The NMPA has recently issued the newly-revised Circular on Matters Related to the Registration of Drug-device Combination Products (No. 52 [2021], hereinafter referred to as Circular No. 52). Now the background of Circular No. 52 and the main contents revised are explained as follows:
I. Revision background
With the rapid development of pharmaceutical industry and the revision and implementation of the Drug Administration Law, the Regulations for the Supervision and Administration of Medical Devices and supporting regulations, the Circular on Matters Related to the Registration of Drug-device Combination Products (the original Circular No. 16 [2009] of the State Food and Drug Administration (SFDA), hereinafter referred to as Circular No. 16) cannot completely adapt to the current laws and regulations and the needs of industry development. Prominent problems are as follows:
Firstly, product marketing certification requirements are not applicable in some circumstances. According to Circular No. 16, upon the registration of imported drug-device combination products, in addition to the certificate of the marketing in the country of origin for such products, the certificate of the marketing in the country of origin or China for relevant drugs should also be submitted. In practice, certain components that play a pharmacological role contained in some imported drug-device combination products are not managed as drugs or are developed only for combination products abroad, thus the certificate of the marketing in the country of origin for drugs cannot be provided. Besides, since active pharmaceutical ingredients are often used in the production of combination products, the dosage and mode of action are different from the drugs marketed independently. Therefore, some drug-device combination products marketed abroad cannot be registered in China.
Secondly, the procedures for defining the attributes of drug-device combination products have changed. The Circular No. 16 clearly stipulated that the Application Center shall be responsible for the definition of the attributes of drug-device combination products jointly with the Center for Drug Evaluation and the Center for Medical Device Evaluation (CMDE), and specified the time limit for attribute definition. However, the Circular on Adjusting Matters Relevant to the Definition of Attributes of Drug-device Combination Products issued in 2019 (Circular No. 28 [2019] of the NMPA, hereinafter referred to as the Circular No. 28) adjusted the functional department of the attribute definition of drug-device combination products to the Center for Medical Device Standard Management, and further defined the process, time limit, work requirements and application requirements, etc.
Therefore, there is an urgent need to revise the Circular No. 16, so as to adapt to the changes in laws and regulations and the needs of industry development.
II. Main contents revised
(I) The requirements for the certificate of the marketing of drug-device combination products are adjusted.
In the Circular No. 52, the requirements that the drugs contained in the imported drug-device combination products should be separately registered in China or approved for marketing in the country (region) of production in Article 6 of the Circular No. 16 was deleted; Article 6 was integrated with Article 2 to specify that the drug-device combination products that mainly act as drugs should be registered according to the relevant requirements for drugs, and that the drug-device combination products that mainly act as medical devices should be registered according to the relevant requirements for medical devices, implementing the requirements for the certificate of the marketing in the country of origin, respectively. For the drugs or medical devices contained in drug-device combination products approved by China or the country (region) of production for marketing, the corresponding marketing certificate should also be submitted when applying for the registration of drug-device combination products to further prove the safety and effectiveness of products. For the drugs or medical devices contained in drug-device combination products not yet separately approved by China or the country (region) of production for marketing, the marketing certificate for such drugs or medical devices is not required when applying for the registration of drug-device combination products when applying for the registration of drug-device combination products.
(II) Contents relevant to the definition of attributes of drug-device combination products are revised.
Given the adjustment of the functional department, procedures, time limit, work requirements and the requirements for application materials for defining the attributes of drug-device combination products, the corresponding contents in Articles 3 and 4 of the Circular No. 52 were revised accordingly. Since Article 8 of the Circular No. 28 specified that “the matters relevant to the registration of other drug-device combination products shall be implemented in accordance with the Circular on Matters Related to the Registration of Drug-device Combination Products (the Circular No. 16 [2009] of the SFDA”, the relevant contents of the Circular No. 28 were adjusted to Annex 1 and Annex 2 of Circular No. 52. Moreover, the time limit for the Center for Medical Device Standard Management to accept and review the application for defining the attributes of drug-device combination products, and the meaning of the “primary mode of action” were further clarified. The Circular No. 28 was abolished simultaneously.
For the drug-device combination products to be applied for registration, if the applicant cannot determine their management attributes, the attribute definition of drug-device combination products should be applied to the Center for Medical Device Standard Management before applying for registration; if the management attributes of products can be determined by referring to the previously registered drug-device combination products or the attribute definition results of drug-device combination products already published, registration can be applied for according to the management attribute determined.
Considering that examples of the attributes of drug-device combination products are not exhaustive, relevant contents of examples of the management attributes of drug-device combination products were deleted and revised to “relevant regulations, for products with management attributes determined in the document, the relevant provisions should be implemented.”
III. Miscellaneous
In the actual application of products, in case of the combination of ingredients that have pharmacological activity and medical devices, such active ingredients are usually not used alone or are developed only for combination products, thus no separate marketing certificate for drugs can be obtained. Whether such active ingredients are included in the pharmacopoeia or not, their combinations with medical devices into a single entity are deemed to meet the definition of drug-device combination products.
I. Revision background
With the rapid development of pharmaceutical industry and the revision and implementation of the Drug Administration Law, the Regulations for the Supervision and Administration of Medical Devices and supporting regulations, the Circular on Matters Related to the Registration of Drug-device Combination Products (the original Circular No. 16 [2009] of the State Food and Drug Administration (SFDA), hereinafter referred to as Circular No. 16) cannot completely adapt to the current laws and regulations and the needs of industry development. Prominent problems are as follows:
Firstly, product marketing certification requirements are not applicable in some circumstances. According to Circular No. 16, upon the registration of imported drug-device combination products, in addition to the certificate of the marketing in the country of origin for such products, the certificate of the marketing in the country of origin or China for relevant drugs should also be submitted. In practice, certain components that play a pharmacological role contained in some imported drug-device combination products are not managed as drugs or are developed only for combination products abroad, thus the certificate of the marketing in the country of origin for drugs cannot be provided. Besides, since active pharmaceutical ingredients are often used in the production of combination products, the dosage and mode of action are different from the drugs marketed independently. Therefore, some drug-device combination products marketed abroad cannot be registered in China.
Secondly, the procedures for defining the attributes of drug-device combination products have changed. The Circular No. 16 clearly stipulated that the Application Center shall be responsible for the definition of the attributes of drug-device combination products jointly with the Center for Drug Evaluation and the Center for Medical Device Evaluation (CMDE), and specified the time limit for attribute definition. However, the Circular on Adjusting Matters Relevant to the Definition of Attributes of Drug-device Combination Products issued in 2019 (Circular No. 28 [2019] of the NMPA, hereinafter referred to as the Circular No. 28) adjusted the functional department of the attribute definition of drug-device combination products to the Center for Medical Device Standard Management, and further defined the process, time limit, work requirements and application requirements, etc.
Therefore, there is an urgent need to revise the Circular No. 16, so as to adapt to the changes in laws and regulations and the needs of industry development.
II. Main contents revised
(I) The requirements for the certificate of the marketing of drug-device combination products are adjusted.
In the Circular No. 52, the requirements that the drugs contained in the imported drug-device combination products should be separately registered in China or approved for marketing in the country (region) of production in Article 6 of the Circular No. 16 was deleted; Article 6 was integrated with Article 2 to specify that the drug-device combination products that mainly act as drugs should be registered according to the relevant requirements for drugs, and that the drug-device combination products that mainly act as medical devices should be registered according to the relevant requirements for medical devices, implementing the requirements for the certificate of the marketing in the country of origin, respectively. For the drugs or medical devices contained in drug-device combination products approved by China or the country (region) of production for marketing, the corresponding marketing certificate should also be submitted when applying for the registration of drug-device combination products to further prove the safety and effectiveness of products. For the drugs or medical devices contained in drug-device combination products not yet separately approved by China or the country (region) of production for marketing, the marketing certificate for such drugs or medical devices is not required when applying for the registration of drug-device combination products when applying for the registration of drug-device combination products.
(II) Contents relevant to the definition of attributes of drug-device combination products are revised.
Given the adjustment of the functional department, procedures, time limit, work requirements and the requirements for application materials for defining the attributes of drug-device combination products, the corresponding contents in Articles 3 and 4 of the Circular No. 52 were revised accordingly. Since Article 8 of the Circular No. 28 specified that “the matters relevant to the registration of other drug-device combination products shall be implemented in accordance with the Circular on Matters Related to the Registration of Drug-device Combination Products (the Circular No. 16 [2009] of the SFDA”, the relevant contents of the Circular No. 28 were adjusted to Annex 1 and Annex 2 of Circular No. 52. Moreover, the time limit for the Center for Medical Device Standard Management to accept and review the application for defining the attributes of drug-device combination products, and the meaning of the “primary mode of action” were further clarified. The Circular No. 28 was abolished simultaneously.
For the drug-device combination products to be applied for registration, if the applicant cannot determine their management attributes, the attribute definition of drug-device combination products should be applied to the Center for Medical Device Standard Management before applying for registration; if the management attributes of products can be determined by referring to the previously registered drug-device combination products or the attribute definition results of drug-device combination products already published, registration can be applied for according to the management attribute determined.
Considering that examples of the attributes of drug-device combination products are not exhaustive, relevant contents of examples of the management attributes of drug-device combination products were deleted and revised to “relevant regulations, for products with management attributes determined in the document, the relevant provisions should be implemented.”
III. Miscellaneous
In the actual application of products, in case of the combination of ingredients that have pharmacological activity and medical devices, such active ingredients are usually not used alone or are developed only for combination products, thus no separate marketing certificate for drugs can be obtained. Whether such active ingredients are included in the pharmacopoeia or not, their combinations with medical devices into a single entity are deemed to meet the definition of drug-device combination products.
Source: National Medical Productions Administration