Research Use Only and Investigational Use Only In Vitro Diagnostic Products - Labeling and Distribution Requirements
This guidance clarifies when in vitro diagnostic (IVD) products should be labeled as Research Use Only (RUO) or Investigational Use Only (IUO). It addresses concerns about the distribution of unapproved/uncleared IVD products labeled as RUO/IUO but used for clinical diagnostic purposes, which can lead to unproven performance characteristics and inadequate manufacturing controls.
What You Need to Know? 👇
What are the key differences between RUO and IUO labeled IVD products?
RUO products are in the laboratory research phase of development, focusing on design and limited-scale performance evaluation. IUO products are in the product testing phase, being evaluated through comparison studies using archived or fresh specimens to determine performance characteristics.
Can manufacturers provide instructions for use with RUO/IUO labeled products?
Basic instructions for proper configuration or use during research phases may be acceptable for RUO products. However, clinical interpretive information or clinical significance discussions would conflict with RUO labeling and suggest clinical diagnostic intent rather than research use.
What distribution practices indicate inappropriate RUO/IUO labeling?
Soliciting business from clinical laboratories, providing clinical validation assistance, making performance claims, or including clinical interpretation instructions all suggest clinical diagnostic intent. These practices conflict with RUO/IUO designations and may indicate misbranding under FDA regulations.
Are user certification programs sufficient to ensure proper RUO/IUO compliance?
No, certification programs alone are insufficient. While they may be considered as one factor, manufacturers remain responsible for ensuring their labeling and distribution practices are consistent with RUO/IUO designations throughout the totality of circumstances surrounding product distribution.
What regulatory consequences apply to inappropriately labeled RUO/IUO products?
Products inappropriately labeled RUO/IUO that don’t qualify for investigational exemptions and aren’t cleared/approved would be considered misbranded under sections 502(a) and 502(o) and adulterated under section 501(f) of the Federal Food, Drug, and Cosmetic Act.
Can software be distributed with RUO or IUO labeling?
Yes, software that is a standalone IVD product or component/accessory of another IVD product may be distributed with RUO or IUO labeling to entities conducting legitimate research or investigations, provided the labeling accurately reflects the intended use.
What You Need to Do 👇
Recommended Actions
- Review current labeling to ensure compliance with RUO/IUO requirements
- Assess distribution practices to ensure consistency with RUO/IUO designation
- Evaluate technical support activities to ensure they don’t suggest clinical use
- Document evidence supporting research or investigational use status
- Implement controls to prevent clinical diagnostic use of RUO/IUO products
- Consider implementing user certification programs as additional control measure
- Consult with FDA when regulatory pathway is unclear
- Ensure compliance with all applicable manufacturing and quality requirements
- Establish process for monitoring and preventing inappropriate clinical use
- Review marketing and promotional materials to avoid suggesting clinical applications
Key Considerations
Clinical testing
- Clinical diagnostic use of RUO/IUO products is not permitted
- Products used in clinical diagnosis must be labeled “For In vitro diagnostic use” and comply with relevant IVD regulations
Non-clinical testing
- RUO products are for laboratory research phase of development
- IUO products are for product testing phase before commercial marketing
- Testing should focus on design, limited-scale performance, and usability evaluation
Labelling
- RUO products must be labeled: “For Research Use Only. Not for use in diagnostic procedures”
- IUO products must be labeled: “For Investigational Use Only. The performance characteristics of this product have not been established”
- Labels should serve as warnings against clinical diagnostic use
- Clinical interpretive information or clinical significance discussions are not appropriate
Software
- Software that is a standalone IVD or component/accessory must follow RUO/IUO labeling requirements when applicable
- Can only be distributed for research or investigational use
Other considerations
- Manufacturers must not engage in practices that conflict with RUO/IUO labeling
- Distribution practices must be consistent with research/investigational use
- Technical support should be limited to general maintenance and non-diagnostic support
- User certification programs alone do not relieve manufacturers of their responsibilities
Relevant Guidances đź”—
- Content of Premarket Submissions for Device Software Functions
- Establishing Performance Characteristics for Human Papillomavirus (HPV) Detection In Vitro Diagnostic Devices
- In Vitro Diagnostic Device Studies Exempt from Investigational Device Exemption Requirements
- Dual Use Molecular Diagnostic Instruments with FDA-Approved and Non-Approved Functions
Related references and norms đź“‚
- 21 CFR 809.3: In vitro diagnostic products definition
- 21 CFR 812: Investigational Device Exemption regulation
- 21 CFR 809.10: Labeling requirements for in vitro diagnostic products
Original guidance
- Research Use Only and Investigational Use Only In Vitro Diagnostic Products - Labeling and Distribution Requirements
- HTML / PDF
- Issue date: 2013-11-25
- Last changed date: 2020-03-02
- Status: FINAL
- Official FDA topics: Medical Devices, Good Clinical Practice (GCP), Laboratory Tests, Premarket, IVDs (In Vitro Diagnostic Devices), Biologics, Investigational Device Exemption (IDE)
- ReguVirta ID: d79d5b0070634ccebea2f0ce6803c9f1