The NMPA released the “Registration Guideline on Combination Products with Device as Primary Mode of Action” on January 11, 2022, directing manufacturers for safety and efficacy evaluation of combination products.
Significantly referred to FDA guidance of “Early Development Considerations for Innovative Combination Products” (2006) and “Technical Considerations for Pen, Jet, and Related Injectors Intended for Use with Drugs and Biological Products” (2013), the NMPA wants to keep in line with international standards on regulating the category of products.
The applicant should evaluate the safety and efficacy of the product using the combination medical device as a single entity, paying special attention to the potential risks introduced by the drug or the interaction between the device and the drug.
The applicant can make an assessment on the drug information, but the safety and efficacy of the drug in the combination product may be different from that of the drug used alone. Usually, when the blood concentration of the drug in the combination product is greater than that of conventional drugs, the systemic toxicity needs to be evaluated.
When necessary, applicants are advised to refer to applicable drug-related guidelines.
The guideline lists the following items when submitting to NMPA for registration of combination products:
1. Submission Requirements for Electronic Filing Materials
2. Product Description
3. Interactions between medical devices and drugs
4. Drug content/dose selection
5. chemical and physical properties
6. Biological properties
7. Animal research
8. Stability study
9. Product technical requirements
10. Manufacturing information
Highlights of the Guideline
- Before conducting clinical evaluation, applicants are advised to clarify the clinical mechanism of action, intended use, possible risks, and possible adverse events of the combination product, etc. For example:
- Check if the device part or the drug part of the combination product when used alone is consistent with or similar to the application scope of the combination product
- Check if the combination product expands or exceeds the scope of application of its components alone, or claims additional clinical benefits
- For patients who use the combination product, check if the route of administration, release or local/systemic drug exposure range of the drug part contained in the combination product has changed compared to when the drug is used alone, and the new risks that may be arouse by the change.
- Applicants can refer to relevant regulation documents when conducting evaluation:
- Quality Management Practice for Medical Device Clinical Trials
- Guideline for Clinical Evaluation of Medical Devices
- Guideline for Medical Device Equivalence Demonstration
- Guideline for Decision-making on Conducting Medical Device Clinical Trials
- The main clinical issues often involve clinical trial design, sample size, statistical methods, clinical endpoints, scope of application/efficacy, and the number of clinical studies (if multiple trials are required).
“Registration Guideline on Qualitative, Quantitative and In Vitro Release Studies of Combination Products with Device as Primary Mode of Action” was issued on the same day. For the English version of the two guidelines, please email info@ChinaMedDevice.com to enquiry our translation services.
Further information on NMPA Combination Products: