TSEAC Meeting July 18, 2003 Topic 4 Ruth Solomon, M.D. DHT/OCTGT

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TSEAC MeetingJuly 18, 2003Topic 4Ruth Solomon,
M.D. DHT/OCTGT

• Methods to decontaminate facilities and equipment
  used in recovery and processing of HCT/Ps to
  prevent contamination and cross-contamination by
  TSE agents

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Distribution of TSE Infectivity in the Human
Body--WHO

• HIGH
• Brain, spinal cord
• Eyesome distinguish optic nerve and retina from
  other eye tissues (cornea, sclera)
• LOW
• Kidney, liver, lung, lymph nodes, spleen,
  placenta
• NO DETECTABLE INFECTIVITY
• Adipose tissue, adrenal, gingival tissue, heart
  muscle, intestine, peripheral nerve, prostate,
  skeletal muscle, testis, thyroid, blood,
  secretions and excretions

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Approaches to Reduce Risk of TSE Transmission by
HCT/P TransplantsTSEAC 6/26/02

• Screen donors for risk factors and clinical
  evidence of TSE disease
• Control recovery and processing to prevent
  contamination
• Use manufacturing steps that remove or inactivate
  TSE Agents

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Revision of FDAs Question to the Committee
6/26/02

• Do the committee members recommend that FDA
  define validated inactivation procedures for TSE
  decontamination of instruments and surfaces, and
  propose methods for removal and/or inactivation
  of TSE agents from HCT/Ps that may be
  contaminated by TSE agents, differentiating
  high-risk from low-risk tissues? ----unanimous
  YES vote

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TSE Infectivity in Ocular Tissue

• Scrapie-infected hamsters
• Brain gt107 ID 50/g
• Optic nerve and retina gt107
• Cornea, choroid, lens 104-107
• Patient with vCJD
• PrPSc detected in brain
• Retina-- 25 of brain level
• Optic nerve-- 2.5 of brain level
• Cornea, sclera, aqueous and vitreous humor, iris,
  lens-- lt0.25 of brain level

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Transmissions of TSE by Tissue Transplantation

• Human dura mater
• 4500 transplants /yr. (1997)
• gt100 cases
• Cornea
• gt50,000 transplants/yr. worldwide
• 3 cases 1 definite (1974) 1 probable (1994)
  1 possible (1997)
• Other tissues
• gt850,000 transplants/yr. No known cases

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FDA Regulation of HCT/PsFinal rules proposed
rules guidance draft guidance

• 1997final rule and guidancescreening and
  testing of donors of musculoskeletal, skin,
  ocular tissues for HIV and hepatitis
• 1999donor suitability rule (not
  final) includes screening for TSE including CJD
• 2001final registration and listing rule
• 2001good tissue practice (GTP) rule (not
  final)
• 2002guidance on validation draft guidance on
  CJD/vCJD for HCT/P donors

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GTP Proposed Rule

• Facilities
• Contact surfaces disinfected between donors
• Equipment
• Cleaned and maintained
• Instruments
• Decontaminated, sterilized as appropriate
• Supplies and reagents
• Verified to meet specifications, not contaminated
• Tracking to HCT/P
• Equipment, instruments, reagents tracked to HCT/P
• Environment
• Controlled and monitored for microbial growth

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WHO Consultation on Infection Control for TSEs

• Instruments kept moist after use mechanically
  cleaned
• Ineffective, sub-optimal decontamination methods
  vs.
• Effective decontamination methods
• Decontamination for confirmed or suspected TSE
  /level of tissue infectivity
• Low or no detectable infectivityno additional
  decontamination, other than routine sterilization
• High infectivityadditional decontamination
  procedures recommended

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WHO Recommended Decontamination Methods

• (in order of decreasing effectiveness and
  severity)
• Incinerationuse for all disposable instruments
  preferred method for all instruments exposed to
  high infectivity

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Autoclave/chemical methods for heat-resistant
instruments

• 1. Immerse in NaOH and heat in gravity
  displacement (g.d.) autoclave121C for 30m
  clean, rinse in water?routine sterilization
• 2. Immerse in NaOH or NaOCl for 1h. transfer to
  water heat in g.d. autoclave 121C for 1hr
  clean ?routine sterilization
• 3. Immerse in NaOH or NaOCl for 1h rinse in
  water transfer to open pan heat in g.d.
  autoclave (121C) or porous load autoclave (134C)
  for 1hr clean ?routine sterilization

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Cont.

• 4. Immerse in NaOH and boil for 10m at
  atmospheric pressure clean rinse in water
  ?routine sterilization
• 5. Immerse in NaOCl or NaOH at ambient
  temperature for 1h. Clean rinse in water
  ?routine sterilization
• 6. Autoclave at 134C for 18m

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Cleaning methods for surfaces and heat-sensitive
instruments

• 1. Flood with 2N NaOH or undiluted NaOCl for 1h
  rinse with water
• 2. Thoroughly clean possibly use one of the
  partially effective methods

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Number of Decontamination CyclesCJD Incidents
Panel

• Decontamination Cycle(1) physical cleaning,
  e.g., washer followed by (2) inactivation of any
  remaining infectious material, e.g., autoclaving
• First cleaning 102 to 103-fold reduction
• Subsequent cleaning 0 to 102 fold reduction
• First autoclaving 103 to 106 fold reduction
• Subsequent autoclaving 0 to 103 fold reduction
• First cleaning and autoclaving at least 105fold
• Most instruments that have undergone 10 cycles
  are unlikely to pose a significant risk.

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Factors to consider

• Any risk assessment has variables which are not
  knownextent of TSE agent reduction during
  processing extent of possible cross-contamination
  
• One important risk is insufficient supply
• Resource limitations of small entities
• Corrosive effect of NaOH and NaOCl on longevity
  of stainless steel instruments

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Questions to Committee

• Considering (a) current practices using
  conventional methods of cleaning facility work
  surfaces, equipment, and instruments used in the
  recovery and processing of HCT/Ps, (b) other
  precautions currently in place (e.g., aseptic
  techniques, donor screening for TSE), and (c )
  concerns about availability of tissues-----

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Questions, cont.

• 1. With regard to the recovery and processing of
  ocular tissue from donors later discovered to
  have TSE or possible TSE
• A. Does the committee believe that surgical
  instruments used in recovery and processing
  should be destroyed by incineration, if practical?

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Questions, cont.

• B. If destruction of instruments is not
  practical, does the committee believe that, at
  this time, there exist established, effective
  methods that are adequate for decontaminating
  instruments and surfaces?
• C. If so, please comment on the specific methods
  listed in the WHO Guidelines. In particular,
  does the committee consider that only those WHO
  methods that use NaOH or NaOCl are adequate?

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Questions, cont.

• D. If so, should such methods by employed by eye
  banks in the circumstances noted above?
• E. Does the committee believe that the number of
  decontamination cycles (physical cleaning and
  autoclaving) performed on the instruments after
  the index donor tissue was recovered and
  processed should determine whether or not these
  additional specified decontamination procedures
  are needed?

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Questions, cont.

• 2. With regard to the recovery and processing of
  ocular tissue, should additional decontamination
  procedures discussed in question 1 be used
  routinely, i.e., even when TSE has not been
  suspected?

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Questions, cont.

• 3. Should similar decontamination procedures be
  used for instruments and surfaces used to recover
  and process other tissues with a low risk of TSE
  infectivity from cases of known or suspected TSE?
• 4. With regard to other tissues with a low risk
  of TSE infectivity, should additional
  decontamination procedures be used routinely,
  i.e., even when TSE has not been suspected?