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 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 and reviewers, but does not
2 / 8
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.
The guideline is a revised version of the Guidelines for technical review of virus
inactivation process verification for allograft implanted medical devices issued in
- The major revisions include: revising the relevant language descriptions in the
guidelines; improving the relevant descriptions of virus types and examples;
adjusting the principles of virus inactivation / removal validation.
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
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
3 / 8
process on the product performance; the recognition, reliability, reproducibility, easy
scalability and economy of the virus inactivation process itself. Examples of common
virus inactivation methods are as follows: - Pasteurization
Pasteurization method is one of the moist heat inactivation methods, and it is a
recognized virus inactivation method globally. 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.
