Tag: Donor Marker Testing

Any or all test methodologies

Operational Effects of the COVID Pandemic–My Experience in Qatar

drzeyd

The COVID-19 pandemic imposed new challenges to our system.  In general, these could be divided into:

  1. Decreased donors
  2. COVID vaccine effects
  3. Decreased available staff
  4. Shortages of supplies
  5. More demands on donor apheresis staff—CCP
  6. More demands on donor processing staff—CCP
  7. More demands on hospital transfusion service/blood bank staff—CCP

There were fewer donors in the early phase and the nurses also had to add a large number of donor plasmapheresis collections for COVID convalescent plasma CCP.  Still they had to maintain all donor and therapeutic apheresis services with no increase in staff.  Although elective procedures had been cancelled, there were still obstetrical, oncologic, and trauma services in full action.

Many of our staff were on leave when the borders were closed.  Some had to wait months before they could return to work.  Others had COVID-19 infection and were quarantined for several weeks.  This further reduced staffing.  We could not just hire outside staff since considerable training is involved in these processes.

I dedicated a separate donor collection space for the CCP program away from the regular donors as well as a quarantine processing area.  Similarly, the CCP plasma was kept segregated from the regular plasma supply and a specially designed location was identified for release of this product.  Working for this program diverted resources from blood collection to this special project, again without increasing resources.

With disruptions to shipments of supplies, including the Reveos whole blood kits and Trima donor apheresis sets, we had to rely on our large in-home inventory until the situation stabilized.  We prescreened the CCP donor candidates before we would collect them to avoid wastage of kits.

Fortunately, our throughput was minimally affected because our equipment and processes had always stressed speed.  We used single-well NAT testing to minimize the need of additional runs.  Also, we used Reveos automated component processing to greatly speed production (one Reveos can process four whole blood units in about 23 minutes or about 12 units in 75 minutes.)  One technologist could operate all 4 of our machines simultaneously and perform other tasks while the machines were working.

In the system I developed in Qatar, we could complete processing into components (RBCs, buffy coat platelet pools, leukodepleted plasma), all marker and immunohematology testing, leukoreduction of the pools and RBCs, Mirasol pathogen inactivation, and platelet additive solution in as little as five hours.

In rapid turn-around events, it is most helpful to have a robust blood bank computer system that can scale to the challenge.  Also, it must mercilessly enforce all the rules starting with donor qualification, screening, collection through testing and production.  At times of emergency, it is difficult to meet Good Manufacturing Processes manually.

I had built parallel separate donor collection, donor processing, and transfusion service/hospital blood bank processes specifically for CCP and had to staff them with available personnel, limited our capability to process regular donors.  The blood bank computer software restricted CCP use to designated physicians and transfusing locations.  For those interested, there is a separate series of posts about the CCP project and its implementation in the dedicated blood bank Medinfo HIIG.

COVID-19 vaccinations should have minimal effect in donor qualification since mRNA or antigen-based ones do not cause donor deferral.  Live attenuated COVID vaccines will defer donors for 2 weeks by current rules—the same as other live vaccines.  Donors who had previously received CCP will be deferred for three (3) months after last receiving this product.

In summary, the COVID pandemic reduced staffing and affected donor recruitment.  We had production mitigations to maximize throughput.  The system was stressed by the reduced staffing and special demands to produce CCP.  However, the extent of our automation allowed us to maintain throughput throughout the crisis.

Teaching Document: Validation Process

drzeyd

This is a teaching document for medical technology and transfusion fellows to explain the general structure of a validation.

Principle:

All validations must be planned.  A validation protocol must be prepared with specific criteria for acceptance.  All validations with attached evidence must approved by the Head, Transfusion Medicine.

Policy:

  1. A written validation protocol must be prepared in the advance and at least including the following:
    1. Specific parameters and number of iterations to be performed
    1. Designated staff to perform validation
    1. Documentary evidence of the testing
    1. Specific acceptability criteria
  2. The completed validation protocol must be submitted to the Division Head, Transfusion Medicine, or designee for review.
  3. Once the validation plan has been reviewed, it must be performed by the designated staff.
    1. Software validations will be performed in a specific test environment, not in the live, production system.
  4. The completed validation document, including screenshots of the software functionality if applicable, must be submitted to the Division Head, Transfusion Medicine for review.
  5. The equipment or software may only be used if the acceptability are met AND the validation is approved by the Division Head, Transfusion Medicine or designee.
  6. The completed validation protocol will be stored in the document control system.

Reference:

Standards for Blood Banks and Transfusion Services, Current Edition, Bethesda, MD, USA

COVID-19 Convalescent Plasma CCP Thawing and Marker Testing

drzeyd

This is a part of a continuing series of posts on the actual Medinfo design of the CCP donation and release processes and covers CCP plasma thawing/labelling and donor marker testing.  It highlights specific changes made for the parallel CCP system.

Thus, the machine interfaces for testing are the same as for regular testing and are not included in this document. Likewise, donor immunohematology testing is the same as for regular donors and is not addressed here

Syphilis and Gonorrhea Donor Deferrals

drzeyd

Principle:

Syphilis, caused by the spirochete Treponema pallidum (T. pallidum), is most often acquired after sexual contact with an infected individual.  Syphilis can also be transmitted from mother to child or, rarely, transmitted by transfusion of blood or blood components from donors with active syphilis.

There are two different types of serologic assays for syphilis:  nontreponemal assays and treponemal assays:

Nontreponemal assays (e.g. VDRL, RPR, ART) are nonspecific and detect “reagin” antibodies directed against an antigen called cardiolipin that is present in a variety of tissues.  Antibodies to cardiolipin appear in the serum of persons with active syphilis or with other medical conditions. However, some individuals who were previously infected with syphilis but successfully treated maintain low levels of antibody to cardiolipin for a long time.

Treponemal assays include enzyme immunoassays (EIA), fluorescent treponemal antibody “absorbed” assays (FTA-ABS), Treponema pallidum microhemagglutination assays (MHA-TPA) and Treponema pallidum particle agglutination assays (TP-PA).  Treponemal assays test for antibodies to antigens that are specific to treponemes.  Treponemal assays are most useful in identifying recent and past syphilis infections.  They are not generally useful in monitoring the response to antibiotic therapy.  With some exceptions, positive results of tests for specific treponemal antibodies remain positive throughout an individual’s life regardless of whether the individual is currently infected or has been cured following successful treatment.  Retesting sera that are reactive in nontreponemal assays using a specific treponemal test is valuable in distinguishing true-positive results that indicate active syphilis infection from biological false-positive results due to other conditions.

Current testing requirements for syphilis are found in 21 CFR 610.40(a)(2).  Individuals who test reactive with a screening test for syphilis must be deferred (21 CFR 610.41(a)) and notified of their deferral (21 CFR 630.40).  You must further test each donation found to be reactive by a donor screening test, except you are not required to perform further testing of a donation found to be reactive by a treponemal screening test for syphilis

Policy:

  1. Assess donors for a history of syphilis or gonorrhea or treatment for syphilis or gonorrhea in the past 3 months.
  2. Defer for 3 months after completion of treatment, an individual with a history of syphilis or gonorrhea or treatment for syphilis or gonorrhea in the past 3 months.
  3. After this 3-month period, the individual may be eligible to donate provided the individual meets all donor eligibility criteria.
  4. Testing and Management if a nontreponemal assay is used to screen for syphilis:
    1. If the nontreponemal screening test is nonreactive, the donor is considered to be negative for syphilis infection.  You may use the donation, provided it meets all other donation suitability requirements
    2. If the nontreponemal screening test is reactive, you must defer the donor indefinitely unless evaluated for reentry.
    3. Reentry from reactive nontreponemal test:
      1. Perform testing using a treponemal assay:
        1. If treponemal assay is negative, then reenter donor.
        2. If treponemal assay is positive, consider as an indefinite deferral.
      2. You may reenter the donor if the donor subsequently reports being treated for syphilis, provided that the treatment was successful and completed at least 3 months before the next donation; and the donor meets all donor eligibility criteria.
      3. Alternatively, the donor may be reentered without treatment if your responsible physician determines that the donor never had syphilis based on subsequent medical evaluation and diagnostic testing for syphilis (i.e., the screening results were falsely positive), and the donor meets all donor eligibility criteria.
      4. You may use either an FDA-cleared nontreponemal screening test or an FDA-cleared treponemal screening test to test the reentered donor’s subsequent donations.
      5. The donor remains indefinitely deferred if the donor was not treated for syphilis or was not medically evaluated for reentry.
  5. Testing and Management if a treponemal assay is used to screen for syphilis:
    1. If the treponemal screening test is nonreactive, the donor is considered to be negative for syphilis infection and you may release the donation, provided it meets all donation suitability requirements, and retain the donor.
    2. If the treponemal screening test is reactive, further testing is not required, and you must defer the donor indefinitely unless evaluated for reentry.
    3. Reentry if a reactive treponemal assay is used to screen for syphilis:
      1. Perform another treponemal screening test that is different from the initial treponemal screening test used.
      2. If negative, reenter the donor.
      3. If positive, defer the donor indefinitely unless the following applies:
        1. Test the sample from the donor which was positive on the additional treponemal screening test using a nontreponemal screening test to assess whether the donor has an active infection.
          1. If the nontreponemal screening test result is negative, the results are consistent with recovery or cure from a previous syphilis infection.
          2.  If the nontreponemal screening test is positive, the results are consistent with an active or recently treated syphilis infection.
          3. In either case, you may reenter the donor if the donor subsequently reports being treated for syphilis, provided the treatment was successful and completed at least 3 months before the next donation; and the donor meets all donor eligibility criteria.
        2. Alternatively, the donor may be reentered if your responsible physician determines that the donor never had syphilis based on subsequent medical evaluation and diagnostic testing for syphilis (i.e., previous test results were falsely positive), and the donor meets all donor eligibility criteria.
        3. You may use either a nontreponemal screening test or a treponemal screening test that has been cleared by FDA for such intended use to test the reentered donor’s subsequent donations.
        4. The donor remains indefinitely deferred if the donor was not treated for syphilis or was not medically evaluated for reentry.

Reference:

Recommendations for Screening, Testing and Management of Blood Donors and Blood and Blood Components Based on Screening Tests for Syphilis—Guidance for Industry,  U.S. Department of Health and Human Services Food and Drug Administration Center for Biologics Evaluation and Research CBER,  December, 2020

New US CBER Guidance for Syphilis and Gonorrhea: December 2020

drzeyd

This is non-binding CBER guidance is a complicated algorithm that involves using treponemal and non-treponemal assays.  Re-entry pathway options are also provided.  I will be posting a summary and its implementation into my previous donor marker testing algorithms. Please see attached PDF link.

Click to access screening-tests-for-syphilis_december_2020.pdf

CBER Guidance Syphilis and Gonorrhea, December 2020

Logistics and Processes for a COVID-19 Convalescent Plasma Program

drzeyd

I prepared the following plan for a CCP program for HMC Qatar in March, 2020.  The workflow is divided into four (4) modules:

  1. Registration/Interview/Physical Examination/Apheresis Collection
  2. Donor Marker Testing and Immunohematology Testing
  3. Production/Aliquoting/Pathogen-Inactivation/Storage
  4. Product Thawing/Product Release

Module 1:

  1. Collection/registration/screening must be in a separate area from regular blood and apheresis donations.
  2. Donors must provide consent.
  3. ISBT specimen labels must be used on each tube collected.
  4. We need a minimum of two apheresis nurses, one for the registration/screening/post-donation observation and one for the actual apheresis procedure.
  5. If there will be multiple serial donors, then we need a waiting area (each donor at least 2 meters apart).
  6. Donor screening must be in sound-proof area so that other waiting donors cannot hear the interview/questionnaire process.
  7. Amount that can be collected depends on body weight:  500 ml for <80 kg and 600 ml for >= 80 kg, collection may occur twice per week
  8. Collection time includes 15 minutes for registration/interview/physical examination, 60-75 minutes and 15 minutes for cleanup/disinfection before the next case, approximately 2 hours per donation.
  9. A post-donation observation area (minimum 15 minutes after collection) with apheresis nurse nearby in case of reactions is needed if there will be multiple donors.
  10. Specimens will

Module 2:

  1. Donor testing and donor immunohematology will be done with other donor specimens in our regular location

Module 3:

  1. Apheresis collection must be processed and stored separately from regular blood/apheresis donations.
  2. Processing will occur only after the results are shown to meet all criteria.
  3. Pre-collection testing (test-only donation) would permit processing without waiting for results.
  4. Storage at minus 80C may be for a minimum of six (6) years but this may be extended if needed.
  5. All acceptable components will have a final ISBT label—no products without the ISBT label will be transfused.  The ISBT label indicates that the unit meets all donor criteria for convalescent plasma.

Module 4:

  1. Product modification (thawing) and release (sign out from blood bank) must be in a separate area(s) from the regular hospital blood bank.
  2. Release of convalescent plasma follows the same process as regular component release
  3. Transfusion of convalescent plasma at the patient’s bedside follows same process as regular component transfusion
  4. Nursing and other staff performing the transfusion must pass competency assessment.
  5. Plasma will be transfused as ABO-identical or compatible unless low ABO-titer group A is used.
  6. Plasma must be free of clinically significant antibodies

Workflow Considerations:

  1. Donors must be restricted to the waiting, collection, or post-donation observation areas.
  2. Donors must NOT pass through production, testing, or component release areas (just as they are currently restricted in the Blood Donor Center and HMC hospital blood banks/transfusion services).

Logistics:

  1. Throughput is a maximum of 4 donors (2000 to 2400 ml plasma) per eight-hour shift with one apheresis nurse and one donor apheresis (Trima) machine.
  2. The processes are scalable with additional staff and machines (e.g. with 3 machines and nurses, then 12 donors and 6000 to 7200 ml of plasma collected).
  3. Thawing of 1-2 units of plasma takes up to one hour.  Contact the quarantine blood bank at least one hour before the desired pick-up time.
  4. The four modules above can be in separate areas not adjacent to one another.  Modules 1, 3, and 4 must be quarantine areas where access is limited.  Module 2 can be performed with regular donor specimens using standard precautions.
  5. We can provide training for transfusion of blood components and competency assessment to any location transfusing this product.

Information Technology:

  1. All modules will be connected to the Medinfo Hematos IIG dedicated blood bank computer system.
  2. All records of collection/production/testing/storage/modification/release will be stored therein.
  3. All ordering of convalescent plasma components will be through Medinfo.
  4. External test results (e.g. future antibody titering) can be added to the component information.
  5. Links to the Hospital Information System (Cerner) may be considered after the Medinfo processes are fully functional.