The new article highlights aspects related to pyrogenicity, (accelerated) aging, packaging, ensuring that the sterility of the device is duly maintained, as well as biocompatibility for all the components and patient-contacting materials.
The Food and Drug Administration (FDA or the Agency), the US regulating authority in the sphere of healthcare products, has published a guidance document dedicated to orthopedic non-spinal bone plates, screws, and washers in the context of premarket notification (510(k)) submissions. Once finalized, the document will provide an overview of the applicable regulatory requirements as well as additional clarifications and recommendations to be taken into consideration by medical device manufacturers and other parties involved in order to ensure compliance. At the same time, provisions of the guidance are non-binding in their legal nature, and they are intended to introduce new rules or impose new obligations. Moreover, the authority explicitly states that an alternative approach could be applied, provided such an approach is in line with the existing regulatory framework and has been agreed upon with the authority in advance.
The scope of the guidance covers specific aspects to be addressed in premarket submissions to ensure the authority receives all the information reasonably necessary to assess the safety and effectiveness of the product in question. The document describes in detail the way each of the said aspects should be addressed and outlines the scope of information to be reflected in the submission.
According to the guidance, pyrogenicity testing is used to help protect patients from the risk of a febrile reaction due to gram-negative bacterial endotoxins and/or chemicals that can leach from a medical device (e.g., material-mediated pyrogens). In order to make sure the risks associated with medical devices are addressed properly, the parties responsible for medical devices should follow the recommendations provided by the authority in the respective guidance document dedicated to the products intended to be supplied sterile. The authority also refers to the document dedicated to pyrogen and endotoxin testing for further guidance on the most important questions. With respect to biocompatibility-related matters, the authority refers to the respective international standard, which is ISO-10993-1. It is also important to mention that if product in question is labeled as “non-pyrogenic”, both bacterial endotoxins and material-mediated pyrogens should be addressed.
Shelf Life and Packin
The scope of the guidance also covers aspects related to the intended shelf life and packaging. According to the document, appropriate testing is important in order to ensure the stability and proper performance of a medical device within the entire intended use period. In the case of sterile products supplied, the authority expects medical device manufacturers to provide a detailed description of the packaging used, paying special attention to the way the sterility of the product is ensured during storage and transportation. Medical device manufacturers should also provide details about the integrity tests conducted to collect additional data supporting the above statements. In particular, the authority recommends that package integrity test methods include simulated distribution and associated package integrity testing, as well as simulated (and/or real-time) aging and associated seal strength testing, to validate package integrity and shelf life claims. The authority also refers to the applicable international standard as ISO 11607 Packaging for terminally sterilized medical devices.
In terms of aging and the way it could affect the safety, and effectiveness of the functionality of the device in question, the authority explains that shelf life studies should evaluate the critical physical and mechanical properties of the device to ensure it will perform adequately and consistently during the entire proposed shelf life. For this purpose, appropriate bench testing could be conducted, addressing specific matters related to the functionality of the device and the extent to which it could be affected by aging.
The authority would also expect medical device manufacturers to provide a summary of any and all testing methods applied with respect to shelf life, as well as the appropriate conclusions. In cases where the methods used provide for accelerated aging, the manufacturer would also have to provide a detailed enough description of the particular accelerated aging method used in order for the authority to be able to assess the accuracy and reliability of the testing results. In this respect, the authority refers to the ASTM F1980 Standard Guide for Accelerated Aging of Sterile Barrier Systems for Medical Devices for further guidance.
The aforementioned description should include details on environmental parameters applied in the course of testing. Should the device or any components thereof contain polymeric materials, the scope of testing should also include the assessment of real-time aged samples – the results of such an assessment should be compared to the ones from the accelerated aging study. The authority additionally emphasizes that the results of the above testing should be duly documented and retained in the device-related files.
Since the products covered by the scope of the present guidance contain patient-contacting materials, aspects related to biocompatibility are vitally important and require rigorous assessment to address the potentially harmful biological response. In particular, the authority expects medical device manufacturers to determine the biocompatibility of any and all patient-contacting materials used in the product. The authority explains that if the device(s) in its finished form are identical in chemical composition, manufacturing, and processing methods, and any differences in geometry or surface properties are not expected to adversely impact the biological response compared to a legally marketed bone plate(s), screw(s), washer(s), or instrument(s) with a history of successful use, [the manufacturer] may reference previous testing experience, or the literature, if appropriate. The authority further refers to the applicable voluntary consensus standards that medical device manufacturers may use to demonstrate compliance with the applicable regulatory requirements their products are subject to. Furthermore, the authority also expects medical device manufacturers to provide data demonstrating that the device in question is identical in terms of composition and materials used to another similar device already on the market. Should the manufacturer be unable to identify such devices already present on the market, a biocompatibility assessment should be conducted, and its results should be provided to the authority, together with details on the biocompatibility risks identified and the way they are duly addressed.
In summary, the present FDA guidance provides additional clarifications regarding the information to be included in premarket submissions with respect to pyrogenicity, shelf life, packaging, and biocompatibility. The document highlights the key points to be taken into consideration in order to ensure the completeness and reliability of the data used to assess the aforementioned matters and also outlines the scope of information the authority expects to be provided.
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