Kevin Robertson PharmD BCPS InspectorInvestigator Arkansas State Board of Pharmacy No conflicts of interest to disclose Pharmacist Objectives List commonly cited issues during recent USPlt797gt compliance inspections ID: 1039081
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1. USP<797>… It’s not “new”… but it must be “news” to you…Kevin Robertson, PharmD, BCPSInspector/InvestigatorArkansas State Board of Pharmacy
2. No conflicts of interest to disclose
3. Pharmacist ObjectivesList commonly cited issues during recent USP<797> compliance inspectionsState the proper approach to beyond use dating assignment for “point of care activated systems”Explain the similarities and dissimilarities to USP<797> compliance between cleanrooms and compounding aseptic isolatorsDescribe core components of an acceptable third party certification report
4. Technician ObjectivesState commonly cited issues during recent USP<797> compliance inspectionsCompare and contrast USP<797> compliance between cleanrooms and compounding aseptic isolatorsUnderstand the third party certification report
5. Commonly cited issues… so far...
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7. Commonly cited issuesCleaning and disinfectionMonthly cleaning is NOT occurringBins with loose materials (e.g., pieces of carboard)Amount of items located in anteroom and/or buffer roomComputers, refrigerators, IV supplies, medications, etc
8. Commonly cited issuesCleaning and disinfection“Ready to use” products vs. “Not ready to use” productsDating on mixed productBuckets (PEC vs. SEC)Dating on “not ready to use” productsOut of date “ready to use” products
9. Commonly cited issuesCleaning and disinfectionSterile water not being used with mixed germicidal detergents in PECGermicidal detergent not being used daily in PECSporicidal agent used at a minimum of monthly (fungicidal ≠ sporicidal)
10. Commonly cited issuesCleaning and disinfectionUse of gowns that are not cleanroom gownsLack of low lint wipes to dry handsFatigue mats – GET RID OF THEM
11. Commonly cited issuesBeyond use datingOpened SDVs within the PEC, refrigerators, etcPoint of care activated systemsMulti-dose vial dated beyond 28 days
12. Commonly cited issuesSEC HVACInadequate ACPHInadequate/Inappropriate pressure gradientsClassification of rooms (i.e., there is not such thing as “hall to chemo room”)Room HEPA filter leak testingHumidity excessive*
13. Commonly cited issuesSECNo line of demarcationSink too small for adequate hand hygiene*Return air return vents at ceiling height*Numerous horizontal surfaces*Exposed sprinkler heads*Ceiling tiles not calked
14. Commonly cited issuesSECNo pressure gauges for roomsPressure gauges not calibratedHD room pressure too negativeTacky mats in a conditioned roomLack of interlock on pass-through*Failures - LAFH vs. vertical workbench
15. Commonly cited issuesMedication storageCheap thermometer – Not calibratable*Incorrect goal range for cold storage*
16. Commonly cited issuesTrainingYearly written exam on garbing, cleaning/disinfection, and aseptic technique (including those “supervising”)Yearly validation of aboveGloved finger tip testing – Initial vs. annual
17. Commonly cited issuesTrainingAppropriately matched media fill testing to match most complex mixture (e.g., ACD)
18. Commonly cited issuesGarbingMakeup, artificial nails, etc in cleanroomLack of beard coversLack of nail picks for hand hygieneExposed skin (usually at the ankles)
19. Commonly cited issuesGarbingLack of waterless alcohol based hand surgical scrubDonning sterile gloves properlyLack of knowledge of why the line of demarcation is there…..
20. Commonly cited issuesEnvironmental monitoringInadequate third party certifierCETA CAG-003-2006-11CETA CAG-002-2006PIC familiar with testing required and interpretation of results
21. Commonly cited issuesEnvironmental monitoringInadequate third party certifierReport includes equipment used (model, last calibration, etc)Lack of HEPA filtration testingLack of ACPH for each roomLack of pressure differential for each room
22. Commonly cited issuesEnvironmental monitoringInadequate third party certifierLack of smoke testing UNDER DYNAMIC CONDITIONSViable sampling (air and surface)Air: ISO5 environment —› 1000 L sampleSurface: Not the floor or walls
23. Commonly cited issuesEnvironmental monitoringViable sampling (air and surface)Air & surface: Control, lot, expiration date of mediaAir & surface: You tell the 3rd party certifier where to sample!Air & surface: If you have a pass-through, it must be part of the sampling
24. Commonly cited issuesEnvironmental monitoringViable sampling (air and surface)Don’t sample close to a sink (i.e., false positives)
25. Commonly cited issuesCompounding ProceduresIPA use with “adequate frequency”Too many items in the hood (e.g., pens, calculators, stickers, etc)Inadequate sanitization of rubber stoppers
26. Commonly cited issuesCompounding ProcedureFilter sterilization: compatibility, volume limit, filter integrity (i.e., bubble test)Extended dating beyond USP<797>Sterility and pyrogen testing of each lot in addition to stability data
27. Commonly cited issuesSOPsNo action limits or thresholds for variances to stop compounding, investigate cause, trigger remediation, notify prescriber / patient / ASBP, etcDirections for mixing germicidal detergentsProper maintenance of tacky mats
28. Commonly cited issuesSOPsAppropriate action levels for gloved finger tip / media fill testingAppropriate action for failed testing in ISO5 environment: HINT… STOP COMPOUNDING UNTIL IT’S FIXED AND VALIDATED THAT IT HAS BEEN FIXED (ONE HOUR BUD)
29. Self-assessment question #1Which findings below is most likely to lead to non-compliance with USP<797>?Lack of hands free soap dispenserUse of tacky mats in controlled spaceExcessive items in the compounding areas leading to inadequate cleaning/disinfection
30. Point of care activation systems
31. Extended BUDsSupported by:Stability (exact match preparation cited including concentration, excipients, storage device, etc)Sterility testing (each batch)Endotoxin testing (each batch)
32. Mini-Bag Plus
33. Mini-Bag PlusManufactured by BaxterCompatible with 20 mm closure, single dose, powered drug vialsAvailable in dextrose and salineCan be docked outside the pharmacy using proper aseptic techniqueCan be activated at point of care using proper aseptic techniqueDo not refrigerate assembled system prior to activation
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35. Mini-Bag PlusManufacturer documents:“..all Mini-Bag Plus container IV solutions should remain in the protective overwrap until ready for use…”“..once assembled, the product should be used promptly…”This does not support extended BUDs
36. addEASE
37. addEASEManufactured by B BraunBCxx00 & N7995: Compatible with B Braun Partial Additive Bag (PAB) and xx mm vials or 250 mL EXCEL bag and 20 mm vials, respectively.Do not refrigerate assembled system prior to activationCan be docked outside the pharmacy using proper aseptic techniqueCan be activated at point of care using proper aseptic technique
38. addEASEManufacturer documents:“..the chemical stability of the drug is not compromised during specified storage…”“…the results of the testing verified the reliability of the connection…”This does not support extended BUDs
39. Self-assessment question #2BUD extension beyond USP<797> is based on:Stability dataSterility testing (each batch)Endotoxin testing (each batch)All of the above
40. Sterile rooms vs. “gloveboxes”
41. CAI vs. CACI
42. Similar ConsiderationsCleaning and disinfectionAreas within segregated compounding area (SCA) designated with LODTraining and validationAnnual testing, media fill, gloved fingertip, etcSOPs
43. Similar ConsiderationsGarbingMust follow USP<797> UNLESS manufacturer documentation provided stating may be alteredEnvironmental monitoringPressure is ante-chamber etcTemperature etcThird party certification
44. Dis-similar ConsiderationsEnvironmental monitoringThird party certification (CETA CAG-002-2006)Certified to maintain ISO5 environment in non-classified environment under DYNAMIC CONDITIONS, including during transfer of product / product preparation
45. Dis-similar ConsiderationsSinkNot within 1 meter of CAI/CACISCALocated in low traffic areaNot close to unsealed windows/doors that connect to outdoors/construction site/warehouse/food preparation areas
46. Self-assessment question #3Which expectations below are similar between CSP operations using a “cleanroom” and a “glovebox”:Sink placementCETA criteria for 3rd party certificationTraining and validation
47. Third party certification reports
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51. Third Party ReportsMust comply with appropriate CETA standardsCETA certified inspectorIf not CETA certified, a comparison and determination the standards used is the same OR BETTER than the applicable CETA standards
52. Third Party ReportsPEC (ideal to show calculations)Equipment used make, model, last calibration, and expriation date of calibrationAirflow velocity supply average with “acceptable” limit stated for the environment testedAverage particle counts with “acceptable” limit stated for environment testedInduction leak/backstreaming test results with “acceptable” limits statedAirflow visualization testHEPA filter integrity (leak) test results with “acceptable” limits stated“PASS” or “FAIL” designation based on USP etc standards
53. Third Party ReportsSEC (ideal to show calculations)Equipment used make, model, last calibration, and expiration date of calibrationAverage particle counts with “acceptable” limit stated for environmentACPH from SEC HEPAs AND PECs (stated separately AND summed)HEPA filter integrity test results with “acceptable” limits stated – Provide diagram showing each HEPA and corresponding numberIf HEPA leaks detected, show on diagram and state if fixed or not while on site“PASS” or “FAIL” designation based on USP etc standards
54. Third Party ReportsISO classificationISO5 = less than 3,520 particles/M3 ISO7 = less than 352,000 particles/M3 ISO8 = less than 3,520,000 particles/M3 ISO classificationISO5: PECISO7: Anteroom and buffer roomISO8: Anteroom for a non-HD buffer room
55. Third Party ReportsAir changes per hour (ACPH)Total CFM Room ft3 60 = ACPHExample: room 12’W X 15’L X 8’H = 1440 ft3941 CFM 1440 ft3 x 60 = 39.2 ACPHACPH: Minimum of 30 for ISO7 (only 50% UP TO 15 may come from PEC)
56. Third Party ReportsAir changes per hour (ACPH)ACPH: Minimum of 30 for ISO7 (only 50% UP TO 15 may come from PEC)Example:SEC: ACPH = 12PEC: ACPH = 20TOTAL DOES NOT EQUAL 32… It’s 12 + 15… 27 ACPH… FAIL for ISO7Exception: HD room… NO recirculation from PEC
57. Third Party ReportsAir changes per hour (ACPH)ACPH: Minimum of 20 for ISO8 (UNLESS it’s anteroom for a HD room – shared or not with a non-HD room)Pressure gradientsAnteroom and non-HD buffer roomsPositive 0.02”WC or greater
58. Third Party ReportsPressure gradientsNon-HD HD buffer roomsNegative 0.03 to 0.01”WCToo negative pulls in contaminationFacility pressure gaugesCalibration
59. Third Party ReportsHEPA filter testingNew installationEvery 6 monthsSmoke test in PEC and SECDuring dynamic conditionsPEC: If nothing to compound, MUST simulate
60. Third Party ReportsViable testingSurface AND air… not just one…Documentation of appropriate growth media (e.g., TSApl)Lot and expiration date of mediaControl utilized
61. Third Party ReportsViable testingAir sample: Minimum of 1000 L in PECPass through: Must include
62. Self-assessment question #4Key components of a third party certification report include:ACPH for the SECHEPA filter leak testing for PEC and SECPressure gradient for SEC“PASS” or “FAIL” designation for each testAll of the above
63. SummaryUSP<797> last updated in 2008What is new… Universal approach to inspection across the countryYou must self-educate if you feel knowledge is inadequateKnow how to read and interpret 3rd party certification reportsNot all 3rd party certifiers are created equal