Sponsor-Investigator
IND Application Submission
Cross-reference Information
New IND applications may rely on previously submitted information regarding the drug
when authorized by the original submitting party (often a pharmaceutical company). This
process is referred to as a “cross-reference”. FDA regulations provide that with
authorization, information previously submitted to the FDA regarding chemistry,
manufacturing, and control (CMC), as well as information regarding pharmacology and
toxicity, may be incorporated by reference into a new IND submission.
21 CFR 312.23 (b)
Instructions:
(See acronyms below)
1. Request a “Letter of Authorization” (LOA) in order to use previously submitted information from
the original submitter (e.g. the pharmaceutical company that has filed a prior IND or NDA on the
drug for which you will be requesting an IND).
2. The LOA must come from the sponsor/holder/ Responsible Official of the IND, NDA or DMF
referenced and must identify the file by name and IND number, be signed by the sponsor of the
cross-referenced file and explicitly give FDA permission to reference that information submitted
previously. See sample LOA text below.
3. Attach the LOA in the IND submission in the section for Additional Information
 If you are requesting use of information from a cross-referenced file regarding CMC,
include the following statement in your submission, “Refer to previously submitted
information (see attached cross-reference authorization letter)”
Be sure to include the LOA that permits the FDA to access the manufacturer’s IND, NDA
or Drug Master File (DMF) for this CMC information.
 If requesting use of information from a cross-referenced file for pharmacology and
toxicology information, include the following statement in the submission “Refer to
previously submitted information (see attached cross-reference authorization letter)”
and attach the LOA that permits the FDA to access the manufacturer’s IND, NDA or DMF
for this pharmacology and toxicology information.
LOA Sample text:
(Sponsor or company name) hereby authorizes the Food and Drug Administration to reference IND
(number) for ( name of drug) in support of an IND application to be requested by (name of sponsorinvestigator) to conduct the following protocol (protocol title) in support of their IND application.
This letter will apply for all relevant (specify: clinical, preclinical toxicology and pharmacology
information, as well as chemistry, manufacturing and controls) information submitted in our IND.
CMC:
IND:
LOA:
NDA:
DMF:
Chemistry, Manufacturing, and Control
Investigational New Drug
Letter of Authorization
New Drug Application
Drug Master File
IND submission
Cross-reference information
Version 12/13/2012