Common Problems with Blood Submissions

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Common Problems with Blood Submissions
Michael Gorman, BA, MT(ASCP)SBB Consumer Safety
Officer, CBER, OBRR, DBA September 16, 2009
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Outline

• Presentation Goal
• SOPs
• Quality Control (QC)
• Product Label
• Apheresis Informed Consent Content
• Comparability Protocol (CP)
• Computer Assisted Self Interviews (CASI) Donor
  Questionnaire
• Summary

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Presentation Goal Reduction In Submission
Problems

• Check submissions are complete before sending
• Review content to ensure compliance with
• Applicable regulations
• Recommendations
• Review checklists, when applicable
• Complete submissions will minimize approval
  process delays

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SOPs 21 CFR 606.100(b)

• Applicable SOPs and/or supporting documents not
  submitted - examples
• Quality Control (QC)
• Equipment maintenance
• Manufacturers instructions or operator manuals

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SOPs (cont.)

• SOPs not applicable to the submission are
  submitted - examples
• Collection of Apheresis, Red Blood Cells
  submission also includes SOPs pertaining to
  Platelets, Pheresis collection
• Infectious Disease Testing SOPs

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SOPs (cont.)

• Process steps or information missing - examples
• Acceptance criteria for product QC
• Steps for documenting results and interpretations
• Steps for entering data into the computer
• Donor deferral criteria for red blood cell and
  plasma loss

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SOPs (cont.)

• Failure Investigation steps missing
• When to initiate a failure investigation (failure
  investigation SOPs)
• Methods for investigating and/or correcting
  failures
• Management of products that do not meet minimum
  manufacturing specifications including QC
  failures
• Role of the quality unit not addressed

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SOPs (cont.)

• SOPs not consistent with manufacturers
  instructions or operator manuals -examples
• Order of steps changed
• Steps omitted
• Wording changed which changes the manufacturer's
  intended meaning

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SOPs (cont.)

• SOPs are not consistent with CFR requirements -
  example
• 21 CFR 606.160(d) Manufacturing record retention
  timeframes changed in the CFR in 2008 from 5
  years to 10 years

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SOPs (cont.)

• SOP not consistent with a firms other SOPs or
  forms examples
• Acceptance criteria in SOP and QC form do not
  agree
• Form names different in SOPs

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Monthly Quality Control (QC) Forms Do Not Include
All Information

• Facility
• 21 CFR 211.194(a)(1)
• Device manufacturer and type
• 21 CFR 211.194(a)(2)
• Sample identification
• 21 CFR 606.140(c)
• Sample collection date
• 21 CFR 211.194(a)(1)
• Date of testing
• 21 CFR 606.160 (a)(1)
• Interpretation of results
• 21 CFR 606.160 (a)(1)

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Monthly Quality Control (QC) Forms Do Not Include
All Information (cont.)

• Yield
• 21 CFR 211.186(b)(7)
• Acceptable criteria
• 21 CFR 211.165(d)
• Initials
• 21 CFR 606.160 (a)(1)
• Evidence of review
• 21 CFR 211.194(a)(8)
• Records of calculations
• 21 CFR 211.194 (a)(5)

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QC Information Not included or Inadequate Examples

• Data not submitted
• Two consecutive months of QC data not submitted
  when applicable
• Summary of validation data
• Insufficient QC sample size
• Refer to FDA Guidance documents

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QC Apheresis Data Not Included Examples

• Monthly Apheresis, Red Blood Cells QC
• Data for fifty units per site submitted but data
  for both single and double units, when applicable
• Data for all collection types including single,
  double and triple units, when applicable

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Product Label Submissions

• Labels submitted for products not currently
  licensed by FDA
• Labels submitted for products currently licensed
  by FDA for which a firm does not presently hold a
  license and is not requesting licensure
• FDA only approves labels for a firms licensed
  products

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Apheresis Informed Consent Content

• All possible adverse effects listed in each
  devices Operator Manual not included
• Exculpatory language inappropriately included in
  the consent form

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Comparability Protocol (CP)

• Original CP (PAS) submissions often do not
  include
• Validation protocols with data summary
• Validation performance/acceptance criteria
• Description of actions to be taken if acceptable
  validation results are not achieved
• Description of implementation
• Proposal to change reporting category (e.g., from
  PAS to CBE30)

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Comparability Protocol (CP) (cont.)

• Subsequent submissions (e.g., CBE30) often do not
  include
• References to previously approved CP STNs
• SOPs or QC criteria that were part of the
  original CP were revised but not submitted

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Computer Assisted Self Interview (CASI) Donor
Questionnaire

• Not included in submissions
• SOPs
• Print screens none submitted or not all
  applicable screens submitted
• Copy of donor health history questionnaire
• Validation protocol
• List of interfaces with other medical devices
  (software, instruments)

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CASI (cont.)

• Not included in submissions
• Software manufacturers name
• Program name
• Version or release number
• Information indicating CASI software is 510(k)
  cleared by FDA i.e., 510(k) number
• Information indicating wireless functionality is
  510(k) cleared by FDA, when applicable (e.g.,
  information from the software manufacturer)

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Summary

• Not an all-inclusive list
• Incomplete submissions can delay reviews and
  approvals