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Revision of the Guideline for the Approval & Review of Angioplasty Catheters, Balloon Dilatation
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The 2021 Guideline for Approval and Review of Angioplasty Catheter (Balloon Dilatation) issued by the Ministry of Food and Drug Safety (MFDS) has been revised and published on December 24, 2024. A balloon angioplasty catheter, a Class 4 medical device in Korea, is used for vascular stenosis, where such balloon catheter is inserted into a narrowed blood vessel and expanded at the target site, pushing out the lesion to help improve blood flow. The general term for this procedure is called Percutaneous Transluminal Angioplasty (PTA), but if the target lesion is in the coronary arteries, it is called Percutaneous Transluminal Coronary Angioplasty (PTCA).
The previous 2021 guideline presented approval and review methods (detailed review methods of technical documents, substantial equivalence, etc.), specific performance testing items, and sample selection and testing methods by referencing relevant domestic and international standards (ISO 10555-1 and 10555-4, FDA guidelines, and ISO 25539-2, the international standard for vascular stents). In this revision, three years since the original guideline, several additional items have been specified as summarized below.
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Clarification on biological safety data (biocompatibility) requirements by category
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In the case of drug-coated balloon catheters, the guideline provides a separate biological safety data requirements for catheters and for drug-coated balloons (in the case of catheters without drug coating, only the catheter scope is applied). The catheter itself is classified as a limited contact medical device (circulating blood contact, use for 24 hours or less), while the drug-coated balloon part is classified as an implant medical device (blood contact, use for more than 30 days). In other words, the revised guideline effectively classifies drug-coated balloon catheters as implant medical devices, focusing on the drug’s effect in the vessel or body persisting for more than 30 days, regardless of the duration of PTA or actual time the catheter is in contact with blood.
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Drug-coated balloons recognized as implant medical devices
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For biological safety data on the drug-coated balloon part, each test data is required to have been performed on the finished product, and some tests can be recognized with appropriate animal test data. Accordingly, the guideline provides that in case of replacing the relevant test items with animal tests, such animal tests should be 1) conducted at a GLP institution in accordance with GLP, 2) including all evaluation and observation items of each test, and 3) conducted for a sufficient period. To this end, it seems very important to set an appropriate evaluation time point and test period that allows for the target safety evaluation of each test. The MFDS notice 'Standards and test methods for biological safety of medical devices' that is based on the international standard ISO 10993 should be referred to, but all tests should be conducted and reviewed with sufficient grounds and analysis reflecting the characteristics of the subject device.
For reference, at MFDS briefing session (Cardiovascular Imaging Device Division) held on November 21, 2024, it was introduced that 6 out of 7 paclitaxel-coated balloon catheters approved in the US set the observation period to at least 180 days up to 210 and 365 days to confirm safety. In addition, it was recommended to set the observation period to at least 6 months when submitting some of the long-term toxicity (chronic) and implant tests with animal test data.
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Genotoxicity test data for catheters
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In addition, for catheters without the drug-coated balloon part and non-drug-coated balloon catheters (boxed in red above), genotoxicity test data may be additionally required where the raw materials are not equivalent to the pre-approved product. However, considering that the raw material information is not available to the public, it would be very difficult to prove equivalence unless manufactured by same company. Therefore, the guideline can be understood as requiring genotoxicity test data through official tests or addressed through supporting data.
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Regarding clinical data submission
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For PTA/PTCA balloon catheters, according to the Regulations on Medical Device Approval/Reporting/Review, Etc., if the intended use and raw materials are different with pre-approved products, clinical trial data must be submitted for review to demonstrate substantial equivalence. In addition, for raw materials, applicant would need to claim that the materials for the parts that are in contact with the human body are equivalent to materials used for pre-approved products; therefore, in the case for drugs-coated products, substantial equivalence will be determined based on the drugs, excipients, and coating materials, etc. Accordingly, if you are preparing for Korean MFDS technical review, it is important to check in advance whether the intended use and raw materials of the subject products are equivalent to the ones of already approved products.
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Others (emphasized, revised test specifications, etc.)
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Moreover, there is continued emphasis that the model names on the application and the one in the test data must match, and the performance test items and methods appear to be based on the international standards ISO 10555-1 and 4 as revised in 2023. Specific test items and test method examples have been provided; however, the premise is that they can be selectively applied depending on the characteristics and functions of the subject product. If an alternative test method set by the manufacture is used to satisfy the quality requirements, evidence (rationale and test records) must be submitted to ensure that the performance have sufficiently been proven. However, since there are no specific criteria for this self-developed testing method, it is recommended to prepare the rationale as clearly as possible, otherwise it may be not accepted.
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Recently, while various drug-coated balloon angioplasty catheters have been developed and are preparing to enter the Korean market, various tests must be conducted to verify safety and efficacy as required by MFDS in the above guideline. Since this may cause delays in market entry, it is necessary to thoroughly prepare to reflect the latest and most accurate requirements with minimal supplementation to avoid undue delays. In addition, for drug-coated balloon catheters, it is important to prove the safety of the drug according to appropriate test standards and evidence.
If you would like further information and/or assistance on this matter,
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