Center for Drug Evaluation and Research (CDER)
The Center for Drug Evaluation and Research (CDER) performs an essential public health task by making sure that safe and effective drugs are available to improve the health of people in the United States.
As part of the U.S. Food and Drug Administration (FDA), CDER regulates over-the-counter and prescription drugs, including biological therapeutics and generic drugs. This work covers more than just medicines. For example, fluoride toothpaste, antiperspirants, dandruff shampoos and sunscreens are all considered “drugs.”
Center for Biologics Evaluation and Research (CBER)
Center for Biologics Evaluation and Research (CBER) is the Center within FDA that regulates biological products for human use under applicable federal laws, including the Public Health Service Act and the Federal Food, Drug and Cosmetic Act. CBER protects and advances the public health by ensuring that biological products are safe and effective and available to those who need them. CBER also provides the public with information to promote the safe and appropriate use of biological products.
Investigational New Drug (IND) Application Defined
An Investigational New Drug Application (IND) is a request for authorization from the Food and Drug Administration (FDA) to administer an investigational drug or biological product to humans. Such authorization must be secured prior to interstate shipment and administration of any new drug or biological product that is not the subject of an approved New Drug Application or Biologics/Product License Application.
Investigational New Drug (IND) Application Template
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.
(typically 1 page or less)
The Cover Letter is used for triaging and routing of an IND application within FDA and is expected to include the following:
The Cover Letter is typically addressed to the Director of the Review Division in the Office of New Drugs and signed by the sponsor of the IND application.
|Form 1571 (PDF – 830KB)||This form includes administrative information pertinent to the IND application Instructions for completion (PDF – 151KB)|
|Form 1572 (PDF -718KB)||This form represents Statement of the Investigator conducting clinical research under the IND application. For frequently asked questions, refer to Information Sheet Guidance for Sponsors, Clinical Investigators, and IRBs (PDF – 105KB).|
|Form 3674 (PDF – 3MB)||This form represents certification of compliance with requirements of ClinicalTrials.gov Data Bank. Instructions for completion (PDF – 129KB)|
|Table of Contents||The Table of Contents for IND application is expected to be detailed enough to permit FDA reviewers to locate items in the application quickly and easily. It is helpful if location of information is provided by volume and page.|
Introductory Statement and General Investigational Plan
(typically 2-3 pages)
|This section is intended to place the clinical development plan for the Investigational New Drug into perspective and to help FDA anticipate the needs of the future program. Upon initial submission of an IND application, the detailed developmental plan may not be well established yet and could be contingent on many factors. In this case, the IND application’s sponsor should state this and provide a brief explanation of future plans for clinical development.|
|Chemistry, Manufacturing, and Control Information||Refer to Non-Clinical Components.|
|Pharmacology Toxicology Information||Refer to Non-Clinical Components.|
Investigators may obtain Investigator’s Brochure (IB) from IND product’s manufacturer. For investigator-initiated IND applications that have a right of reference to an existing manufacturer’s IND application, submission of the IB is not required. IB is updated as the development program progresses and new information becomes available. IB is expected to contain the following information:
For suggested format of Investigator’s Brochure refer to Guidance for Industry: E6 Good Clinical Practice: Consolidated Guidance (PDF – 262KB).
|Clinical Protocol(s)||Refer to Clinical Components.|
|Summary of Previous Human Experience with the Investigational Drug||Refer to Clinical Components.|
In certain applications, information on special topics may be needed. Such additional information may include: drug dependence and abuse potential (e.g., for psychotropic IND products), radiation absorption calculations for radioactive drugs, plans for pediatric studies, or any other information pertinent to development of the IND product. If no additional information is relevant, this section may be considered not applicable.
For information on abuse potential evaluation, see the draft Guidance for Industry: Assessment of Abuse Potential of Drugs (PDF – 175KB).
|Other Relevant Information||If requested by FDA, other relevant information pertinent to review of the IND application may need to be submitted.|
Types of Investigational New Drug (IND) Applications
There are two general categories of an IND: non-commercial (research IND) and commercial.
Research Investigational New Drug Applications – What You Need to Know
FDA recently released an update to clarify when ‘Research’ vs. ‘Commercial’ should be selected on FDA Form 1571, and thus when electronic common technical document (eCTD) requirements apply for an investigational new drug (IND) application.
A commercial IND is one for which the sponsor (usually a corporate entity) intends to commercialize the product by eventually submitting a marketing application. In this case, the sponsor should select “Commercial IND” on FDA Form 1571 Field 6B. FDA may also designate an IND as commercial if it is clear that the sponsor intends for the product to be commercialized at a later date.
In comparison, a research IND (also called a non-commercial IND) is one for which the sponsor (generally an individual investigator, academic institution or non-profit entity) does not intend to later commercialize the product. These studies are strictly for research, are usually shorter in duration and may result in publications in peer-reviewed journals.
IND Application. Commercial and research INDs are both expected to contain the following as described HERE:
- Cover Letter
- FDA Forms:
o 1571 – Investigational New Drug Application
o 1572 – Statement of Investigator
o 3674 – Certification of Compliance with Requirements of ClinicalTrials.gov Data Bank
- Table of Contents
- Introductory Statement and General Investigational Plan
- Investigator Brochure
- Clinical Components*
o Summary of Previous Human Experience with the Investigational Drug
- Nonclinical Components*
o Animal Pharmacology and Toxicology (PT)
- Chemistry, Manufacturing and Controls (CMC)
- Other information as necessary
Often investigator-sponsored research INDs will address the requirements for nonclinical and CMC information by providing a Letter of Authorization (LOA) from the commercial manufacturer. The LOA allows FDA to reference the nonclinical and CMC information in the commercial manufacturer’s IND on behalf of the sponsor-investigator, to fulfill the requirements.
The key difference between the submission of commercial vs. research INDs is that commercial INDs must be submitted in electronic format, whereas electronic submission standards for research INDs are highly encouraged but optional.
When a sponsor of a research IND submits either a Phase 2 or Phase 3 protocol, the IND will normally then be considered “commercial” and eCTD requirements would become applicable. In this case, the sponsor should select “Commercial” on FDA Form 1571 Field 6B: IND Type. However, if the product under investigation is not intended to be commercialized at a later date (i.e., the intent of the Phase 2 or Phase 3 protocol is still solely for research), the sponsor should submit a justification explaining their rationale in the cover letter, along with the protocol, and the sponsor should select “Research” on FDA Form 1571. If the FDA agrees, the IND will remain a “Research” IND and the eCTD requirements will not apply. Note that in all cases, expanded access INDs and protocols should be marked as “Research” on FDA Form 1571 and are exempt from eCTD requirements.
The IND application goes into effect 30 days after FDA receives the application, unless FDA notifies the sponsor that the investigations described in the application are subject to a clinical hold, or on earlier notification by FDA that the clinical investigations in the IND may begin. Once an IND application is in effect, a drug manufacturer may ship the investigational new drug to the investigator(s) named in the application. An investigator may not administer an investigational new drug to human subjects until the IND application goes into effect.
Additional information on submission of research INDs is located on our Investigator-Initiated Investigational New Drug (IND) Applications webpage.
Research INDs in paper format should be mailed to the Central Document Room. Sponsors submitting in paper are expected to send their applications in triplicate (one original and two copies). FDA will notify the sponsor of the date it receives the application through an IND acknowledgment letter.
CDER Small Business and Industry Assistance
Division of Drug Information
Office of Communications
10001 New Hampshire Avenue
Hillandale Bldg, 4th Floor
Silver Spring, MD 20993
(866) 405-5367 or (301) 796-6707
Investigational New Drug Application Sponsorship
FDA requires naming of a Sponsor for each IND. The Sponsor can be an investigator, an academic institution, a pharmaceutical company or other appropriate groups. All of these types of sponsorship are available to NU inventors. The Sponsor is responsible for the proper conduct of the clinical studies, safety of the study participants and reporting of safety and efficacy data resultant from these clinical trials. FDA does not require an IND when the clinical trial includes a drug that is used in an approved indication and in an approved dose; other exemptions apply to the use of approved drugs in clinical trials. If a clinical trial tests an unapproved drug to support commercialization or tests an approved drug in an unapproved indication, an IND is required. The types of Sponsors are listed below.
Investigator Initiated trials (non-commercial, research IND, Investigator IND).
The Sponsor of an IND application is the party who submits the application to FDA. In the absence of any other Sponsor (e.g. pharmaceutical company, academic institution), the investigator conducting the proposed clinical investigation is the Sponsor of the IND application. “An Investigator IND is submitted by a physician who both initiates and conducts an investigation, and under whose immediate direction the investigational drug is administered or dispensed. A physician might submit a research IND to propose studying an unapproved drug, or an approved product for a new indication or in a new patient population.”
IND from an organization other than NU.
In most instances, an inventor will create a startup company to negotiate licensing the invention from INVO and the startup will hold the IND. In these cases, NU does not under take any of the responsibilities of Sponsor.
NU Sponsored commercial IND
Under limited circumstances, NU has agreed to take on the responsibilities of an IND Sponsor but only after other possibilities of Sponsorship have been fully explored. As a general rule, when NU agrees to become the Sponsor of an IND or a NU investigator undertakes the responsibilities of an Investigator-Sponsor of an IND, it is recommended that all clinical personnel associated with the clinical trial attend classes related to FDA regulations concerning conduct of clinical trials to include Good Clinical Practice Regulations and classes to update changes in the regulations. This training can be accomplished thru NUCATS programs. For single site Phase I trial, it is highly recommended that the trial be conducted in special NU clinical trial facilities where the clinical personnel are trained on the appropriate conduct of clinical trials. For multiple site trials, it is highly recommended that the investigator contracts with a Clinical Research Organization to conduct the trial and fulfill FDA requirements for proper conduct of the clinical study, safety of the study participants and reporting of safety and efficacy data resultant from the clinical trial. As IND Sponsor, NU does not take any financial responsibility for the conduct of the clinical trials.
NIH grants requiring sponsorship
In some instances, NIH will act as the Sponsor for intramural clinical trials, i.e., those conducted at NIH. For extramural clinical trials, NIH requires a Sponsor and identification of the “Responsible Party” for Applicable Clinical Trials. The Responsible Party is the entity or individual who is responsible for registering a clinical investigation and submitting Clinical Trial Information to the Clinical Trial Registry Data Bank. Two major scenarios exist under these regulations. First, if the clinical trial does not involve an existing IND, the grantee institution would generally be considered the Sponsor of the IND and therefore be the responsible party under FDAAA (Section 801 of the Food and Drug Administration Amendments Act of 2007). This would be true unless as Sponsor, the grantee institution designated the PI of the trial as the responsible party. If NU is the Sponsor of the investigation, see above recommendations for the conduct of the trial(s). In the second case, if the clinical trial will be conducted under an existing IND, the IND holder would generally be considered the sponsor and therefore the responsible party under FDAAA. The sponsor could designate the PI of the trial as the responsible party.
NIH funds only applicable clinical trials which it defines as studies involving human participants; the participants are prospectively assigned to an intervention; the studies are designed to evaluate the effect of the intervention on the participants; and the effect being evaluated is a health-related biomedical or behavioral outcome. A Phase I clinical trial is not considered an applicable clinical trial.
Expedited Approval Designations
|Type of Data Required||Data Should Demonstrate||Benefits|
|Fast Track||Preliminary nonclinical, mechanistic, or clinical data||Potential to address an unmet medical need for a serious condition||
More frequent meetings with FDA
§ More frequent written communication from FDA
|Preliminary clinical data||Substantial improvement on clinically significant endpoint(s) over available therapies||
§ More frequent meetings with FDA
§ More frequent written communication from FDA
§ Rolling review
§ Intensive guidance on an efficient drug development program
Involvement of FDA senior managers to expedite development
|Not specified; Sponsor should make justification of alternate endpoint based scientific support||Generally, provides a meaningful advantage over available therapies AND demonstrates an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit or a clinical endpoint that can be measured earlier than irreversible morbidity or mortality||Approval based on a surrogate or intermediate endpoint (often allows for shorter development time) Note: FDA requires clinical trials to be conducted post-approval to confirm clinical benefit|
|Priority Review Designation||Data contained in the final NDA submission||Significant improvement in safety or effectiveness of the treatment, prevention, or diagnosis of a serious condition||Review of application in 6 months|
Regenerative Medicine Advanced Therapy (RMAT) designation speeds the review of cell therapies, therapeutic tissue engineering products, human cell and tissue products or any combination product using such therapies or products if it “is intended to treat, modify, reverse, or cure a serious or life-threatening disease or condition” and “preliminary clinical evidence indicates that the drug has the potential to address unmet medical needs for such disease or condition.”
Advantages of the RMAT designation include all the benefits of the fast track and breakthrough designations, including early interactions between the agency and sponsors, though unlike the breakthrough designation, the RMAT designation does not require evidence to indicate that the drug may offer a substantial improvement over available therapies. Gene therapies now not included.
Office of Orphan Products Development
- Orphan Drug Designation – The Orphan Drug Designation program provides orphan status to drugs and biologics which are defined as those intended for the safe and effective treatment, diagnosis or prevention of rare diseases/disorders that affect fewer than 200,000 people in the U.S., or that affect more than 200,000 persons but are not expected to recover the costs of developing and marketing a treatment drug. Orphan designation qualifies the sponsor of the drug for various development incentives of the ODA, including tax credits for qualified clinical testing.
- Rare Pediatric Disease Priority Review Voucher – The Rare Pediatric Disease Priority Review Voucher Program says that a sponsor who receives an approval for a drug or biologic for a “rare pediatric disease” may qualify for a voucher that can be redeemed to receive a priority review of a subsequent marketing application for a different product.
- Humanitarian Use Device Program – The Humanitarian Use Device (HUD) program designates medical devices that are intended to benefit patients in the treatment or diagnosis of a disease or condition that affects or is manifested in not more than 8,000 individuals in the United States per year as eligible for Humanitarian Device Exemption
Food and Drug Administration (FDA) Recognized Exclusivity
FDA Recognized Exclusivity
- New Chemical Exclusivity (NCE) – 5 years Granted to a drug that contains no active moiety that has been approved by FDA under section 505(b). Runs from time of NDA approval Bars FDA from accepting for review any ANDA or 505(b)(2) application for a drug containing the same active moiety for: – five years if an ANDA or 505(b)(2) does not contain a paragraph IV certification to a listed patent – four years if an ANDA or 505(b)(2) is submitted containing a paragraph IV certification to a listed patent. Described in 21 CFR 314.108.
- “Other” Exclusivity – 3 years for a “change” if criteria are met: Granted to drug when application or supplement contains reports of new clinical investigations (not bioavailability studies) conducted or sponsored by applicant and essential for approval Runs from time of NDA approval Bars FDA from approving, for a three year period, any ANDA or 505(b)(2) application that relies on the information supporting the approval of the drug or the change to the drug for which the information was submitted and the exclusivity granted Described in 21 CFR 314.108
- Pediatric Exclusivity (PED) – 6 months added to existing Patents/Exclusivity Grants an additional 6 months of market protection at the end of listed patents and/or exclusivity for sponsor’s drug products containing the active moiety, when the sponsor has conducted and submitted pediatric studies on the active moiety in response to a Written Request from FDA Pediatric exclusivity takes on characteristics of five year, three year or orphan exclusivity when it attaches to those protections. Described in the Best Pharmaceuticals for Children Act (BCPA) and Section 505(A) of the Food and Drug Administration Modernization Act of 1997. Note also that under the Generating Antibiotic Incentives Now (GAIN) Title VIII of the FDA Safety and Innovation Act (FDASIA), at the time of approval FDA will grant an additional five years to certain exclusivity periods for products that have been granted a Qualified Infectious Disease Product (QIDP) designation (with some exceptions).
- 180-Day Exclusivity: FDA may also grant exclusivity to abbreviated new drug applications (ANDAs) for generic drugs. Under the Drug Price Competition and Patent Term Restoration Act, or the Hatch-Waxman Act, a company can seek approval from FDA to market a generic drug before the expiration of a patent relating to the brand name drug upon which the generic is based. The first company to submit an ANDA with the FDA has the exclusive right to market the generic drug for 180 days. This is called 180-day exclusivity.
• Provides an incentive of 180 days of market exclusivity to the “first” generic applicant who challenges a listed patent by filing a paragraph IV certification and running the risk of having to defend a patent infringement suit
• Begins either from the date the sponsor begins commercial marketing of the generic drug product, or from the date of a court decision finding the patent invalid, unenforceable or not infringed, whichever is first
• In some circumstances, an applicant who obtains 180-day exclusivity may be the sole marketer of a generic competitor to the innovator product for 180 days
• FDA does not send letters to the sponsor indicating the grant of exclusivity. The Orange Book is the official vehicle for dissemination of this information. Note that some drugs have both patent and exclusivity protections while others have just one or none. Patents and exclusivity may or may not run concurrently and may or may not encompass the same claims.
CDER Exclusivity Board: CDER has established an Exclusivity Board to provide oversight and recommendations regarding exclusivity determinations made by the Center, with a primary focus on clarity and consistency of decisions. The CDER Exclusivity Board oversees certain exclusivity determinations, including whether and what type of exclusivity should be granted and the appropriate scope of exclusivity grants. The Board will focus on 5-year new chemical entity (NCE) exclusivity, 3-year new clinical trial exclusivity, and exclusivity for biological products. The Board will not review or make recommendations with respect to all exclusivity determinations in these areas, but will assist the Center in resolving certain matters, including issues that arise in the context of specific requests for exclusivity.
Food and Drug Administration (FDA) Meetings
- Meeting with FDA about a development plan can occur at any time and are encouraged by FDA. If the NU invention is licensed, these meeting are at the discretion of the licensing company. However, if the invention is patented and Northwestern is the Sponsor or the invention is not licensed, Northwestern requires that inventors receive Department of Research approval before initiating contact with FDA.
- NU support for preparing for FDA meetings can be obtained from the Entrepreneur-in-Residence and NUCATS
- Formal Meetings Between the FDA and Sponsors or Applicants of PDUFA Products Guidance for Industry
- CBER INTERACT Meetings
- Pre IND Consultation Program – antimicrobials
- See Guidance Listing for additional document