On November 6, the CMDE (Center for Medical Device Evaluation) of the NMPA (National Medical Products Administration) published information about the common issues and technical difficulties for applicants registering drug-device combination products in China.
This news is important because it shows the high growth of combination products within China.
The analysis covered the following 5 common issues:
Insufficient information of the drug(s) involved
- Information about the drug’s usage and dosage is important to ensure the drug’s safety and potency
- Applicants should include any related study research data (pharmacy, pharmacology, toxicology, pharmacokinetics, and adverse reactions) when submitting the application and state the source and standard requirements of the drug
- If the pharmaceutical ingredient is a new active substance, the safety and potency of the drug should be evaluated first
Rationality for the choice of drug and medical device combination
The following questions address the risks and benefits that the applicant should consider:
- Any clinically effective treatment cases of the drug in the past?
- Any drug resistance cases in the Chinese population?
- Any research conducted on the drug’s antibacterial properties?
- Any preliminary in vitro and in vivo evaluation conducted regarding the antibacterial mechanism, safety and effectiveness of the product?
Chemical reaction affecting the combination product and its components
The applicant should always take into consideration that the final product characteristics can be affected chemically and physically when combining multiple entities together.
Research studies evaluating the chemical reaction between the drug and the medical device can help justify the manufacturer’s decision for selecting specific production processes (including product assembly) and quality control measures to create the expected final product.
If the final combination product contains more than one drug, the applicant is required to submit the research studies on the chemical reaction between the drugs.
The increased risks occurred due to the drug and device interactions
Each individual drug and device component may already be registered in China, however, the drug stability can still be affected by the following factors:
- Material ageing
- Formula ratio
- Changes in the polymer carrier
The dossier submission requires an evaluation of the stability of the polymer carrier, the formulation of the drug coating, and the reactions between the drug and the polymer carrier.
In addition, research studies should be updated for the dossier submission if there is a respective change in the original drug dosage amount that may alter the original sterilization and virus inactivation methods as well as storage conditions.
The intended clinical performance of the combination product
Drug dosage is the key to achieve the desired effects of a clinical treatment and also the key indicator to determine if the combination product is safe to use, hence applicants are recommended to indicate the dosage range contained in the device.
Under certain circumstances, applicants will be expected to conduct supplementary safety studies or carry out histopathological research studies to assess the corresponding toxicological risks.
The NMPA encourages manufacturers of combination products to set up early communication (before the application) with the related government officials, in order to make better preparations for the registration in China.
By Jacky Li. Contact Cisema if you would like to learn more.