TSEAC MeetingJuly 18, 2003

Topic 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

Distribution of TSE Infectivity in the Human Body--WHO

• HIGH– Brain, spinal cord– Eye—some 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

Approaches to Reduce Risk of TSE Transmission by HCT/P Transplants—TSEAC 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

Revision of FDA’s 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

TSE Infectivity in Ocular Tissue

• Scrapie-infected hamsters:– Brain >107 ID 50/g– Optic nerve and retina >107

– 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-- <0.25% of brain level

Transmissions of TSE by Tissue Transplantation

• Human dura mater– 4500 transplants /yr. (1997)

– >100 cases

• Cornea– >50,000 transplants/yr. worldwide

– 3 cases: 1 definite (1974); 1 probable (1994); 1 possible (1997)

• Other tissues– >850,000 transplants/yr. No known cases

FDA Regulation of HCT/Ps—Final rules; proposed rules;

guidance; draft guidance• 1997—final rule and guidance—screening and

testing of donors of musculoskeletal, skin, ocular tissues for HIV and hepatitis

• 1999—donor suitability rule (not final)—includes screening for TSE including CJD

• 2001—final registration and listing rule• 2001—good tissue practice (GTP) rule (not

final)• 2002—guidance on validation; draft guidance

on CJD/vCJD for HCT/P donors

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

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 infectivity—no additional

decontamination, other than routine sterilization• High infectivity—additional decontamination

procedures recommended

WHO Recommended Decontamination Methods

• (in order of decreasing effectiveness and severity)

• Incineration—use for all disposable instruments; preferred method for all instruments exposed to high infectivity

Autoclave/chemical methods for heat-resistant instruments• 1. Immerse in NaOH and heat in gravity

displacement (g.d.) autoclave—121C for 30m; clean, rinse in waterroutine 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

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

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

Number of Decontamination Cycles—CJD 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 105–fold• Most instruments that have undergone 10 cycles

are unlikely to pose a significant risk.

Factors to consider

• Any risk assessment has variables which are not known—extent 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

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-----

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?

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?

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?

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?

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?