Red Blood Cell Immunization Programs - PowerPoint

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					Red Blood Cell Immunization
        Programs
       Judy Ellen Ciaraldi
      BS, MT(ASCP)SBB, CQA(ASQ)
           CBER, OBRR, DBA

                                  C B
          September 16, 2009
                                  E R
                           Outline
•   RBC Immunization Processes
    •   Source Plasma (donor and product)
    •   RBCs (donor and product)
    •   Immunogen RBC qualification and preparation
    •   RBC immunization procedures
•   Considerations on how to submit for a RBC
    immunization program
•   CBER review of RBC immunization programs

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                                                      2   E R
               Source Plasma Donor

   Must meet all donor suitability criteria in
    640.63, 640.65, and 610.40
    –   Physical examination within 1 week before first
        immunization (640.63(b)(2)) unless active donor
   Should not have child-bearing capability
    –   Male
    –   Female who is post-menopausal or surgically sterile
   Tested for RBC antigen profile
    –   D, C, E, c, e, K, Fya, others as needed

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                                                              3   E R
               Source Plasma Donor
                               (cont.)
   If donors elicit no response (no antibodies
    develop), they can return to normal Source
    Plasma donor pool if they meet normal donor
    suitability criteria
    –   Deferred for 12 months after last injection (640.63(c)(13))
        unless…
    –   Documented proof that only qualified cells were injected
    –   Request for an alternative procedure under 640.120 to
        donate in less than 12 months has been approved


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                                                               4   E R
             Source Plasma Product
•   Contains high titer of RBC antibody
•   Made into injectable and noninjectable
    products
•   Must meet standards for normal Source
    Plasma
    •   640.64 & 640.69 – Collection and storage
    •   640.70 & 640.76 – Storage and shipping temps; labeling
    •   610.40 – Infectious disease testing
•   Label must state the immunizing antigen or
    specific antibody present (640.70(a)(7))
                                                                 C B
                                                            5    E R
              Donors of Immunogen
                Red Blood Cells
   Must meet all Whole Blood donor suitability
    criteria (640.3 and 610.40)
   Must not have been transfused within previous
    12 months (640.3(c)(3))
   Should be available for infectious disease
    testing for the qualification process
   May also be a Source Plasma donor
    –   Track RBC and plasma volumes donated or lost
    –   Track donation intervals
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                                                       6   E R
             Whole Blood Collection
   Procedures must be consistent with 640.4
   Volumes and frequency must not exceed those
    for routine Whole Blood donations (640.3)
   If implementing Whole Blood collection in
    Source Plasma center, report to FDA as
    follows:
    –   PAS – Using new SOPs for donor selection and collection
    –   AR – Using previously approved SOPs
    –   Blood establishment registration form updated to include
        Whole Blood collection
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                                                           7   E R
        Whole Blood/Red Blood Cells
•   Must meet standards for Whole Blood
    •   600.15, 610.53, 640.5 – Storage and shipping temps,
        processing
    •   610.40 – Infectious disease testing
•   With FDA approval, may ship to lab before testing
    completed (610.40(g))
    •   Label unit with tests completed and pending (606.121(h))
•   These blood components need not be licensed if
    collected as part of approved RBC immunization
    program
    •   Label contains applicant name, address, collection facility
        registration number (606.121.(c))
    •   No license number on Whole Blood/Red Blood Cells         C B
                                                              8   E R
        Whole Blood/Red Blood Cells
                               (cont.)
   Tested for RBC antigen profile
    –   D, C, E, c, e, K, Fya, others as needed
   Storage:
    –   Liquid – 1-6 C (shelf life determined by anticoagulant)
    –   Frozen - -65 C or colder for up to 10 years
    –   Deglycerolized – 1-6 C for approved shelf life based on
        sterility data




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                                                             9    E R
              Immunogen RBC
              Qualifying Process
   Test new RBC donors for all infectious diseases in
    610.40
   If negative, freeze RBC for 12 months
   After 12 months, retest RBC donor
   If negative, inject deglycerolized RBCs into no more
    than 3 acceptable Source Plasma donors
   Test Source Plasma donors for infectious diseases at
    3, 6, 9 and 12 months after immunization
   If Source Plasma (SP) donors are negative, RBCs are
    qualified to be used to immunize other SP donors
                                                       C B
                                                  10   E R
NEW RBC DONORS
 Test potential donor for all
infectious disease markers
                NR
  Collect RBCs and store
   frozen for 12 months


 Test donor and intended
 recipients for all markers
                NR
     Immunize up to 3
       Recipients

Test recipients at 3, 6, 9, 12
  months for all markers
                NR
 Frozen cells qualified for
  routine use – Donor is
       “pedigreed”                    C B
                                 11   E R
QUALIFIED (PEDIGREED) RBC DONORS

       Test donor for all infectious
             disease markers

                      NR

         Collect RBCs and store
          frozen for 12 months



            Retest donor for all
        infectious disease markers

                      NR

         Frozen Red Blood Cells
         qualified for routine use




                                            C B
                                       12   E R
    Preparation of Immunogen RBCs
   RBCs glycerolized and frozen
   RBCs thawed and deglycerolized
   Sterility testing done on 1 sample from each lot
   Aseptically aliquoted into sterile, pyrogen-free
    single-dose labeled vials
   Shipped to Source Plasma donor; visually
    inspected
   RBCs drawn into syringe
                                                   C B
                                              13   E R
         RBC Immunization Procedure
   De Novo (donors who do not have pre-existing RBC
    antibodies) immunization only allowed for anti-D
     –   Maximum 50 mL in 4 month period
     –   Donor not responding after 150 mL should be dropped
   Re-stimulation (boost) of pre-existing antibody
     –   Maximum of 4 mL up to 5 times/month
     –   Not to exceed 40 mL in 6 month period
   Immunization only done with qualified RBCs
   May immunize on same day as plasmapheresis, but
    only after plasmapheresis procedure
   Physician (or trained individual) can do injections
                                                               C B
                                                          14   E R
         Submitting RBC Immunization
                   Programs
   RBC immunization programs have been
    approved by CBER
    –   PAS supplement
    –   Pre-approval inspections
   RBC immunization programs are “site-
    specific” approvals
   Contractual arrangements are possible
    –   Perform injections
    –   Collect plasma
    –   Supply Whole Blood and/or immunogen RBCs
                                                        C B
                                                   15   E R
            Submission Content
   Forms: 356h and 2567
   Applicant name and license number
   Contact name and information
   Facility name, address and registration number
   Contractor information
   Medical oversight


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                                            16   E R
          Submission Content (cont.)
   Informed consent form (640.61 & 640.72(a)(3))
   RBC immunization program SOPs
   Immunization records for 5 donors
   Sterility data for 10 lots
    –   Support deglycerolized RBC expiration date
   Labels
   May reference previously approved SOPs,
    forms, labels
    –   Include approved reference number
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                                                     17   E R
              Contractor Information
   Name and license number
   Address and registration number
   List of activities done under contract
   Where records are maintained
   Describe quality oversight of contractor
   Contract manufacturers must be registered
    and licensed in many cases
    –   Exception: Sterility testing lab exempt from registration
                                                                    C B
                                                              18    E R
           Medical Supervision of
         RBC Immunization Program
   Physician must: (640.66)
    –   Certify the donor’s health to participate
    –   Administer the informed consent
    –   Approve injection schedule
    –   Select the antigen to be injected
    –   Evaluate clinical response (including monitoring reactions)
   Physician must be on premises during RBC
    immunization (640.62)
   Keep donor at center after immunization to
    observe for immediate reactions
                                                                 C B
                                                            19   E R
                  Informed Consent
   Volume, route and schedule of injections
   Criteria for discontinuation from program
   Participate in only one immunization program
    at a time
   May not be eligible for other donation
    programs
   Possible adverse reactions
    –   May develop unexpected antibodies that cause delays in
        obtaining compatible blood for transfusions
   Restrictions for female participants                       C B
                                                          20   E R
                               SOPs
   Immunization procedures must be on file at
    centers where immunizations are performed
    (640.66)
   Medical oversight, responsibilities
   Evaluation of clinical responses and adverse
    reactions
   Whole Blood and Source Plasma donor
    selection procedures and testing
    –   Criteria for participation in and discontinuation from
        program                                                       C B
                                                                 21   E R
                       SOPs (cont.)
   Whole Blood collection and preparation of
    immunogen RBCs
    –   Immunogen RBC qualification
    –   Sterility testing
    –   Aliquoting
    –   Quality control procedures
    –   Freezing and deglycerolizing
   Transport/ship immunogen RBCs to Source
    Plasma donor
                                                 C B
                                            22   E R
                       SOPs (cont.)
   Evaluation of immunogen RBCs received from
    supplier
   Immunization procedures
    –   Physician approval
    –   Preparation of injection
    –   Injection volume and schedule, administration route
    –   When titrations will be performed
    –   Handling and storing of vials (1-6 C)
   Monitor for unexpected antibodies (e.g.,
    additional antibodies)
   Proper documentation procedures                                C B
                                                              23   E R
             Immunization Records
   Donor name, ID number
   Injection preparation – date, employee name,
    visual inspection
   Injection – date, employee name, route, volume
   Immunogen RBCs – lot number, expiration
    date
   Physician approval
    –   Selection of immunogen RBCs
    –   Injection – date and volume
                                                 C B
                                            24   E R
         Immunization Records (cont.)
   Adverse reactions (640.72(d))
   Antibody name, test results and titers
    –   Unexpected antibodies (e.g., additional antibodies)
   ABO group, Rh type and RBC phenotyping




                                                                   C B
                                                              25   E R
Other Records (606.160 & 640.72)
   Whole Blood and Source Plasma donor
    selection and testing
   Informed consent for immunization (640.61,
    640.72(a)(3))
   Freezing and deglycerolizing, including quality
    control tests
   Ongoing sterility test results
   Trace immunogen RBCs to Whole Blood donor
                                                  C B
                                             26   E R
                Other Records (cont.)
   Storage and shipping temperatures
   Collection procedures
    –   Volume
    –   RBC loss
    –   Donation reactions
   Immunogen RBC qualification procedures
   Evidence of review done to identify and correct
    deficiencies (606.100(c))

                                                  C B
                                             27   E R
               CBER Review of
          RBC Immunization Programs
   Based on desk review and inspection
   Donor selection consistent with applicable
    regulations and guidance documents
   SOPs include all critical procedures
    –   Medical oversight
   Informed consent includes recommendations
    in guidance document
   Forms contain all information and show
    evidence of QA review
                                                  C B
                                             28   E R
           CBER Review of
    RBC Immunization Programs (cont.)
   All facilities (including contractors) are FDA
    registered and licensed when required, and
    have acceptable compliance checks
   Labels consistent with 640.70
    –   Include immunizing antigen
   Pre-approval inspection scheduled after desk
    review
    –   Observe operations are consistent with SOPs and
        regulations
    –   Observe all procedures requested in submission
                                                               C B
                                                          29   E R
                          References
   Blood memorandum: Revised Recommendations for
    Red Blood Cells Immunization Programs for Source
    Plasma Donors (3/14/95)
    –   http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianc
        eRegulatoryInformation/OtherRecommendationsforManufacturer
        s/MemorandumtoBloodEstablishments/default.htm
   Guidelines for Immunization of Source Plasma
    (Human) Donors with Blood Substances (6/80)
    –   http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianc
        eRegulatoryInformation/Guidances/Blood/default.htm

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                                                          30   E R
                  References (cont.)
   Guidance for Industry: Informed Consent
    Recommendations for Source Plasma Donors
    Participating in Plasmapheresis and Immunization
    Programs (8/8/07)
    –   http://www.fda.gov/BiologicsBloodVaccines/GuidanceComp
        lianceRegulatoryInformation/Guidances/Blood/ucm073433.h
        tm




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