Draft Technical Guideline For Virus Inactivation Process Verification For Allograft Implanted Medical Device (2011 Revision)
2021-06-22
I. Preface Allogeneic implantable medical devices are products processed or composed of tissues of the same source. At present, most of the virus screening for tissue donors of allogeneic implanted medical device products in China adopts the method of detecting virus-specific antibodies or antigens in serum. Among them, human immunodeficiency virus (HIV) also requires detection of viral nucleic acids in serum. However, despite rigorous screening of donors, there are still risks of missed detection and unknown virus contamination, as well as the risk of foreign viruses being introduced during production. Therefore, it is required that an allogeneic implantable medical device product adopt an effective virus inactivation process in the production process, and scientifically verify the effectiveness of the virus inactivation process. The guideline is a general requirement for verifying the effectiveness of specific virus inactivation processes during the production of allogeneic implantable medical devices. Applicants/Manufacturer should enrich and refine the content of registration application documents based on the characteristics of specific products, such as the virus inactivation process and related parameters used, and the specific content of the product is determined based on the characteristics of the specific product. The guideline is a guidance document for applicants/manufacturer and reviewers, but does not include administrative matters involved in registration approval, nor is it enforced as regulations. If there are other methods that can meet the requirements of relevant regulations, they can also be used, but detailed research and verification information shall be provided. The guideline shall be used in compliance with relevant regulations. The guideline is formulated under the current system of laws and standards and the current level of cognition. With the continuous improvement of laws and standards and the continuous development of science and technology, the relevant content of this guideline will also be adjusted in a timely manner. II. Scope of application The guideline applies to allogeneic implanted medical devices that require verification of the effectiveness of specific virus inactivation processes during production. III. Basic requirements (I) Commonly virus inactivation methods There are multiple methods for virus inactivation of allogeneic implanted medical devices, and companies shall choose the appropriate virus inactivation Draft Technical Guideline for Virus Inactivation Process Verification for Allograft Implanted Medical Device 2 / 5 process based on the characteristics of the product. The following issues shall be comprehensively considered when adopting the virus inactivation process, including the verification of the effect of virus inactivation; the impact of the virus inactivation process on the products; the recognition, reliability, reproducibility, easy scalability and economy of the virus inactivation process itself.
Pasteurization Pasteurization method is one of the moist heat inactivation methods, and it is a recognized virus inactivation method globally. It has been successfully used in human albumin products for decades, and the inactivation conditions are perfect. This inactivation method can inactivate lipid-enveloped and partially non-lipid-enveloped viruses. After allogeneic implanted medical devices have sufficiently washed the blood and bone marrow components, this method can be used for virus inactivation. The uniformity of temperature distribution and inactivation time should be considered when using this method.
Dry heat inactivation method Dry heat inactivation is mainly used for virus inactivation of lyophilized products. The virus inactivation effect of this method has been confirmed by laboratory verification and clinical application. It can inactivate various viruses such as HIV, hepatitis B virus (HBV), hepatitis C virus (HCV) and hepatitis A virus (HAV) . The advantage of dry heat inactivation is that it can be used for allogeneic implanted medical devices after lyophilization. In this method, the uniformity of temperature distribution, lyophilization process and product moisture residue should be considered.
Gamma-ray irradiation inactivation method The main advantages of γ-ray irradiation inactivation methods include high inactivation efficiency, strong penetrating power, easy dose control, no harmful substance residues, and no significant temperature increase. This method inactivates viruses primarily by destroying nucleic acids. Because the virus has different resistance to radiation in different media, when this method is used for virus inactivation of allogeneic implanted medical devices, the host tissues and cells in the product should be removed as much as possible. For example, allogeneic bone should be fully washed with blood. And bone marrow components. The radiation dose should be determined according to the characteristics of the product. The distribution of radiation dose and inactivation time should be considered when using this method.
