FDA 1243.5741 Center For Veterinary Medicine Program Policy Instruction Manual
- June 9, 2024
- FDA
Table of Contents
1243.5741 Center For Veterinary Medicine Program Policy
Instruction Manual
CENTER FOR VETERINARY MEDICINE
PROGRAM POLICY AND PROCEDURES MANUAL
MEMORANDUM RECOMMENDING APPROVAL (MRA) FOR ORIGINAL AND SUPPLEMENTAL (ABBREVIATED) NEW ANIMAL DRUG APPLICATIONS ((A)NADA)
PURPOSE
This document provides instructions on how to use the Office of New Animal Drug Evaluation’s template to prepare a Memorandum Recommending Approval (MRA) for an original or B1 supplemental (abbreviated) new animal drug application [(A)NADA]. An MRA should always be part of the approval package for an (A)NADA (see P&P 1243.3800). This P&P does not apply to (A)NADAs for Animal Drug Availability Act feed combinations or to manufacturing supplements, minor labeling supplements (NFs and NLs) or conditional approvals (see P&P 1243.6020 and 1243.6030 for information on minor labeling supplements).
PURPOSE OF AN MRA
An MRA briefs the individuals signing the approval (i.e., the center director, office director) on the basis for our recommendation to approve an (A)NADA. The MRA incorporates by reference the data, information, and reviews that support our recommendation. The Office of New Animal Drug Evaluation (ONADE) prepares an MRA as part of the final action package for the approval of an original (A)NADA. In addition, ONADE prepares an MRA for supplemental NADA approvals that includes safety and/or effectiveness data (B1 supplements)1. For questions about which applications need an MRA, consult your team leader (TL).
WHO PREPARES THE MRA USING THE OFFICE TEMPLATE?
The MRA is prepared by the reviewer, consumer safety officer, or other individual designated by the division to prepare the approval package for an application. If the reviewer has questions about who prepares the MRA, they should consult with their TL or division director (DD). TLs and DDs are responsible for ensuring that the correct version of the office template was used to create the (A)NADA MRA and confirming the accuracy of the dates and submission codes referenced in the MRA.
GENERAL INSTRUCTIONS FOR USING THE OFFICE TEMPLATE MRA
Use the appropriate ONADE MRA template located on the ONADE Template
SharePoint. For questions about which MRA template to use, consult your TL.
This section describes the contents of each section of the MRA in more detail
than the template. Refer to this section as you use the MRA template.
¹Supplemental ANADA approvals (outside of NF and NL labeling supplements) are
very rare and not covered here.
A. General Instructions for Using the MRA Template:
- Certain template boilerplate text is contained in shaded fill-in text fields or drop-down menus. Choose the appropriate information relating to your specific application. If none of the templated text is applicable, the fill-in or drop-down can be deleted and the text can be entered.
- Words in brackets or italics may provide instruction, describe the information you are to provide, or give examples of the type of information that you are to include in a particular portion of the MRA.
- Where you see brackets, italics, shaded areas or text fields, provide information relating to your specific application.
- Based on the type of application, select the appropriate boilerplate language for each section in the template.
- Include all sections and subsections of the MRA (unless a comment bubble specifically allows for deletion of a (sub)section) identified in the template. For each section, include the boilerplate language or appropriate information described in the (A)NADA MRA template.
- The header will appear on all pages (except the first page) of the MRA template. Double click in the header to insert the Submission Tracking and Reporting System information (i.e., (A)NADA number and submission ID, and subclass code) in place of <A/N-000000-X-0000-XX>.
- When writing the proprietary name, use the appropriate trademark symbols (i.e.,® or ™). See P&P 1243.3015 Proprietary Names for information on how to format the proprietary name.
B. The “To” Line of the MRA
-
Original (A)NADA approvals
Address the MRA to the Center Director, through the Director, ONADE. -
Supplemental NADA approvals
Address most MRAs for supplemental approvals to the Director, ONADE, through the appropriate DD, except for supplements that would approve a new species, significant new indications, or change in Rx/OTC status, which will be addressed to the Center Director, through the Director, ONADE.²
C. General Information Table
The MRA’s General Information table should be identical in all aspects to the
General Information table in the FOI Summary, except the INAD number will not
appear in the FOI Summary.³
²Note: If there is uncertainty about who the approver/signer of a supplemental
approval should be, the DD or TL should always speak with the ONADE Office
Director.
³For NADAs under the Division of Animal Bioengineering and Cellular Therapies
(DABCT), the sections may be modified based on the product type. The preparer
should consult with the DABCT TL or DD for more information.
-
File Number
Insert the (A)NADA application number and, if applicable, the INAD number. -
Sponsor, their address, Drug Labeler Code, and U.S. Agent⁴
If this is not the first approval for a sponsor, copy the sponsor name, address, and drug labeler code exactly as it appears in 21 CFR 510.600(c). Do not copy the sponsor address provided in submitter in this section. Use the listing in the electronic CFR to obtain the most recent information.
If this is a sponsor’s first approval, consult your TL.If the sponsor does not reside or have a place of business within the U.S., insert the name and address of the authorized U.S. agent provided in “U.S. Agent/U.S. Employee Information” section in submitter⁶. Delete the U.S. agent field if not applicable. -
Proprietary Name(s)
The proprietary name is the exclusive name the sponsor assigns to the approved drug product. It is commonly known as the tradename and may include trademarked and non-trademarked words. The proprietary name should match the product labeling. Use the proprietary name consistently throughout the MRA. Format the proprietary name per P&P 1243.3015. -
Drug Product Established Name(s)₇
The drug product established name is the non-proprietary name of the drug product and may or may not include the route of administration and dosage form. To identify the drug product established name, refer to the product labeling.⁸ The established name is typically presented within parenthesis under the proprietary name. Some examples include “(carprofen tablets)” and “(mebendazole oral suspension)”. There may be exceptions, such as “(cyclosporine capsules) USP MODIFIED.” Use the drug product established name consistently throughout the MRA. -
Pharmacological Category
This section describes the action of the drug product (e.g., anticoccidial, antimicrobial, or ant parasitic). Include the schedule if this is a controlled substance. -
Dosage Form(s)
Include the dosage form(s) even if it is part of the proprietary name or drug product established name. The dosage form refers to the physical description
⁴See P&P 1243.2020 on U.S agents
⁵The electronic CFR (elf) provides the most up to date information. It is a different site than the online CFR,
which is an electronic copy of the most recent printed CFR (issued in April of each year).
621 CFR §514.1(a).
7ONADE Policy: Drug Product Established Name for New Animal Drugs
8In some cases, the product established name as written on the labeling may be inconsistent. In these cases, refer to the ONADE Policy: Drug Product Established Name for New Animal Drugs or discuss with your TL. of the approved manufactured product. For example, aerosol, capsule, cream, emulsion, gel, granule, implant, paste, soluble powder, suspension, or Type A medicated article. For additional dosage form examples, consult Appendix I of Guidance for Industry (GFI) #191 and the dosage form worksheet. -
Amount of Active Ingredient(s)
This section describes the amount of drug(s) per tablet, mL, percentage, or
other measure of concentration. The amount should be expressed exactly as
on product labeling, which may be on the basis of the active moiety, the active
ingredient, or both. -
How Supplied
This section describes the size and description of the containers (e.g., 50- and
100-mL vials, 50-lb bag). This information should be expressed exactly as on
product labeling. -
Dispensing Status
This section identifies whether the marketing status is by prescription (Rx),
over-the-counter (OTC), or veterinary feed directive (VFD). -
Dosage Regimen
This section describes the approved dose, frequency, and duration of treatment as printed on the approved labeling. Detailed dosage and administration information from the product insert (e.g., dosing tables provided for the convenience of calculating dosage) should not reside here; however, wording included in this section should match the wording on the approved labeling. Tables that provide information on different doses by weight bands, clarifying the amount of new animal drug to give or apply when there are multiple concentrations or tablet sizes/strengths approved for the new animal drug, can be included here. -
Route(s) of Administration
This section describes how the product is administered.⁹ For example, transdermal, immersion, infiltration, inhalation, intradermal, intramuscular, inframammary, ocular, oral, optic, or topical. For additional examples of routes of administration, consult Appendix II of GFI #191 and the route of administration worksheet. -
Species/Class(es)
This section identifies the target animal species to which the approval applies exactly as stated on product labeling in the “Indications” section. Some approvals apply to a specific class(es) within a species (e.g., lactating dairy cows). If there is a specific class(es) for the approval, include that information here. If there is no class limitation, enter the species in plain language (e.g., cattle rather than bovine, dogs rather than canine). For supplemental approvals, only list the species for which the supplement is approved. For additional examples of classes of major food animals, consult GFI #191, Appendix III.
9For an original approval, list all information. For supplemental NADAs, abbreviate the information to include only that to which the supplement applies, unless the currently approved information is needed to provide context. If you include all of the previously approved information with the new or modified information, then highlight (by bolding) the new or modified information so that the new or modified information is readily distinguishable. -
Indication(s)
In this section, include any new indication(s) we are approving. If no new indication is being approved, include only the indication(s) impacted by the supplemental approval or indication(s) necessary to provide context for the supplemental approval. (Examples: for an approval with multiple species, if the approval is for a reduced withdrawal period for swine, include only the swine indication(s). For an approval adding a new pathogen to an approved indication, include the complete indication with all previously approved pathogens and the added pathogen.) Indication(s) should always be provided, even for supplemental approvals that do not change any existing indications, so readers will know what indication(s) the approval applies to.
Copy the indication(s) verbatim from the indication(s) section of the package insert. If there isn’t a package insert copy it from the immediate container’s carton labeling or the immediate container label. If the proprietary name appears in the indication, format the name the same way the proprietary name is formatted elsewhere in the approval package; i.e., if the indications section of the package insert does not use the trademark symbol for the drug ( ® , ™), still include it here for consistency across documents -
Effect(s) of Supplement (NADA only)
If this is a supplemental approval, this section should briefly describe the changes we are approving. For original approvals, delete this row from the General Information section. -
Reference Listed New Animal Drug (ANADA only)
Provide the RLNAD proprietary name, drug product established name, (A)NADA number and sponsor name as indicated in the template.
D. Suitability Petition (ANADA only)
Suitability petitions (SP) allow sponsors of generic new animal drugs to
request permission to submit an ANADA for a generic that differs from the
RLNAD in specific ways, as defined under section 512(n)(3) of the Federal
Food, Drug, and Cosmetic Act. The permissible differences include:
- route of administration,
- dosage form, strength (concentration),
- a change in one active ingredient in a combination drug, and
- a change in one Type A medicated article in a feed-use combination.
To approve a SP, the proposed change should not require the petitioner to
conduct investigations to demonstrate the safety or effectiveness of the
generic new animal drug for its intended uses. If the generic drug product is
the subject of an approved SP, provide the information requested in the
template for this section.
E. Effectiveness (NADA only)
This section identifies the submission/review document(s) and technical
section complete (TSC) letters (if applicable) that contain the effectiveness
data pertinent to this approval. If necessary, include additional
effectiveness information unique to the application. For supplemental NADAs
that do not contain new effectiveness studies, use the boilerplate language in
the template.
F. Target Animal Safety (NADA only)
This section identifies the submission/review document(s) and TSC letters (if
applicable) that contain the safety data pertinent to this approval. If
necessary, include additional target animal safety information unique to the
application. For supplemental NADAs that do not contain new target animal
safety studies, use the boilerplate language in the template.
G. Bioequivalence (ANADA only)
This section identifies the submission/review document(s) and TSC letter (if
applicable) that contain the bioequivalence data pertinent to this approval.
If a waiver from the requirement to demonstrate in vivo bioequivalence
(biowaiver) was granted, provide that information using the first paragraph in
the MRA template. If an in vivo bioequivalence study was performed, provide
the appropriate information as outlined in the second paragraph of the MRA
template.
H. Human Food Safety (HFS)
This section identifies the submission/review document(s) and TS complete
letters (if applicable) that contain the safety data pertinent to this
approval. If necessary, include additional HFS information unique to the
application.
If the product is for use in non-food producing animal species, then include
the standard language in the template explaining that we did not require HSF
data. For approvals that result in a tolerance change for an approved drug,
the preparer should document in the MRA that an email was sent to the Office
of Surveillance and Compliance. See P&P 1243.3760 for drug tolerance
notification process.
I. Chemistry, Manufacturing Methods, and Controls
This section identifies the submission/review document(s) and TSC letters (if
applicable) that contain the chemistry and manufacturing data pertinent to the
approval and also documents the current GMP compliance status of the drug
manufacturing facility. For all the original applications the expiration date
of the approved drug should also be documented. If a supplemental approval
did not include a change in expiration dating, it should be documented as “Not
applicable”. See P&P 1243.3800 for information on how to perform cGMP status
checks for approvals
J. Environmental Impact
This section identifies the reviews, TSC letters (if applicable),
environmental information in the end-game meeting memo (if applicable), and
any other environmental review documents [e.g., finding of no significant
impact (FONSI)] (if applicable). Also include the appropriate boilerplate
language for accepting a claim of categorical exclusion, preparation of an
environmental assessment and FONSI, or preparation of an environmental impact
statement and record of decision.
K. Freedom of Information Summary
Include the boilerplate language provided in the MRA template. If applicable
reference the reviews and letters that are relevant to the application.
L. Labeling
This section identifies the submission/reviews and TSC letters (if applicable)
that contain the approved labeling information. If the labeling needs to be
updated due to typographical errors, that information should be included in
this section.
M. All Other Information (AOI) (NADA only)
This section identifies the submission/reviews and TSC letters (if applicable)
that contain the sponsor’s affirmative statement that there is no AOI that are
applicable to this submission. If the sponsor provides an affirmative
statement via email, the preparer should reference the email in this section
and include a copy of the email in the approval package.
N. Special Concurrence
For most approvals include the boilerplate language “None” from the template.
If the approval required communication between the ONADE Policy Team and
Office of Chief Council on legal issues, consult with the ONADE Policy Team
for the verbiage to be included in this section.
O. Bioresearch Monitoring Status
Document the BIMO status check in this section. If there are issues associated
with the status check consult with your TL. See P&P 1243.3800 for information
on how to perform status checks for approvals
P. Drug Experience Report (DER) Status
This section is where we include information provided by the individual who
reviewed the adverse drug experience/event history for the approved drug
product report. If the DER is reviewed by the Division of Surveillance
reference the email confirmation in this section. If necessary, add any
additional information for further clarification of the DER report. See P&P
1243.3800 for information on how to perform status check approvals.
Q. Supplemental Applications (NADA only)
For supplemental approvals, include the boilerplate language in the MRA to
state whether there was a need for the reevaluation of the safety and
effectiveness data in the original NADA. For original approvals, delete the
boilerplate language and insert “Not applicable”.
R. Patent Term (NADA only) or Patent Certification (ANADA only)
NADA: This section identifies any relevant patents and the expiration date for
each patent that was provided by the sponsor in the application or in the
labeling technical section. If the sponsor provides an affirmative statement
in the application stating that there is no patent information include the
boilerplate language in the template. If the sponsor provides an affirmative
statement via email, the preparer should reference the email in this section
and include a copy of the email in the approval package.
ANADA: This section identifies any relevant RLNAD patents and the expiration
date for each patent. Choose the appropriate patent certification information
in the MRA template. The template contains boilerplate language documenting
that the reviewer confirmed the patent information provided by the sponsor
with what is listed in the Green Book on Animal Drugs @ FDA.
S. Exclusivity (NADA only) or Marketing Exclusivity (ANADA only)
NADA: This section contains information on whether marketing exclusivity was
granted or not to the sponsor. Include the appropriate boilerplate language
provided in the MRA template. The boilerplate language explains why we have
or have not granted exclusivity. In some cases, the boilerplate language in
the MRA template may not be appropriate; in such a case, see P&P 1243.5780
for additional language or if necessary, contact the ONADE Policy Team.
ANADA: This section contains information on whether there are any unexpired
marketing exclusivity periods listed for the RLNAD. Include the appropriate
boilerplate language provided in the MRA template. The template includes
boilerplate language to describe any RLNAD indications protected by marketing
exclusivity (if applicable).
T. Regulation
This section contains information on the draft regulation amending the animal
drug regulations (Title 21 of the Code of Federal Regulations) to reflect the
supplemental or original approval. Use the appropriate boilerplate language
provided in the MRA template.
U. Communication Staff Notification
This section provides information on whether the division has or has not sent
advance notification of the upcoming approval to the communication staff
(FDA’s Office of External Affairs and the Strategic Communications and Public
Engagement Staff). See P&P 1243.3800 to follow the instructions for the
notification process.
V. Citizen’s Petition Status
The preparer should reference the confirmatory email from the Policy and
Regulations Staff in this section and include it in the approval package. In
cases where the approval has an impact on an existing citizen’s petition, the
preparer should consult with their TL or DD to determine the appropriate
boilerplate language to include in this section.
W. Recommendation
Include the boilerplate language provided in the MRA template to confirm that
all the technical sections are complete and support the approval of the
application.
REFERENCES
§ 510.600, Names, addresses, and drug labeler codes of sponsors of approved
applications
§ 514.1, Applications
GFI #191, Changes to Approved NADAs – New NADAs vs. Category II Supplemental
NADAs
CVM Program Policies and Procedure Manual
1240.2325 – CVM Guidance on Media Inquiries
CVM Program Policies and Procedure Manual – ONADE Reviewer’s Chapter
1243.3015 – Proprietary Names
1243.3760 – Drug Tolerance Notification Process
1243.3800 – Reviewing, Preparing and Routing of Approval Packages for Certain
Abbreviated and New Animal Drug Applications
1243.5761 – Freedom of Information Summary (FOI) for Original and Supplemental
New Animal Drug Applications (NADA)
1243.5780 – Exclusivity and Exclusive Marketing Rights Boilerplate Language
for
Use in the Following Documents: Memorandum Recommending Approval, Letter to
Applicant, and Freedom of Information Summary
1243.6020 – Review of New Animal Drug Application and Abbreviated New Animal
Drug Application Supplements (NL Subclass)
1243.6030 – Review of Labeling Changes in Manufacturing Supplements
1243.8220 – Requesting a Bioresearch Monitoring (BIMO) Status Check
Beta Test Dosage Forms Detailed Worksheet
Beta Test Route of Administration (ROA) Worksheet
VERSION HISTORY
August 31, 2016 – Original version.
August 28, 2019 – Removed section on distribution copies of the MRA and filing
paper copies of the MRA as this is no longer current practice. Revised also to
include reference to the proprietary names P&P and information about speaking
the ONADE director if there is any uncertainty about who should sign the
approval package for the addition of a new indication. Updated the format to
the current format for ONADE P&Ps.
November 2, 2020- Updated to add information on all the sections in the MRA
template for NADA and ANADA approvals.
January 26, 2021 – Minor edits to fix typographical errors and errors in the
titles of some references.
February 17, 2021 – Updated to remove the line that says to send an email to
the Environmental Team in the Environmental Impact section J.
July 12, 2021 – Quality systems review for minor formatting updates.
March 14, 2023 – Updated footnote 8 on page 3 to remove the mention the
established name P&P, which is still in draft, and direct them to the ONADE
policy on the established name.
Responsible Office: Office of New
Animal Drug Evaluation
Date: March 14, 2023
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