Regulatory Roundup 4Q '23

January 12, 2024
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On December 13, 2023, FDA issued a draft guidance for the industry titled “Advanced Manufacturing Technologies Designation Program.” This guidance fulfills the requirement placed on FDA by the Food and Drug Omnibus Reform Act of 2022 (FDORA), which added section 506L (21 U.S.C. 356l) to the Federal Food, Drug, and Cosmetic Act (FD&C Act), to initiate and issue guidance on an advanced manufacturing technologies (AMT) designation program. Comments on the draft guidance may be submitted through February 12, 2024 here. FDORA requires FDA to issue a final guidance no later than December 29, 2024. 

The purpose of the AMT Designation program is to facilitate early adoption of AMTs that have the potential to benefit patients by improving manufacturing and supply dependability and optimizing development time of drug and biological products. AMTs can be integral to ensuring quality and supporting a robust supply of drugs that are life-supporting, life-sustaining, of critical importance to providing healthcare, or in shortage.

Criteria for AMT Designation

Section 506L(b) of the FD&C Act described that a method of manufacturing or combination of methods is eligible for AMT designation if it incorporates a novel technology or uses an established technique or technology in a novel way that will substantially improve the manufacturing process for a drug while maintaining equivalent, or providing superior, drug quality, including by:

  • reducing development time for a drug using the designated manufacturing method; or
  • increasing or maintaining the supply of a drug that is life-supporting, life-sustaining, or of critical importance to providing health care; or
  • a drug that is on the drug shortage list under section section 506E of the FD&C Act (21 U.S.C. 356e)

The Draft Guidance added that AMTs proposed for AMT designation should also generally meet the eligibility criteria described in CDER’s Emerging Technology Program and CBER’s Advanced Technologies Program because engagement with ETT or CATT is strongly recommended as a first step. Information on CBER’s CATT Program is available at FDA notes that it may not be appropriate to go through the ETT or CATT first when “a method of manufacturing could already be at a stage where it is ready for commercial scale production” or when the person submitting a designation request is not a IND or BLA sponsor.

Content of the AMT designation request

The Draft Guidance states that an AMT designation request “must include data or information demonstrating that the method of manufacturing meets the statutory criteria in a particular context of use. In addition, the request must demonstrate the ability of the proposed AMT to substantially improve the manufacturing process for a drug while maintaining or improving upon its quality, including by reducing drug development time or increasing or maintaining the supply of a drug that is life-supporting, life-sustaining, of critical importance to providing health care, or in shortage.”  Those interested in applying for AMT Designation should review the list of specific information to include in the request and the process for submission.    

Review of requests

FDA is required to review and decide on requests for AMT designation within 180 days of receipt. A team of FDA experts (relative to the technology in the designation request) “will evaluate the data and information submitted in the request, including information relating to the context of use, and will seek input from subject matter experts, as needed, to determine if the proposed AMT meets the designation criteria and should therefore be granted AMT designation.” The Draft Guidance further states that a primary subject matter expert for the request will be selected from the FDA team. This designated lead may facilitate contact with the requestor to obtain additional information about the AMT designation request or to coordinate discussions with the team concerning specific aspects of the proposed AMT during the designation determination process. The designated lead will facilitate the involvement of senior FDA managers and other experienced FDA staff in a collaborative, cross-disciplinary review of the proposed AMT.

The Draft Guidance’s description of the AMT designation request review team differs from that of requests for Fast Track (FT), Breakthrough (BT), or Regenerative Medicine Advanced Therapy (RMAT) designation.  One reason is likely that FT, BT, and RMAT designation requests are submitted to an existing IND for which there is an assigned review team and corresponding supervisors.  An AMT Designation request may be submitted in the context of a specific IND or BLA by the sponsor or may be submitted by the AMT developer independent of a specific product.  We will be interested to learn more on how CDER and CBER plan to constitute teams to review AMT designation requests and will look for public presentations on the topic or potential issuance of a MAPP or SOPP. 

There is no cap on the number of AMT designations that the Agency may make.  This differs from the recent CMC Development Readiness Pilot (CDRP) and the START Rare Disease Pilot (see our prior summaries of these pilots: CDRP and START, which is listed as II. here).

Benefits of AMT Designation

As with existing designation programs (FT, BT, and RMAT) and the CDRP and START pilots, the primary benefit is the potential for early and additional interactions with FDA. However, unlike most of these other programs and pilots, no additional meetings or expedited timing are specified. The Draft Guidance states “as resources permit, FDA intends to provide timely advice and to engage in additional communication, in the form of written correspondence or meetings, with requestors, designated AMT holders, and applicants for a drug manufactured using a designated AMT. Such communication may take place during both early drug development and subsequent application assessment and will be used to address proposed or designated AMT-related questions and issues, including AMT design or development issues, submission content related to a designated AMT, and other AMT-related topics.”

Despite the lack of specified meeting benefits, those interested in AMT designation should be encouraged by the chance for FDA meetings and the intent of FDORA for the AMT Designation process to shorten or otherwise optimize drug development. Currently, AMT developers in the CGT space may request a CATT meeting, but there is no clear path for additional meetings outside of a specific IND or BLA. For example, OTP does not routinely grant meetings prior to submission of a Master File. The Draft Guidance offers additional encouragement about a meetings benefit to AMT designation, “FDA expects to prioritize applicant interactions that are intended to discuss the use of a designated AMT in drug development or commercial manufacturing, with higher priority being given to drug development activities and applications using a designated AMT with the potential to significantly improve product quality, address known quality issues for a drug or class of  drugs, or increase or maintain the supply of drugs that are currently in shortage or imminently at risk of being in shortage.”  We believe FDA intends to grant additional meetings for designated AMTs but opted not to make a commitment in the Draft Guidance due to the broad nature of the technologies and types of drugs and biologic products involved.  


The Draft Guidance “Advanced Manufacturing Technologies Designation Program” is the next step in FDA’s implementation of the legislation on AMTs.  It is not yet clear how FDA will interpret the criteria for designation and the benefits available to designated AMTs.  We see potential for multiple technologies used in the CGT field to qualify for AMT designation and to continue to push the field forward.  We encourage stakeholders to review the Draft Guidance and take the opportunity to submit comments to the docket to encourage FDA to add clarifications and modifications to make the Final Guidance more beneficial to CGT.  


The big BLA news of the 4th quarter of 2023 was the approval of both bluebird bio’s Lyfgenia (lovo-cel) and Vertex’s Casgevy (exa-cel) for sickle cell disease on December 8, 2023. This brings the total of new BLA approvals for 2023 to seven. 

To start out the 1st quarter of 2024, FDA approved the indication of transfusion-dependent beta thalassemia (TDT) for Vertex’s Casgevy (exa-cel) on January 16, 2024.

Brainstorm withdrew their BLA submission for debamestrocel for treatment of amyotrophic lateral sclerosis (ALS).  

III. CGT BLAs under US FDA Review 

The following information on BLAs under US FDA review was obtained from company press releases.


No upcoming meetings of the Cellular, Tissue, and Gene Therapies Advisory committee have been announced. 

A date for the Oncologic Drug Advisory Committee (ODAC) meeting to discuss data from BMS’s BLA supplement for approval of ABECMA for earlier line of treatment has not yet been announced.


Communications From Firms to Health Care Providers Regarding Scientific Information on Unapproved Uses of Approved/Cleared Medical Products Questions and Answers
Draft open for comment until 1/5/2024

Advanced Manufacturing Technologies Designation Program
Draft open for comment until 2/12/2024

Translation of Good Laboratory Practice Study Reports: Questions and Answer
Draft open for comment until 2/20/2024

Master Protocols for Drug and Biological Product Development
Draft open for comment until 2/22/2024

Potency Assurance for Cellular and Gene Therapy Products; Draft Guidance for Industry
Draft open for comment until 3/27/2024

FDA also posted a webinar providing a high-level overview of this draft guidance document


Rare Diseases: Considerations for the Development of Drugs and Biological Products

Data Standards for Drug and Biological Product Submissions Containing Real-World Data

Submitting Patient-Reported Outcome Data in Cancer Clinical Trials

Submitting Clinical Trial Datasets and Documentation for Clinical Outcome Assessments Using Item Response Theory

Remote Interactive Evaluations of Drug Manufacturing and Bioresearch Monitoring Facilities 

Guidance for Industry: Voluntary Consensus Standards Recognitions Program for Regenerative Medicine Therapies


In October 2023, FDA published “Guidance for Industry: Voluntary Consensus Standards Recognitions Program for Regenerative Medicine Therapies”. This guidance describes a standards recognition program (SRP-RMT) at CBER designed to identify and recognize Voluntary Consensus Standards (VCS) to facilitate the development and assessment of regenerative medicine therapy (RMT) products regulated by CBER when such standards are appropriate. The use of recognized VCS can assist stakeholders in meeting regulatory requirements more efficiently and increasing regulatory predictability for RMT products.

CBER’s list of recognized standards can be found at

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