Category: Apheresis

Includes therapeutic and donor apheresis

Plasma Project Considerations for Middle East

drzeyd

This is an update of a previous post.

I have been involved with planning for several plasma fractionation projects in the Middle East.

Many clients expressed the interest in using local plasma to make plasma derivatives (e.g. factor concentrates, intravenous gamma globulin, albumin), feeling that local plasma was safer than using imported plasma.  Some of these are in short supply in the world market so the only way to ensure their uninterrupted availability is to consider to manufacture them for local consumption.

Still, the major issue today is that it is difficult for any country in the region to collect enough plasma to make such a project feasible.  When I first considered such planning, we were looking for as much as 250,000 raw liters of plasma annually.  Since then, there are newer technologies that allow much smaller batches to be cost-effective.  Alternatively, one could charge higher prices for using smaller batches from local plasma.

Still, it is likely that plasma must be imported to sustain a plant.  There are different regulations for plasma donor qualification country-to-country.  Many of these jurisdictions may do less screening and testing than is done for normal blood and apheresis donors.  Other countries use their blood donors with the same requirement for both commercial plasma and blood donations.

In this era of emerging infectious diseases, I personally favor using the stringent blood donor criteria—same as routine collections.  It is not what we know, but the unknown pathogens that are potentially the most dangerous.

In addition to building a fractionation plant, one must train staff for this highly technical operation.  This may require developing a special curriculum to prepare students for these jobs.

To export the plasma to certain regions, one may have to use plasma quarantine.  In this protocol, plasma is held or quarantined until the next donation is collected and passes screening.  This requires a robust blood bank production software such as Medinfo to track serial donations.

There are other processes to consider:  how to develop a transport network to keep plasma frozen at minus 80C viable in a region that reaches very high ambient temperatures.

I would recommend a graded approach to develop such an industry.  First I would negotiate a plasma self-sufficiency arrangement.  We would collect local plasma in the country and export it to a manufacturing plant in another country and the derivatives would be returned to us.  This may require inspection by the accreditation agency of the processing country to allow importation of the raw plasma for manufacture.

Since it is unlikely any one country has enough plasma for manufacture, recruiting neighboring countries to participate in a manufacturing plant is important.  Technology for such a plant is complex so establishing a joint venture with one of the plasma industry companies is essential.  Some manufacturers are very keen to develop extra capacity since there is a world-wide shortage of plasma fractionation and are even willing to help obtain external plasma sources for such a plant.

Such a plant is an excellent way to develop local talent to run such a plant, including training of local staff to be the industrial engineers in the plasma fractionation process.  It would take approximately two years of training to prepare engineers on-site at a plasma fractionation site if they have studied the necessary science and mathematics subjects.

Such a program would take several years of planning and development.  Some of the major steps needed include:

  1. Acquiring software for a blood center with plasma brokering capabilities.
  2. Passing accreditations such as international AABB and CE for transfusion medicine to allow export of our plasma to the external manufacturing site in the initial plasma self-sufficiency phase
  3. Identifying extended sources of plasma to feed a manufacturing plant.
  4. Preparing a curriculum suitable for training as staff for the plant.
  5. Establishing a joint venture to share technology with a major plasma company to design, build, and operate a plasma fractionation plant.

Therapeutic Apheresis Process

drzeyd

This is an update of a previous post.

Principle:

All therapeutic apheresis procedures are potentially life-threatening and must only occur by an order from a transfusion medicine physician with experience/competence in such procedures.

Definitions:

  • Referring Physician is the clinical physician requesting a therapeutic apheresis procedure.
  • Transfusion Medicine Physician is a physician in the Transfusion Medicine Section with medical privileges for therapeutic apheresis procedures.  This includes the Head, Transfusion Medicine, consultants in Transfusion Medicine, and designated specialist physicians in Transfusion Medicine.  The final decision to accept/reject the patient is made by the transfusion medicine physician.
  • Covering Physician is the clinical physician designated by the referring physician to be physically present and covering the patient in case of any adverse reactions during a therapeutic apheresis procedure.
  • Apheresis Nurses are nurses in Transfusion Medicine who are designated by this section for performing therapeutic apheresis procedures.
  • Medical Privileges are determined by the Department of Pathology and Laboratory Medicine in conjunction with the medical staff medical privileging by the Hospital Medical Director.

Policy:

  1. The referral physician will discuss the request for a therapeutic apheresis with the designated transfusion medicine physician.  The referral physician must certify that the patient can tolerate the procedure based on his medical condition.
  2. The transfusion medicine physician will review the patient’s clinical and laboratory data, with special note of the history of allergies, medications, previous transfusion reactions, and current vital signs.
  3. Vascular access will be initially assessed by the apheresis nurse.  Any questionable situations will be reviewed by the transfusion medicine physician.
    1. It is the responsibility of the referring physician to provide vascular access.
  4. The following laboratory values (less than 24 hours old) must be available before the procedure may begin—additional tests also as per transfusion medicine physician:
    1. CBC including platelet count
    2. PT and APTT
    3. Fibrinogen
    4. Serum calcium
    5. Serum protein and albumin
    6. LDH for TTP cases
  5. A valid type and screen must have been done within the previous three (3) days of the procedure.
  6. Upon review of # 2 through 5, the transfusion medicine physician will determine if the procedure is indicated and will communicate this to the referral physician, who will sign written order in the patient chart.  Appropriate replacement fluids will also be mutually agreed upon in advance of the procedure and ordered by the transfusion medicine physician.  The order specification must include:
    1. Name of procedure and specification (e.g. therapeutic plasma exchange, isovolemic)
    2. Replacement fluid type and volume (e.g. 3 liters 5% albumin, 2 liters, FFP, cryoprecipitate, normal saline)
    3. Blood component orders if indicated (e.g. RBC exchange) and timing (before, during, and/or after the procedure)
    4. Calcium replacement (e.g. 2 grams calcium gluconate IV in 100 ml normal saline to run during the procedure)
    5. Any special laboratory testing post-procedure
  7. Use of a remote vital signs/oximeter/EKG device such as the Umana T1 should be considered in high-risk patients.
  8. The apheresis nurse takes orders ONLY from the responsible transfusion medicine physician.
    1. If the referring physician wants any other orders or changes, he must get the approval of the responsible transfusion medicine physician.  He does NOT give orders to the apheresis nurse
  9. The apheresis nurse will follow the orders of the necessary prescribed replacement fluids (FFP, albumin, PPF) in the quantities necessary for the exchange..
  10. The referring physician (not the apheresis nurse) will obtain the signed, informed consent from the patient.
  11. If vascular access is unsatisfactory, the referring physician will obtain the proper access (central line, AV shunt, etc.).
  12. The referring physician will arrange for a physician member of his team to be present at the actual therapeutic procedure.  This physician designate will be responsible to treat any complications arising from the procedure.
  13. Vital signs and weight will be obtained before starting the procedure.
  14. When approved by the Blood Bank Director or designate with proper venous access and informed consent, the apheresis may start the procedure in the presence of the patient’s covering physician.  The procedure will be performed in a designated hospital area.
  15. The procedure must be documented on the appropriate therapeutic apheresis order and procedure worksheets.

References:

  1. Standards for Blood Banks and Transfusion Services Current Edition, AABB, Bethesda, MD, USA
  2. CAP Standard TRM.42245 regarding therapeutic apheresis procedures

COVID-19 Donor Qualification

drzeyd

Principle:

This is the latest update on donor qualifications during the COVID-19 pandemic and addresses issues about COVID-19 vaccination, COVID convalescent plasma use and donation, return of donors into the donor pool after COVID-19 vaccination.  All of this information is subject to change as new regulations are released.

Policy:

  1. All donors must be in good health and meet all donor eligibility criteria at the time of the donation.
  2. Individuals diagnosed with COVID-19 or who are suspected of having COVID-19, and who had symptomatic disease, must refrain from donating blood for at least 14 days after complete resolution of symptoms.
  3. Individuals who had a positive diagnostic test for SARS-CoV-2 (e.g., a nasopharyngeal swab), but never developed symptoms, must refrain from donating at least 14 days after the date of the positive test result.
  4. Individuals who are tested and found positive for SARS-CoV-2 antibodies, but who did not have prior diagnostic testing and never developed symptoms, can donate without a waiting period and without performing a diagnostic test (e.g., a nasopharyngeal swab).
  5. Individuals who received a non-replicating, inactivated, or mRNA-based COVID-19 vaccine can donate blood without a waiting period.
  6. Individuals who received a live-attenuated viral COVID-19 vaccine, must refrain from donating blood for 14 days after receipt of the vaccine.
  7. Individuals who are uncertain about which COVID-19 vaccine was administered must refrain from donating for 14 days if it is possible that the individual received a live-attenuated viral vaccine.
  8. Individuals who received monoclonal antibodies should be deferred for three months from the last dose.
  9. Donors who have received blood components, including COVID-19 convalescent plasma are deferred for 3 months since the last transfusion.
  10. Recovered COVID-19 patients who are eligible to donate CCP and receive an approved COVID-19 vaccine may donate if they:
    1. Had symptoms of COVID-19 and a positive test result from an approved diagnostic test
    2. Received the COVID-19 vaccine after the diagnosis of COVID-19
    3. Are within 6 months after complete resolution of COVID-19 symptoms

References:

  1. Summary:  Donation of CCP, Blood Components, and HCT/Ps Following COVID-19 Vaccines or Treatment with CCP or Monoclonals, Updated 3/2/21, AABB, Bethesda, MD, USA
  2. Updated Information for Blood Establishments Regarding COVID-19 Pandemic and Blood Donation, US FDA, 19/1/21
  3. Toolkit for COVID-19 Convalescent Plasma (CCP) Under Emergency Use Authorization Issued 02 04 21 Revision 12/2/21, AABB, Bethesda, MD, USA

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.

Traceability of Processes in Transfusion Medicine using Medinfo Hematos IIG

drzeyd

Principle:

As part of good manufacturing process, we must trace everything in Transfusion Medicine, from registration through release of components.  The adoption of the Medinfo Hematos IIG computer system allows us to document anyone and everyone who “touches” the blood components and all processes.

Policy:

  1. Each staff member must use his/her personal log-in to sign into Medinfo Hematos IIG HIIG).  Each transaction is recorded with the User ID.
  2. Through the Medinfo Hematos IIG  computer system, we can trace:
    1. Each staff member who handled every step of every process.
    2. Which equipment was used in processing
    3. Which materials were used, including serial number of blood bags and selected reagents
    4. For each component, the donor is identified, including review of all test results, physical examinations, and questionnaire
    5. For each patient, all components received (from which each donor can be traced) and all testing results including transfusion reactions and any applicable protocols
    6. For each reagent lot numbers, expiration dates
    7. For each blood component, test results, serial numbers of blood, transfer, and pathogen-inactivation bags, dates and types of all modifications, including any changes in component outdates, disposition of unit (transfused, discarded, quarantined, etc.)
  3. Units can be quarantined based on each of the above parameters to block release to and/or usage at all blood transfusion services/hospital blood banks.
  4. Upon request of the Division Head, Transfusion Medicine/LIS, designated Transfusion Medicine and HIIG staff have access to trace any of the above.
  5. All traceability incidents will be reported as variances and documented according to standard procedures.

References:

  1. Workflow processes for Medinfo HIIG, Current Versions
  2. Standards for Blood Banks and Transfusion Services, Current Edition, AABB, Bethesda, MD, USA

COVID-19 Convalescent Plasma CCP Product Issue

drzeyd

This is the conclusion of a continuing series of posts on the actual Medinfo design of the CCP donation and release processes and covers the transfer of completed units to the hospital blood banks.  It highlights specific changes made for the parallel CCP system I developed at HMC Doha.

A blood component is either located at a production site, a destination hospital blood bank site, or in transit.  Here a quarantine production site is specified.  The actual release process is documented in this post.

In summary, with the exception of the donor marker testing and immunohematology testing, all other CCP processes are handled by special quarantine processes.  There are abbreviated marker testing specific for plasma and a special Predonation screening to minimize wastage of the expensive apheresis kits.