Frequently Asked Questions (FAQs) Regarding MTB Screening Criteria

On August 7, 2023, AATB released Bulletin 23-6, which contains mandatory requirements and recommendations for accredited establishments designed to reduce the risk of tuberculosis (TB) transmission through tissues. As announced in Bulletin 24-5, those requirements are being superseded by revisions to Standards for Tissue Banking that will become effective with the 15th edition on January 31, 2025. 

This FAQ is intended to provide additional clarification and will be updated as needed to provide the most current information to accredited institutions. Please submit additional questions to standards@aatb.org. 

Frequently asked questions (FAQ) last updated July 22, 2024.

 

Physicians Council MTB Working Group: Interim Mycobacterium tuberculosis (MTB) Donor Screening Requirements (webinar recording) - August 21, 2023

 

A. Tissues Containing Viable Cells

A1: Why are individuals over 65 years of age ineligible to donate tissues that will be processed into grafts containing viable cells? 

These new donor eligibility criteria are related both to the risk of MTB exposure (the incidence of MTB was much higher in the United States in the past) and the risk of [latent] TB infection reactivation in people aged 65 and older (due to factors including immune senescence, atypical presentation including extrapulmonary disease, and more frequent co-morbidities, which can increase the chances of TB reactivation).  See FAQ A4 for exception to this criterion for donors of cryopreserved skin only.

Complete background, including literature references, for MTB screening criteria can be found in the article, “The American Association of Tissue Banks tissue donor screening for Mycobacterium tuberculosis—Recommended criteria and literature review” (Transpl Infect Dis. 2024; e14294. https://doi.org/10.1111/tid.14294).

 

A2: Will AATB define “exposure” as used in “Exposure to an individual with tuberculosis disease in the last 2 years”? In previous bulletins, “exposure” (COVID and Monkeypox) has been defined.

Exposure is not defined for TB because the CDC doesn’t define “exposure” with respect to TB.  Any time spent with someone with TB disease could result in TB transmission. There is no reliable way to narrow that down to be more specific about the exposure, e.g., household contacts, a quantified period of time spent, etc.

 

A3: Can AATB provide clarification or additional detail regarding what constitutes “tissues containing viable cells”? 

For purposes of donor screening, the term “tissues containing viable cells” is described in Appendix II as, “…all products comprising or containing tissues that are processed in a manner to retain live cells—including reproductive cells.” It is up to the manufacturer to determine and document whether they process their tissues in a manner to retain live cells. Many manufacturers of tissues containing viable cells make statements about cell viability, including in the Instructions for Use (IFU), research papers, white papers, or advertisements to end users that make it clear that the tissue comprises or contains living cells.  

Tissues that are considered “cryopreserved” and where the degree of preservation of living cells may be less clear, require the manufacturer to conduct and document a risk assessment. Issues to consider in making such a risk assessment include but are not limited to, the following:

• Reasons for the “cryopreservation” – such as maintaining structural characteristics of the tissue vs. maintaining cell viability.
• Information related to the presence of viable cells provided in IFU, published research, advertising matter, or oral or written statements.
• Processing methods.
• Method of freezing used, e.g., use of cryoprotectants and freezing rate as compared with data on how Mycobacterium tuberculosis (MTB) is (intentionally) cryopreserved. References noted at end of FAQ.
• Do you have data indicating a functional assessment of living cells in your tissues? 
• Do you have data indicating the presence of living cells for your tissues? Did you document why that assessment was or was not performed and did you use that data to inform your end users as a claim or attribute of the tissue? 
• Whether there is any possibility of living bone marrow cells or white blood cells being retained in any part of the tissue (which would be considered higher risk).

It is not required that tissues be decellularized to conclude they do not contain viable cells. The tissue establishment can determine whether tissues have sufficient cellular function or numbers of viable cells to present a risk of transmission of MTB. The available information should be considered in total.
 
The following are examples of tissue types that may or may not be subject to the new donor screening criteria and recommendations. Please note that the examples below are not all-inclusive.   

Examples of tissue types that are subject to MTB screening criteria and recommendations: 

• Cellular bone matrix tissue, osteochondral allografts, and birth tissue processed or advertised to preserve viable cells. 

Examples of tissues that should be evaluated to determine whether there are sufficient viable cells to present a risk of transmission of MTB: 

• Bone, tendon, ligaments, cartilage, skin, nerve, cardiovascular tissues, saphenous veins, birth tissues and dermal tissue that undergo processes to remove or destroy living cells through exposure to detergents, chemical disinfectant or terminal sterilization, lyophilization, cryopreservation, or low temperature freezing. 

It is the responsibility of each tissue establishment to document an evaluation of their tissues and a rationale for why the tissues are not subject to the MTB criteria and recommendations in the bulletin. 
 

 

A4: How do requirements for cryopreserved skin differ from other tissue containing viable cells? 

Because cryopreserved skin is largely obtained from donors >65 years of age, and incidence of cutaneous tuberculosis (<2%) relative to bone (11-20%) and other extra-pulmonary types of tuberculosis is comparatively quite low, cryopreserved skin was carved out from some of the MTB exclusionary criteria. Specifically,

1. Cryopreserved skin is excepted from the requirement that tissues intended to ultimately retain viable cells may not come from donors aged ≥ 65, as specified in item 33a of Appendix II. All other criteria in item 33 of Appendix II apply.  
2. Donors of cryopreserved skin who are aged ≥ 65 still must be evaluated against the risk factors for exposure to, and/or reactivation of, tuberculosis as listed in item 34 of Appendix II. The suitability of cryopreserved skin from donors with at least one risk factor from each column is subject to Medical Director discretion. 

 

B. Implementation

B1: When will the requirements of the revised Appendix II become effective

The Appendix II revision, including the MTB screening requirements, will be included in the 15th edition of Standards, which will be released on July 29, 2024 and become effective on January 31, 2025. As such, conformance with these requirements is not necessary until January 31, 2025. As of that date, these requirements will supersede those specified in Bulletin 23-6. Accredited establishments may, however, choose to adopt the new requirements at any time prior to January 31, 2025.

 

C. Donor History of Tuberculosis

C1: Is the recommendation that any positive test for tuberculosis, even if a pursuant blood test or chest x-ray are negative, will render the donation ineligible? For example, if a PPD skin test is positive, but follow-up testing is negative, as might be caused by historical administration of Bacille Calmette-Guérin (BCG) vaccine?

Yes, if someone has a tuberculosis infection (a positive TB test result), they are ineligible to donate tissues containing viable cells. If the positive TB test result was within the past two years, they are ineligible to donate any tissues. Information about individuals who had BCG vaccine previously can be found at https://www.cdc.gov/tb/topic/testing/testingbcgvaccinated.htm. 

 

D. Testing

D1: Can AATB provide a list of FDA-licensed tests for MTB? What type of test was used on tissues associated with the latest transmission episode?

There are no FDA licensed/cleared/approved tests for tuberculosis for deceased tissue donors. The 2 approved tests for clinical/diagnostic purposes are QuantiFERON-TB Gold Plus and T-SPOT TB test. These interferon gamma release assays (IGRA) rely on the ability of white blood cells to release interferon gamma in response to TB antigen, and therefore require living cells. As a result, testing must be completed in a very short timeframe that is not possible with deceased tissue donors. Furthermore, poor immune function will negatively impact the ability to obtain positive test results. More information about IGRA testing can be found at https://www.cdc.gov/tb/publications/factsheets/testing/igra.htm.

For the 2023 tuberculosis transmission event, the viable bone matrix tissue was tested for MTB using polymerase chain reaction (PCR) methodology. 

 

E. Additional Risk Factors

E1: How does AATB describe “experiencing homelessness” as a risk factor for TB? 

For donor screening purposes, people are considered to be experiencing homelessness if they stay in a shelter or other congregate settings. See https://www.cdc.gov/orr/science/homelessness/about.html and 
https://www.cdc.gov/tb/publications/factsheets/statistics/tbtrends.htm.

 

F. UDRAI

F1: With the revision of the UDRAIs, may I cease using the MTB Addendum?

Yes, the revised UDRAIs and new DRAI for donors of birth tissue incorporate the minimum information that must be collected to comply with the updated requirements in Appendix II. Once the updated questionnaires are implemented, no addendums will be necessary. As always, you may ask additional questions during an interview, for example to ensure compliance with state-specific or other non-AATB requirements. 

 

Version History

August 11, 2023 – initial release
August 18, 2023 – Modified question numbering. Revised A1 (formerly Q1); added A4, E1, E2, and F1
July 22, 2024 – Substantive revisions concurrent with release of revised Appendix II as described in Bulletin 24-5. Former questions A4 and E2 and references were removed. References are replaced by article cited in A1.