cover letter fda template

510k Cover Letter and FDA Form 3514 – How to Webinar

In this webinar, you will learn how to complete a 510k Cover Letter and you will receive a 510k cover letter template. Your cart is empty

Why you should register for the 510k Cover Letter Webinar?

A 510k Cover Letter needs to include the administrative information that is needed to properly identify you, your company, the 510k submission type, applicable regulations, product classification, the review panel, the device product code, and any previous submissions related to this 510k submission. The 510k Cover Letter also includes an eCopy statement (no longer required for a 510k due to FDA eSTAR template ). There are also specific questions that the reviewer needs to answer about your product in order to identify specific specialists that may need to be involved, such as:

• Is the device provided sterile?
• Does the device contain a drug?
• Does the device use software?
• Does the submission include clinical information?
• Is the device implanted?

In addition to the 510k Cover Letter, there is also a submission cover sheet that must be prepared (i.e., FDA Form 3514). The submission cover sheet includes details that are used to create a database entry for you, your company, and your product submission. The submission cover sheet is also used for pre-submission requests, De Novo applications, and other types of device submissions. During this presentation, I will review each section of FDA Form 3514 and explain when each section applies and how to complete it. If you are looking for updated FDA Forms we have an article on this topic.

Does the Webinar Still Matter for the FDA eSTAR?

The FDA eSTAR incorporates all of the elements of FDA Form 3514, and you no longer have to fill in that form. However, the instructions for Form 3514 may be helpful. The 510k course we updated for the eSTAR shows how to fill in each section from beginning to end. The eSTAR has a section near the beginning where you need to attach a cover letter. The cover letter template we use in this webinar has only changed with regard to the eCopy statement.

What’s Included in the 510k Cover Letter Webinar?

• a recording of the webinar you can replay anytime
• my updated 510k Cover Letter Template
• a copy of FDA Form 3514
• a template I created for a supplement to FDA Form 3514
• the native slide deck for this webinar

This presentation has 22 slides and is 20 minutes long. It is recorded, but please email me questions at [email protected] .

510k Cover Letter Webinar ($29)

Additional Resources for 510k submissions

If you would like additional training on 510k submissions or you would like to access Medical Device Academy’s templates, you can purchase all of our templates and 510k webinars on our 510k course webpage .

About Your Instructor

Rob Packard is a regulatory consultant with ~25 years of experience in the medical device, pharmaceutical, and biotechnology industries. He is a graduate of UConn in Chemical Engineering. Rob was a senior manager at several medical device companies—including the President/CEO of a laparoscopic imaging company. His Quality Management System expertise covers all aspects of developing, training, implementing, and maintaining ISO 13485 and ISO 14971 certifications. From 2009 to 2012, he was a lead auditor and instructor for one of the largest Notified Bodies. Rob’s specialty is regulatory submissions for high-risk medical devices, such as implants and drug/device combination products for CE marking applications, Canadian medical device applications, and 510(k) submissions. The most favorite part of his job is training others. He can be reached via phone at +1.802.281.4381 or by  email . You can also follow him on  YouTube ,  LinkedIn , or  Twitter .

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• Initial IND submission

IND Template

Video explanation

This initial IND submission template is designed for sponsor-investigators conducting 'simple' clinical studies where commercially marketed drugs are being evaluated.

Maintain all of the headings in this document. If some are not applicable, simply state this under the appropriate headings.

Form FDA 1571 - IND Application

Current version of Form FDA 1571 Form FDA 1571 Instructions

What is the FDA 1571 form?

Form FDA 1571 is used for two purposes: 1) to obtain agreement from the sponsor (or sponsor-investigator) to conduct research according to all appropriate FDA regulations; and 2) to serve as a cover sheet for all submissions to the FDA on behalf of a particular IND.

When is the FDA 1571 necessary?

Form FDA 1571 should be completed for every submission sent to the FDA on behalf of a particular IND.

What information do I need to fill out the Form FDA 1571?

Include the following information on Form FDA 1571:

Contact information and mailing address of the sponsor (or sponsor-investigator)

IND number, if it has been issued

Serial number (see below)

The name(s) of the drug/biologic and the indication being studied

The contents of the submission

Name and title of the individuals responsible for monitoring the study and reviewing safety data.

What is the serial number in box 10?

Each submission to the FDA regarding a particular IND is given a consecutive serial number. The initial submission will be 0000, and all subsequent correspondence will have a new serial number (0001, 0002, etc.)

Form FDA 1572

Frequently Asked Questions – Statement of Investigator (Form FDA 1572)) Current version of Form FDA 1572 Form FDA 1572 Instructions

The intent of the Form FDA 1572 is two-fold. It is a signed agreement from the Investigator that he/she will conduct the research in compliance with FDA regulations. Additionally, it collects all the clinical site and investigator information needed by the sponsor (or sponsor-investigator) to assure the FDA that all investigators have the experience and background needed to conduct the trial. The sponsor of the study is responsible for ensuring that updated Form FDA 1572 is submitted to the FDA. The site investigator is responsible for updating his/her Form FDA 1572 and providing it to the sponsor in a timely manner so the information can be sent to the FDA.

When is the Form FDA 1572 necessary?

When filing an Initial IND Submission, a completed Form FDA 1572 must be sent from each site.

When adding a new investigator (or new site), or replacing an investigator at an existing site. Note: a Form FDA 1572 must be submitted to the FDA within 30 days of the investigator being added.

When changing any site information: IRB, laboratory, or clinical site.

What information do I need to fill out the Form FDA 1572?

A current CV or statement of qualifications of the investigator listed on the Form FDA 1572. It does not need to be signed.

Name and address of the location where the clinical investigation will be conducted, the clinical laboratories that will be used, and the IRB reviewing the study.

Names of the sub-investigators at the site

Form FDA 3674 - Certification of Compliance

Current version of Form FDA 3674 Adobe Reader may be needed to view this document Form FDA 3674 Instructions

The FDA form 3674 is a document that must accompany all FDA IND initial submissions and submission of new protocols to INDs. It is a signed statement from the sponsor-investigator that they will comply with clinicaltrials.gov requirements concerning their investigation.

BOX A Should be checked if there is not a clinical investigation covered in the IND submission.

BOX B Should be checked if there is a clinical investigation, but the requirements of 42 U.S.C. § 282(j), Section 402(j) of the Public Health Service Act do not apply. This is the case for most Phase I studies.

BOX C Should be checked if there is a clinical investigation and the requirements of 42 U.S.C. § 282(j), Section 402(j) of the Public Health Service Act do apply. By checking this box, the investigator certifies that they will comply with those requirements.

If a clinical trial is funded all or in part through the NIH, it is a federal requirement that the human clinical trial be registered on clinicaltrials.gov .

Please see FDAAA 801 Requirements at clinicaltrials.gov for more information.

Cover Letter

The cover letter is the first piece of information that the FDA sees upon receipt of an Initial IND submission. It expresses the intent of the sponsor-investigator to request FDA review of the enclosed information, and briefly describes the proposed research.

Items to include in the cover letter:

The cover letter should be on departmental letterhead

Title the cover letter: "Initial Investigational New Drug Application"

Brief explanation of the investigation (i.e., use the study title)

Disease or condition being studied

Name, formulation, and proposed dose of drug product.

Contact information (phone, email, address) of the sponsor-investigator and (recommended) a designated individual authorized to interact with the FDA on the sponsor-investigator's behalf.

More about the cover letter

Keep cover letter short, ~ 1-2 pages.

For a Drug:

For a Therapeutic Biological Product:

For a Biological Product:

Ensure the date of the cover letter matches the date on the signed copy of Form FDA 1571.

If the sponsor-investigator and FDA have already had a Pre-IND meeting, then this should be noted in the letter, and reference the PIND number and date of meeting.

Refer to sample cover letter, see below. The text is intended to provide a general example of the flow of a cover letter. It can be changed to fit the particular needs of different studies.

IND Cover Letter Template

Letter of Support / Authorization

If a sponsor-investigator is proposing to evaluate a drug that is the subject of an existing IND (being developed by a commercial sponsor), they can request a letter of cross-reference authorization from the sponsor of that IND. This permits the sponsor-investigator to refer the FDA to the information contained in the commercial sponsor's IND, and maintain the confidentiality of their proprietary information. The FDA can use the original IND material, along with their own internal reviews of that material to assist in their review process.

Additionally, an IND for a drug that has been approved by the FDA for commercial use, may require more information than what is provided in the package insert. Again, the sponsor-investigator may request a letter of cross-reference authorization from the commercial sponsor.

Commercial sponsors should provide the IND, NDA, or BLA file name, reference number, volume, and page numbers where the FDA can find the information relevant to the sponsor-investigator's IND application.

Sections of an IND submission

The initial IND submission to the FDA is broken down into several distinct sections. Each section addresses a topic necessary for FDA review. The links below will provide a detailed description of each section and provide guidance on what information should be included in the IND submission.

Refer to FDA's Guidance entitled Investigational New Drug Applications Prepared and Submitted by sponsor-investigators for more information.

Introduction

Introductory statement.

Briefly describe the research plan submitted in this IND. This section should be 2-3 pages long. This should include a brief discussion of the disease state to be assessed. The intent of this section is to place the use of the drugs with this indication into perspective for the FDA. Refer to 21 CFR 312.23(a)(3)

Name of the Drug and All Active Ingredients

Include all known names of the drug: generic and marketed names, chemical name.

Pharmacological Class of the Drug

Include the pharmacological class of the drug.

Structural Formula of the Drug

Both the structural and chemical formulas should be here.

This section may not be applicable to biologics. You could describe the protein or complex of proteins instead (e.g. 341 amino acids with a molecular weight of 150 g/mol)

Formulation of the Dosage Form(s) to be Used

Include a brief description of the formulation and dosage. Describe formulations/dosages of every active component of a combination therapy.

Include placebo information, if applicable.

Route of Administration

Briefly describe the route of administration and the planned exposure (ie duration of study drug administration).

Objectives and Duration of the Proposed Clinical Investigation(s)

If more than one protocol is being submitted under this IND, detail each separately, and clearly indicate that there is more than one planned investigation.

Summary of Previous Human Experience

This is a brief summary of previous human experience with the drug(s), with reference to the relevant literature or other INDs, if pertinent. Also, investigational or marketing experience in other countries may be relevant to the safety of the proposed clinical investigation(s). This topic will be written up in detail in the Previous Human Experience section; however, for many sponsor-investigator INDs that use commercially available drugs, the summary included in the Introduction and Previous Human Experience section are often identical.

If an IND application or other document previously submitted to the FDA is to be referenced, then the sponsor must identify the file/document by: Name Reference number Volume Page number where the information may be found

In order to reference an IND application previously submitted by others (i.e. other sponsor's INDs), such a reference is required to contain a written statement that authorizes the reference and that is signed by the person who submitted the referenced information.

Status of Drug in Other Countries

This section is likely not applicable to a standard sponsor-investigator IND submission. If the drug has been withdrawn from investigation or marketing in any country for any reason related to safety or effectiveness, identification of the country(ies) where the drug was withdrawn and the reasons for the withdrawal are stated here. For a sponsor-investigator IND, you may simply state you are not aware of any withdrawals.

List any references used in this section.

General Investigational Plan

As the studies contained in this IND progress from phase 1 to phases 2 and 3, the contents of this section will change. For the purpose of the initial submission, provide information that will be relevant for the first year of investigation. Changes to the plan and additional protocols can be included in future annual reports and amendments.

The rationale for the drug and/or research study. Provide enough background information on the topic for the FDA to understand the scientific justification for the investigation.

Indication to be Studied

Identify the indication to be studied in this investigation. Describe sub-sets of a more general study population if needed.

General Approach for Evaluation of Treatment

Provide a high-level description of data to be collected and its use in evaluation of the efficacy of the intervention being studied.

Description of First Year Trial(s)

The FDA understands that study plans may change over time. In this section provide a high-level description of the plan for the first 12 months of clinical investigation.

Number of Subjects to be Evaluated

Provide the planned number of subjects to be enrolled in the first year of IND activity.

Drug Related Risks

Any risks of particular severity or seriousness anticipated on the basis of the toxicological data in animals or prior studies in humans with the drug(s) or related drugs. Include any study procedures that carry risks of more than minimal severity.

Investigator Brochure

For sponsor-investigator initiated INDs, there is no requirement to produce an Investigator Brochure if you have a single site study. You may incorporate the following statement:

If an approved drug is being investigated, then it is appropriate to refer to the labeling and provide a URL link to the most current product label. You may find these links useful for finding current product labeling:

• Drugs@FDA: FDA Approved Drug Products

You may also reference Letters of Authorization in this section.

Multi-Site Investigations

If there will be a multi-center (external site) clinical investigation under a University-based, sponsor-investigator IND application, an Investigator's Brochure should be developed for dissemination to each of the involved study sites and should address the following information:

• A brief description of the active drug substance and the drug product formulation, including the structural formula of the active drug substance, if known.
• A summary of the pharmacological and toxicological effects of the drug in animals and, to the extent known, in humans.
• A summary of the pharmacokinetics and biological distribution of the drug in animals and, if known, in humans.
• A summary of information relating to the safety and effectiveness of the drug in humans obtained from prior clinical studies. (Reprints of published articles describing such studies may be appended to the Brochure if they are anticipated to be useful.)
• A description of possible risks and side effects to be anticipated on the basis of prior experience with the drug under investigation or related drugs, and of precautions or special monitoring to be done as part of the investigational use of the drug.

Proposed Clinical Research

Provide a protocol and informed consent document for each planned study.

Study Protocol

The NIH and FDA have developed a protocol template with guidance and example text to assist investigators when applying for an IND.

Refer to 21 CFR 312.23(6) for complete protocol requirements. The general summary of the overall research plan should be followed by the "Executive Summary" section(s) of the protocol template (or some similar brief protocol summary) for each protocol to be included in this IND application. The actual full protocol(s) is/are to be included as an attachment to this application (see last section below describing attachments).

Due to the unpredictable nature of Phase 1 studies, Phase 1 protocols can be flexible and more focused on providing a general outline of the clinical investigation (dosing plan, safety precautions). Additionally, following IND approval, changes to Phase 1 protocols that do not affect the safety of subjects need only be included in IND annual reports, not more frequent amendments.

The main components of a clinical protocol are described in Guidance for Industry – E6 Good Clinical Practice: Consolidated Guidance . Some of the information listed in this guidance document may be contained in other protocol referenced documents, such as the IB.

The NIH-FDA Protocol Template is a highly recommended template that guides investigators through the information that should be included in a protocol.

Informed Consent

Informed consent documents (ICD) do not need to be included in the IND submission, but it is recommended that they be included. If a sponsor does not submit an ICD as part of its IND submission, the review division may request and review the ICD at any time. The request will reference 21 CFR 312.23(a)(11) , which states that if requested by the FDA, the sponsor must submit "any other relevant information needed for review of the application."

Informed consent documents are institution-specific but all forms will address the same required topics. Some guidelines are listed below to assist in drafting an informed consent document:

Informed Consent Checklist

• A statement that the study involves research
• An explanation of the purposes of the research
• The expected duration of the subject's participation
• A description of the procedures to be followed
• Identification of any procedures which are experimental (i.e., not standard of care)
• A description of any reasonably foreseeable risks or discomforts to the subject (ideally subdivided by frequency and severity)
• A description of any benefits to the subject or to others which may reasonably be expected from the research
• A disclosure of appropriate alternative procedures or courses of treatment, if any, that might be advantageous to the subject
• A statement describing the extent, if any, to which confidentiality of records identifying the subject will be maintained
• For research involving more than minimal risk, an explanation as to whether any compensation, and an explanation as to whether any medical treatments are available, if injury occurs and, if so, what they consist of, or where further information may be obtained
• An explanation of whom to contact for answers to pertinent questions about research subjects' rights, about the research and in the event of research-related injury.
• A statement that participation is voluntary, refusal to participate will involve no penalty or loss of benefits to which the subject is otherwise entitled, and the subject may discontinue participation at any time without penalty or loss of benefits, to which the subject is otherwise entitled
• Include clinicaltrials.gov language
• FDA-regulated clinical investigations: Subjects must be informed that the FDA may inspect the records of the study.
• A statement that the particular treatment or procedure may involve risks to the subject (or to the embryo or fetus, if the subject is or may become pregnant), which are currently unforeseeable
• Anticipated circumstances under which the subject's participation may be terminated by the investigator without regard to the subject's consent
• Any additional costs to the subject that may result from participation in the research
• The consequences of a subject's decision to withdraw from the research and procedures for orderly termination of participation by the subject
• Statement that significant new findings developed during the course of the research, which may relate to the subject's willingness to continue participation, will be provided to the subject
• The approximate number of subjects involved in the study
• A clear description of the operation of the bio-specimen resource. This description could include details that may be of interest to human research participants, such as whether identifiable information will be maintained by the bio-specimen resource and/or whether research results will be linked to the bio-specimen.
• The conditions under which samples and data will be released to recipient investigators. Procedures for protecting the privacy of human research participants and confidentiality of data.
• Specific descriptions of the nature and purpose of the research.
• Information about the consequences of DNA typing if human genetic research is anticipated.
• Specific and meaningful description of what will be used or disclosed.
• The name or other specific identification of the person, or class of persons, authorized to make the use or disclosure.
• The name or other specific identification of the person, or class of persons, to whom the covered entity may make the requested use or disclosure.
• A description of each purpose of the requested use or disclosure.
• An expiration date/expiration event that relates to the individual or the purpose of the use or disclosure.
• Statement regarding the right of the individual to revoke the authorization in writing, and the limits of that right.
• Statement regarding the right of the individual to refuse to sign authorization
• Statement regarding ability or inability to condition treatment, payment, enrollment or eligibility for benefits on the authorization
• Re-disclosure Statement - Information disclosed to others not subject to the Privacy Rule may be re-disclosed by them without the Privacy Rule protections (cannot promise that information will definitely be protected)

Disclaimer:

Informed Consent documents should be written in such a way that they can be understood by the general public. Language should be targeted at a 5th grade reading level. It is advisable to keep the document concise for the benefit of the reader.

If the investigation involves an exception from informed consent requirements, this should be stated and the reasoning explained.

For more detailed information on informed consent regulations, check Guide to Informed Consent - Information Sheet .

Investigator and Facilities Data

Provide the name, address, and a statement of the qualifications (curriculum vitae or other statement of qualifications) of each investigator as well as the name of each sub-investigator (i.e., research fellow, resident) working under the supervision of the investigator. Also needed are the name(s) and address(es) of the research facility(ies) to be used as well as the name and address of each reviewing Institutional Review Board (IRB).

The information needed for this section is provided to the FDA on the Form FDA 1572 along with copies of the sponsor-investigator's CV, medical license, and financial disclosure forms (Form FDA 3454 and Form FDA 3455; see below for additional guidance). While not required, the sponsor-investigator may also provide copies of the CVs, medical or other professional licenses (if applicable), and financial disclosure forms (Form FDA 3454 and Form FDA 3455) for all sub-investigators listed in Box 6 of the Form FDA 1572. If the sponsor-investigator chooses not provide the sub-investigators' information in the application, the applicant MUST maintain copies of this documentation in an IND regulatory binder. Additional guidance on the completion of the FDA forms for this section as well the website where fillable PDF forms can be found are provided below.

The FDA forms, CVs, and licenses may either 1) be placed after the appropriate subheading in this section or 2) placed in the Attachments.

Insert completed Form FDA 1572, or indicate "Signed and dated Form FDA 1572 in Attachments."

Disclosure of Financial Interests

IND sponsors are not required to submit information regarding clinical investigator financial interests or arrangements in IND applications. They are, however, required to collect this information before a clinical investigator participates in a clinical study and clinical investigators are required to disclose financial information to sponsors. The information does not need to be submitted to FDA until a marketing application is submitted containing the results of the covered clinical study.

Form FDA 3454

In the interested of collecting this information at the stage of an IND, clinical investigators could complete a Form FDA 3454 if they have no financial interests or arrangements to disclose or Form FDA 3455 to disclose the nature of their interests and arrangements.

For more information, see FDA's Guidance for Clinical Investigators, Industry, and FDA Staff Financial Disclosure by Clinical Investigators .

Chemistry, Manufacturing and Control Information

Chemistry, manufacturing and control.

If the investigational drug has been marketed, this section may be covered by referring to the product labeling. You may refer back to the URL identified in the Investigator's Brochure section. Alternatively, it might be appropriate to refer to a 'Letter of Authorization' if using a drug provided by a commercial company.

This section describes the composition, manufacture, and control of the drug substance and the drug product according to 21 CFR 312.23(7) . Note: Reference to the current edition of the United States Pharmacopoeia – National Formulary may satisfy relevant requirements in this section.

Drug Substance

• Description of drug; include physical, chemical, or biological characteristics and evidence supporting structure and identity of the active pharmaceutical ingredient(s)
• Name and address of manufacturer of drug product
• Description of the general method of preparation of the drug substance, including a list of the reagents, solvents, and catalysts used. A detailed flow diagram is suggested as the most effective presentation. More information may be needed to assess the safety of biotechnology-derived drugs or drugs extracted from human or animal or plant sources
• The acceptable limits and analytical methods used to ensure the identity, strength, quality, and purity of the drug substance, with a brief description of the test methods used (i.e., Nuclear Magnetic Resonance, Infrared, UV spectra to prove the identity, and High Performance Liquid chromatograms to support the purity level and impurities, etc.). Submission of certificates of analysis is also suggested.
• Information to support stability of the drug substance during storage in the intended container closure and during the toxicological and clinical studies

Drug Product

• List all components used in the manufacture of the investigational drug product, including both those components intended to appear in the drug product and those which may not appear but which are used in the manufacturing process
• Where possible, the quantitative composition of the investigational drug product, including any reasonable variations that may be expected during the investigational stage
• Brief general description of the manufacturing process (in the form of a flow diagram is suggested) and packaging procedure, as well as other relevant tests, as appropriate for the product. Final specifications for the drug product intended to be used in toxicological and clinical studies should be included. For injectable products, sterility and pyrogenicity tests, endotoxin levels and particulate matter should be included. Submitting a copy of the certificate of analysis of the clinical batch is also suggested. Information sufficient to assure the product's stability during the planned clinical studies.
• The acceptable limits and analytical methods used to ensure the identity, strength, quality, and purity of the drug product
• Information to support stability of the drug product during the planned clinical studies

Placebo Product

Note: Delete this section if not applicable

Include a brief general description of the composition, manufacture, and control of any placebo used in the controlled clinical trial.

Include copies of the label constructed for the study drug and any associated package.

Note: Labels must contain the phrase: "Caution: New Drug - Limited by Federal law to investigational use".

Environmental Assessment

Insert the statement below, unless there is a reason to believe the distribution and use of the drug could have an environmental impact. The FDA may require an environmental analysis to ensure the study agent does not impose an undue environmental hazard {21 CFR 312.23(7)(e) }. For products already marketed, it may be possible to request and exemption from the requirement to conduct an environmental analysis. Details around the expectation of the FDA for this section should be discussed in the pre-IND meeting held between the sponsor-investigator and the FDA to discuss the IND application.

For more detailed information, take the FDA "Chemistry, Manufacturing, and Controls (CMC) Perspective of the IND" Training Course .

Pharmacology and Toxicology Information

As was true for the Chemistry, Manufacturing and Controls section, you may use an authorization letter(s) or cite the drug label to satisfy this section.

Per 21 CFR 312.23(8) , this section is expected to include information about pharmacological and toxicological (laboratory animals or in vitro) studies on the basis of which the sponsor of the IND application has concluded that it is reasonably safe to conduct the proposed clinical investigations. The kind, duration, and scope of animal and other studies required in the application will depend on the duration and nature of the proposed clinical investigations. For recommendations regarding study types and duration, refer to the FDA Guidance for Industry: M3(R2) Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorizations for Pharmaceuticals .

Compliance with Good Laboratory Practice (GLP) is generally expected for pivotal in vitro and in vivo studies submitted in support of an IND application. For each non-clinical laboratory study subject to the GLP regulations, investigators are expected to state in the study report that the study was conducted in compliance with the GLP regulations. If the study was not conducted in compliance with the GLP regulations, investigators should submit a brief statement of the reason for noncompliance. FDA Guidance documents relevant to Pharmacology and Toxicology information are available at the FDA website.

The IND sponsor should also provide a statement describing where the non-clinical investigations were conducted and the location of all records available for inspection.

Pharmacology and Drug Distribution

• Description of the pharmacologic effects and mechanism(s) of actions of the drug in animals
• Information on the absorption, distribution, metabolism, and excretions of the drug

Note: The regulations do not further describe the presentation of these data, in contrast to the more detailed description of how to submit toxicological data. A summary report, without individual animal records or individual study results, usually suffices. In most circumstances, five pages or less should suffice for this summary. If this information is not known, it should simply be so stated.

Pharmacology Summary and Conclusions

Toxicology: integrated summary.

Expected content elements for describing specific toxicology studies for this section typically include:

• Study title
• Study drug formulation/vehicle
• Brief description of the design of the trials
• Systematic presentation of the findings from the animal toxicology and toxicokenetic studies. The format of this part of the summary may be approached from a "systems review" perspective: i.e. CNS, cardiovascular, gastrointestinal, renal, hepatic, genitourinary, hematopoietic and immunologic, and dermal.
• Provide high-level summary and general conclusions of the preceding toxicology findings.
• Identification and qualifications of the individual(s) who evaluated the animal safety data and concluded that it is reasonably safe to begin the proposed human study. This person(s) should sign the summary attesting that the summary accurately reflects the animal toxicology data from the completed studies.
• A statement of where the animal studies were conducted and where the records of the studies are available for inspection, should an inspection occur.
• According to 21 CFR 312.23(8)(iii) , a statement that the study was conducted in compliance with the good laboratory practices (GLP) in 21 CFR 58 , or, if the study was not conducted in compliance with those regulations, a brief statement of the reason for the noncompliance and the sponsor's view on how such noncompliance might affect the interpretations of the findings.

Toxicology: Full Data Tabulation

The sponsor should submit, for each animal toxicology study that is intended to support the safety of the proposed clinical investigation, a full tabulation of data suitable for detailed review. This should consist of line listings of the individual data points, including laboratory data points, for each animal in these trials along with summary tabulations of these data points. To allow interpretation of the line listings, accompanying the line listings should be either: 1) a brief description (i.e., a technical report or abstract including a methods description section) of the study, or 2) a copy of the study protocol and amendments.

Previous Human Experience

A summary of previous human experience with the drug known to the applicant. If the drug(s) is already marketed in the US, then you may be able to simply refer to the product labeling.

There is no specific format for describing previous human experience with an investigational drug in an IND application; however, the FDA website provides helpful points to consider when writing a summary of previous human experience .

If the drug is a combination of drugs previously investigated or marketed, the information should be provided for each active drug component. However, if any component in such combination is subject to an approved marketing application or is otherwise lawfully marketed in the United States, the sponsor is not required to submit published material concerning that active drug component unless such material relates directly to the proposed investigational use (including publications relevant to component- component interaction).

If there is no data on previous human experience for this drug, insert a statement reflecting that under each subheading.

Marketed Experience

Overview any FDA-approved marketed indications for the study drug. Reference to the FDA drug labeling for approved indications should be noted here.

Prior Clinical Research Experience

If the drug has been the subject of controlled trials, detailed information on trials that are relevant to an assessment of the drug's effectiveness for the proposed investigational use(s) should also be provided. Any published material that is relevant to the safety of the proposed investigation or to an assessment of the drug's effectiveness for its proposed investigational use should be provided in full. Published material that is less directly relevant may be supplied by a bibliography.

If there has been no previous human experience, the submission should so state.

Clinical Care Experience

Note: Delete this sub-section if not applicable.

It is not uncommon for marketed drugs to be used in clinical care settings to treat patients for indications that do not have an FDA approval. This is often termed "off-label" use. Any published literature on the safety of the drug in that setting, and if available, published practice guidelines of the use of the drug for standard-of-care and the associated safety information could be referenced here. This is particularly relevant if the patient population treated with this off-label use of the drug is similar to the proposed study population for this IND application.

List any references used in this section. Complete reprints of select articles may be provided to aid the FDA reviewers, but do not attach more than two to three reprints. Remember that FDA does not have access to all journal articles and so including selected reprints can help facilitate the review of an IND application.

Additional Information

In certain applications, as described below, information on special topics may be needed. Such information shall be submitted in this section as outlined below. Otherwise you may simply state 'not applicable'.

Drug Dependence and Abuse Potential

If the drug is a psychotropic substance or otherwise has abuse potential, a section describing relevant clinical studies and experience and studies in test animals.

If this section is relevant to your investigation, please see Guidance for Industry – Assessment of Abuse Potential of Drugs .

Radioactive Drugs

If the drug is a radioactive drug, sufficient data from animal or human studies should be provided, to allow a reasonable calculation of radiation-absorbed dose to the whole body and critical organs upon administration to a human subject. Phase 1 studies of radioactive drugs must include studies which will obtain sufficient data for dosimetry calculations.

If this section is relevant to your investigation, please see Medical Imaging and Drug Development .

Pediatric Studies

If the investigational drug will be studied in pediatric setting, plans for assessing pediatric safety and effectiveness should be provided.

If this section is relevant to your investigation, please see Pediatric Product Development .

Other Information

A brief statement of any other information that would aid evaluation of the proposed clinical investigations with respect to their safety or their design and potential as controlled clinical trials to support marketing of the drug.

Selected References

If you are including reprints with your submission, list them in this section.

Relevant Information

If requested by FDA, any other relevant information needed for review of the application.

Submission Formatting

Commercial INDs, where the sponsor intends to conduct clinical research to support a future marketing application, must be submitted electronically in Common Technical Document format (eCTD) through the FDA Electronic Submissions Gateway (ESG) . However, research INDs, where the sponsor intends to conduct clinical research for publishing and general knowledge and does NOT intend to commercialize the product, are not required to be submitted in eCTD format and may be submitted on paper as described below. Additionally, research INDs can be submitted electronically through the ESG in either eCTD or non-eCTD format. Research INDs reviewed by CDER can also be submitted electronically through the CDER NextGen Portal .

General Formatting Guidelines for Paper Submissions

Use 1 ½" left margin to allow for binding space. FDA prefers 12pt font, but smaller fonts will still be accepted. The font should be consistent throughout the entire submission. Use black typeface, with standard blue formatting for hyperlinks if included. Any pictures should be printed in color.

Three copies (original and 2 exact copies) must be sent to the FDA at the appropriate address below:

A "courtesy e-copy" may be sent as well. The e-copy should be an exact copy of the original, in PDF format. If use of multimedia is necessary for the submission (i.e. large detailed images, or videos), then the submission cover letter should indicate the additional information contained on the e-copy. The e-copy is submitted on a CD, DVD, or thumb drive. Make sure that the information is not encrypted, or accompanied by loading software (especially common on thumb drives). Ensure that the e-copy is secured in a pocket page divider and has a label just like the paper submissions. (See below)

The paper submissions should be bound individually in 3-hole punch ACCO-style folders. The original submission should be in a gray folder. The other two copies may be in different colors. Submissions that are inadequately bound will not be reviewed.

A label should be attached to the front of each folder. If more than one volume is needed, indicate the volume number on the folder. The e-copy should have a label.

Headers and Footers

Top Left <Name of Investigation, Initial IND>

Top Right Sponsor: <Name of sponsor-investigator>

Bottom Left <University> Confidential and Proprietary

Bottom Right <Page Number>

USFDA draft guidance on : Cover Letter for Controlled Correspondences & ANDA Submissions

On December 10, 2021, the FDA published the draft guidance for industry entitled “ Cover Letter Attachments for Controlled Correspondences and ANDA Submissions .”

This draft guidance is intended to assist prospective applicants, applicants, and holders of abbreviated new drug applications (ANDAs) with optional attachments that can be used when preparing cover letters that accompany controlled correspondence to the Office of Generic Drugs, as well as original ANDAs, amendments to ANDAs, and supplements to approved ANDAs submitted to FDA.

These attachments do not replace the recommendations for the content of cover letters provided in other FDA guidances.

The cover letter attachments provided in this guidance have been developed by the disciplines that receive and respond to controlled correspondence and that assess ANDAs (including amendments and supplements). By publishing this guidance, FDA hopes to:

Provide greater clarity on the content and format of cover letters that accompany controlled correspondence, original ANDAs, amendments to ANDAs, and supplements to approved ANDAs submitted to FDA

Improve the overall efficiency of the ANDA submissions process by ensuring these submissions are properly triaged and effectively managed by FDA and acted upon within the performance review goal dates set by GDUFA

FDA is issuing this guidance as part of our Drug Competition Action Plan (DCAP), which seeks to foster generic competition and help address the high cost of drugs.

Under DCAP, FDA committed to enhancing the efficiency of the development and approval of ANDAs, with the ultimate goal of more approvals, thereby helping to increase access to high-quality, lower cost generic drugs.

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IND Applications for Clinical Investigations: Regulatory and Administrative Components

The following table includes explanations of various components of an IND application and links to additional information related to application submission.     

Other FDA’s Public Use Forms can be found on FDA’s Forms & Reports Page .

Related Information

• Investigator-Initiated IND Applications