It is important to recognize that there is additional regulatory scrutiny for human tissue transplantation used to improve quality of life (bone, skin or soft tissue) compared to life-saving transplanted tissues (organs, vascular or optical tissues). This document focuses on those tissues transplanted for improving quality of life.
Safety concerns for the test laboratory
When performing tissue testing, the primary concern for the test laboratory is to minimize the risk of transmitting infection and communicable disease. Infection can occur from a variety of sources in the transplantation process, whether it is collection, storage, tissue processing, testing, transportation, transplantation or a combination of these factors. Other factors to be considered include the type of tissue and the source of the tissue, including cause of death and other health conditions of the donor (e.g. TSE, malignancy, drug use). Risk should be mitigated through a robust quality program and routine audits of pre- and post-processed tissue. Testing of the donor for communicable diseases, such as HIV or Hepatitis, should also be performed prior to submission of samples to a test laboratory for microbiological analysis to ensure technician safety during testing.
The audit program includes the microbiological evaluation of pre-processed tissue by bioburden assay. The method used to recover bacteria and fungi from the pre-processed tissue must be validated in order to account for the efficiency of the bioburden method for removal of organisms. Additionally, the tissue tested after disinfection processing, particularly if there is antibiotic or chemical disinfection, should be assessed for inhibitory properties. An example of potential inhibition could be the antibiotic treatment that a donor was placed on prior to death. ISO 11737-1 Annex B states that samples should be screened for the release of substances affecting bioburden determinations and for the adverse effects of physical stress. This testing is performed by inoculation of low levels of different organism types and recovering acceptable populations against a set of control samples.
Considerations for bioburden assay should include the significance of the sample size, consistency of sample quality and size, and physical cleanliness of tissue samples. Lipids, oils and other debris can confound the bioburden assay and lead to inconsistency in reported results.
Contamination and recipient considerations
Incubation conditions of the test assay should be evaluated to address recovery of problematic organisms. Organisms recovered should be identified to determine pathogenicity of the contaminated donor tissue. Donors found to have pathogenic organisms should undergo terminal sterilization, such as gamma irradiation. Donors found to have organisms of less virulence may either undergo a validated disinfection process or be terminally sterilized.
Bacterial endotoxin testing is also performed to ensure the tissue does not generate a pyrogenic response to the recipient due to Gram-negative bacteria endotoxin. Testing should consider the impact of beta-glucan-like chemicals that can interfere with the testing. The method used for LAL testing should reconcile issues of inhibition or enhancement.
Sterility testing must also be tested for inhibition of organism growth. The sterility method suitability test (also known as Bacteriostasis/Fungistasis test) must be performed to eliminate the potential for false negative results.
GUIDANCE ON THE MICROBIOLOGICAL SAFETY OF HUMAN ORGANS, TISSUES AND CELLS USED IN TRANSPLANTATION. Advisory Committee on the Safety of Blood, Tissue, and Organs. 21February 2011
ISO 11737-1:2006 (R2011) Sterilization of medical devices — Microbiological methods — Part 1: Determination of a population of microorganisms on products
ANSI/AAMI ST72:2011 Bacterial Endotoxin – Test Methodologies, routine monitoring, and alternatives to batch testing
Biological Indicator Population Verification Test
Purpose In a sterilization process where biological indicator (BI) sterility results are used as part of product release criteria, the BIs shall be procured from an approved supplier with a minimum population of test organisms defined. The population o
Screening for Adverse and Inhibitory Substances
Test method validation for adverse and/or inhibitory substances is important to ensure that the measurement of contamination on a device is not impacted by substances present in the test. Adverse substances and/or inhibitory substances (e.g. antimicrob
What is Bioburden Recovery Efficiency and How to Approach Lower Than Desired Recovery Results
What is Recovery Efficiency (RE)? Recovery Efficiency (RE) is an important part of the validation of the bioburden test method. It is intended to provide an assessment of the efficiency of the extraction technique to remove viable microorganisms from a