Hot Topics New Blood and Plasma Issues

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Hot TopicsNew Blood and Plasma Issues

• Barbara Carmichael
• Investigator, U.S. Food Drug Administration
• Florida District - Jacksonville, FL Resident Post
• June 2, 2011

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Lecture Outline

• Clarification of various issues
• Top 10 Biologics Observations
• New Guidance Documents
• NAT Reentry (May 2010)
• Anti-HBc Reentry (May 2010)
• HCV Lookback (December 2010)
• Leukocyte Reduction, Draft ( January 2011)
• CJD/vCJD (May 2010)
• Chagas (December 2010)
• Operations (November 2010)

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Storage of Thawed FFP or PF24 up to 24 hrs -
Requesting a Variance

• Storage of thawed FFP or PF24 _at_ 1-6C for up to
  24 hrs as recommended by BPAC, instead of 6
  hours (21 CFR 606.122 (m)(3)). Until the
  regulation is revised a variance must be
  requested.
• Written request to
• Director, Div. Blood Applications,
  OBRR/CBER/FDA/HFM-370
• c/o Document control Center/HFM-99
• 1401 Rockville Pike, Suite 200N
• Rockville, MD 20852-1448
• Phone no. [phone]

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MTS Gel Card - Off Label Use

• MTS Anti-IgG Card - states it is for direct and
  indirect antiglobulin test
• MTS Buffered Gel Card states it is for detection
  of antibodies to RBCs
• Neither product includes labeling/directions for
  use as an immediate spin compatibility test
• The card is not a reliable detector of ABO
  incompatibilities (which are predominantly IgM)
  published studies document reported compatibility
  test failures
• Discrepancy between AABB Manual device labeling
• Cannot be used as sole cross-match until Ortho
  submits data for BLA supplement approval and
  labeling change will result in 483 citation

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Overlay Label?

• Can we overlay a Codabar label with an ISBT
  label?
• Can we overlay the whole label when we further
  process one of our units (e.g., irradiate)?
• Can we overlay the whole label when we further
  process a unit from an outside supplier?

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Overlay Label?FDA Response

• We believe it is acceptable to overlay an
  original label provided the current computer
  software or recordkeeping system has the
  capability to preserve the information on the
  original label. If the software or records
  cannot record the information from the original
  label, then overlaying the whole label is not
  permitted.
• Original information includes collection
  facility, ABO/Rh, special antigen typings,
  anticoagulants, etc.

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Top 10 Biologics Observations in 2010 As of
05/31/2011

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Citation 1 Cited 127 times /ID 76

• Written SOPs Not Maintained or Followed or
  Accessible
• 21 CFR 606.100(b) Written standard operating
  procedures including all steps to be followed in
  the collection processing compatibility
  testing storage distribution of blood and
  blood components for homologous transfusion
  autologous transfusion further manufacturing
  purposes are not always maintained followed
  maintained on the premises.

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Citation 2 Cited 49 times /ID 98

• Investigations Not Conducted or Completed
• 21 CFR 606.100(c) Failure to perform a
  thorough
• investigation make a record of the conclusions
  and
• follow-up of an unexplained discrepancy a
  failure of a
• lot or unit to meet any of its specifications.

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Citation 3 Cited 29 times /ID 155

• Failure to Maintain Records
• 21 CFR 606.160(b) Failure to maintain donor
• processing storage and distribution
• compatibility testing quality control
  general
• Records.

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Citation 4 Cited 29 times /ID 9225

• BPD Reporting
• 21 CFR 606.171 Failure to submit a biological
• product deviation report within 45 days from the
• date you acquired information suggesting that a
• reportable event occurred.

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Citation 5 Cited 29 times /ID 154

• Records Not Concurrent with Performance
• 21 CFR 606.160(a)(1) Records are not
  concurrently
• maintained with the performance of each
  significant step
• in the collection processing compatibility
  testing
• storage distribution of each unit of blood
  and blood
• components so that all steps can be clearly
  traced.

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Citation 6 Cited 28 times /ID 160

• Records Fail to Provide Complete History
• 21 CFR 606.160(a)(1) Records fail to identify
  the
• person performing the work include dates of the
• various entries show test results include
  interpretation
• of the results show the expiration date
  assigned to
• specific products be as detailed as necessary
  so as to
• provide a complete history of the work performed.

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Citation 7 Cited 21 times /ID 31

• Personnel/Training
• 21 CFR 606.20(b) The personnel responsible for
  the collection
• processing compatibility testing storage
  distribution of
• blood or blood components are not adequate in
  number
• educational background training and
  experience, including
• professional training as necessary to assure
  competent
• performance of their assigned functions, and to
  ensure that the
• final product has the safety, purity, potency,
  identity and
• effectiveness it purports or is represented to
  possess.

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Citation 8 Cited 14 times /ID 4425

• Equipment Not Maintained
• 21 CFR 606.60(a) Equipment used in the
  collection
• processing compatibility testing storage and
• distribution of blood and blood components is
  not
• observed standardized calibrated on a
  regularly
• scheduled basis as prescribed in the SOP Manual.

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Citation 9 Cited 13 times /ID 12202

• Thorough Investigation of Adverse Reaction
• 21 CFR 606.170(a)
• A thorough investigation of each reported
  adverse report was not made.
• This citation is new to the Top 10 this year
  while Records are Illegible fell off the Top 10
  list this year.

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Citation 10 Cited 12 times /ID 67

• Supplies Reagents
• 21 CFR 606.65(e) Failure to use supplies and
• reagents in a manner consistent with instructions
• provided by the manufacturer.

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New Guidance Documents
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NAT HIV-1 HCV Reentry

• May 2010 Guidance (finalizes draft dated July
  2005)
• 4 new simplified algorithms for reentry
• Retests - should use the same test as that used
  for the original reactive sample if not
  available use one of same or greater sensitivity
  (e.g. HIV-1 Group O)
• SOP Revisions will be considered minor change
  to an approved license so date of SOP
  implementation should be reported in Annual
  Report

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• HIV-1 Donor Re-entry Algorithm

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HCV Donor Re-entry Algorithm
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Anti-HBc Reentry if tested RR on gt1 occasion

• May 2010 Guidance finalizes draft from 2008.
• Change due to availability of FDA-licensed HBV
  NAT improved specificity of anti-HBc assays
• Obtain a new pre-donation blood sample after a
  minimum of 8 wks following last RR anti-HBc test
• Must be Neg. for HBsAg, anti-HBc AND HBV by NAT
• If f/u medical testing done during this 8 week
  period, any reactive/positive results would make
  the donor NOT eligible for reentry and indefinite
  deferral is recommended.
• If implement this method then report in Annual
  Report. If want to use an alternate method,
  licensed establishments must submit a supplement
  for prior approval

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Lookback for HCV Guidance was updated December
2010 orig. 2007

• Reflects new anti-HCV testing technologies
• Changes to make guidance consistent with regs,
  e.g.
• 21 CFR 610.48 - One time review of historical HCV
  testing records, requires completion of actions
  specified by 2/19/09
• Asked to go back to Jan 1988, but are aware that
  prior to implementation the requirement for
  record retention was 5 years
• notification by the transfusion service was
  expanded to include a recipients physician of
  record within the specified time frame 3 days
  after becoming aware of test results

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Pre-Storage Leukoreduction

• Draft Guidance January 2011 (replacing 2001
  draft)
• Recommendations for validation and QC for
  monitoring the process, including an algorithm
  for sample size calculation
• Testing of donors for traits that affect the
  process, such as hemoglobin S
• Use of mixing devices during collection
• Option for supplemental labeling of components
  with low WBC count
• Calculation of RBC recovery by RBC mass

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CJD/vCJD

• Guidance for Industry
• Revised Preventative Measures to Reduce the
  Possible Risk of Transmission of
  Creutzfeldt-Jakob Disease (CJD) and Variant
  Creutzfeldt-Jakob Disease (vCJD) by Blood and
  Blood Products
• May 2010
• (Implement by January 2011)

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CJD/vCJD (cont.)

• No changes in CJD deferral policies
• Blood and plasma donors who have received a blood
  component transfusion in France since 1980 are
  deferred indefinitely for vCJD risk
• Recognized the AABB full-length DHQ materials
  (v.1.3) as an acceptable mechanism to screen
  blood donors
• DHQ contains transfusion in France question
• Guidance advises licensed firms how to report if
  using AABB DHQ (v.1.3)

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Chagas

• Guidance for Industry
• Use of Serological Tests to Reduce the Risk of
  Transmission of Trypanosoma cruzi Infection in
  Whole Blood and Blood Components Intended for
  Transfusion
• December 2010
• (Implement by December 2011)

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Chagas (cont.)

• Only applies to blood components for transfusion
  (not to Source Plasma)
• Includes question to ask all donors at each
  donation if they ever had Chagas disease
• Recommends one-time (selective) testing of
  allogeneic donors and autologous donors whose
  units will be crossed over
• Nonreactive donors do not need to be tested again
  at subsequent donations
• Blood banks should have records for testing
  history
• Reactive donors or donors with history of Chagas
  are indefinitely deferred

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Chagas (cont.)

• No donor re-entry at this time
• Disposition of reactive units
• Destroy reactive donations
• Can be used for research or plasma used for
  noninjectable reagents
• Autologous use only
• Lookback of units from reactive donor
• Statement in Circular that blood is from donors
  tested for T. cruzi on at least one donation
• Advises licensed firms on how to report changes
  to FDA

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Operational Procedures

• Guidance for Industry
• Recommendations for Blood Establishments
  Training of Back-up Personnel, Assessment of
  Blood Donor Suitability and Reporting Certain
  Changes to an Approved Application
• November 2010
• (Implement immediately)

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Operational Procedures (cont.)

• Replaces November 2009 draft H1N1 guidance
  document
• Removed reference to H1N1 since pandemic is over,
  but retained those provisions with general
  applicability
• Training of Back-up Personnel
• Have adequate trained back-up personnel in the
  event of personnel shortages (e.g., pandemics,
  natural disasters, bioterrorism)
• Use existing training program recommend train
  more than 1 back-up person for each critical
  function
• And of course...Document training

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Operational Procedures (cont.)

• Donor Suitability 24 Hours to Clarify
• 640.3(a) and 640.63(a) determine donor
  suitability on day of collection regs dont
  define day of collection
• Firm may clarify a donors response to a question
  or obtain omitted responses within 24 hours of
  the time of collection
• Does not apply to missing/unacceptable vital
  signs or hgb/hct
• Licensed firms must have CBER approved SOPs for
  this, including contacting donor, determine
  donors identity and if in confidential setting
• Should be handled as deviation included in QA
  tracking and investigation procedures

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Operational Procedures (cont.)

• Reporting certain changes to FDA as Changes Being
  Effected (CBE) under 601.12(c)(5)
• Changes were previously reported as CBE-30
• Using a different registered outside/contract
  testing lab to perform donor testing
• However, submit as PAS if using lab not
  registered for donor screening
• Implementation of written or audio/visual methods
  to self-administer your currently approved donor
  history questionnaire
• Supersedes July 2003 Guidance for
  self-administered questionnaire that required a
  CBE-30
• Still follow CCPs described in the July 2003
  Guidance
• Computer-Assisted DHQ process is still a CBE-30

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Where can I find the guidances?

• CBER website
• Click on Vaccine, Blood Biologics link
• Scroll down to Forms and Regulatory Information
• Click on Blood Guidances
• http//www.fda.gov/BiologicsBloodVaccines/Guidanc
  eComplianceRegulatoryInformation/Guidances/Blood/d
  efault.htm

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• THANK YOU!
• Enjoy the rest of your day!