Advanced

Manufacturing
Technologies
Designation Program
Guidance for Industry

U.S. Department of Health and Human Services

Food and Drug Administration
Center for Drug Evaluation and Research (CDER)
Center for Biologics Evaluation and Research (CBER)

December 2024
Pharmaceutical Quality/CMC
 Advanced
Manufacturing
Technologies
Designation Program
Guidance for Industry
Additional copies are available from:
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Food and Drug Administration
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https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics/biologics-guidances

U.S. Department of Health and Human Services

Food and Drug Administration
Center for Drug Evaluation and Research (CDER)
Center for Biologics Evaluation and Research (CBER)

December 2024
Pharmaceutical Quality/CMC
 Contains Nonbinding Recommendations

TABLE OF CONTENTS

I. INTRODUCTION............................................................................................................. 1
II. BACKGROUND ............................................................................................................... 2
III. AMT DESIGNATION REQUESTS ............................................................................... 3
A. Criteria ............................................................................................................................................ 4
B. Content of the Request .................................................................................................................. 4
C. Submission Process ........................................................................................................................ 6
D. Designation Determination ........................................................................................................... 6
E. Lifecycle .......................................................................................................................................... 7
IV. BENEFITS OF AMT DESIGNATION .......................................................................... 8
A. Drug Development ......................................................................................................................... 9
B. Application Assessment ............................................................................................................... 10
V. QUESTIONS AND ANSWERS ..................................................................................... 10

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Advanced Manufacturing Technologies Designation Program

Guidance for Industry1

This guidance represents the current thinking of the Food and Drug Administration (FDA or Agency) on
this topic. It does not establish any rights for any person and is not binding on FDA or the public. You can
use an alternative approach if it satisfies the requirements of the applicable statutes and regulations. To
discuss an alternative approach, contact the FDA office responsible for this guidance as listed on the title
page.

I. INTRODUCTION

Advanced manufacturing is a general term for an innovative pharmaceutical manufacturing

approach or technology that has the potential to improve the reliability and robustness of the
manufacturing process and supply chain and increase timely access to quality medicines.
Advanced manufacturing can integrate novel technological approaches, use established
techniques in an innovative way, or apply production methods in a new domain where there are
no defined best practices or experience. 2

FDA encourages the early adoption of specific advanced manufacturing technologies (AMTs)
that have the potential to benefit patients by improving manufacturing and supply dependability
and optimizing development time of drugs. 3 These technologies can be integral to ensuring
quality and supporting a robust supply of drugs that are life-supporting, life-sustaining, of critical
importance to providing health care, or in shortage. AMTs can directly improve product quality
(e.g., through better manufacturing controls and fewer human interventions).

This guidance provides recommendations to persons and organizations interested in participating

in FDA’s Advanced Manufacturing Technologies Designation Program, which facilitates the
development of drugs manufactured using an AMT that has been designated as such under the
program (hereinafter designated AMT). The guidance outlines the eligibility criteria for AMT
designation, the submission and assessment process for requests, and the benefits of receiving an
AMT designation and includes a questions and answers section to cover additional details about
key concepts important for program utilization. Specifically, the guidance describes:

1
This guidance has been prepared by the Office of Pharmaceutical Quality in the Center for Drug Evaluation and
Research in cooperation with the Center for Biologics Evaluation and Research at the Food and Drug
Administration.
2
For additional information about advanced manufacturing in general, see FDA’s web page “Advanced
Manufacturing” at https://www.fda.gov/emergency-preparedness-and-response/mcm-issues/advanced-
manufacturing.
3
In this guidance, the term drug refers to human drug products and biological products, other than biological
products that meet the definition of a device under section 201(h)(1) of the FD&C Act (21 U.S.C. 321(h)(1)).

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• The process for submitting an AMT designation request, including a description of

eligibility criteria and the data and other information to be included.

• When and how FDA will assess AMT designation requests.

• The process by which FDA will engage with requestors, holders of designated AMTs,
and applicants for drugs manufactured using, referencing, or relying upon a designated
AMT.

• Benefits related to drug development and application assessment. 4

In general, FDA’s guidance documents do not establish legally enforceable responsibilities.

Instead, guidances describe the Agency’s current thinking on a topic and should be viewed only
as recommendations, unless specific regulatory or statutory requirements are cited. The use of
the word should in Agency guidances means that something is suggested or recommended, but
not required.

II. BACKGROUND

FDA’s Advanced Manufacturing Technologies Designation Program, which is required under

section 506L of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 5 offers a framework for
persons or organizations (e.g., applicants, contract manufacturers, technology developers) to
request designation of a method or combination of methods of manufacturing 6 a drug as an
AMT. The program facilitates the development of drugs as described in section 506L(b) of the
FD&C Act that are manufactured using a designated AMT, submitted in an application under
section 505 of the FD&C Act (21 U.S.C. 355) or section 351 of the Public Health Service Act
(PHS Act, 42 U.S.C. 262), and regulated by the Center for Drug Evaluation and Research
(CDER) or the Center for Biologics Evaluation and Research (CBER). The holder of the AMT
designation or another authorized party may reference or rely upon data or information about the
designated AMT in an application in the same context of use for which the designation was
granted. 7 FDA will facilitate development and expedite assessment of an application, including

4
In this guidance, the term assessment also means review. Assessment is the term that the Center for Drug
Evaluation and Research’s Office of Pharmaceutical Quality and Office of Generic Drugs will generally use in place
of review. Assessment means the process of both evaluating and analyzing submitted data and information to
determine whether the application meets the requirements for approval and documenting that determination.
5
Section 3213 of the Food and Drug Omnibus Reform Act of 2022 (FDORA) amended the FD&C Act, in part, to
add section 506L (21 U.S.C. 356l).
6
In this guidance, the term manufacturing includes the steps outlined in the definition of manufacture in 21 CFR
207.1.
7
See sections 506L(c)(1) and 506L(d)(2) of the FD&C Act. In this guidance, context of use refers to the specified
purpose and manner of use for a designated AMT that will be used in developing and manufacturing a particular
drug type (e.g., dosage form or class). For more information about how FDA interprets the term context of use as it
relates to AMT designation, see the questions and answers section of this guidance (section V, Q1).

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supplements, for drugs that are manufactured using a designated AMT as described in section
506L(d)(1) of the FD&C Act. 8

Use of designated AMTs can provide greater assurance of quality, shorten drug development
time, assist industry in more efficiently meeting regulatory requirements for commercial
manufacturing, and strengthen regulatory predictability for products that use a designated AMT.
To encourage the adoption of designated AMTs, the Advanced Manufacturing Technologies
Designation Program offers early interaction opportunities, before application submission, with
designated AMT holders and applicants to advise on designated AMTs and their implementation
in drug manufacturing. 9

III. AMT DESIGNATION REQUESTS

AMT designation requests are made independently of application submissions. Therefore, there
is no predetermined stage during which AMT designation requests should be submitted to FDA.
Before submitting an AMT designation request, persons or organizations seeking designation of
a method of manufacturing as an AMT (hereinafter requestors) should familiarize themselves
with the data requirements described in section 506L of the FD&C Act, the recommendations
outlined in this guidance, and other publicly available sources of product development
information. 10

Any technology can be considered for AMT designation provided that the technology meets the
eligibility criteria described in section 506L(b) of the FD&C 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 for which AMT designation
is sought.

For developers of technologies that do not yet meet the data requirements to support eligibility
for AMT designation, FDA recommends early engagement with CDER’s Emerging Technology
Team (ETT), which manages CDER’s Emerging Technology Program, or CBER’s Advanced
Technologies Team (CATT), which is part of CBER’s Advanced Technologies Program, if a
technology meets the criteria for these programs. 11 ETT and CATT assist companies interested
in implementing emerging or advanced technologies in drug development, and their programs
are suitable for technologies in various stages of maturity.

This section covers eligibility criteria, the data and information needed to demonstrate eligibility,
the submission process, AMT designation determination, and lifecycle considerations.

8
In this guidance, an expedited assessment does not refer to an expedited user fee review goal.
9
For a description of the differences between requestor, designated AMT holder, and applicant, see section V, Q2.
10
See, e.g., International Council for Harmonisation guidance for industry Q8(R2) Pharmaceutical Development
(November 2009). We update guidances periodically. For the most recent version of a guidance, check the FDA
guidance web page at https://www.fda.gov/regulatory-information/search-fda-guidance-documents.
11
For information about these two programs, how they differ from the Advanced Manufacturing Technologies
Designation Program, and the benefits of early engagement with ETT or CATT, see section V, Q7 and Q8.

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A. Criteria

Per the criteria described in section 506L(b) of the FD&C Act, 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 12 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; 13 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 506E of the FD&C Act (21 U.S.C. 356e).

B. Content of the Request

An AMT designation request must include data or information demonstrating that the method of
manufacturing for which a requestor is seeking designation (hereinafter proposed AMT) meets
the statutory criteria in a particular context of use. 14 The types of supportive data and information
to include in a request depend on the specific method of manufacturing and its proposed context
of use and should be determined by the requestor in preparing its request. 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. 15 The robustness of the
data and information should be commensurate with the level of risk inherent to the process and
proposed context of use.

Specifically, an AMT designation request should include the following information:

• A brief description of the method of manufacturing or combination of methods and why

it should be considered for AMT designation, including a brief explanation of how the
method, in part or in whole, incorporates a novel technology or uses an established
technique or technology in a novel way.

• The context of use under which the proposed AMT will be used, including information
(e.g., dosage form, class of drug) about the model (i.e., representative) drug used to
generate manufacturing or development data submitted in the request.

12
For an explanation of how FDA interprets the term novel in the context of AMT designation, see section V, Q3.
13
In this guidance, reducing development time means decreasing the time it takes for a product to get to market,
such as through more efficient manufacturing or faster generation of higher quality data to support application
approval.
14
Section 506L(c)(1) of the FD&C Act.
15
Section 506L(b) of the FD&C Act.

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• A detailed description of how the method of manufacturing or combination of methods

meets the eligibility criteria described in section 506L(b) of the FD&C Act in a particular
context of use. This description should include:

o An outline of the steps of the proposed AMT, including information about where in
the overall manufacturing process the proposed AMT is intended to be used.

o Information about how the proposed AMT will ensure equivalent or superior drug
quality, including the proposed control strategy. 16

o A description of how the proposed AMT will reduce drug development time or how it
will address a critical drug supply need.

o Developmental data, including quality-related data generated through process

development studies that evaluate the proposed AMT, and information that describes
and justifies the proposed AMT’s context of use.

• Perceived regulatory, technical, or other challenges to implementation of the proposed

AMT.

• For requestors who are also applicants or prospective applicants, and if known at the time
of the AMT designation request, the anticipated timeline for drug development activities
that incorporate the proposed AMT, including the planned submission of any applications
that would use, reference, or rely upon data and information about the proposed AMT in
the same context of use.

• If applicable, information about previous engagement with ETT or CATT.

• For a proposed AMT that is intended for use in manufacturing an existing drug (i.e., a
drug that is the subject of a previously approved application) that meets the criteria in
section 506L(b)(2)(A) or (B) of the FD&C Act:

o A cross-reference to the existing application. 17

o Information demonstrating that the proposed AMT will increase or maintain the
supply of the drug.

o 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).

16
For more information on control strategies, see ICH Q8(R2).
17
If the requestor plans to leverage confidential commercial information from a previously approved application in
their request, but they are not also the applicant, they should obtain a right of reference to such information.

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FDA acknowledges that requestors who are not also applicants may not have data about a
specific drug to include in their AMT designation request. In these cases, FDA recommends that
requestors include data generated using a model drug to provide the Agency with a clear
understanding of the proposed AMT’s parameters, limitations, and context of use.

C. Submission Process

Requestors should only submit a request once supporting data and information to demonstrate
eligibility for AMT designation are available and ready for inclusion in the request. Requestors
should submit their AMT designation request electronically to
AMT_designation_requests@fda.hhs.gov. 18 The subject line should be REQUEST FOR AMT
DESIGNATION in uppercase letters. In addition to the data and information described in section
III.B of this guidance, the email should include the requestor’s contact information—including
the name, address, email address, and telephone number for their main point of contact in the
United States—and indicate if the request is specific to CDER, CBER, or both.

Upon receipt of the AMT designation request, FDA intends to acknowledge receipt, confirm
whether the request is complete, and begin an evaluation to determine whether to designate the
proposed AMT.

D. Designation Determination

AMT designations will be limited to those methods of manufacturing that meet the criteria
described in section 506L(b) of the FD&C Act and explained in section III.A of this guidance.
To determine eligibility, a team of FDA experts from the center with jurisdiction over the type of
drug that would incorporate the proposed AMT will review the request. This team, including
members of ETT or CATT, where applicable, 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. For proposed AMTs that have potential cross-
center impact, a cross-disciplinary team, including members from CDER and CBER, will
evaluate the requests. 19

The team will include a designated lead with demonstrated expertise in the manufacturing
process, product type, or other elements specific to the proposed AMT to serve as the primary
subject matter expert for the request. The designated lead may facilitate contact with the
requestor to obtain additional information about the AMT designation request or to coordinate
discussions between FDA and the requestor regarding specific aspects of the proposed AMT
during the designation determination process. 20 The format of such discussions will be
determined by FDA on a case-by-case basis. As appropriate, the designated lead will facilitate

18
If the request includes confidential commercial information, it is the responsibility of the company to ensure it is
submitted using one of FDA’s secure messaging partners. Requestors can ask to be added to the list of FDA’s secure
messaging partners by emailing SecureEmail@fda.hhs.gov. Confidential commercial or trade secret information
should be clearly marked as such in accordance with 21 CFR 20.61(d).
19
See section 506L(c)(1)(B) of the FD&C Act.
20
See section 506L(c)(1)(A) of the FD&C Act.

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the involvement of senior FDA managers and other experienced FDA staff in a collaborative,
cross-disciplinary review of the proposed AMT. 21

Section 506L(c)(2) of the FD&C Act requires FDA to complete AMT designation
determinations regarding designation for a particular context of use and program acceptance or
denial within 180 calendar days of FDA’s receipt of the request. Submission of an AMT
designation request does not guarantee designation or acceptance into the program. FDA expects
to deny requests that are incomplete or are submitted for methods of manufacturing that do not
meet the criteria described in section 506L(b) of the FD&C Act. Denial of an AMT designation
request does not preclude a requestor from submitting a new request if additional data and
information to support eligibility become available.

E. Lifecycle

Designated AMT holders should communicate updates or proposed changes that could affect the
context of use or eligibility of their designated AMTs, such as when additional supportive data
become available (e.g., additional batch analysis data), by emailing
AMT_designation_requests@fda.hhs.gov. The subject line should be PROPOSED CHANGE
FOR DESIGNATED AMT in uppercase letters. In addition to the requestor’s contact
information described in section III.C of this guidance, the email requesting a change should
include the product center that reviewed the request (CDER, CBER, or both), a brief description
of the proposed change, supporting data for the proposed change, and a list of persons or entities
who have been given a right of reference to the designated AMT. 22 The email should also
address the potential impact of the proposed change on the criteria for designation or the
particular context of use for which the AMT was designated, as defined at the time of initial
designation.

FDA intends to assess the proposed changes, including supporting data, to confirm that the
designated AMT continues to meet criteria for designation and maintains the same context of use
for which the AMT was designated. FDA will also determine whether additional data or a new
designation request are necessary. Once assessment of the proposed change is complete, FDA
will communicate results to the AMT holder. It is the responsibility of the AMT holder to inform
applicants about any changes to their designated AMT, including changes to the context of use.

Once FDA has gained significant experience assessing a designated AMT and the designated
AMT has been used in multiple approved applications, FDA may decide to graduate the
technology and transfer the review of future applications that use, reference, or rely upon that
AMT—including supplements to an original application that had previously been granted the
designation—to the standard quality assessment process (rather than an expedited process). FDA
intends to make such graduation decisions on a case-by-case basis. Graduation would keep AMT
designation aligned with the statutory prerequisite of novelty 23 and facilitate further innovation

21
See section 506L(c)(1)(B) of the FD&C Act.
22
Entities that obtain a right of reference to reference or rely upon a designated AMT should ensure that the
agreement (i.e., letter of authorization) includes mechanisms for communication regarding future changes.
23
See section 506L(b) of the FD&C Act.

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over the program’s duration 24 by leveraging FDA’s available AMT-related resources on new
AMTs that continue to meet the program’s goal of encouraging adoption of novel technologies to
shorten drug development times for critical medicines while maintaining or improving product
quality. As a designated AMT reaches graduation, the designated lead will facilitate
communication with the AMT holder, relevant applicants, and FDA assessment teams about
pending and final changes to an AMT’s designation status, including a justification for such
changes.

Similar to other established methods of manufacturing, a graduated AMT is not precluded from
reentry into the Advanced Manufacturing Technologies Designation Program, provided that the
technology is proposed for use in a novel way (i.e., different from its previously designated
context of use or its role in a manufacturing process) such that it again meets the eligibility
criteria described in section 506L(b) of the FD&C Act.

IV. BENEFITS OF AMT DESIGNATION

A key benefit of AMT designation is FDA’s early interaction with applicants regarding the
development and manufacture of drugs using a designated AMT. 25 As resources permit, FDA
intends to provide timely advice and to engage in additional communication, in the form of
written correspondence or meetings, with 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 designated AMT-related questions and issues,
including submission content related to implementation of a designated AMT and other AMT-
related topics. When appropriate, the designated lead for the AMT request will coordinate with
the appropriate FDA quality assessment team.

FDA expects to prioritize applicant interactions involving 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 life-supporting, life-sustaining,
of critical importance to providing health care, or in shortage. For new drug applications
(NDAs), biologics license applications (BLAs), and abbreviated new drug applications (ANDAs)
involving complex generic drugs, these interactions would typically occur under the appropriate

24
Under section 506L(f) of the FD&C Act, FDA may not consider requests for AMT designation after October 1,
2032.
25
See sections 506L(c) and (d) of the FD&C Act.

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user fee meeting type. 26 For ANDAs not involving complex generic drugs, these interactions
would typically take place through controlled correspondence. 27 However, applicants with a
designated AMT—whether the ANDA involves a complex product or a non-complex product—
can also request product development and presubmission meetings. 28 Any additional interaction
deemed necessary by FDA will be facilitated by the designated lead for the AMT request.

The designated lead will facilitate communication with the applicant regarding advice and
information relevant to product quality to support the successful adoption of a designated AMT.
As needed, the designated lead will also connect applicants with other FDA disciplines outside
the scope of product quality when an applicant requires expertise or advice from these other
disciplines.

Although knowledge gained during the AMT designation process will be leveraged during
FDA’s assessment of an application that uses a designated AMT, it is the applicant’s
responsibility to demonstrate, through the required technical data submitted in the chemistry,
manufacturing, and controls (CMC) section, 29 that a designated AMT is suitable for inclusion in
their application.

A. Drug Development

Applicants are encouraged to take advantage of the benefits afforded under the program to
engage with the team that designated the AMT to discuss, early in the development process, how
the designated AMT can be used to shorten or otherwise optimize drug development time. 30 The
designated lead will work to:

• Ensure that meetings with the applicant are collaborative and productive.

• Answer applicant questions about the information appropriate to be included in their

application.

• Discuss the quality assessment of the applicant’s future applications that plan to use,
reference, or rely upon a designated AMT.

26
See draft guidances for industry Formal Meetings Between the FDA and Sponsors or Applicants of PDUFA
Products, Revision 1 (September 2023) and Formal Meetings Between the FDA and Sponsors or Applicants of
BsUFA Products, Revision 1 (August 2023). When final, these guidances will represent FDA’s current thinking on
these topics. See also guidances for industry Formal Meetings Between FDA and ANDA Applicants of Complex
Products Under GDUFA, Revision 1 (October 2022) and Expedited Programs for Regenerative Medicine Therapies
for Serious Conditions (February 2019).
27
See guidance for industry Controlled Correspondence Related to Generic Drug Development, Revision 1 (March
2024).
28
Applicants should submit requests for a product development meeting in an appropriate format, such as the format
described in the guidance for industry Formal Meetings Between FDA and ANDA Applicants of Complex Products
Under GDUFA, Revision 1. In addition to the applicable information identified in sections V and VIII of the Formal
Meetings guidance, applicants should provide documentation of the AMT designation.
29
See 21 CFR 314.50(d)(1), 21 CFR 314.94(a)(9), and 21 CFR 601.2.
30
See section V, Q10, in this guidance for information about requesting engagement.

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B. Application Assessment

The designated lead will facilitate the quality assessment of an application for a drug
manufactured using the designated AMT with the aim of making the assessment process more
efficient than the process for applications using manufacturing methods not designated under the
program. FDA intends to use this approach to support applicants while they are developing the
CMC section of their applications such that the incorporation of a designated AMT will not
increase the time or number of assessment cycles required to arrive at a quality-related decision
and, as a result, will not increase the time required to arrive at a decision regarding overall
application approval. The knowledge and familiarity gained by FDA though the assessment of
applications that use a particular designated AMT should streamline the assessment of
subsequent applications that use the same designated AMT.

When a designated AMT graduates from the program as described in section III.E of this
guidance, FDA will take appropriate steps to transfer information about the previously
designated AMT to the appropriate assessment team for applications that used, referenced, or
relied upon the previously designated AMT. New applications received after the transfer will
receive the standard level of FDA communication and interaction afforded to all applicants.
Graduation of a designated AMT will not affect approved applications that reference the
previously designated AMT or the ability of an applicant to continue to use that technology with
an appropriate right of reference.

V. QUESTIONS AND ANSWERS

Q1. How is context of use considered when determining AMT designation and assessing
applications for other products (i.e., not the model drug used for the AMT designation
request)?

Consistent with section 506L(c) of the FD&C Act, AMT designation applies to a method of
manufacturing within a particular context of use rather than to a specific application. For this
reason, requestors can use model (i.e., representative) drugs instead of application-specific drugs
to generate the supporting data for proposed AMTs to be included in their designation requests.
The data and information generated using a model drug should, at a minimum, be specific to a
particular class of drugs and, as described in section III of this guidance, should include
development data, including batch analysis data generated using either a developmental
candidate molecule or a model drug. Requestors should fully and clearly describe the context of
use within which they are requesting the AMT be designated, including how it will be used to
develop and manufacture a specific type or range of drugs.

Whether the use of a designated AMT for manufacturing a specific drug that is the subject of an
application would be considered to be the same context of use for which the AMT was
designated can be discussed in presubmission meetings and will be determined during the
application assessment process.

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Q2. What is the difference between a requestor, a designated AMT holder, and an
applicant?

Multiple entities can be involved in the development or use of a designated AMT over its
lifecycle. These entities include requestors, designated AMT holders, and applicants. An entity
might meet the definition of all three terms described below.

In this guidance, the term requestor describes a person or organization that has developed a
technology and has submitted an AMT designation request to FDA for that technology. As
described in sections III.B and III.C of this guidance, requestors define the context of use for
their proposed AMTs, determine the types of supporting data and information to include in AMT
designation requests, and prepare and submit the requests to FDA. FDA may facilitate
communication with requestors as described in section 506L(c)(1)(A) of the FD&C Act.

In this guidance, the term designated AMT holder describes a person or organization whose
AMT designation request has been evaluated by FDA and granted designation under the
program. 31 As described in section III.E of this guidance, designated AMT holders should
communicate changes that could impact eligibility or the context of use for their designated
AMTs to FDA. They can also authorize applicants to incorporate by reference data and
information about the designated AMT in their application (see Q5 and Q6).

In this guidance, the term applicant describes an entity that has submitted or plans to submit to
FDA an NDA, ANDA, BLA, or investigational new drug application (IND). An applicant can
use, reference, or rely upon a designated AMT in the development or manufacturing of a drug
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. 32 When doing so, applicants determine if the
designated AMT is appropriate for their specific drug, incorporate the designated AMT into the
drug’s development and manufacture, and submit drug-specific data in the application.

Q3. What does FDA consider a novel technology or use of an established technique or
technology in a novel way?

For purposes of evaluating eligibility for AMT designation, FDA generally considers a novel
technology or an established technique or technology used in a novel way to be one for which
FDA has limited assessment or inspectional experience. A novel technology can be a completely
new technology that FDA has not previously seen in a submission or a technology with which
FDA has experience but with a significantly different use than is now being proposed.

Although novelty is an essential element of AMT designation, it is not the only defining
characteristic of a designated AMT. Certain technologies might be considered novel based on the
above description, but their incorporation into the manufacturing process alone would not meet
statutory eligibility criteria to qualify for AMT designation.

31
See section 506L(c)(2) of the FD&C Act.
32
See section 506L(d)(2) of the FD&C Act.

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Q4. What happens if FDA independently receives more than one AMT designation
request for a similar technology?

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.

Q5. How can an NDA, ANDA, or IND applicant reference or rely upon a designated
AMT in an application?

When an NDA, ANDA, or IND applicant and designated AMT holder are different entities, the
designated AMT holder, who can also be the holder of a drug master file (DMF) that contains the
designated AMT, can authorize the applicant to incorporate by reference data and information
about the designated AMT in their application. 33 An application that references or relies upon a
designated AMT can receive the benefits provided by the AMT designation with the appropriate
authorization if the referenced AMT is used to manufacture a drug in the same context of use for
which the designation was granted as described above.

Although multiple applications can reference the same designated AMT, each application
referencing a particular designated AMT will be assessed on its own merits. When referencing or
relying upon a designated AMT in an application, applicants should explain how the designated
AMT will be used to manufacture the drug that is the subject of the application and why that
context of use is consistent with the context of use for which the AMT received designation.

Q6. How can a BLA applicant reference or rely upon a designated AMT in an
application?

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. 34

However, because a BLA holder is expected to have knowledge of and control over the
manufacturing process for the biological product for which it has a license, FDA expects that
supporting data and information for the drug substance, drug substance intermediate, and drug
product (DS/DSI/DP) be submitted directly to the BLA rather than be incorporated by reference

33
For more information about DMFs, see 21 CFR 314.420 and draft guidance for industry Drug Master Files,
Revision 1 (October 2019). When final, this guidance will represent FDA’s current thinking on this topic.
34
See section 506L(d)(2) of the FD&C Act.

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to a DMF, consistent with 21 CFR 601.2(g). 35 For this reason, even when using a designated
AMT, BLA applicants should have access to such supporting data and information, including the
controls and validation of the manufacturing process and other information critical to evaluating
the BLA holder’s control over product quality, and should include this information in their
BLA. 36

The exclusion in 21 CFR 601.2(g) against cross-referencing a DMF in a BLA is limited to

information about the DS, DSI, and DP. Some AMT-related data and information can be
included in a DMF, such as certain equipment used in manufacturing the DS, DSI, and DP. FDA
will evaluate whether it is permissible to include such data and information in a DMF on a case-
by-case basis. For a drug-biologic combination product, 37 an applicant can incorporate by
reference a DMF for nonbiological product constituent parts. 38

Q7. How does the Advanced Manufacturing Technologies Designation Program differ
from CDER’s Emerging Technology Program and CBER’s Advanced Technologies
Program?

All three programs focus on engagement between FDA and prospective drug developers to
discuss potential regulatory challenges and clarify related questions about using novel
technologies for which CDER or CBER have limited assessment experience. Despite these
similarities, there are also several differences between the three programs, including the maturity
level of the technology accepted into the program and the timing, intended participants, and
scope of each program.

In some cases, a technology that is not eligible for CDER’s Emerging Technology Program or
CBER’s Advanced Technologies Program could nevertheless be eligible for AMT designation.
The opposite could also be the case. For example, as noted in section III, the data and
information necessary for AMT designation might not yet be available for a technology granted
acceptance into either of the other two programs.

CDER’s Emerging Technology Program allows potential applicants to submit to ETT questions
and proposals about the use of a specific emerging technology (e.g., questions about regulatory

35
In the preamble to codification of this final rule, FDA noted that “the inability to incorporate by reference
DS/DSI/DP information contained in a master file does not remove BLA applicants’ incentives or ability to proceed
with product development. An applicant who does not intend to manufacture all aspects of the product for licensure
may…consider other types of cooperative manufacturing arrangements, while still assuming responsibility for
meeting the applicable product and establishment standards. These other arrangements would provide alternatives in
cases where the incorporation by reference of a master file is not permitted” (89 FR 9743 at 9746, February 12,
2024).
36
The preamble, in discussing the general complexity of biological products, noted “As a scientific matter, for
biological products, the Agency considers it to be generally impractical for the applicant to confirm DS/DSI/DP
quality characteristics without complete knowledge of, and control over, all aspects of the manufacturing process,
including the manufacturing process for the DS/DSI/DP” (89 FR 9743 at 9746, February 12, 2024).
37
For more information, see FDA’s web page “Frequently Asked Questions About Combination Products” at
https://www.fda.gov/combination-products/about-combination-products/frequently-asked-questions-about-
combination-products#CP and 21 CFR 3.2(e).
38
See 21 CFR 601.2(g)(3).

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issues or submission of CMC information). ETT serves as the primary point of contact for
companies interested in implementing an emerging technology into CDER-regulated products.
CBER’s Advanced Technologies Program promotes dialogue, education, and input between
CBER and prospective developers of advanced manufacturing and testing technologies. CATT
facilitates such communications to promote the implementation of these technologies in the
development of CBER-regulated products. 39

ETT and CATT discussions can begin earlier in the drug development process. In contrast, the
Advanced Manufacturing Technologies Designation Program is intended for methods and
technologies that, while still novel (or used in a novel way), are more mature, such as those for
which model drug-specific data to support eligibility are available.

As discussed elsewhere in this guidance, the designated AMT holder may not necessarily be the
same entity as the applicant who ultimately uses a designated AMT in their application.
Although ETT engagement can occur before a specific product is in development, CDER’s
Emerging Technology Program is primarily designed for companies that intend to eventually
incorporate an emerging technology into the CMC section of their application. For CBER’s
Advanced Technologies Program, CATT is limited to early engagement before regulatory
submission. Therefore, any meetings regarding the use of a designated AMT that take place after
application submission would generally occur through the Advanced Manufacturing
Technologies Designation Program.

Finally, CDER’s Emerging Technology Program and CBER’s Advanced Technologies Program
may involve activities outside the scope of AMT designation, including discussions with
industry about other elements such as novel dosage forms or drug delivery systems. Of note,
only the statutory Advanced Manufacturing Technologies Designation Program confers an
official designation for technologies accepted into the program.

Q8. What are the benefits of engaging with ETT or CATT before requesting AMT
designation?

Although AMT designation should not be requested at the same time as ETT or CATT
engagement, early engagement with ETT or CATT can provide an avenue for potential
requestors to elicit FDA feedback about the technical components of a technology before it has
reached a maturity level appropriate for AMT designation. ETT and CATT are not suitable,
however, to address whether a technology has reached a maturity level appropriate for AMT
designation or provide decisions on AMT eligibility or designation.

39
For more information about CDER’s Emerging Technology Program, see guidance for industry Advancement of
Emerging Technology Applications for Pharmaceutical Innovation and Modernization (September 2017) and
https://www.fda.gov/about-fda/center-drug-evaluation-and-research-cder/emerging-technology-program. For more
information about CBER’s Advanced Technologies Program, see https://www.fda.gov/vaccines-blood-
biologics/industry-biologics/cber-advanced-technologies-program.

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Q9. How does the Advanced Manufacturing Technologies Designation Program differ
from the Platform Technology Designation Program?

Both the Advanced Manufacturing Technologies Designation Program and the Platform
Technology Designation Program 40 aim to increase the efficiency of drug development and
manufacturing. However, the two programs generally serve different purposes and apply to
different types of technologies at different maturity levels.

Regarding program purpose, one of the distinguishing criteria for a method of manufacturing or
combination of methods being proposed for AMT designation is that it must incorporate a novel
technology or an established technique or technology used in a novel way. 41 In contrast, one of
the distinguishing criteria of a designated platform technology is that it is a well-understood and
reproducible technology that is incorporated in or used by an approved drug or licensed
biological product. 42 For this reason, FDA expects to have previous assessment or inspectional
experience with a designated platform technology at the time of designation.

Regarding eligible methods of manufacturing, a designated AMT is limited to a method or

combination of methods of manufacturing a drug. In contrast, a broader range of technologies
(e.g., nucleic acid sequences, molecular structures, mechanisms of action, delivery methods) is
eligible for platform technology designation, and applicants must demonstrate, among other
criteria, 43 that the platform technology is incorporated in or used by a drug and is essential to the
structure or function of such drug to receive designation. 44

Because of the differences between the two programs, FDA recommends requesting only the
designation that is appropriate for the particular method or technology in question. There should
be no expectation that requesting both designations simultaneously would offer additional
benefits.

Q10. How should an applicant request engagement with FDA regarding the use of a
designated AMT?

Applicants can request a meeting with FDA to have a preliminary discussion about using a
designated AMT and request subsequent meetings throughout the drug development process. As
described in section IV of this guidance, such meeting requests will typically occur under the
appropriate user fee meeting type and should be made in accordance with the electronic
submission guidance 45 and other guidances related to formal meetings between FDA and

40
See section 506K of the FD&C Act (21 U.S.C. 356k) and draft guidance for industry Platform Technology
Designation Program for Drug Development (May 2024). When final, this guidance will represent FDA’s current
thinking on this topic.
41
See section 506L(b) of the FD&C Act.
42
See sections 506K(b)(1) and 506K(h)(1) of the FD&C Act.
43
See section 506K(h)(1) of the FD&C Act.
44
See section 506K(h)(1)(A) of the FD&C Act.
45
See guidance for industry Providing Regulatory Submissions in Electronic Format—Certain Human
Pharmaceutical Product Applications and Related Submissions Using the eCTD Specifications, Revision 7
(February 2020).

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applicants. 46 Although applicants can request such a meeting at any milestone during the
application assessment process, FDA encourages earlier engagement to enable prompt resolution
of regulatory challenges and more efficient application assessment. Any such submissions should
be clearly identified as a REQUEST FOR A MEETING UNDER THE ADVANCED
MANUFACTURING TECHNOLOGIES DESIGNATION PROGRAM in bold, uppercase
letters. In addition to the content recommended in relevant guidances, 47 the meeting background
package should include the timing for application submission and a summary of how the
designated AMT will be used to manufacture the drug.

46
See footnotes 26 and 28.
47
Ibid.

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