Regulatory Applications

The FDA regulates a wide range of products, including foods, human and veterinary drugs, vaccines and other biological products, medical devices intended for human use, radiation-emitting electronic products, cosmetics, dietary supplements, and tobacco products. The regulations are defined in the Code of Federal Regulations (CFR), specifically Title 21 Food and Drugs.  There are specific regulations that apply to research with human participants and this page will cover the fundamental information needed to conduct an investigator initiated clinical trial with an FDA-regulated product.

The first step in the process is determining if the product you are using and the way in which you are using it meets the definition of a drug or medical device. If you have developed the product please first review Product Development.  For guidance, please contact OCR Regulatory via psom-ind-ide@pobox.upenn.edu.

Drug Defined

The FDA defines a drug, in part, as a product “intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease” and “articles (other than food) intended to affect the structure or any function of the body of man or other animals.” Refer to Drugs@FDA Glossary of Terms.

For additional information please see the Penn IRB Research with Drug Products.

Medical Device Defined

The FDA defines a medical device as:

An instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including a component part, or accessory which is:

(A) recognized in the official National Formulary, or the United States Pharmacopoeia, or any supplement to them,

(B) intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, in man or other animals, or

(C) intended to affect the structure or any function of the body of man or other animals, and which does not achieve its primary intended purposes through chemical action within or on the body of man or other animals and which is not dependent upon being metabolized for the achievement of its primary intended purposes. The term "device" does not include software functions excluded pursuant to section 520(o).

Certain software and mobile medical apps, including those using artificial intelligence and/or machine learning algorithms, can also fall under the medical device regulations. Please see the link above for more information.

For more information, please see the UPenn Research with Device Products, the FDA website “How to Determine if Your Product is a Medical Device”, and GreenLightGuru “How do I Determine if my Product is a Medical Device.”

Drug or Medical Device

After determining that you are using a drug or medical device, you need to know the regulatory requirements that apply to your clinical trial. Drug regulations can be found in [21 CFR 312] and device regulations can be found in [21 CFR 812]. For further guidance, please contact OCR Regulatory via email at  psom-ind-ide@pobox.upenn.edu

Drugs and the IND Regulations

Drug studies may fall into three different categories:

• IND application not required,
• IND exempt, and
• IND application required.

The following scenarios are examples and are not all-inclusive.

Scenario 1: FDA-approved drugs used per their labels. 

An IND application or IND exemption review is typically not required. Please contact OCR Regulatory for further guidance via psom-ind-ide@pobox.upenn.edu.

Scenario 2: FDA-approved drugs used differently from the approved labels may be considered IND Exempt if they meet the criteria listed below.

Please note that Penn investigators are not permitted to self-exempt from IND regulations. For IND exemption guidance, please contact OCR Regulatory via email psom-ind-ide@pobox.upenn.edu.

• The investigational drug is lawfully marketed in the United States.  
• The investigation is not intended to be reported to the FDA as a well-controlled study in support of a new indication for use of the drug product.  
• The investigation is not intended to support a significant change in advertising to an existing lawfully marketed prescription drug product.  
• The investigation does not involve a route of administration or dosage level or use in a patient population or other factor that significantly increases the risks (or decreases the acceptability of the risks) associated with the use of the drug product.  
• The investigation will continue to be conducted in compliance with the requirements for institutional review set forth in FDA regulations 21 CFR 56, and requirements for informed consent as set forth in FDA regulations 21 CFR 50.  
• The investigation will continue to be conducted in compliance with FDA regulations 21 CFR 312.7: i.e., the drug may not be represented as safe or effective, nor may it be commercially distributed, for the purposes for which it is under investigation.  

Scenario 3: FDA-approved drugs may require an IND Application if the clinical trial changes how the drug is used when compared to the approved label and does not meet all of the IND exemption criteria in Scenario 2.

Drug changes may include:  

• New route of administration 
• New dose or duration of exposure 
• New form of the drug (e.g., capsule vs. tablet) 
• New treatment indications (e.g., target disease, age, gender) 
• New use with concomitant medications

Scenario 4: Drugs not approved for any indication would require an IND Application.

Medical Devices and the IDE Regulations

Medical device studies may fall into different categories describe below:

• Scenario 1: Investigations exempt from IDE regulations,
• Scenario 2: Investigations subject to FDA Enforcement Discretion,
• Scenario 3: Investigations of non-significant risk (NSR) devices subject to abbreviated IDE requirements (Abbreviated IDE application), and 
• Scenario 4: Investigations of significant risk (SR) devices subject to full IDE requirements (full IDE application).

The following scenarios are examples and are not all-inclusive.

Scenario 1: FDA-approved or cleared medical devices that are used per label may be IDE Exempt.   

Please note that Penn investigators are not permitted to self-exempt from IDE regulations. For more information please see the UPenn IRB Exemption from IDE Regulations guidance and contact OCR Regulatory via psom-ind-ide@pobox.upenn.edu. 

Scenario 2: Certain software may fall under FDA enforcement discretion.

This means the device may meet the FDA definition of a medical device; however, at this time the FDA is not enforcing medical device regulations.  Please see the following for: Examples of Software Functions for Which the FDA Will Exercise Enforcement Discretion.

Scenario 3: FDA-approved or cleared medical devices that are used in an off-label fashion in a clinical trial require an IDE Application.  

The type of application (full or abbreviated) depends on the determined risk of the device in the trial. The Sponsor is responsible for making the initial risk determination based on the proposed use of a device in the study. A thorough discussion of how to make risk determinations for devices is available from the FDA guidance on medical device studies. The IRB makes its own determination of risk based on the information provided by the Sponsor. More information on this can be found here. 

Scenario 4: Medical Devices that are not FDA approved or cleared for any indication would be considered new devices and require an IDE Application.

The type of application (full or abbreviated) depends on the determined risk of the device in the trial. The Sponsor is responsible for making the initial risk determination based on the proposed use of a device in the study. A thorough discussion of how to make risk determinations for devices is available from the FDA guidance on medical device studies. The IRB makes its own determination of risk based on the information provided by the Sponsor. More information on this can be found here. 

If it has been determined that your clinical trial requires an IND or IDE application, please complete the Sponsor Registration Survey, as indicated in PSOM SOP006.

When conducting research with drugs or medical devices, it is possible that you may have or develop Intellectual Property (IP) over the course of the clinical trial.  Therefore, consultation and close communication with the Penn Center for Innovation is essential to protecting your IP.

Additionally, many trials will require posting on ClinicalTrials.gov. Please reference additional guidance here.

Now that you have become familiar with the regulatory requirements for your clinical trial, you can begin putting together your regulatory exemption request or application.

Drug and Device Exemption Requests

The OCR Regulatory team can evaluate your protocol for applicability of IND and/or IDE Exemption requirements. If needed, the OCR Regulatory team can also support you in preparing an exemption request to the FDA.  Please contact OCR Regulatory via psom-ind-ide@pobox.upenn.edu.

Drug: IND Applications and pre-submission feedback with the FDA

There are mechanisms available to obtain feedback from the FDA prior to submission of an IND application, which include Pre-IND and INTERACT Meetings.  The following FDA guidance can be used for Pre-IND Meeting requests (Type B Meetings); Formal Meetings Between the FDA and Sponsors.  For assistance, please contact OCR Regulatory via psom-ind-ide@pobox.upenn.edu.

The OCR Regulatory team can assist you with preparing your IND Application and has templates, as well as work instructions on how to submit your application. Please contact us at psom-ind-ide@pobox.upenn.edu. The FDA also has an informative website for Investigator Initiated Investigational New Drug (ND) Applications.

After an IND application is submitted, the FDA has 30 days to review your application. You may proceed with your clinical trial if:

• The FDA has indicated you may proceed, OR
• 30 days have passed, and you have not heard back from the FDA.

Often, the FDA will contact you with questions during this 30-day review period. Please note that FDA questions during this period will have response deadlines that are often short. You should be available during this time, even if another person on your team is the main contact with the FDA.

Device: IDE Applications and pre-submission feedback from the FDA

There is a mechanism available to obtain feedback from the FDA prior to submission of an IDE application through the FDA Q-submission process. The following FDA guidance can be used for Pre-IDE Meeting requests: Requests for Feedback and Meeting for Medical Device Submission: The Q-Submission Program. For assistance, please contact OCR Regulatory via psom-ind-ide@pobox.upenn.edu.

The OCR Regulatory team can assist you with preparing your IDE Application and has templates, as well as work instructions on how to submit your application. Please contact us at psom-ind-ide@pobox.upenn.edu. The FDA also has an informative website for preparing IDE Applications.

If you plan to submit an abbreviated IDE application (non-significant risk device), there is no requirement to submit to the FDA; however, some components of the IDE application will be submitted to the IRB. Please reference the IRB website for additional details and contact psom-ind-ide@pobox.upenn.edu for assistance.

If you plan to submit a full IDE application (significant risk device), you will submit an application to the FDA. Once submitted, the FDA has 30 days to review your application. You may proceed with the clinical trial only once the FDA approves your application. Often, the FDA will contact you with questions during this 30-day review period. Please note that FDA questions during this period will have response deadlines that are often short. You should be available during this time, even if another person on your team is the main contact with the FDA.