Regulatory Open Forum

"Review Time for initial submission of an Investigational New Drug application is 30 days from the date FDA receives the IND. An IND applicant may proceed with a clinical investigation once the applicant has been notified by FDA that the investigation may proceed or after 30 days if the IND is not placed on Clinical Hold.

IND Applications for Clinical Investigations: Overview

Out of an abundance of caution, many IND applicants do not proceed, regardless, until FDA gives the affirmative OK.  Many IRBs will insist on waiting for an affirmative response before the study begins; although shipping and preparation may proceed, but not the administration of the investigational product to a subject.

Good luck!

This advice is rendered in my capacity as an instructor at Johns Hopkins, and not as an FDA employee. You may seek an FDA response form the CDER Office of Small Business Assistance http://www.fda.gov/Drugs/DevelopmentApprovalProcess/SmallBusinessAssistance/

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Andrea Chamblee RAC, FRAPS
Silver Spring MD
United States
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Lakshmi,

Annex 13 section 43 of the EU directives on investigational trials and the 2001/20/EC directive 4 April 2001 are informative.  Specifically section (11) of the 2001 directive states the following:

(11) As a rule, authorization should be implicit, i.e. if there has been a vote in favor by the Ethics Committee and the competent authority has not objected within a given period, it should be possible to begin the clinical trials. In exceptional cases raising especially complex problems, explicit authorization should, however, be required. 

Annex 13 emphasizes that the Investigational products should remain under the control of the sponsor until after a two step procedure: certification by the QP and release by the sponsor following fulfillment of the requirements of Article 9 (Commencement of a clinical trial) of Directive 2001/20/EC.

Please note the time periods for authorization, 30 days is a US requirement for an original IND, the time periods for trial commencement and shipping supplies are not the same.

Hope these are helpful. I have always waited for formal approval  from the EC and CA to avoid any issues. 

All the best,

Dar

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Darlene Rosario RAC
Principal Consultant RA, Quality and Compliance
Velocity Consulting
Ventura CA
United States
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Hi Lakshmi.

As others have noted it is legal for you to ship the product in interstate commerce either after formal FDA approval of your IND or 30 days after the receipt of the IND by FDA.  That is the easy part of the discussion because as Andrea noted there are specific references available for that part of the issue.

On the other hand, the IRB approval of the study is a bit more tricky in some instances.  My answer to whether you can ship is (unfortunately) "It depends."  It depends on the reason for the conditional approval.  IRB typically have 2 basic reasons for conditionally approving studies: (1) there are substantive questions about the study and the planned administration for the study that do not rise to the level of rejection of the research but which the IRB members need the answers to understand the study plan sufficiently to formally approve the study OR (2) procedural questions for which the IRB members have requirements in their review process to receive certain information prior to formally approving the study.

An example of the first group of issues would be things like reworking your informed consent document or questions around your study design that might potentially impact your documentation of the consent or that might impact the study subjects' safety.  In this instance I am far less likely to ship product until these sorts of questions are resolved because these are typically things that the FDA might come back and question in the long run which could result in a clinical hold being issued.

In contrast, the second group could be something so simple as to involve the IRB's requirement that the study be approved by FDA prior to formal IRB approval.  In this instance it is often sufficient to provide the IRB with documentation that shows that the FDA received the document on date X with a request 30 days later to the IRB for formal approval based on the implicit approval of the FDA.  The documentation should usually include a copy of the cover information for the FDA, any proof of delivery you might have to document the date the information was delivered, and a copy or reference to the regulatory citation for this standard implicit approval.  In practice it is also probably a good idea to anticipate that the FDA received the package late in the day and therefore the FDA considers the package to be "received" the next business day.  That will eliminate the potential for the FDA to physically receive the package say on the day before Thanksgiving in the US at 4:45 PM and having the agency "receive the package" for regulatory purposes on the following Monday.  So if you simply assume that this is the case in general you will never be in a position where 2 days or 3 days later the agency comes back with substantive questions/issues on your IND.

Hope some of this helps!  And good luck with your IND!

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Victor Mencarelli
Sr. Manager - Regulatory Affairs
United States
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Hi, Lakshmi!

My two cents is that, yes, you can, but...don't you dare! :)

I think the sponsor is responsible for FDA approval and the PI is responsible for IRB approval

Sec. 312.40 General requirements for use of an investigational new drug in a clinical investigation.

(c) A sponsor may ship an investigational new drug to investigators named in the IND:

(1) Thirty days after FDA receives the IND; or

(2) On earlier FDA authorization to ship the drug.

(d) An investigator may not administer an investigational new drug to human subjects until the IND goes into effect under paragraph (b) of this section.

Sec. 312.66 Assurance of IRB review.

An investigator shall assure that an IRB that complies with the requirements set forth in part 56 will be responsible for the initial and continuing review and approval of the proposed clinical study.

I think the sponsor is free to ship and then the PI is responsible for not starting the study until the IRB has approved it... which includes assuring that any conditions that must be met before the study starts have, in fact, been met.

Practically speaking, if you put investigational product into the hands of the PI before all i's are dotted and all t's are crossed, chances are discouragingly high that they will jump the gun on you.  As the sponsor, I don't think this affects you directly...this is the PI's responsibility, not yours.  Your monitor will pick it up on their first visit, by which point it may be moot, and it will be duly noted.  Indirectly, I think it could jeopardize the regulatory acceptance of the study, so I wouldn't do it.

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Julie Omohundro RAC
Durham NC
United States
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