On September 10, 2020, the Office of Responsible Research Practices held a webinar for researchers titled FDA-Regulated Research: Myth vs. Reality – Part 1: Drugs. In this follow-up blog post, we cover where to find session materials, introduce a “Test your knowledge” exercise, and answer questions that we weren’t able to address during the session or that fell outside the scope of the learning objectives.
Session materials
The webinar reviewed key definitions and concepts related to FDA-regulated drug research, explained how to determine if a study requires an IND, and introduced new investigator tools to help researchers complete Buck-IRB application pages related to drugs.
We encourage all researchers conducting drug research to bookmark or download our FDA-Regulated Drug Studies: Tools for Investigators packet.
The materials provide step-by-step guidance on how to complete the Buck-IRB application form when a study reviewed by one of Ohio State’s IRBs involves articles regulated by the FDA as drugs.
Access session materials any time from our Past Educational Sessions page (arranged in reverse chronological order) or use the buttons below.
New tool: “Test your knowledge”
We’ve created a new, interactive tool for you to test your knowledge of FDA-regulated drug research!
During the webinar, we quizzed the audience on a number of questions and case scenarios.
Click “Take me to the tool!” below to explore the questions, review correct responses, and discover how webinar attendees answered.
Q&A
Q: Does the IRB alone decide whether a study is IND exempt, or does the FDA have to provide input?
A: IND exemption determinations can occur in one of two ways: Either (1) the FDA makes a formal determination of exemption or (2) the study sponsor (i.e., the PI for investigator-initiated studies) makes an initial assessment that the study is IND exempt, provides a rationale for exemption to the IRB, and receives IRB confirmation that an IND is not needed, all without FDA input. However, if the IRB disagrees with the investigator’s assessment or is unsure if an IND is needed, they will defer the study and instruct the investigator to consult the FDA. Note that the FDA’s decision is final: FDA can override the IRB’s determination but not vice versa.
Sometimes it is abundantly clear that a study meets the exemption criteria; other times, it’s questionable. While it’s always a good idea to contact the appropriate FDA review division during the study planning stage, it’s especially important to do so for the murkier studies. During the screening (pre-review) process, ORRP staff may prompt researchers to contact FDA prior to IRB review because we anticipate the IRB may question or disagree with the investigator’s assessment. When that happens, it is in your best interest to contact the FDA, as it may prevent a deferral during the review process. ORRP staff may also contact the FDA for guidance prior to IRB review.
For industry-initiated studies or investigations led by another institution, the lead sponsor or investigator typically has already obtained IND approval or documented IND exemption before Ohio State joins as a sub-site.
Q: My study doesn’t specify which version of a drug must be used; we plan to use any commercially available version. How should I list the drug(s) in Buck-IRB? Do I have to upload a package insert from every possible manufacturer?
A: In general, the same drug manufactured by different companies only needs to be listed once in the application form, with a single package insert provided. When listing the drug in Buck-IRB, note in the manufacturer section that any commercially available formulation may be used.
What if the study may use any available drug in a particular class of drugs? In that case, add a separate entry for each agent that has a unique chemical structure or mechanism of action. For example, if participants will be given one of several NSAIDs after a research procedure, then aspirin, ibuprofen, naproxen, etc. should be listed separately, rather than grouping them together in a single entry labeled “NSAIDs.”
Q: Can electronic consent be used for FDA-regulated studies?
A: It depends on what is meant by “electronic consent.”
Let’s start with the question, Do FDA-regulated studies require a legally valid signature? While obtaining a written signature, FDA allows consent to be obtained verbally or online without a legally valid signature for studies that are minimal risk and involve no procedures for which written consent is normally required outside the research context (21 CFR 56.109(c)(1)). For studies meeting these criteria, consent may be obtained electronically without a legal signature; researchers should request a Waiver of Documentation of the Consent Process in Buck-IRB, and the IRB will confirm that the criteria are met.
But let’s assume your study does require a legally valid signature. Does FDA permit legally valid signatures to be obtained electronically? Yes, if the platform used to obtain consent is Part 11 compliant. At this time, Ohio State’s electronic consent options do not meet the Part 11 criteria. That means most FDA studies need to obtain a “wet signature.” There are still options for conducting the consent process remotely. For example, some study teams mail/email consent documents to prospective participants, conduct the consent discussion via phone, then have participants sign and return the consent form (mail, scan & email, or fax) before research interventions commence.
In sum: At Ohio State, all greater than minimal risk and some minimal risk FDA studies require a “wet signature” to document consent. Some minimal risk studies may be eligible to waive the signature requirement and may therefore obtain consent verbally or electronically.
– Joint FDA & HHS Guidance: Use of Electronic Informed Consent in Clinical Investigations – Questions and Answers (2016)
– FDA draft guidance on documenting consent (2014) (includes options for obtaining a legally valid signature remotely)
Q: COVID-19 has provided an opportunity to conduct studies via telehealth. What guidance is there for virtual health appointments and mailing investigational drugs to participants during the pandemic?
A: The best resource for FDA-regulated research is FDA Guidance on the Conduct of Clinical Trials of Medical Products during the COVID-19 Public Health Emergency: Guidance for Industry, Investigators, and Institutional Review Boards (updated September 2020). The document and attached Q&A address many concerns that may arise during the pandemic, including remote study visits and alternative arrangements for administration of investigational drugs. For study-specific advice, FDA recommends contacting the appropriate review division (contact info is in the guidance document above). General questions can be directed to clinicaltrialconduct-covid19@fda.hhs.gov.
Q: I’ve seen dietary supplements and herbal medicines on the market that make disease claims. How can they be sold without FDA approval as a drug product?
A: The short answer is: a product cannot legally be sold in the U.S. as a dietary or herbal supplement if it makes a disease claim (with very few exceptions). Of course, that’s not to say it doesn’t happen!
When the FDA becomes aware that a product is unlawfully marketed because it is making disease claims (i.e., claims regarding the product’s ability to diagnose, cure, mitigate, treat, or prevent disease) without drug approval, they will issue a Warning Letter to the manufacturer/supplier listing the claims that make the product a “new drug” under the FD&C Act. Check out some examples here. The public can also alert the FDA about products that make unlawful drug claims.
As we discussed in the webinar, foods (including dietary supplements & herbal medicines) can make claims related to the structure or function of the body without drug approval, and the line between “disease claims” and “structure/function claims” can be difficult to discern. If your study involves a dietary supplement, we recommend seeking advice from FDA as to whether the intended use in the research meets the definition of a drug.
Q: What kind of data may be used to support a commercial IND versus a research IND application?
A: The application components are the same for commercial INDs and research (or “investigator-initiated”) INDs; however, the latter are often shorter/take less work because (1) the scope of the study usually small and less complex and (2) the FDA often already has safety, pharmacology, and toxicity information for the drug on file as part of a prior submission from the manufacturer. Typically, research INDs involve off-label use of an approved drug or a drug that already has a commercial IND approved; in this situation, FDA allows sponsor-investigators to cross-reference an existing New Drug Application (NDA) or existing IND for the drug, which eliminates the need to duplicate (or generate) safety and pre-clinical study information. The drug manufacturer has to provide a Letter of Authorization to the sponsor-investigator permitting the cross-reference. More info on the difference between the two can be found here.
FDA’s Research IND page has more information about what data is needed–see the links for Non-Clinical Components and Clinical Components in particular. And of course ReGARDD has great information on what is needed for the IND application.
Q: Where can I find information about completing an initial application in Buck-IRB?
A: A great place to start is our recorded educational session Buck-IRB and Initial Submissions (slide deck here). Our Past Educational Sessions page lists other sessions that may be useful as well.
For Buck-IRB basics, see the resources here.
ORRP also offers remote office hours on Thursdays to assist researchers preparing IRB or exempt submissions. Consultations can be scheduled online and are limited to thirty-minute appointments.
Q: Where can I find information about emergency use and/or expanded access of investigational drugs?
A: FDA’s Expanded Access program allows physicians to obtain investigational medical products to treat patients outside of clinical trials in both emergency and non-emergency situations.
If you’re new to the Expanded Access program (sometimes called “compassionate use”) or want a basic refresher, check out the brief video below.
Although Expanded Access is treatment and not research, the IRB is still required to provide some oversight of the activity because the investigational agent is not yet approved. Depending on the specific situation, the degree of oversight ranges from IRB Chair concurrence that treatment may proceed to full IRB review and approval of large-scale Expanded Access treatment protocols.
Clinicians who are considering this treatment pathway should contact ORRP’s Expanded Access point of contact, Paul Montesanti, for assistance at montesanti.2@osu.edu or 614-292-9804.
See also: FDA final guidance, Expanded Access to Investigational Drugs for Treatment Use – Questions & Answers (2016)