How could COVID-19 impact allograft safety?

It is well known that viruses can sequester in organs and tissues, creating the possibility of transmission during transplant. Until more is known about COVID-19 transmission and sequestration, it’s best to presume that there could be potential risks to patients receiving allografts. Therefore, implementation of guidelines which restrict tissue donation are necessary to preserve the safety of the nation’s allograft supply.

Fortunately, the Physician’s Council of the American Association of Tissue Banks has issued guidance on this matter to the US tissue banking community. Per Dr. Roman Hitchev of the Association, here is a summary of those guidelines:

  • Travel within the last 28 days prior to donation to an area designated by the CDC as Alert Level 2 or Warning Level 3 may constitute grounds for exclusion of a deceased donor regardless of symptoms, or deferral of a living donor for as much time is necessary to ensure at least 28 consecutive days without symptoms1 following the last travel date to the designated area.
  • Fever with severe acute lower respiratory illness (e.g., pneumonia, ARDS) requiring hospitalization without alternative explanatory diagnosis (e.g., influenza) and without a negative SARS-CoV-2 diagnostic test, may constitute grounds for exclusion of a deceased donor, or deferral of a living donor for as much time is necessary to ensure at least 28 consecutive days without these syndromic symptoms.
  • Close contact3 within the last 28 days prior to donation with a person who has confirmed COVID-19 infection or with a Person under Investigation2 (PUI) as defined by the CDC may constitute grounds for exclusion of a deceased donor, or a deferral of a living donor for as much time is necessary to ensure at least 28 consecutive days without symptoms1 following the contact.
  • Confirmed infection or designation of a Person under Investigation2(PUI) as defined by the CDC within the last 28 days prior to donation may constitute grounds for exclusion of a deceased donor or deferral of a living donor for as much time is necessary to ensure at least 28 consecutive days without symptoms after the PUI status is lifted.  

 

  1. Symptoms: Refer to the CDC website – https://www.cdc.gov/coronavirus/2019-ncov/about/symptoms.html
  2. Person under Investigation(PUI): Refer to CDC Criteria to Guide Evaluation of PUI for COVID-19 – https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-criteria.html
  3. Close Contact: Refer to the CDC website – https://www.cdc.gov/coronavirus/2019-ncov/faq.html

 

Due to the dynamically changing outbreak geography, medical directors are advised to refer to the CDC on countries at risk for transmission and community spread and the latest travel advisories.

Our country’s tissue banking community is committed to patient safety. The Association and member banks are engaged in research to answer key questions about the new coronavirus and its effects on donated tissues. Allografts.com will be providing updates to the surgical community on the scientific knowledge base as it evolves.

FDA Revises Screening Guidelines for Zika Virus Based on Study Data

The Food and Drug Administration (FDA) has revised their guidance for screening donated whole blood and blood components for Zika virus, replacing the guidance put in place during the height of the Zika outbreak in August 2016. The revised guidance allows blood establishments to utilize pooled testing of donations, instead of testing each donation individually. Testing of individual donations is still required if there is an increased risk of mosquito-borne transmission of Zika. At this time, Zika has local transmission in Puerto Rico and the U.S. Virgin Islands, which would require testing of individual donations, but this revised guidance excludes all 50 incorporated states since they do not currently have mosquito-borne transmission of the virus.1 The FDA’s decision to use pooled testing brings Zika screening in line with the way blood donations are screened for other diseases, including HIV, West Nile, and hepatitis B.2

Zika first emerged in Brazil in late 2015, and was quickly detected in the United States in travellers originating from Brazil and, as the epidemic spread, surrounding countries. As 2016 progressed, local transmission of the Zika virus was detected in both Florida and Texas, though such mosquito-borne transmission is believed to have been eliminated by the summer of 2017. The epidemic both domestically and internationally has dramatically dwindled since then, due to a combination of factors including mosquito control, prevention measures, and decreased host susceptibility due to the high initial incidence of the disease.3 In the U.S., there have been no cases of mosquito-borne transmission of Zika virus in 2018, and only 41 cases in travellers.4

The association of Zika virus with severe birth defects, its persistence in whole blood, and four cases of possible transmission of Zika by blood transfusion in Brazil all raised significant questions about the safety of the blood supply.5 In February 2016, the FDA recommended screening blood where the outbreak was active, which at the time was only U.S. territories;6 within six weeks, all blood donations were being screened in Puerto Rico, where the outbreak was, and remains, much more severe than the rest of the United States.5 On August 26, 2016, in response to the widespread nature of the outbreak, the risks posed by infection, and the large proportion of asymptomatic cases, the FDA issued revised recommendations directing that all whole blood donations and blood components in the U.S. be screened for Zika virus.7

The American Red Cross supplies roughly 40% of the blood and blood products in the United States and its territories.8 Starting June 20, 2016, the Red Cross began screening all of its whole blood donations and blood components in the U.S. for Zika RNA using the Procleix Zika Virus Assay manufactured by Grifols Diagnostic Solutions, under a special emergency use authorization as an investigational new drug for Zika virus applications.9,10

Between June 2016 and September 2017, 4,325,889 donations were screened by the Red Cross in the United States; 160 were initially reactive for Zika and 9 were confirmed positive. Of these, 4 were IgM negative, meaning they were likely not infective, and one was the recipient of an experimental vaccine.9

Researchers estimated that each RNA-positive donor cost $5.3 million per year to detect using individual donation screening, regardless of whether they were infectious or not, when testing is done by this type of transcription-mediated amplification (TMA) assay. Testing for Zika within the pooled blood supply remains expensive, but the pooled testing method will lower costs compared to the individual assay by an average of $4 per donation.9

Data collected during the 15-month trial period showed that pooled testing of samples were equally effective as the individual assay at detecting confirmed positive samples, but the pooled testing had a better positive predictive value and specificity than the individual assay (5.6% and 99.997%, respectively).9

References

  1. (2018, July 6). FDA announces revised guidance on the testing of donated blood and blood components for Zika virus. U.S. Food & Drug Administration. Retrieved from https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm518218.htm
  2. Branswell, H. (2018, May 9). Testing for Zika virus in blood donors finds few infections — at a cost of about $5.3 million each. STAT. Retrieved from https://www.statnews.com/2018/05/09/zika-testing-blood-donors
  3. Bunch, C. (2018). Hot topics: Zika virus and allografts, part 1. com. Retrieved from https://allografts.com/hot-topics-zika-virus-and-allografts-part-1/
  4. (2018, September 5). Zika case counts in the US. Reporting and Surveillance. Retrieved from https://www.cdc.gov/zika/reporting/2018-case-counts.html
  5. Saa, P., Proctor, M., Foster, G., Krysztof, D., Winton, C., Linnen, J. M., … Stramer, S. L. (2018, May 10). Investigational testing for Zika virus among U.S. blood donors. New England Journal of Medicine, 378: 1778-1788. doi:1056/NEJMoa1714977
  6. (2016, February 16). FDA issues recommendations to reduce the risk for Zika virus blood transmission in the United States. U.S. Food & Drug Administration. Retrieved from https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm486359.htm
  7. (2016, August 26). FDA advises testing for Zika virus in all donated blood and blood components in the US. U.S. Food & Drug Administration. Retrieved from https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm518218.htm
  8. American Red Cross. (2018). Blood supply statistics. Retrieved from https://www.redcrossblood.org/donate-blood/how-to-donate/how-blood-donations-help/blood-needs-blood-supply.html
  9. Bloch, E. M., Ness, P. M., Tobian, A. A. R., & Sugarman, J. (2018, May 10). Revisiting blood safety practices given emerging data about Zika virus. New England Journal of Medicine, 378: 1937-1841. doi:1056/NEJMsb1704752
  10. (2018, August 3). Emergency Use Authorizations. Medical Devices. Retrieved from https://www.fda.gov/MedicalDevices/Safety/EmergencySituations/ucm161496.htm
  11. Photo Credit: Jefferies, P. (2009, 25 September). Units of blood collected during the 69th ADA Blood Drive at the Robertson Blood Center at Fort Hood, Texas on September 18, 2009. United States Army. Retrieved from http://www.army.mil/-images/2009/09/25/51565/
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Good Tissue Bank Standards of Practice

What helps make a tissue bank good?

Following Standards of Practice (SOPs) in tissue banking is vital to ensure that every step of human tissue procurement, preparation, and distribution is held to the highest standards. This is done to ensure the safety, quality, and traceability of tissues for surgical use.

The internal Standards of Practice for tissue banks include documents that cover every aspect of this process. These standards cover topics including monitoring tissue recovery sites, the audit of tissue recovery partners, necessary body cooling protocols, microbiological surveillance programs, providing service to tissue donor families, prevention of contamination and cross-contamination at recovery, and many more.

However, the most relevant guide to understanding what makes a “good tissue bank” are the factors that govern “Good Tissue Practice,” defined by the steps that the FDA defines in the manufacturing of human allografts for surgical use: recovery, donor screening and testing, packaging, labeling, distribution, processing, and storage.1 Detailed guidelines for these areas of “Good Tissue Practice” have been developed by the national organization which audits and accredits participating US tissue banks.2

Recovery of Allografts

Recovery is the process of obtaining from a donor either cells or tissues that are intended for human use via implantation, transplantation, infusion, or transfer.1 It is the responsibility of the donor recovery agency to have a program in place that ensures donor information is received, investigated, evaluated, documented, and shared with all agencies that receive tissues from the donor to ensure donor suitability. There are specific SOPs in place to ensure that all recovery personnel are well trained and competent.

There are very specific steps that are taken by the donor recovery operation to control contamination and cross-contamination during retrieval. These steps include adherence to appropriate donor eligibility guidelines such as specific body cooling parameters and time limits for retrieval; ensuring a suitable location for recovery site activities; using clean techniques appropriate to the specific cells/tissues being recovered; cleaning, disinfecting, and sterilization of equipment, supplies, and instruments; monitoring recovery activities for microorganism contamination, such as by culture results; and sharing of all records related to donor eligibility determinations.

Donor Screening and Testing

The main step to prevent potential infectious diseases in the donor tissue supply is primary prevention, which comes from donor screening and testing, first in the form of the detailed medical-social interview (Donor Risk Assessment) of the donor and exhaustive review of their medical records and sexual history. There are multiple levels of review of every record, including by an independent medical doctor specializing in cytopathology. All tissues are also required to be tested by a range of FDA-licensed, cleared, or approved donor screening tests, as applicable by tissue type, such as for HIV, HBV, HCV, syphilis, HTLV, CMV, etc.3 Testing laboratories must also be registered as tissue establishments by the FDA, and are subject to the same rigorous oversight as tissue banks and procurement organizations.

Processing and Storage

Processing is defined by the FDA as “any activity performed on an HCT/P, other than recovery, donor screening, donor testing, storage, labeling, packaging, or distribution, such as testing for microorganisms, preparation, sterilization, steps to inactivate or remove adventitious agents, preservation for storage, and removal from storage.”4 Generally, processing includes cutting, grinding, shaping, culturing, enzymatic digestion, and decellularization of recovered tissues to make them suitable for surgical use.3 Processing must be conducted in a suitable clean room environment with appropriate environmental controls and monitoring.

Processing may also include a sterilization step such as gamma or e-beam radiation. Both are validated, controlled methods of improving allograft tissue safety. Most tissue banks employ a sterilization step in the face of infectious disease risks. To learn more about sterilization through radiation, see this post: Understanding Tissue Sterilization, Part 2: Radiation Round-up.”

Storage of allografts must be maintained at appropriate temperatures within each tissue’s tolerance limits. A temperature monitoring system must be in place to document storage temperatures and alert staff of deviations before straying outside of acceptable limits. Each unit of stored tissue should be packaged to facilitate sterile storage and prevent contamination or cross-contamination.

Packaging and Labeling

Packaging and shipping are not part of processing, and are therefore not required to be validated or verified in the same way as manufacturing. However, appropriate procedures must be in place to ensure the tissues are protected from contamination and cross-contamination, and that appropriate storage parameters are maintained during transport, particularly that temperature ranges are kept within acceptable limits.

Tissue labeling must make appropriate claims that are supported by verification and validation data to ensure that they are true and accurate. This could include information on sterilization procedures. Labeling also must include a method of internal donor identification, usually a lot-based identifying number on the label to allow for tracking and traceability of every tissue.

Distribution of Allografts

Strict regulations govern the transport and distribution of allografts, including an expiration date for their use. The expiration date is the maximum allowable storage period for the tissue, and expired tissues should not be transplanted. It is also critical to ensuring a safe allograft supply that the distribution of tissues be completely traceable from the original donor, to the retrieval agency, to the intermediary or processor, and on to any other tissue manufacturer or distributors to the ultimate end-user. The information that should travel with an allograft includes tissue ID numbers, tissue type, quantity, time of transport and delivery, recipient of delivery, and who transported and accepted tissues.

If you need help developing a tracking process for your surgical facility, there are resources available to guide you. In addition to the information above, a tissue tracking log should reflect the date of implantation and recipient of every graft. More information on tracking requirements can be found at the FDAs website .

 

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Tissue Banks: Standards and Accreditation

At present, there are about 167 tissue banks operating across the United States.1 Their role is vital to ensuring the quality, safety, and availability of allografts, as tissue banks are responsible for screening donors and preparing acceptable tissues for surgical use. While all tissue banks are expected to be registered with the FDA, there are no regulations for greater transparency and only limited federal standardization of policies and procedures.

Into this void of accountability stepped the American Assoc. of Tissue Banks. Established in 1976 by the same group of doctors and scientists who started the nation’s first tissue bank with the U.S. Navy, the association’s mission is “improving and saving lives by promoting the safety, quality and availability of donated human tissue.2

The association is responsible for establishing the highest level of modern day tissue bank operations and has created guidelines for standard practice. The areas covered by these guidelines include all tissue bank activities and operations from procurement to donor testing, from processing and sterilization to packaging. The association has helped quality tissue banks by crafting a framework to establish their own internal Standards of Practice (SOPs).

Only roughly 71% of tissue banks in the United States are actually accredited by the association. It is a voluntary process that requires a lengthy inspection and external review of the tissue bank’s policies and procedures. It is only those banks adhering to the high standards can achieve accreditation. Furthermore, this process must be repeated every three years during accreditation renewal to ensure that accredited tissue banks maintain those high standards of professional practice.

You can check if your tissue bank provider is accredited here and see which specific products and activities they are able to perform (e.g. acquisition, processing, storage, distribution).

Have you ever wondered what types of standards are for tissue procurement and processing? You can learn more about the Standards of Practice followed by America’s best tissue banks in our next blog post: What Makes a Tissue Bank “Good”?