FDA Gives New IVD Guidance

In Clinical, FDA, Regulatory by Valynda Machen

On November 25th, FDA released its final guidance on “Distribution of In Vitro Diagnostic Products Labeled for Research Use Only or Investigational Use Only”.  This guidance document provides information to In Vitro Diagnostic (IVD) manufacturers on FDA’s current thinking regarding when IVDs are properly labeled “for research use only” (RUO) or “for investigational use only” (IUO).  FDA has concerns that the use of unapproved or uncleared RUO or IUO products that may have inadequate manufacturing controls could result in serious adverse health consequences to patients who may not be aware that they are being treated based on the results of these tests.

FDA has defined an RUO product as one that is in the laboratory research phase of development and is being shipped or delivered for an investigation that is not subject to the  Investigational Device Exemption (IDE) regulations  in 21 CFR 812.  In addition, FDA has acknowledged that there are some RUO products that are only intended to be used to conduct non-clinical laboratory research with goals other than developing a commercial IVD product.

IVD products should not be labeled as RUO if they will be used in clinical investigation or clinical diagnosis.  In these situations, FDA believes that if products are labeled “For Research Use Only”, they are considered misbranded because the labeling would be considered false or misleading.

IUO products are defined as products being shipped or delivered for product testing that is not subject to 21 CFR 812.  For example, IUO labeled product would be appropriate when comparison studies are being conducted on archived or fresh specimens to determine performance characteristics.  Products should not be labeled IUO if they are to be used for clinical diagnosis, and would be considered misbranded in this situation.

FDA will focus on the “objective intent” of the labeler when determining whether or not products are appropriately labeled as RUO or IUO.  This involves an analysis of the totality of information available including, but not limited to:

  • Labeling and advertising,
  • Product design,
  • Statements by the manufacturer about the device, and
  • How the device is sold and distributed.

FDA specifically cautions manufacturers regarding any type of written or verbal statements that may suggest that an IVD product labeled as RUO or IUO is being used for clinical diagnostics.  This includes any suggestions that clinical laboratories can validate a test through their own internal procedures and then offer it for clinical diagnostic use as a laboratory developed test.  Manufacturers must also be cautious in the types of technical support provided to laboratories using RUO or IUO products so that there is no appearance that the manufacturer is providing assistance in performing clinical validation to the laboratory.  FDA does, however, indicate that technical support services such as general repairs and maintenance and non-diagnostic use-specific support are appropriate for RUO or IUO products.

The guidance also provides direction to manufacturers regarding the content of the Instructions for Use of an RUO or IUO product.  Specific to RUOs, instructions should address how to properly use the product for research and should not include any information on clinical interpretation of results, clinical significance, or other indications of clinical applicability. For IVD products labeled as IUO that are undergoing a clinical investigation by a sponsor, the manufacturer may provide instructions for use in the format provided in 21 CFR 809.10(b).

Many manufacturers use a certification program, where end user must certify that they will not use RUO/IUO products for purposes not described in the labeling.  Manufacturers must be aware that even with the use of a certification program, they must still ensure that their labeling and distribution practices are consistent with the product labeling.

Authors:

Valynda Machen (CQA, RAC-US) has over 20 years of medical device experience in the areas of In Vitro Diagnostic (IVD) manufacturing, new product development, quality assurance and regulatory affairs. She holds a B.S. in Bacteriology from Iowa State University and obtained certifications in quality auditing and regulatory affairs. Valynda is currently a Senior Medical Research Manager for NAMSA.