6 min read
3 min read
Many sponsors underestimate how much support the Food and Drug Administration (FDA) can offer during early drug development, often believing they need more data than is truly required before engaging. But once your proof-of-concept data, clinical strategy, and funding begin to align, it’s the right moment to prioritize your regulatory pathway.This blog, presented in a question-and-answer format, explores when and how sponsors should begin planning for an Investigational New Drug (IND) application, with expert insights from Veristat.
👉 When in development should sponsors begin planning for IND activities?
Many factors play a role, but it ultimately depends on when they want to start conducting clinical trials in the US. That is the purpose of an IND. However, sponsors may also initiate their clinical programs outside the US, so they may not need an IND immediately. It is also possible, though uncommon, to file a New Drug Application (NDA) using only data collected outside the US, bypassing the need for an IND entirely. It is valuable to open an IND in the US to enable access to the relevant Reviewing Division for guidance and to have the option to include US sites in larger pivotal studies.
If part of the clinical program is being conducted in the US, the next consideration is the scientific strength of the development program. If the proof-of-concept data is convincing to scientists outside the organization, it is likely to be convincing to the FDA as well. That includes considerations such as replication of results, being able to show the molecule or product’s activity, and a reasonable hypothesis for how the product might treat, cure, prevent, or diagnose human disease. It is not necessary to fully demonstrate a mechanism of action before submitting an IND; however, scientific evidence supporting the use of the drug in the target indication would be expected.
Watch our video that highlights what sponsors need to know about when to submit an IND to the FDA
👉 At which point do you have enough data to support an IND?
It varies by product class and indication, as well as the clinical development plan, but a few key pieces should be in place:
-
Proof-of-concept scientific data (usually in relevant nonclinical models)
-
A target clinical indication so that the FDA can apply the appropriate context to the application
-
A clinical development plan or clinical study profile, such as a draft protocol or detailed synopsis of the initial IND opening study
-
Good Laboratory Practice (GLP)-compliant animal toxicology data, usually in two species, that supports the proposed dose, dosing schedule, route of administration, and treatment duration in the IND opening clinical protocol. The central principle is that the nonclinical safety data must support the conclusion that it is reasonably safe to proceed with clinical trials
-
Evidence that the sponsor can manufacture the product following good manufacturing practices (GMP). The amount of data depends on the stage of the program when the IND is submitted. Assuming the sponsor is submitting the IND to support the first-in-human trial, they need to be able to describe the manufacturing process, have analytical tests confirming the quality of the product, and test results for several batches of the product, including at least one GMP-compliant batch
-
Data demonstrating the stability of the drug under defined storage conditions covering the period of use for the clinical trial.
👉 Do sponsors skip some steps? Are any steps problematic or difficult?
In general, stability data is often the rate-limiting step to IND submission. New sponsors may not understand that a leading GMP batch of their drug product is needed for the original IND and that updates can be submitted in a rolling fashion.
Also, while most sponsors understand that final reports of GLP toxicology studies are needed for their IND, it can be difficult to determine exactly what studies are needed. It should be anticipated that FDA will expect compliance with existing guidelines that relate to nonclinical safety data needed to support clinical trials. Since guidelines are not regulations, it may be possible to propose alternatives. For example, early nonclinical safety studies may not be required (or even possible) to conduct in full compliance with GLP operating conditions. Obtaining FDA input on a proposed approach through a pre-IND meeting is often very valuable for these studies.
In general, sponsors should become familiar with the entirety of required information for an IND per the current US regulations, as well as the provisions provided in the large collection of guidance documents the FDA has published. That said, there is no substitute for experience. Sponsors can rely on a subject matter expert who has experience with building multiple INDs and can review the nonclinical program and provide a gap analysis to identify missing information or weaknesses in the results that are not sufficient to support the proposed clinical trials. This individual could be a full-time employee or a qualified third-party consultant with regulatory expertise. The FDA can also provide support based on questions posed in various guidance meetings.
👉 Should you plan a pre-IND meeting with the FDA?
Yes. Sponsors are encouraged to view FDA as a valuable development partner. In many cases, the Agency has shown strong interest in engaging with sponsors to encourage the efficient development of new drugs in a safe, effective, and efficient manner. FDA reviewers have a tremendous amount of experience, and while engaging the Agency effectively takes some skill, it is well worth the investment.
Veristat can help you develop a successful IND strategy and facilitate every step of your IND submission process — from gap analysis and study planning to FDA engagement and dossier preparation.
To learn more about our clinical trial planning services and how we can support your development program contact us here: