Using Remnant Biospecimens In Medical Research

Remnant biospecimens:  What biospecimens are encompassed under the “remnant” umbrella, and what are the legal, moral and appropriate applications of remnant biospecimens?

We are frequently asked “What are the limitations of ‘remnant specimens’ for research and product development purposes?”.  We meet with partners that frequently have a narrow view of the practical application of remnant specimens, and in some cases, commercial partners have avoided them altogether, assuming that data from remnant specimens cannot be published or presented at scientific conferences.  While the applications of remnant biospecimens are limited in scope, some applications of remnants are appropriate and in line with regulatory and legal considerations.

First, what biospecimens can be considered “remnant”?  The FDA defines leftover specimens as:  “A leftover specimen is the remnant of a human specimen collected for routine clinical care or analysis that would otherwise have been discarded.”1  This encompasses leftover tissues and biofluids that are collected for routine clinical care.

Note that remnant biospecimens may be collected for routine clinical care, or they may be collected for previous clinical research, as described by FDA:  “FDA also intends to include in this policy specimens obtained from specimen repositories and specimens that are leftover from specimens previously collected for other unrelated research, as long as these specimens are not individually identifiable.”1  Thus, tissues and biofluids collected either for routine clinical care or within a biospecimen archive collected as part of a previous clinical study can be classified as “remnant” or leftover.

FDA stated clearly in their 2006 Guidance that they will use enforcement discretion to obtain Informed Consent for these types of biospecimens, as long as they are used in IDE-exempt studies, and as long as they are properly de-identified such that the specimens are not individually identifiable.  Specifically, FDA requires the following for remnant specimens to be used in research:

  • The study must be exempt from IDE requirements (21 CFR 812.2(c) (3)).
  • Specimens must be de-identified such that  “the identity of the subject is not known to and may not readily be ascertained by the investigator or any other individuals associated with the investigation, including the sponsor.”
  • Clinical information may be provided as long as it does not provide the identity of the donor.
  • The study is IRB approved.  Note that IRB approval may be at the level of the laboratory that evaluated the specimens for routine care or for previous research.  That is, an IRB approval may be granted to a lab to make remnant biospecimens available to researchers consistent with written policies and procedures. 

 

The FDA policy on remnant or leftover human specimens is reinforced by HHS regulations on Human Subject Protection, specifically CFR 46.101(b) which states that the following is exempt:  

“(4)  Research involving the collection or study of existing data, documents, records, pathological specimens, or diagnostic specimens, if these sources are publicly available or if the information is recorded by the investigator in such a manner that subjects cannot be identified, directly or through identifiers linked to the subjects.”

CFR 46.101 also states that:

“Private information must be individually identifiable (i.e., the identity of the subject is or may readily be ascertained by the investigator or associated with the information) in order for obtaining the information to constitute research involving human subjects.”

Thus, research that uses de-identified biospecimens is not considered “research involving human subjects” and is therefore exempt from requirements for Informed consent.

If the requirements outlined by HHS and FDA are met, data derived using remnant biospecimens may be used to support publications, presentations at medical conferences, and even to support FDA submissions.  The FDA does caution that while submissions will not be rejected solely because specimens were used that did not require Informed Consent, the use of remnant biospecimens only may not be sufficient to support a regulatory submission.  That is a matter of judgment and should be determined in consultation with the Agency.

Please feel free to comment on the use of remnant biospecimens:  Do you have experience with the use of remnant leftover specimens from routine clinical research or from previous clinical studies?  Were they tissues or biofluids?  Did you publish or present the data?  What clinical data or characteristics are appropriate for end-users of remnant specimens to be aware of, consistent with FDA requirements for de-identification? What was the nature of IRB approval that you obtained to use remnant biospecimens? Have you submitted data derived using remnant or leftover biospecimens to FDA and how was that received by the Agency?

 
Category: 
© 2018 Medical Research Networx