Combination Products, Combination Medical Devices, Kit Products, Combination Drugs

*Please note that the majority of references are in Japanese. This is due to accuracy and a significant lack of official documents available in English.
*Communication with regulatory authorities and other organizations is mostly in Japanese. Also, given the subtle nuances and business customs that are hard for non-Japanese to grasp, I recommend you to secure a local Japanese resident (even on a part-time or contract basis).

In documents under the PMD Act, product classifications such as combination products, combination medical devices, kit products, set products, and combination drugs appear, whose differences can be difficult to understand at first glance.Especially as combination products and combination medical devices affect the approval application process, it is necessary to proceed with development based on a clear understanding.Here, for each product classification, we will present the definitions from official documents verbatim and provide a concise explanation of their content.

• Combination Products コンビネーション製品
  • Original Definition"A combination product is a single product composed of two or more different types of pharmaceuticals, medical devices, or regenerative medicine products (hereinafter referred to as 'constituent parts')."
    (Source: MHLW, "Partial Amendment to the Handling of Marketing Approval Applications for Combination Products," https://www.mhlw.go.jp/web/t_doc?dataId=00tc2324&dataType=1&pageNo=1)
  • Plain Language Explanation: This refers to a product that is treated as a single new product by combining products from different regulatory categories (e.g., a drug and a medical device). The key feature is that the overall regulatory classification is determined by the product's most important function (its Primary Mode of Action, or PMOA).
• Combination Medical Devices　組合せ医療機器
  • Original Definition"Refers to a medical device that is packaged, etc., by a marketing authorization holder as a single medical device for the purpose of being used as an integrated unit by combining multiple medical devices."
    (Source: MHLW, Notification No. 0331002, March 31, 2009, "Handling of Marketing Approval Applications, Marketing Certification Applications, and Marketing Notifications for Combination Medical Devices," https://www.pmda.go.jp/files/000158673.pdf)
  • Plain Language Explanation
    This is a product where all constituent parts are "medical devices" and there is a "clinical necessity" for using them together as a set. This notification defined that such products are not mere assortments but are intentionally packaged as a single product by the marketing authorization holder.
• Kit Products (Pharmaceuticals) キット製品
  • Original Definition"'Kit Product' refers to a pharmaceutical product that combines a formulation containing an active ingredient (hereinafter 'primary agent') with a solution, suspension, or another formulation containing other active ingredients (hereinafter 'accompanying agent') for the purpose of dissolution, suspension, or mixing at the time of use, in accordance with its dosage and administration."
    (Source: MHLW, Notification No. 0213005, February 13, 2004, "Handling of Kit Products," https://www.pmda.go.jp/files/000155938.pdf)
  • Plain Language Explanation: This refers to multiple pharmaceutical products that need to be mixed immediately before use and are packaged as a single product. It mainly applies to injectable drugs, and the primary agent and accompanying agent are considered "one pharmaceutical product."
• Combination Drugs　組合せ医薬品
  • Original Definition "'Combination drugs' are combinations of individually approved pharmaceuticals, etc., and shall be such that the statutory labeling of each individual product is visible from the outside when combined." (Source: Handling of Combination Drugs, etc., December 25, 1997, Ministry of Health and Welfare, Pharmaceutical and Medical Safety Bureau, Monitoring and Guidance Division, Administrative Communication, https://www.yakujihou.com/content/pdf/10-C2.pdf?utm_medium=cpc&utm_source=yahoo&yclid=YSS.1001245642.EAIaIQobChMIh4vI-sGc-AIVwtGWCh39Bw69EAAYASADEgIDkfD_BwE)
  • Plain Language Explanation: This is a regulation concerning "assortment products" where products that have already received individual approval are placed in a single box for sales convenience. Since the products themselves are not modified, new approval is deemed unnecessary.
• Combination Products: Key Points for Approval Application
  • Explanation: A typical example is a product like a pre-filled syringe, where a drug (medicinal solution) and a medical device (syringe) function as an integrated unit. If the primary function of the entire product is pharmacological, an approval application is filed for it as a "pharmaceutical"; if the primary function is physical, it is filed for as a "medical device," as a single product.
  • Questions and Answers (Q&A) regarding the Handling of Approval Applications for Combination Products https://www.pmda.go.jp/files/000218548.pdf
  • Key Points in Approval Application
    • "One Product, One Application" Principle: Although it consists of multiple constituent elements, the regulatory approval application is filed as a single product in one application.
  • Inclusion of Information on Secondary Constituent Elements: The application dossier must include information on the quality and safety of the secondary constituent elements, in addition to the primary constituent element.
  • Evaluation of Interactions: Interaction between constituent elements of different categories (e.g., compatibility of drug and container) is a critical evaluation item.
  • "Clinical Necessity" for Set Products: For set products where constituent elements are separable, it is required to clearly explain the clinical necessity of that specific combination at the time of application.
• Combination Medical Devices: Key Points for Approval Application
  • Explanation: This refers to products like "procedural kits" that bundle scalpels, forceps, and sutures used in surgery, where all components are medical devices, and there is clinical significance in using them as a set.
  • https://www.pmda.go.jp/files/000158202.pdf
  • Key Points in Approval Application
    • Demonstration of Integrity as a System: The focus of the application is not only on the performance of individual devices but on demonstrating the quality, safety, and effectiveness of the entire set when used as a system.
    • Interoperability and Human Factors: Evaluation of interoperability when connecting and operating multiple devices, and usability to prevent misuse, are extremely important.
    • Handling of Constituent Medical Devices: If the individual constituent medical devices have already received approval, etc., the application can be simplified by referencing their approval numbers.

​@K.Kamitani