The combination product market continues to grow as pharmaceutical, medtech, biotech, and life science companies keep innovating. Combination devices and drug products can provide more targeted treatment, enable better drug delivery, and improve the efficacy of both medical devices and drugs. The definition of combination products and their governing regulations varies between countries.

In 2014, the Japanese Pharmaceuticals and Medical Devices Agency (PMDA) issued a notification titled ‘Handling of Marketing Application for Combination Products.’  Here we will briefly explain the combination products within the purview of Japanese regulations, covering the definition, and product categories falling under the definition and categories excluded from it, citing respective examples.

Definition

According to the aforementioned notification, a combination product is a single drug, medical device, or cellular and tissue-based product that combines two or more types of drugs, devices, and processed cells. They should be categorized as drugs, medical devices, or cellular and tissue-based products if marketed individually.

What are the Products Included in the ‘Combination Products’ Definition?

• Combination products in which their constituent drug, medical device, or cellular and tissue-based parts can be marketed individually.
• Kit products, as per the definition of notification no. 2-98/March 12, 1986.
• Combination products in which their constituents cannot be used individually.
• ‘Drugs Approved for Integral Marketing with Devices,’ specified in Article 98-2 and Article 228-20-3; ‘Medical Devices Approved for Integral Marketing with Drugs,’ specified in Article 114-60-2; and ‘Cellular and Tissue-based Products Approved for Integral Marketing with Devices, etc.,’ specified in Article 137-60 of the Ministerial Ordinance for Enforcement of the Act for Ensuring the Quality, Efficacy, and Safety of Drugs, Medical Devices and Other Products(Ministry of Health and Welfare Ministerial Ordinance No. 1, 1961).

What are the Products Not Included in the ‘Combination Products’ Definition?

• Combinations of medical devices for puncture and external disinfectants are treated as ‘combination medical devices’ and not as ‘combination products’ and are covered by different regulations.
• Products in which marketed drugs, medical devices, or cellular or tissue-based products are sold together by distributors are treated as ‘combination drugs’ and not as ‘combination products,’ and these are covered by different regulations.

Categories of Combination Products in Japan

• Drugs
• Medical Devices
• Cellular and tissue-based products (biological products)

What Determines the Combination Product Category?

Combination products may be a drug/device, cellular and tissue-based products/device, drug/cellular and tissue-based products, or drug/device/cellular and tissue-based products. What determines the combination product category is its primary function and purpose.

Some Examples of Combination Products

1. Drug-eluting stents, heparin-coated catheters, and antibacterial bone cements are all drug/device combination products. Their primary functions and purposes make them function as medical devices; hence, they fall under the ‘Medical Device’ category of combination products.
2. Pre-filled syringe injections, injections with injector pens (with adjustable dosing systems), and asthma iinhalers (with adjustable respiratory intake systems) are all drug/device combination products. Their primary functions and purposes make them function as drugs; hence, they fall under the ‘Drugs’ category of combination products.
3. Cell suspension in a pre-filled syringe is a cellular and tissue-based product/device combination product. It is used after it is impregnated (soaked) in clinical settings. Its primary function and purpose are related to the cellular and tissue-based part of the product and not the device part. Hence, it is classified under the ‘tissue-based product’ category.

In Japan, as there are three (03) different categories for ‘combination products’, Manufacturers applying for PMDA marketing permission shall pay attention to the definition to which their devices belong.

In case manufacturers are confused as to which pathway would be suitable, they can consult with the PMDA. Manufacturers willing to market their combination products in Japan must understand the local Regulatory complexities and partner with a trusted Regulatory expert.

To decode more about combination products regulation in Japan, reach out to our Regulatory expert now! Stay informed. Stay compliant.