On November 25, 2013, FDA issued a final guidance on research use only (RUO) and investigational use only (IUO) products.  FDA describes RUO products as devices in the laboratory phase of development and IUO products as devices in the product testing phase of development.  RUO products also may be offered and promoted for non-clinical purposes, such as basic research activities.

The final guidance characterizes RUO and IUO labeling “as a warning, to prevent such products from being used in clinical diagnosis, patient management, or human clinical trials that are not exempt from 21 C.F.R. part 812” requirements.  FDA expresses concern that improperly labeling products as RUO or IUO might lead to “clinical diagnostic use of products with unproven performance characteristics and with manufacturing controls that are inadequate to ensure consistent manufacturing of the finished product.”

The final guidance provides FDA’s current thinking on when products are properly labeled and distributed as RUO and IUO products and includes some significant differences from a draft guidance issued in June 2011.

As we previously discussed, and as other stakeholders noted (see, for example, this letter from Members of Congress to the Commissioner of Food and Drugs and a news article here), the draft guidance departed from the general principle that FDA determines a product’s intended use through the manufacturer’s representations.  Specifically, the draft guidance stated that a manufacturer that “knows, or has reason to know” of a customer’s inappropriate uses of an RUO/IUO product should halt sales to the customer or comply with premarket review requirements.

The final guidance abandons these positions.  Instead, the final guidance states that FDA will consider a manufacturer’s “overt expressions,” as well as product design and “how the device is sold and distributed by or on behalf of the manufacturer,” to determine whether the product is properly labeled RUO or IUO.  The final guidance also provides the following examples of evidence that would appear to conflict with RUO or IUO labeling, “depending on the totality of the circumstances”:

  • Written or verbal statements suggesting the product may be used for clinical diagnostic use.  FDA may consider the manufacturer’s statements in labeling, advertising, or promotion, including any performance claims, instructions for clinical interpretation, clinical information product names, workshops, or presentations.  For example, in FDA’s view, instructions for an RUO product that discuss clinical significance of test results are evidence of intent to market the product for clinical diagnostic purposes.
  • Written or verbal statements suggesting that clinical laboratories can validate the test through their own procedures and offer it for clinical diagnostic use as a laboratory developed test.  FDA may find that a manufacturer of an RUO-labeled product intends for the product to be used in clinical applications if its sales force makes routine calls to clinical laboratories that do not perform research or clinical studies.
  • Provision of specialized technical support to clinical laboratories.  FDA does not consider support services such as general repair or maintenance, or general software updates, as evidence of non-research or non-investigational intended use.  But FDA would consider, for example, a manufacturer’s assistance to a lab in validating or verifying a clinical diagnostic assay that uses the RUO or IUO product as evidence of the manufacturer’s intended use.
  • Other relevant practices.  Though not determinative, FDA stated it would consider whether a product was previously intended for clinical diagnostic use as an analyte specific reagent (ASR) and then labeled RUO or IUO without any change in its distribution practices.  According to FDA, “the ‘new’ RUO/IUO labeling is likely to be inconsistent with the intended use of the manufacturer” in these situations.

The final guidance also takes a different approach to “certification programs” than both the draft guidance and FDA’s 1998 draft compliance policy guide (CPG) on RUO and IUO products.  Pursuant to these programs, users of RUO and IUO products could certify to the manufacturer that they will not use products in a manner inconsistent with labeling.  The draft guidance did not mention such programs, although the 1998 CPG stated that a firm with a certification program “is likely to be able to provide FDA with documentation to establish that a particular IVD labeled [RUO or IUO] . . . is not being commercialized for diagnostic or prognostic use.”  Unlike the draft guidance, the final guidance mentions certification programs, but it appears to assign less weight to them than the 1998 CPG.   Namely, the final guidance states that such programs “would be viewed as one factor to consider” in determining a manufacturer’s intended use and “would not relieve manufacturers from their responsibilities to ensure that their labeling and distribution practices for RUO/IUO products are consistent with the product’s RUO/IUO label.”

Although some have suggested that the final guidance portends increased enforcement efforts in this area, it is too soon tell.  Also, a bill regarding FDA’s authority over RUO products was introduced in August and, if enacted, would affect the RUO landscape.  Under the bill, FDA could not deem an RUO product misbranded because the manufacturer or distributor engaged in certain business communications (including technical support and customer service) with the user or sold to end users that used the product in a manner inconsistent with its labeling.