CDSCO releases draft guidance document on stability studies of IVD Medical Devices
 The Central Drugs Standard Control Organisation (CDSCO) has released a draft guidance document on stability studies of In-vitro Diagnostic Medical Device (IVDMD) to aid manufacturers in the preparation of premarket review documents for the import or manufacturing license applications.The document, released earlier this month, is intended to aid manufacturers in the preparation of scientific information to be provided in support of claimed shelf life, in use stability and shipping studies for IVDMD license applications and Post approval change application filed in pursuant to the Medical Devices Rules (MDR), 2017, according to the drug regulator. It added that the CDSCO is looking to adopt the use of the guidance for premarket license applications and post approval change applications and strongly encourages manufacturers to follow the guidance when submitting applications. Stability of the IVD reagent affects the performance of the device and therefore has an impact on patient results and it is the manufacturer’s responsibility to determine and monitor stability of IVD product to ensure that performance characteristics of the product are maintained. The guidance document is applicable to the stability evaluation of in vitro diagnostic medical devices, including reagents, calibrators, control materials, diluents, buffers and reagent kits, while it is not applicable to IVD analysers, instruments, apparatus, equipment, software and systems. Manufacturers should describe claimed shelf life, in use stability and shipping stability studies and should provide information on stability testing studies to support the claimed shelf life. The guidance document says that stability testing should be performed on at least three different lots manufactured under conditions that are essentially equivalent to routine production conditions (these lots do not need to be consecutive lots). Accelerated studies or extrapolated data from real time data are acceptable for initial shelf life claims but need to be followed up with real time stability studies. The in use stability section with study on one lot reflecting actual routine use of the device should include open vial stability, and/or on board stability for automated instruments. In the case of automated instrumentation if calibration stability is claimed, supporting data should be included. The shipping stability section should provide information on shipping stability studies for one lot to evaluate the tolerance of products to the anticipated shipping conditions. Shipping studies can be done under real and/or simulated conditions and should include variable shipping conditions such as extreme heat or cold. The CDSCO also recommended latest standards such as IS/ISO 23640 (In vitro diagnostic medical devices for evaluation of stability of in vitro diagnostic reagents), CLSI-EP25-A, ASTM4169-14 and WHO TGS2, for use in establishment of stability claims for IVD medical devices. “It is recommended that manufacturers be familiar with the standard and consider them when designing and planning their stability studies,” it added. The stability studies submitted to CDSCO should accurately reflect the expected environmental conditions and the normal usage conditions/ methods encountered by the users in India’s States such as estremes of temperature for in-use conditions and during transportation, extremes of humidity encountered during these situations and storage, dust, light, both the amount required for accurate testing and results interpretation, and details of microorganisms. Meeting predetermined user expectations, not merely evaluating the capability of an IVD, is a fundamental aspect of development of IVDs. It is a proactive means for the manufacturer to prevent quality problems at lot release and in the post-production and marketing phase, it stated. The process to establish product stability claims follows four steps – provide an operational definition of stability for the given product; develop a stability testing protocol to generate experimental data; execute the plan; and derive and document stability claims from analysis of the experimental data, it said. A well-designed stability study must generate evidence of the stability of each of the critical constituents of the IVD (risk-evaluated critical constituents), each of the claimed analytes, and any particular level of performance including precision, sensitivity and specificity of the kit. The guidance document elaborates on various studies to be conducted in various stages of the product cycle, including the transportation and in-use conditions. |
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