so by the designated AMT holder or are themselves the AMT holder.”

Yet FDA expects that supporting information for the drug substance, drug substance intermediate, and drug product be submitted directly to the BLA rather than be incorporated by reference to a DMF as the “BLA holder is expected to have knowledge of and control over the manufacturing process for the biological product for which it has a license.”

The draft said that BLA sponsors could not reference a designated AMT in their applications.

The Pharmaceutical Research and Manufacturers of America (PhRMA), the American Society of Cell and Gene Therapy (ASGCT), and the Biotechnology Innovation Organization (BIO) had requested the change.

PhRMA had asserted that “prohibiting use of a DMF for BLAs utilizing designated AMTs undermines the plain language of the statute and Congress’s intent in facilitating broad use of advanced manufacturing technologies and encouraging innovation in this space.”

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FDA finalizes advanced manufacturing technology designation guidance

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