Here is feedback we received from FDA on the use of non-US-sourced material in a US clinical trial. Note that the question was asked in the context of a therapeutic protein comparator, but the feedback doesn't mention anywhere that their feedback is specific to that product type. It may be easier to get the information for a generic product or to do a comparability analysis to show equivalence but it seems to me that you would have to provide that information. But I have no familiarity with generics so I could be wrong. I second Rosario's suggestion to consult with FDA, especially since, beyond getting approval to use it in your trial, using non-US-sourced material can also impact how you might be able to use that data on your label.
A non-U.S.-licensed comparator product is considered an investigational new drug in the United States, and thus would require an IND for importation and use in the United States (see 21 CFR 312.110(a)). If a sponsor intends to conduct a clinical investigation in the United States using a non-U.S.-licensed comparator product, then the IND requirements in 21 CFR part 312 also would apply to this product (see, e.g., 21 CFR 312.2).
Certain IND requirements may be addressed by publicly available information regarding licensure by a regulatory authority that has similar scientific and regulatory standards as FDA (e.g., International Conference on Harmonisation [ICH] countries). Certain IND requirements regarding a non-U.S.-licensed comparator product may be addressed by the EPAR, current product labeling (EPAR-Product information), and any other publicly available information relevant to the safety of the non-U.S.-licensed comparator product.
With respect to chemistry, manufacturing, controls (CMC) information, a sponsor should submit to the IND as much of the CMC information required by 21 CFR 312.23(a)(7) as is available. However, FDA recognizes that a sponsor may not be able to obtain all of the CMC information required by 21 CFR 312.23(a)(7) for a non-U.S.-licensed comparator product for which it is not the manufacturer. In these circumstances, the sponsor can request that FDA waive the requirement for complete CMC information on the non-U.S.-licensed comparator product (21CFR 312.10). The IND should include, as part of the waiver request:
- A sufficient explanation why compliance with the complete requirements of 21 CFR 312.23(a)(7) is unnecessary or cannot be achieved;
- Information that will satisfy the purpose of the requirement by helping to ensure that the investigational drug will have the proper identity, strength, quality, and purity, such as information indicating that the investigational drug has been licensed by a regulatory authority that has similar scientific and regulatory standards as FDA (e.g., ICH countries);
- Other information justifying a waiver.
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Rachel Thornton
Associate Director
Smyrna GA
United States
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Original Message:
Sent: 28-Mar-2022 17:02
From: Prasanna Reddy
Subject: IND Submission 3.2.P Additional Drug product
Hi Glen,
Thank you very much for the response. Yes, this is to use as comparator or concomitant therapy as mentioned below.
If these are generic drugs and already approved in US and available from a local supplier can we still use the drug procured from EU in the study?? In that case what documentation is needed?
Regards
Prasanna
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Prasanna Reddy
Associate Director, Global Regulatory Affairs, CMC
Branchburg NJ
United States
Original Message:
Sent: 27-Mar-2022 15:23
From: Glen Park
Subject: IND Submission 3.2.P Additional Drug product
Hi Prasanna,
I am going to take a leap and respond to what I think you are asking. You would like to use an EU approved drug in a clinical trial, either as a comparator or concomitant therapy? If that is the case, and the drug product is not approved for marketing in the US by FDA or for a different indication/dose/etc., it is an investigational agent. Just providing MA holder details would not be sufficient. How much more you would need to provide will depend on the drug and how it is being used. Without more detail of the drug and intended use a more complete answer doesn't seem possible.
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Glen Park PharmD
Vice President, Regulatory Affairs and Quality Assurance
New York NY
United States
Original Message:
Sent: 26-Mar-2022 09:02
From: Prasanna Reddy
Subject: IND Submission 3.2.P Additional Drug product
Does FDA accepts EU approved drugs as ADPs? If so in the 3.2.P what information to be provided other than Marketing authorization holder name, address and number? Any other information is needed??
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Prasanna Reddy
Associate Director, Global Regulatory Affairs, CMC
Branchburg NJ
United States
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