Draft Guidance for Industry: Preventive Measures to Reduce the Possible Risk of Transmission of Creutzfeldt-Jakob Disease (CJD) and Variant Creutzfeldt-Jakob Disease (vCJD) by Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps)

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Draft Guidance for Industry Preventive Measures
to Reduce the Possible Risk of Transmission of
Creutzfeldt-Jakob Disease (CJD) and Variant
Creutzfeldt-Jakob Disease (vCJD) by Human Cells,
Tissues, and Cellular and Tissue-Based Products
(HCT/Ps)

• TSEAC 26 June 2002

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CJD/vCJD Draft Guidance

• Background Information
• Differences between Blood CJD/vCJD Guidance and
  Tissue Draft Guidance
• Draft Guidance and Recommendations
• Committee Considerations

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Background

• January 2001 TSEAC Meeting
• Unanimous agreement that there is a significant
  risk of transmission of vCJD from HCT/Ps as
  compared to the risk of vCJD from blood
  transfusion
• Greatest risk dura mater and cornea
• No reason to believe risk of vCJD less than that
  for sporadic CJD

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Background (cont.)

• January 2001 TSEAC (cont.)
• Majority agreement that FDA should recommend
  donor deferral criteria for possible exposure to
  the BSE agent
• Exception for Hematopoietic Stem Cells (HSC)
  should be provided

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Background (Cont.)

• January 2001 TSEAC (Cont.)
• No advice from committee regarding specific
  deferral criteria
• Countries
• Time periods of potential exposure
• Duration of exposure
• No vote regarding donor history interview
  requirement for ALL HCT/P donors

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Background (cont.)

• Tissue Draft Guidance published June 2002
• Guidance modeled after blood guidance
• Same criteria used
• No information available about risk as reduction
  versus supply for tissues like for blood (i.e.
  REDS data)

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Differences between blood Guidance and tissue
Draft Guidance

• No two-phase implementation
• Exception made for HLA-matched hematopoietic stem
  cell collection
• Includes request to submit data to assess the
  impact of these recommendations on supply

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Tissue Draft Guidance

• Background information
• Establishes regulatory authority
• Statement of public health concern
• TSEAC recommendations
• General information about CJD and vCJD
• Clinical presentation
• Diagnosis
• Epidemic information

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Tissue Draft Guidance (cont.)

• Basis for CJD Recommendations
• Previous recommendations in guidance
• Discussion of known cases of CJD transmission by
  tissues (dura mater and cornea)

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Tissue Draft Guidance (cont.)

• Basis for vCJD Recommendations
• Lists 5 currently recognized risks of exposure to
  BSE agent
• Includes information to support exposure risks

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Tissue Draft Guidance (cont.)

• Recommendations for Donor Eligibility
• Determine ineligible any donor who
• 1. Has been diagnosed with vCJD or any other
  form of CJD

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Tissue Draft Guidance (cont.)

• Determine ineligible any donor who
• (cont.)
• 2. Has been diagnosed with dementia or any
  degenerative or demyelinating disease of the
  central nervous system (CNS) or other
  neurological disease of unknown etiology
• (tissue from donor with dementia may be
  acceptable based upon evaluation by the medical
  director if confirmed by gross and microscopic
  examination to be caused by CVA, brain tumor,
  head trauma, or toxic/metabolic and not by TSE)

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Tissue Draft Guidance (cont.)

• Determine ineligible any donor who
• Is at increased risk for CJD
• Dura mater transplant recipient
• Human pituitary-derived growth hormone
• gt/ 1 blood relative with CJD

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Tissue Draft Guidance (cont.)

• Determine ineligible any donor who
• Spent three months or more cumulatively in the
  U.K. from 1980 through end of 1996

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Tissue Draft Guidance (cont.)

• Determine ineligible any donor who
• 5. Is a current or former U.S. military member,
  civilian military employee, or dependent of
  military or civilian employee who resided at U.S.
  military bases in Northern Europe for 6 months or
  more from 1980 through 1990, or elsewhere in
  Europe for 6 months or more from 1980 through 1996

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Tissue Draft Guidance (cont.)

• Determine ineligible any donor who
• 6. Lived cumulatively for 5 years or more in
  Europe from 1980 until the present (including
  time spent in the U.K. from 1980-1996)

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Tissue Draft Guidance (cont.)

• Determine ineligible any donor who
• Received any transfusion of blood or blood
  components in the U.K. between 1980 and the
  present
• Has injected bovine insulin since 1980, unless
  confirmed not manufactured after 1980 from cattle
  in the U.K.

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Tissue Draft Guidance (cont.)

• All geographical references in the deferral
  recommendations are defined in the document.
  e.g. Northern Europe
• Recognition is given to HLA-matching issues with
  HSC. If a HSC donor would otherwise be
  determined ineligible by recommendations 3-8, the
  risks of using the cells may be outweighed by the
  benefits. HSC may be collected and stored. Use
  of the HSCs in this circumstance may be
  considered an urgent medical need.

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Tissue Draft Guidance (cont.)

• CJD/vCJD screening questions to be included in
  the donors medical history.
• Unfamiliarity with term CJD may be taken as a
  negative response.
• CJD in blood relative excluded unless
• Diagnosis of CJD subsequently found inaccurate
• The CJD was iatrogenic
• Lab testing shows donor without mutation
  associated with familial CJD

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Tissue Draft Guidance (cont.)

• HCT/Ps from donors considered ineligible for
  donation may be retained for nonclinical
  scientific or educational uses with proper
  labeling and storage.
• Industry affected by this draft guidance are
  encouraged to submit any data they have now, or
  could obtain through studies, concerning the
  effect of implementation of these recommendations
  on the tissue supply.

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Tissue Draft Guidance (cont.)

• This is draft guidance and it is not necessary to
  implement at this time.
• When a final guidance is issued, there will not
  be a two step phase-in period as there is for the
  blood guidance.

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Charge to TSEAC

• Comment on recommendations made in the draft
  guidance.
• Consider how information can be obtained about
  the effect of implementing these tissue donor
  deferral criteria on the tissue supply in the
  United States.