FDA is proposing to exempt from the IND requirements clinical investigations of lawfully marketed foods (including both conventional foods and dietary supplements) and cosmetics. In other words, clinical studies on disease end points can be conducted without an IND. Until now that has been a major roadblock for the industry. In this article, take a deep dive into the stringent requirements that the FDA requests for all sponsors and CRO’s.
What is an IND?
An Investigational New Drug (IND) application was part of a piece of regulation drafted by the Food and Drug Administration (FDA). It was mandatory for any company developing new therapeutic products, to submit and receive authorization from the FDA to administer investigational drugs to humans.
An IND was referred to by the U.S. Food & Drug administration as
“a request for Food and Drug Administration (FDA) authorization to administer an investigational drug to humans. Such authorization must be secured prior to interstate shipment and administration of any new drug that is not subject of an approved new drug application” .
There are 3 types of IND. As referred to by the FDA, they are classified as:
- Investigator IND
- Emergency use IND
- Treatment IND
A requirement of submitting an IND, is the inclusion of information around these 3 broad areas:
- Animal Pharmacology and Toxicology studies
- Manufacturing information
- Clinical Protocols and Investigator information
In this article we will focus in on Clinical protocols and investigator information. This includes submitting detailed protocols for proposed clinical studies. Any clinical study that Atlantia submits adheres to FDA clinical requirements. This is to assess whether the initial phase trials will expose subjects to unnecessary risks. The qualifications of the clinical trial professionals are examined to determine if they are qualified to fulfil their clinical trial duties. The informed consent of participants of the study is required to obtain review of the study by an IRB (institutional review board) and to adhere to the IND regulations.
IND update that will shape the industry
A major FDA (Food and Drug Administration) update was announced in late 2022 with regards to amending the IND requirements to exempt marketed foods (including both conventional foods and dietary supplements) and cosmetics from this procedure.
Until now this has been a major roadblock for the industry as previously, ‘‘foods and cosmetics’’ as defined by the FDA document, had to undergo the authorization procedure required by an IND.
Currently, drug products that are legally marketed were exempted of this step. As studies with marketed products do not significantly increase the risk of the product through a change in the dose level or route of administration, or a shift in patient populations, for example. The proposed rule would expand these exemptions to include food and cosmetic products.
What products will be exempt of an IND as per the FDA?
FDA has proposed exact definition for products that could potentially qualify for this new exception including the terms food, dietary supplement, cosmetic and drug.
‘‘Food’’ is defined as food or drink for man or other animals, chewing gum, and articles used for components. For purposes of the proposed exemptions, ‘‘food’’ does not include animal feed, pet food, or other food intended for consumption by animals other than humans. Examples of food include, but are not limited to, fruits, vegetables, fish, dairy products, eggs, raw agricultural commodities for use as food or as components of food, food ingredients, food additives (including substances that migrate into food from packaging and other articles that contact food), dietary supplements, dietary ingredients, infant formula, medical foods, beverages (including alcoholic beverages and bottled water), bakery goods, snack foods, candy, and canned foods.
‘‘Dietary supplement’’ is defined, as a product that is intended for ingestion to supplement the diet and that contains one or more dietary ingredients. Dietary ingredients include vitamins, minerals, herbs and other botanicals, amino acids, other dietary substances intended to supplement the diet by increasing the total dietary intake, and concentrates, metabolites, constituents, extracts, and combinations of the preceding types of ingredients. Because dietary supplements are deemed to be food for most purposes, the term ‘‘food’’ includes dietary supplements.
A ‘‘cosmetic’’ is an article (other than soap) intended to be rubbed, poured, sprinkled, or sprayed on, introduced into, or otherwise applied to the human body or any part thereof for cleansing, beautifying, promoting attractiveness, or altering the appearance, or an article intended for use as a component of any such article.
For instance, any company wanting to conduct a clinical study in their functional product, won’t have to obtain IND authorizations in order to start a human clinical investigation.
New pathways of exemptions for an IND
This new proposal has 2 ways of obtaining an exemption: a self-determined exemption and an FDA determined exemption. What does this mean?
For the self-determination pathway:
For this route, the company sponsoring the study (sponsor) the above mentioned products can determine the study is exempt from the IND regulations.
This exemption can only be made if it is under the following criteria:
- The investigation is not intended to support a drug development plan for the product (including a future IND or application for marketing approval) or a labelling change that would cause the lawfully marketed product to become an unlawfully marketed drug.
- The investigation is conducted in compliance with the requirements for IRB review and informed consent.
- The investigation is conducted in compliance with the regulations governing promotion and commercial distribution of investigational drugs.
- The route of administration of the product in the investigation is the same as that of the lawfully marketed product.
- The investigation meets certain criteria designed to protect the health, safety, and welfare of subjects.
For the FDA determined exemption:
When the investigation meets all the self-determined criteria listed above except for one or more, the sponsor could ask for an exception if they conclude that the investigation does not present a significant risk to subjects.
To obtain such an exemption, the sponsor would submit a written request that includes information on the sponsor, the proposed investigation, and the product to be studied, as well as a description of why the investigation does not present a potential for significant risk to health, safety, or welfare of patients.
Benefits for Industry
There will be potential benefits involved in this amendment. It could be valuable to the industry in promoting new research into drugs use for these products that were previously unavailable without the burden of an IND. The FDA has opened up comments to the rule up until the 9th of March 2023.
There is a particular need for clinical data to be used as a tool to help differentiate products in the marketplace today. Clinical data collected through human clinical trials is vital to help substantiate products with health claims. Consumers are increasingly seeking products that are backed by science. By investing in clinical research, it will provide added value to companies as they become more competitive in the marketplace today.
Quantifiable benefits of this proposed rule are cost savings that come from reducing the burden of submitting INDs to FDA for clinical investigations. The cost savings go to sponsors and sponsor investigators, typically physicians and other researchers at hospitals and academic institutions, who would no longer need to submit as many INDs because the proposed rule provides exemptions for qualifying drug studies of products lawfully marketed as a food or cosmetic. The proposed rule would also provide cost savings to FDA, which would not need to evaluate and monitor as many INDs. FDA expects the average present value of the benefits to be $28 million at a 7 percent discount rate and $34 million at a 3 percent discount rate over a 10-year time horizon.
FDA estimates that 557 sponsors would read the rule the first year and 279 additional sponsors would read the rule in subsequent years. FDA estimate the cost of reading the rule to be $153 per sponsor. FDA expects the average present value of the reading cost to be $418,000 at a 3 percent discount rate and $364,000 at a 7 percent discount rate over a 10-year time horizon. In addition, there would be costs to FDA associated with a new type of IND-related submission, a request for an FDA-determined exemption. FDA has analyzed this cost as a partial offset to the cost savings of the rule. The total net benefit of the rule is estimated to be $33 million at a 3 percent discount rate and $27 million at a 7 percent discount rate.
This news comes as a positive to the industry. At Atlantia, we are delighted to see the regulatory authority making steps to facilitate food and cosmetic companies to conduct more trials for the overall advancement of research and preservation of human health and wellbeing. We are very much looking forward to any company wanting to benefit from this potential exception and start substantiating their health claims through human trials. Learn more about our clinical trial services and feel free to book an online consultation with our experts to discuss your future clinical research project.
Center for Drug Evaluation and Research, FDA