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USP <797>: Ensuring a State of Control AAHP Fall Seminar 2016 Thanks to Critical Point LLC (www.criticalpoint.info) for allowing me to use their slides: Kate Douglas, MS, RN, CRNI Eric Kastango, MBA, BS Pharm, FASHP James Wagner Learning and Performance Objectives At the end of this session you will be able to: • Describe documented patient harm caused by inadequate sterile compounding operations • List common sources of contamination of a compounded sterile product • Describe methods to ensure a proper state of control for sterile compounding operations • State commonly violations of USP <797> by the Arkansas Board of Pharmacy History of Sterile Compounding • Despite the chapter’s uniform sterile compounding standards, schools of pharmacy may not always include sterile compounding • Only 1 in 6 graduates are prepared for sterile compounding work* • In 2014, less than 10 schools of pharmacy conducted training in real cleanroom settings *Hellums M, Alverson SP, Monk-Tutor MR. Instruction on compounded sterile preparations at U.S. schools of pharmacy. AJHP. Volume 64, Nov 1, 2007: 2267-74. Copyright © 2013-2017 CriticalPoint's Sterile Compounding Boot Camp® - All rights reserved Use of this educational material by a 3rd party does not constitute endorsement from CriticalPoint or Clinical IQ. DQSA • Section 503A (21USC353a) - Traditional compounding State-based regulations – State Boards of Pharmacy Traditional, individualized prescriptions Requires compliance with USP chapters on compounding • Section 503B (21USC353b) - Outsourcing facilities FDA jurisdiction; registration; reporting; cGMPs Manufacture and interstate shipment of larger quantities of compounded drugs without prescriptions Under direct supervision of a pharmacist Copyright © 2013-2017 CriticalPoint's Sterile Compounding Boot Camp® - All rights reserved Use of this educational material by a 3rd party does not constitute endorsement from CriticalPoint or Clinical IQ. Patient Harm Caused by Inadequate Compounding Operations “Our patients have never had a problem” Copyright © 2013-2017 CriticalPoint's Sterile Compounding Boot Camp® - All rights reserved Use of this educational material by a 3rd party does not constitute endorsement from CriticalPoint or Clinical IQ. What’s the past damage? • U.S. Illnesses and Deaths Associated With Compounded Medications • Contamination of sterile preparations was the most common compounding error, though others were the result of pharmacists' and technicians' miscalculations and mistakes in filling prescriptions. Since 2001 over 25 pharmacy compounding incidents with 1,049 adverse events, including 89 deaths, have been reported. Copyright © 2013-2017 CriticalPoint's Sterile Compounding Boot Camp® - All rights reserved Use of this educational material by a 3rd party does not constitute endorsement from CriticalPoint or Clinical IQ. Brutal Facts Year 1990 1990 State Nebraska Description 4 patients died of a bacterial infection from non-sterile cardioplegia solution compounded in a hospital Pennsylvania 2 patients lost their vision after becoming infected by Pseudomonas aeruginosa found in indomethacin eye drops compounded in a drug store even though commercial non-steroidal drops were available at the time 1998 California 11 children became septic—10 tested positive for Enterobacter cloacae bloodstream infections associated with contaminated prefilled saline syringes 2001 Missouri 4 children contracted Enterobacter cloacae infections from IV ranitidine compounded in a hospital pharmacy Copyright © 2013-2017 CriticalPoint's Sterile Compounding Boot Camp® - All rights reserved Use of this educational material by a 3rd party does not constitute endorsement from CriticalPoint or Clinical IQ. Brutal Facts (continued) Year 2002 State North Carolina, South Carolina 2002 Michigan 2003 Missouri 2004 Description 5 patients developed Exophiala infections from contaminated injectable methylPREDNISolone that was prepared by a compounding pharmacy; one patient died Pharmacy preparing injectable methylPREDNISolone and baclofen recalled the products because of contamination with Penicillium mold, Methylobacterium, and/or Mycobacterium chelonae Bacteria contamination with Burkholderia cepacia found in at least 2 batches of a compounded inhalant solution used by 19,000 patients with chronic lung diseases Texas, New York, 36 patients developed Pseudomonas bloodstream infections after Michigan, Missouri receiving heparin/saline flushes from multiple lots of preloaded syringes. Copyright © 2013-2017 CriticalPoint's Sterile Compounding Boot Camp® - All rights reserved Use of this educational material by a 3rd party does not constitute endorsement from CriticalPoint or Clinical IQ. Brutal Facts (continued) Year 2005 2005 State Description New Jersey, Up to 25 patients contracted Serratia marcescens infections due to California contaminated magnesium sulfate mini-bags prepared by a compounding pharmacy Minnesota 2 patients were blinded after receiving a compounded trypan blue ophthalmic injection contaminated with Pseudomonas aeruginosa and Burkholderia cepacia; the injectable product is a commercially available product 2005 California Sterile talc vials with unwashed stoppers were not sterility tested before distribution from an outsourcing compounding pharmacy 2005 Maryland 10 patients died after exposure to cardioplegia solution from 2 lots contaminated with gram-negative rods Copyright © 2013-2017 CriticalPoint's Sterile Compounding Boot Camp® - All rights reserved Use of this educational material by a 3rd party does not constitute endorsement from CriticalPoint or Clinical IQ. Brutal Facts (continued) Year 2011 State California, Florida, Tennessee Description 16 patients being treated for wet macular degeneration developed severe eye infections due to contamination of AVASTIN (bevacizumab) during compounding; one patient blinded, another patient developed brain infection 2011 Alabama 9 patients among 19 died when PN solutions that were administered were contaminated with Serratia marcescens during compounding using non-sterile components to prepare amino acids Link to: CDC/USP Webinar on Incident 2012 California 9 patients developed fungal endophthalmitis after use of the compounded product Brilliant Blue-G (BBG) or receiving injections of triamcinolonecontaining products dispensed from the same compounding pharmacy Copyright © 2013-2017 CriticalPoint's Sterile Compounding Boot Camp® - All rights reserved Use of this educational material by a 3rd party does not constitute endorsement from CriticalPoint or Clinical IQ. New England Compounding Center (NECC) Meningitis Outbreak Date September 21, 2012– October 23, 2013 (no further CDC updates expected) Location USA (20 States) Cause Fungal meningitis contamination of steroid medication Injuries 751 total case count; 384 meningitis and spinal infection; 7 stroke; 325 paraspinal/spinal infection; 33 peripheral joint infection; 2 spinal and peripheral joint Some patients recovering from the meningitis are falling ill again. Sufferers of the new infection are now coping with epidural abscesses and infections near the injection site. Death(s) 64 Litigation More than 20 lawsuits filed against NECC The scale of the meningitis outbreak makes this event the worst among a series of fatal or harmful infections and overdoses linked to pharmacy compounding practices in the US rivaling other key drug safety issues in the past that have led to substantial drug safety legislation. Copyright © 2013-2017 CriticalPoint's Sterile Compounding Boot Camp® - All rights reserved Use of this educational material by a 3rd party does not constitute endorsement from CriticalPoint or Clinical IQ. Brutal Facts Continue Since NECC 2013 & 2014 Year 2013 State Connecticut Description FDA announced that a compounding pharmacy in New Jersey was voluntarily recalling all of its products after a Connecticut hospital reported that 5 bags of magnesium sulfate from the pharmacy were contaminated with mold. The pharmacy has since been closed by the NJ Division of Consumer Affairs Georgia, A compounding pharmacy in Augusta, Georgia, is voluntarily recalling 79 lots Louisiana, of bevacizumab-filled syringes (Avastin, Genentech) intended for retinal South Carolina injections because of the risk for eye infection, the US Food and Drug and Indiana Administration (FDA) announced yesterday. Texas A batch of compounded IV Calcium Gluconate found to be contaminated with Rhondococcus equii. 15 infected patients, 2 deaths (relationship to drug not known) Copyright © 2013-2017 CriticalPoint's Sterile Compounding Boot Camp® - All rights reserved Use of this educational material by a 3rd party does not constitute endorsement from CriticalPoint or Clinical IQ. Another Recent Event • Outbreak of Burkholderia contaminans linked to Intravenous Fentanyl from an Institutional Compounding Pharmacy Occurred at Duke University Hospital from August 31-Sept 6, 2012 7 patients affected Prepared drug from bulk API: High-risk compounding Report published in JAMA Available online: JAMA Intern Med. Published online February 03, 2014. doi:10.1001/jamainternmed.2013.13768 Copyright © 2013-2017 CriticalPoint's Sterile Compounding Boot Camp® - All rights reserved Use of this educational material by a 3rd party does not constitute endorsement from CriticalPoint or Clinical IQ. FDA Inspection of Compounding Pharmacies Figures do not include pharmacies dedicated to producing veterinary drugs. Note: years represent fiscal years October 1 – September 30. Fiscal year 2014 includes data through 9/12. Source: US Food and Drug Administration, USA Today Research. Table excerpted from: Eisler P and Schmaars C. Safety, sanitary problems prompt scores of drug recalls. USA Today. October 7, 2014 retrieved from http://www.usatoday.com/story/news/nation/2014/10/ 07/compounding-pharmacy-recalls-inspectionscontamination/16472741/ on October 7, 2014. Copyright © 2013-2017 CriticalPoint's Sterile Compounding Boot Camp® - All rights reserved Use of this educational material by a 3rd party does not constitute endorsement from CriticalPoint or Clinical IQ. What went wrong? • Leadership: Inadequate and ineffective • • • oversight Education, competence and proficiency Untrained employees Lack of competency and proficiency evaluation systems Hand Hygiene and Garbing Engineering controls and equipment Inadequate for intended activities Improper use Failure of Leadership Image courtesy http://www.guardian.co.uk/uk/2009/jan/21/1 Copyright © 2013-2017 CriticalPoint's Sterile Compounding Boot Camp® - All rights reserved Use of this educational material by a 3rd party does not constitute endorsement from CriticalPoint or Clinical IQ. What went wrong? (continued) • Inadequate cleaning/disinfecting practices • Inadequate preventive maintenance • Inadequate policies and procedures • Equipment Improper use of sterilizing equipment Failure to validate systems • Record keeping Inadequate quality assurance Inadequate documentation Copyright © 2013-2017 CriticalPoint's Sterile Compounding Boot Camp® - All rights reserved Use of this educational material by a 3rd party does not constitute endorsement from CriticalPoint or Clinical IQ. "Unfortunately, there are too many in health care who feel that if it hasn't happened to them, the adverse experiences of others do not apply. “ Michael Cohen, MS, FASHP Institute for Safe Medication Practices (ISMP) Copyright © 2013-2017 CriticalPoint's Sterile Compounding Boot Camp® - All rights reserved Use of this educational material by a 3rd party does not constitute endorsement from CriticalPoint or Clinical IQ. What’s the past damage? • Since 2001 over 25 pharmacy documented compounding incidents with 1,049 adverse events, including 89 deaths, have been reported • True • False Sources of Contamination Why is garbing important? • Humans are the biggest “particle • • generators” Though we can’t see them, we shed about 9 pounds of dead skin cells from the outer layer of the skin each year1 Particles generated by humans, our clothes, and our activities can act as transport vehicles for microorganisms and introduce them into the compounding process 1Donovan S. ©Photo Quest Ltd/Science Photo Library/Corbis Stay Clear!: What You Should Know about Skin Care. Health Zone. Lerner Books. September 2008. Copyright © 2013-2017 CriticalPoint's Sterile Compounding Boot Camp® - All rights reserved Use of this educational material by a 3rd party does not constitute endorsement from CriticalPoint or Clinical IQ. Just how many bacteria? • Each of us carries 3-5 pounds of bacteria in our • • bodies! Bacteria cells outnumber human cells 10:1 Bacterial cells are much smaller than human cells so they only account for 1-2% of our body mass The bacteria in our body would fill a large soup can like this one Source: Lita Proctor, National Institutes of Health’s Human Microbiome Project Copyright © 2013-2017 CriticalPoint's Sterile Compounding Boot Camp® - All rights reserved Use of this educational material by a 3rd party does not constitute endorsement from CriticalPoint or Clinical IQ. Garbing…why? Compounding personnel are the chief particle generators. 1Particle Activity1 Particles Generated Sitting quietly 100,000/minute Walking slowly (1.9 miles/hour) 5,000,000/minute Walking medium (3 miles/hour) 7,500,000/minute Walking fast (5 miles/hour) 10,000,000/minute Makeup/Cosmetics2 Particles/Application Eye shadow 82,000,000 Typical mascara application 3,000,000,000 Total for typical makeup application 5,100,000,000 Measuring Systems. Basic Guide to Particle Counters and Counting. 2011. K. Cosmetics in Cleanrooms…again. Cleanrooms. 2001 2Goldstein Copyright © 2013-2017 CriticalPoint's Sterile Compounding Boot Camp® - All rights reserved Why is hand hygiene important? • • There are 10,000 to 10,000,000 microbes on each hand1 • It only takes one to make a patient sick! So even if hand hygiene is performed with an agent that is 99.99% effective (assuming your hand washing technique is perfect), there will still be 100 to 100,000 left on your hands Hand hygiene is the single most important factor in preventing the spread of pathogens in healthcare settings. 1 Health Protection Agency. Fun Facts about Handwashing. http://www.hpa.org.uk/webc/HPAwebFile/HPAweb_C/1254510461483 Copyright © 2013-2017 CriticalPoint's Sterile Compounding Boot Camp® - All rights reserved Use of this educational material by a 3rd party does not constitute endorsement from CriticalPoint or Clinical IQ. Critical Factors in Aseptic Technique • Illnesses in Children's Hospital Prompts Discovery of Contaminated Alcohol Pads Science Daily (June 12, 2012): A small cluster of unusual illnesses at a Colorado children's hospital prompted an investigation that swiftly identified alcohol prep pads contaminated with Bacillus cereus bacteria, according to a report in the July issue of Infection Control and Hospital Epidemiology, the journal of the Society for Healthcare Epidemiology of America. The investigation ultimately led to an international recall of the contaminated products. Copyright © 2013-2017 CriticalPoint's Sterile Compounding Boot Camp® - All rights reserved Use of this educational material by a 3rd party does not constitute endorsement from CriticalPoint or Clinical IQ. Contamination CONTROL If it doesn’t get into controlled environments, then it doesn’t pose a risk! • • Seasonal variation: Spring and Summer • Cleaning is necessary to address mistakes in contamination control Be careful of EVERYTHING you bring into controlled environments (e.g., sharpie marker caused fungal contamination) Copyright © 2013-2017 CriticalPoint's Sterile Compounding Boot Camp® - All rights reserved Use of this educational material by a 3rd party does not constitute endorsement from CriticalPoint or Clinical IQ. A Word about Material Handling • 60% packaging contaminated with bacteria and • • • 40% with bacterial spores* If wipe with IPA (not a sporicidal) only 27.6% of spores would be removed through mechanical means* Spraying alone not effective since bacteria and spores can create a protective biofilm that must be removed by wiping** Mold is endemic to all brown cardboard and if it gets damp mold actively grows *Cockcroft et al. Validation of Liquid Transfer Disinfection Techniques for Transfer of Components into Hospital Pharmacy Cleanrooms. Hospital Pharmacist. 2001;8:226-32 **Stubbs S. How to Minimize Contamination When Transferring Items Into Hospital Cleanrooms. Controlled Environments. June. 2006. Copyright © 2013-2017 CriticalPoint's Sterile Compounding Boot Camp® - All rights reserved Use of this educational material by a 3rd party does not constitute endorsement from CriticalPoint or Clinical IQ. When to use Sterile Water? • Sterile water (SWInj or SWIrrig) is • strongly recommended to dilute disinfectant solution concentrates (not ready to use) that are used inside of the ISO Class 5 areas. Though these areas and cleaning Type Water supplies are not sterile, use of sterile water reduces pyrogens and potential Tap Water Purified Water bioburden. Water for Inj. CFU/mL* Pyrogens* 500 100 < 10 100 EU/mL 0.25 EU/mL < 0.25 EU/mL *Sources: USP NF defines standards for Purified water and Water for Injection; US EPA defines drinking water standards Copyright © 2013-2017 CriticalPoint's Sterile Compounding Boot Camp® - All rights reserved Use of this educational material by a 3rd party does not constitute endorsement from CriticalPoint or Clinical IQ. Sterility Assurance Level (SAL) • Aseptic processing only achieves a SAL of 10-3 versus 10-6 when terminally sterilized Aseptically Prepared SAL 10-3 1 contaminated CSP 1000 CSPs Terminally Sterilized SAL 10-6 1 contaminated CSP per million CSPs Copyright © 2013-2017 CriticalPoint's Sterile Compounding Boot Camp® - All rights reserved Use of this educational material by a 3rd party does not constitute endorsement from CriticalPoint or Clinical IQ. Which of the following are SOME of the potential sources of contamination for CSP preparation? A. Improper hand hygiene, clothing, and cardboard B. Tap water, non-sterile alcohol, and exposed skin C. Non-sterile gloves, spring, and summer D. All of the above Ensuring a “State of Control” Take advantage of this free resource Register at http://797gaptool.com Take advantage of this free resource Register at http://800gaptool.com Copyright © 2013-2017 CriticalPoint's Sterile Compounding Boot Camp® - All rights reserved Use of this educational material by a 3rd party does not constitute endorsement from CriticalPoint or Clinical IQ. Copyright © 2013-2017 CriticalPoint's Sterile Compounding Boot Camp® - All rights reserved Use of this educational material by a 3rd party does not constitute endorsement from CriticalPoint or Clinical IQ. Cleaning Mechanical process (scrubbing) using soap Cleaning or detergent and water to remove dirt, debris and many germs. It also removes invisible debris that interferes with disinfection. Sanitizing Sanitizing Chemical process of reducing the number of disease-causing germs on cleaned surfaces to a safe level. Definitions Disinfecting Chemical process that uses specific productsDisinfecting to destroy 100% harmful bacteria, viruses and fungi but not necessarily their spores on environmental surfaces. Sporicidal Agents ChemicalSporicidal process that destroys 100% of harmful microorganisms and spores Copyright © 2013-2017 CriticalPoint's Sterile Compounding Boot Camp® - All rights reserved Use of this educational material by a 3rd party does not constitute endorsement from CriticalPoint or Clinical IQ. Factors in Selecting Agents for Cleaning • Cleaning is a mechanical process enhanced by germicidal detergents to remove dirt, debris, biofilm and microbes • • • • • Cleaning prepares a surface to be disinfected Most general cleaning agents have a surfactant that removes dirt Bleach is not a cleaning agent and does not have surfactant Alcohol is not a cleaning agent, it is a disinfectant Many cleaning agents also work to disinfect but application of a cleaning agent that also disinfects does NOT replace the use of sterile 70% IPA inside C-PECs! Copyright © 2013-2017 CriticalPoint's Sterile Compounding Boot Camp® - All rights reserved Use of this educational material by a 3rd party does not constitute endorsement from CriticalPoint or Clinical IQ. Cleaning Agent Classes Hydrogen Peroxide Agents •No residues, no rinsing, not corrosive •Effective against yeast, fungi, bacteria, virus and spores based on concentration •Easy to store and stable Peroxyacetic Acid and Hydrogen Peroxide Agents •Broad-spectrum; sporicidal at low concentrations and ambient temperatures •Inactivates gram+, gram-, fungi, yeasts, viruses and spores •Not inactivated by organics and enhance their removal; Byproducts: oxygen, acetic acid and water Phenolic Agents •Many of these also EPA-registered disinfectants on environmental surfaces •Based on dilution are fungicidal, virucidal and bactericidal •Unpleasant odor; leave gummy residue that requires rinsing; may damage surfaces Quaternary Ammonium Compounds •Never sporicidal; poor activity against mycobacterium; poor activity against hydrophilic viruses •Must be rinsed; may be irritating to eyes •Efficacy reduces by hard water and organic material Copyright © 2013-2017 CriticalPoint's Sterile Compounding Boot Camp® - All rights reserved Use of this educational material by a 3rd party does not constitute endorsement from CriticalPoint or Clinical IQ. Material Handling DOES MATTER! USP Chapter <797>: • "Supplies and equipment removed from shipping cartons shall be wiped with a suitable disinfecting agent (e.g., 70% IPA) delivered from a spray bottle or other suitable delivery method. After the disinfectant is sprayed or wiped on a surface to be disinfected, the disinfectant shall be allowed to dry, during which time the item shall not be used for compounding purposes." Best Practice: • Suggest use of a sporicidal agent such as PeridoxRTU® Bleach (5000 ppm = 0.5%) Other Sporicidal agents • Instead of IPA since there have been • reports of mold spores in corrugated cardboard. IPA is also used by laboratories as a transport vehicle for spores. Copyright © 2013-2017 CriticalPoint's Sterile Compounding Boot Camp® - All rights reserved Use of this educational material by a 3rd party does not constitute endorsement from CriticalPoint or Clinical IQ. When to perform daily cleaning? This is excerpt from 797 but was not the intended meaning. • The daily cleaning (and disinfection) best occurs at the end of the day to leave the • room to rest clean. Disinfection with sterile 70% IPA (sIPA) must occur to the interior surfaces of the PEC before compounding is begun the next day (or the same day for 24 hour pharmacies) • Cleaning activities may not occur while compounding is taking place Copyright © 2013-2017 CriticalPoint's Sterile Compounding Boot Camp® - All rights reserved Use of this educational material by a 3rd party does not constitute endorsement from CriticalPoint or Clinical IQ. A cleanable step stool is essential…. • Some type of step stool must be available in controlled spaces to properly clean: Wall clocks Life Safety Signs Top of PECs Tops of doors Copyright © 2013-2017 CriticalPoint's Sterile Compounding Boot Camp® - All rights reserved Use of this educational material by a 3rd party does not constitute endorsement from CriticalPoint or Clinical IQ. Cleaning Procedures • Clean from cleanest to dirtiest • • ISO 5 PEC Buffer area Ante area General supply area Use suitable dedicated mops and cleaners Must use germicidal detergent everywhere including PEC Copyright © 2013-2017 CriticalPoint's Sterile Compounding Boot Camp® - All rights reserved Use of this educational material by a 3rd party does not constitute endorsement from CriticalPoint or Clinical IQ. Environmental Sampling • Designed to demonstrate that the primary and secondary engineering controls, disinfecting procedures, and work practices result in a suitable environment for aseptic compounding • Utilizes several approaches to assess and evaluate: Total particle counts Air viable organism cfu Surface viable organism cfu Finger touch plates Monitors State of Control Copyright © 2013-2017 CriticalPoint's Sterile Compounding Boot Camp® - All rights reserved Use of this educational material by a 3rd party does not constitute endorsement from CriticalPoint or Clinical IQ. Why Is ES Important? • Facilitates early detection of contamination and its source which may include: Personnel Work surfaces Supplies Equipment Failure of engineering controls Courtesy CBS News This is a image of the fungus growing from a sample taken from a patient’s spinal fluid. Copyright © 2013-2017 CriticalPoint's Sterile Compounding Boot Camp® - All rights reserved Use of this educational material by a 3rd party does not constitute endorsement from CriticalPoint or Clinical IQ. Environmental Sampling (continued) • • Facility Related Metrics Non Viable Sampling Temperature Pressure/Velocity Particle Sampling Personnel Related Metrics • Surface Sampling • Gloved Fingertip Sampling • Media-Fill Testing Viable Air Sampling Copyright © 2013-2017 CriticalPoint's Sterile Compounding Boot Camp® - All rights reserved Use of this educational material by a 3rd party does not constitute endorsement from CriticalPoint or Clinical IQ. Actions to Take When Action Levels Exceeded • An investigation into the source of the • contamination must be conducted. Sources: HVAC systems: changes externally Damaged HEPA filters Changes in personnel garbing habits Changes in work practices Failure to follow PnP New employees Copyright © 2013-2017 CriticalPoint's Sterile Compounding Boot Camp® - All rights reserved Use of this educational material by a 3rd party does not constitute endorsement from CriticalPoint or Clinical IQ. Environmental Sampling Plan Requirements • An ES program provides a way to monitor that the equipment, cleaning and other work practice controls result in a compounding facility controlled environment that is suited for compounding sterile preparations and detects any drift from an ongoing state of control. • When sampling occurs • Where sampling occurs • Number/size of samples • Under what conditions sampling • • • • occurs Materials required including media types and incubation conditions Action Levels Documentation Actions required in the event of excursions Copyright © 2013-2017 CriticalPoint's Sterile Compounding Boot Camp® - All rights reserved Use of this educational material by a 3rd party does not constitute endorsement from CriticalPoint or Clinical IQ. Speciation to Genus Level Currently Required “Regardless of the number of cfu identified in the pharmacy, further corrective actions will be dictated by the identification of micro-organisms recovered (at least the genus level) by an appropriate credentialed laboratory of any microbial bioburden…” - USP Chapter <797> USP 34-NF 29 Proposed Chapter requires that when samples exceed the action levels, genus must be identified and if possible, the species of microorganisms must be identified with the assistance of a credentialed microbiology laboratory Copyright © 2013-2017 CriticalPoint's Sterile Compounding Boot Camp® - All rights reserved Use of this educational material by a 3rd party does not constitute endorsement from CriticalPoint or Clinical IQ. CFU Identification and Sources Microorganisms Staphylococcus/ Micrococcus Gram negative rods Bacillus species Molds Yeast Diptheroids/ coryneforms Indication Personnel habits or gowning problems Water condensation, leaking, aerosols Dust, dirt, floor traffic, possible air handling Influx of unfiltered air, mold from street clothing or moldcontaminated cardboard, water reservoir, i.e. incubator humidification system Possible outdoor air influx; clothing-borne, especially in late summer/ fall; possible human contaminant Poor air conditioning (leading to sweating and personnel discharge from gowns) Source: Microbiological Environments (www.microbioenv.com) Copyright © 2013-2017 CriticalPoint's Sterile Compounding Boot Camp® - All rights reserved Use of this educational material by a 3rd party does not constitute endorsement from CriticalPoint or Clinical IQ. What are SOME methods to ensure a state of control? A. PROPER selection of cleaning, disinfection, and sporicidal agents B. PROPER order of cleaning, disinfection, etc C. PROPER staff training, validation, and accountability D. PROPER environmental monitoring and trending of this data E. All of the above “Opportunities” Recommended by the ABoP Arkansas Board of Pharmacy • Design of sterile compounding area – Discuss proper design for non-HD and HD rooms • Pressure differentials between classified and non-classified rooms • Insufficient air-exchanges in classified areas • Lack of HEPA filter leak tests (discuss access port expectations) • HEPA air supply expectations • Certification company expectations • “Clean” and “dirty” side designation for anterooms • Volumetric/viable air sampling expectations • Plan for corrective actions when alert levels reached/exceeded Copyright © 2013-2017 CriticalPoint's Sterile Compounding Boot Camp® - All rights reserved Use of this educational material by a 3rd party does not constitute endorsement from CriticalPoint or Clinical IQ. Arkansas Board of Pharmacy (cont.) • Inadequate documentation of • Temperature, pressure, and humidity • PEC and SEC cleaning/disinfection • Personnel training , media fill, and glove fingertip testing (initial and ongoing) • Improper storage of chemotherapy medications • Stored with other medications • Not stored in a negative pressure room with at least 12 ACH (don’t make non-HD room negative pressure) Copyright © 2013-2017 CriticalPoint's Sterile Compounding Boot Camp® - All rights reserved Use of this educational material by a 3rd party does not constitute endorsement from CriticalPoint or Clinical IQ. Environment vs. Personnel “ The most important variable affecting microbial contamination of admixtures was the aseptic technique of personnel, not the environment in which the drugs were compounded.* ” *Thomas M, Sanborn M, Couldry R. IV admixture contamination rates: Traditional practice site versus a class 1000 cleanroom. Am J HealthSyst Pharm. 2005; 62:2386-92 Copyright © 2013-2017 CriticalPoint's Sterile Compounding Boot Camp® - All rights reserved Use of this educational material by a 3rd party does not constitute endorsement from CriticalPoint or Clinical IQ. Facility Design and Equipment • • • • • • • Classified space function and design Primary engineering controls Buffer area Ante area Air supply HEPA Pressure Segregated compounding area Equipment, surfaces, and supplies Copyright © 2013-2017 CriticalPoint's Sterile Compounding Boot Camp® - All rights reserved Use of this educational material by a 3rd party does not constitute endorsement from CriticalPoint or Clinical IQ. Airflow Definitions Turbulent flow • Dilution control to reduce particulate levels • Adequate HEPA filtered airflow supplied to the cleanroom and anteroom is required to maintain cleanliness classification during operational activity Copyright © 2013-2016 CriticalPoint’s Sterile Compounding Boot Camp - All rights reserved Ante-Area Non-hazardous applications: • Anteroom must achieve at least ISO class 8 conditions & be positive pressure to uncontrolled spaces Negative to compounding room Copyright © 2013-2016 CriticalPoint’s Sterile Compounding Boot Camp - All rights reserved Ante-Area Hazardous applications: Anteroom must achieve at least ISO class 7 & be positive to uncontrolled spaces Positive to the HD compounding room Copyright © 2013-2016 CriticalPoint’s Sterile Compounding Boot Camp - All rights reserved Secondary Engineering Controls • Adequate HEPA filtered airflow supplied to the cleanroom and anteroom is required to maintain cleanliness classification during operational activity through the number of air changes per hour. Minimum of 30 HEPA filtered Air Changes Per Hour (ACPH) in Buffer Area No less than 15 ACPH must be provided as fresh HEPA air supplied through the room’s HVAC system This assumes additional HEPA filtered air is provided to the room through the primary engineering control. Supply airflow typically not continuously monitored Room pressure monitored Copyright © 2013-2016 CriticalPoint’s Sterile Compounding Boot Camp - All rights reserved Secondary Engineering Controls Ventilation efficiency • HEPA filtered supply air is introduced at the ceiling with low-wall mounted returns, creating a general top-down dilution of room air with HEPA filtered make-up air. Ceiling-mounted returns are not recommended • • • Recommend ceiling-mounted HEPA filters HEPA filters and returns well distributed throughout the room Return locations at least as important as supply inlet locations Copyright © 2013-2016 CriticalPoint’s Sterile Compounding Boot Camp - All rights reserved Ceiling mounted HEPA filters Low-wall mounted returns Copyright © 2013-2016 CriticalPoint’s Sterile Compounding Boot Camp - All rights reserved Secondary Engineering Controls • All HEPA filters should be efficiency • • tested at the most penetrating particle size leak tested at the factory and leak tested again in situ after installation. IEST type C or K HEPA filter CETA guide CAG-003-2006 for field certification Filter leak tested and repaired Copyright © 2013-2016 CriticalPoint’s Sterile Compounding Boot Camp - All rights reserved Hazardous Drug (HD) Applications • Hazardous drugs shall be stored separately from other inventory in a manner to prevent contamination and personnel exposure. • • • Minimum of 12 ACPH • HD Buffer rooms housing CACIs must meet the minimum 0.01” w.c. negative pressure and 12 ACPH requirements. Negative pressure The ISO class 5 BSC or CACI shall be placed in an ISO class 7 room that is physically separated, e.g., a different room from other preparation areas, and optimally has no less than 0.01 inches water column (w.c.) negative pressure to adjacent rooms. Copyright © 2013-2016 CriticalPoint’s Sterile Compounding Boot Camp - All rights reserved Pass-Through Usage/Location • Pass-Through Position Classified to Classified Classified to Unclassified FDA Position BOP Positions Copyright © 2013-2016 CriticalPoint’s Sterile Compounding Boot Camp - All rights reserved Secondary Engineering Certification NSF certification for BSC CAG-003-2006: CETA Certification Guide for Sterile Compounding Facilities • Airflow testing • Airflow smoke pattern test • HEPA Filter Installation Leak Test • Particle Count Survey • Optional tests Light, sound, temperature, humidity Copyright © 2013-2016 CriticalPoint’s Sterile Compounding Boot Camp - All rights reserved Secondary Engineering Controls Test Non Haz Buffer Anteroom C-SEC C-SCA Airflow ≥30 ACPH (at least 15 ACPH from outside the room) usually more ≥ 20 ACPH (from FDA guidance) but usually more is desirable ≥ 30 ACPH ≥ 12 ACPH for C-SCA or any area where HDs are stored Room Segregation Minimum differential pressure of 0.02” w.c. positive from buffer to anteroom and then again from anteroom to adjacent spaces If displacement airflow (will no longer be acceptable when Proposed USP 797 becomes official), then velocity of 40 feet/minute from cleanroom to the anteroom across the entire opening Minimum differential pressure of negative 0.01 to 0.03” w.c. from CSEC/C-SCA to adjacent space Displacement airflow not allowed in HD compounding HEPA Filter Leak Test All HEPA filters in the secondary engineering controls are tested at each certification. Maximum allowable leakage is 0.01% of the upstream aerosol concentration. Smoke Pattern Testing Buffer rooms must be segregated from the ante-area and all other adjacent spaces. Use smoke around the opening of doors to ensure air is traveling in the correct direction. Non-Viable Particle Counts ISO Class 7 ISO Class 8 unless it serves HD buffer then ISO Class 7 ISO Class 7 in buffer room No ISO classification required in C-SCA Airborne particle counter used to sample particle levels in all ISO classified locations under dynamic operating conditions. Temperature Comfortable, typically a temperature of 64-66°F but Proposed USP 797 requires 20°C or cooler Humidity Not mandatory at this time but Proposed USP 797 requires relative humidity at or below 60% at all times Adapted from CETA Certification Matrix for Sterile Compounding Facilities CAG-003-2006-13, USP <797>, Proposed USP <797>, and USP <800> on 3/11/2016. Copyright © 2013-2016 CriticalPoint’s Sterile Compounding Boot Camp - All rights reserved What is the best pressure gradient between a HD room and its associated anteroom? A. Greater than + 0.02 W.C. (with at least 12 ACPH) B. Greater than - 0.01 W.C. (with at least 12 ACPH) C. Between - 0.01 and - 0.03 W.C. (with at least 12 ACPH) Thanks again to Critical Point LLC (www.criticalpoint.info) and especially Kate Douglas, MS, RN, CRNI