Mouse Embryo Assay Testing for Assisted Reproduction Technology Devices

What You Need to Know? 👇

What is the Mouse Embryo Assay (MEA) and when is it required for ART devices?

MEA is a test to assess embryotoxicity of assisted reproduction technology devices that contact gametes and/or embryos. It’s required for devices classified under 21 CFR 884 with special controls and may support other premarket submissions for devices contacting reproductive cells.

How many embryos are needed for a valid MEA test according to FDA guidance?

A minimum of 21 embryos should be exposed to the test article and 15 embryos to the control medium. This sample size is considered sufficient to evaluate potential embryotoxicity and control for biological variability based on previous submissions.

What are the acceptance criteria for MEA testing in one-cell versus two-cell systems?

For one-cell systems, ≥80% embryos must develop to expanded blastocyst at 96 hours. For two-cell systems, ≥80% embryos must develop to expanded blastocyst at 72 hours. Both criteria ensure adequate embryo development for safety assessment.

How should solid ART devices be prepared for MEA testing?

Solid devices not indicated for embryo culture should be extracted in standard embryo culture medium at 37°C. Extraction time should be at least 30 minutes for devices used <30 minutes clinically, or twice the clinical use time for longer exposures.

What mouse strains are recommended for MEA testing and why?

Hybrid mouse strains like CBA/B6 are recommended because they are sufficiently sensitive to detect embryotoxicity. The mouse strain selection should be scientifically justified, and the guidance emphasizes using strains with proven sensitivity for reliable results.

What information must be included in device labeling when MEA testing is conducted?

Package labels, vial labels, and instructions for use must state the MEA acceptance criterion used. Additionally, any Certificate of Analysis should include the MEA acceptance criterion and lot-specific pass/fail results for transparency and quality control.

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What You Need to Do 👇

Recommended Actions

1. Develop MEA testing protocol according to device type and intended use
2. Validate mouse strain selection and justify embryo culture conditions
3. Implement appropriate test article preparation methods
4. Establish quality control procedures for testing
5. Document test results in accordance with FDA’s recommended format
6. Update device labeling to include MEA acceptance criteria
7. Develop Certificate of Analysis template including MEA results
8. Establish shelf-life testing protocol including MEA
9. Create procedures for lot release testing incorporating MEA requirements
10. Maintain records of all MEA testing for regulatory compliance

Key Considerations

Non-clinical testing

• MEA testing should be conducted on devices in their final finished form
• Minimum of three individual devices should be evaluated in each test
• Testing should be performed at time zero and end of shelf-life
• One-cell or two-cell embryos should be obtained from hybrid mouse strains
• Minimum of 21 embryos for test article and 15 embryos for control medium
• Test duration: 96 hours for one-cell system or 72 hours for two-cell system
• Acceptance criteria: ≥80% embryos developed to expanded blastocyst

Labelling

• Package and vial labels should state the MEA acceptance criterion used
• Instructions for use should include MEA acceptance criterion
• Certificate of Analysis should state MEA acceptance criterion and lot-specific pass/fail results

Biocompatibility

• Test articles should be prepared according to device type (liquid-based, oil, plates/dishes, solid devices)
• Extraction conditions should follow ISO 10993-12 guidelines
• Culture media and labware should be intended for ART procedures

Other considerations

• Culture conditions should be maintained at 37°C and 5% CO2
• Test reports should follow FDA’s guidance for non-clinical bench performance testing
• Special considerations for different device types (one-step medium, culture oil, sequential solutions)

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Relevant Guidances 🔗

• Bayesian Statistics in Medical Device Clinical Trials: Design, Analysis and Implementation
• Use of ISO 10993-1 for Biological Evaluation and Testing of Medical Devices
• Recommended Format and Content for Non-Clinical Bench Performance Testing in Medical Device Premarket Submissions
• Shelf Life and Stability Testing for Medical Devices

Related references and norms 📂

• ASTM F1980: Standard Guide for Accelerated Aging of Sterile Barrier Systems for Medical Devices
• ISO 10993-12: Biological evaluation of medical devices – Part 12: Sample preparation and reference materials

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Original guidance

• Mouse Embryo Assay Testing for Assisted Reproduction Technology Devices
• HTML / PDF
• Issue date: 2021-01-05
• Last changed date: 2021-01-04
• Status: FINAL
• Official FDA topics: Medical Devices, Obstetrical & Gynecological, Premarket Approval (PMA), 510(k), Premarket, Investigational Device Exemption (IDE)
• ReguVirta ID: bf33020bc72c17ff431553418695f6db