In recent years, the number of applications of drug and medical device combination products is increasing. The NMPA made an interpretation on common problems and technical evaluation difficulties in the application materials of drug and medical device combination products.
1. Definition of combination product
A combination product is a product consisting of a drug and a medical device and produced as a single entity. The definition of product attribute is based on the definition of drug and device combination product and the main mode of action of the product, and the basic principle is not to cause the intersection of medicine and medical device management
2. Analysis of common problems in the declaration data
a. Not enough consideration is given to the adequacy of the pharmaceutical data
The drug part is a very important part of the combination products.The declaration data should have sufficient data to determine the usage and dosage of the drug to be used in the medical device containing drugs or to formulate the overall safety and effectiveness of the intended use. The applicant shall fully understand and consider the safety and effectiveness of the selected drug during the research and development stage of the drug combination product. It is suggested that the applicant explain the source and quality requirements of the drug used, and submit a review of the pharmaceutical, toxicological and other research data of the drug. If used drugs ingredients are listed, proposal the clinical adverse reactions were reviewed, and the medical apparatus and instruments used in medicated drug alone as a medicine in the formulation, drug delivery way and function way, compared to the drug dose, clarify the selected drugs in medical apparatus and instruments used in medicated applicability; If the drug ingredient used is a new active substance, the safety and effectiveness of the substance itself should be considered first.
The applicant should fully demonstrate the rationality of the combination of drugs. There are a number of factors are requried. For instance, the use of antibiotics on medical devices, the possible risks of adding antibiotics, and whether Chinese people have drug resistance, etc. It is necessary to consider whether the antibiotics used have a clinical history of local tissue application, and whether they are effective recommended therapeutic drugs for local tissue infection. Studies should be carried out on their antibacterial properties, and in vitro and in vivo tests should be conducted to preliminarily evaluate the antibacterial mechanism, safety and effectiveness of the products.
c. The interaction between different components of medical devices containing drugs is not fully considered
In the production process of the combination products, drug carrier materials, packaging materials and production technology may have a great impact on the activity, quality stability of the drugs contained. In particular, drug carrier materials are in direct contact with drugs, and the quality change of carrier materials affects the final performance of drug device combination products. Applicant filings in the medicine medical apparatus and instruments, the need to focus on medical apparatus and instruments in medicated potential interaction between different components, based on the physical and chemical characteristics of drugs and drug carrier and drug interaction with the carrier, the reasonable combination way to select the suitable drugs and drug carrier, to provide research data of drugs and medical devices combined with process, make the reasonable production process and quality control measures, control index, and submit the drug-containing medical equipment production process flow and key control points of research data.
d. New risks of medical devices containing drugs are not fully considered
Although medical devices containing drugs may be composed of drugs and devices that have been listed separately, new risks may arise when drugs and devices are combined together. The applicant should fully consider the new risks of medical devices containing drugs when researching, developing and declaring. If aging of the material, formulation ratio or carrier polymer change all affect the stability of the drug, the stability of the carrier polymer material, drug coating formulation and drug-carrier polymer interaction should be evaluated in the application data
e. The basis for determining drug content in medical devices containing drugs is not fully considered
Drug content is the key point of whether a drug can play its expected role in clinical use, and is also one of the concerns to evaluate the safety of medical devices containing drugs. It is suggested that the applicant should clearly specify the range of drug content in the product, in the application data, and submit relevant research data according to the basis for the selection and determination of drug content, as well as the release of drugs.