Seven Deadly Myths of USP <797>

Transcription

1 Quality Management Software for USP 797 Temperature Logs Competency Tracking Batch Processing Policies & Procedures Get a free demo today at Simplifi797.com!

2 Seven Deadly Myths of USP <797> Eric S. Kastango, MBA, RPh, FASHP Clinical IQ, LLC 1

3 Disclaimer "Although I am a member of the USP Sterile Compounding Expert Committee, I am speaking today in my individual capacity and not as a member of the Committee or as a USP representative. ese e. The views and opinions presented are entirely my own. They do not necessarily reflect the views of USP, nor should they be construed as an official explanation or interpretation of <797>. 2

4 Compliance is an endpoint Paper is bad in the cleanroom Facility construction = compliance Outsourcing shifts our risk My state board doesn't reference <797>, so I don't need to be in compliance Having a gap gpanalysis is enough to prove ongoing g efforts at compliance The Chapter is not evidence based 3

5 Myths and not sins TOPICS THAT WILL NOT BE DISCUSSED TODAY Lust (Latin, luxuria) Gluttony (Latin, gula) Greed d(latin, avaritia) Sloth (Latin, acedia) Wrath (Latin, ira) Envy (Latin, invidia) Pride (Latin, superbia) 4

7 Seeking <797> Compliance Because the process to achieve compliance is not clearly defined, it is impossible to say products comply with <797>. People, equipment, or products may help or harm compliance efforts, but they affect the aggregate process. There is no official i certification process for products for <797>. There is no Good Housekeeping seal for <797> compliance of pharmacy products The only way to meet the 797 requirements is to understand its various quality elements and incorporate them into the daily practices of all compounding activities performed by all persons who prepared p CSPs. 6of 71

8 Compliance is an endpoint? Think about compliance as a two step process: Achieve compliance Maintain compliance Consider: Linear process of achieving compliance (get to a point in time) Cyclical aspect of process improvement (maintain your state of compliance) Compliance isn t an endpoint or a finish line State of Compliance (point in time) Achieve Compliance Process Improvement 7

10 There Is No Such Thing as Zero Particulate: Concept of Particle Limits 1. Rapid elimination of particles from DCA 2. Movement from cleanto dirtier areas 3. Dilution into air with a higher and higher particle limit (one particle among many) ISO Class Particles/m 3 US Class Particles/ft 3 Stockroom Uncontrolled (no particle limits) Ante Area ISO Class 8 Class 100,000 3,520, ,000 Buffer Area ISO Class 7 Class 10, ,000 10,000 PEC (Hood, ISO Class 5 Class 100 Isolator) 3, Used with permission, BD Medical Direct Compounding Area (DCA) 9

11 Refining Language Based on Evidence USP <797> 2004 Objects that shed particles cannot be brought into the buffer or clean area, including pencils, cardboardcartons cartons, papertowels, and cotton items. Only nonshedding paper related products (boxes, work records, and so forth) can be brought into the buffer or clean area. USP <797> 2009 Nonessential objects that shed particles shall not be brought into the buffer area, including pencils, cardboardcartons cartons, papertowels, and cotton items (e.g., gauze pads). Essential paper relatedrelated products (e.g., paper syringe overwraps, work records contained in a protective sleeve) shall be wiped down with an appropriate disinfecting agent prior to being brought into the buffer area Clinical IQ, LLC. All rights reserved 10

12 Particles from opening syringes Kastango, ES, Wagner JT, Kastango KB, Kastango NE, and Wagner TJ. Generation of particulate matter during handling of needle and syringe packaging. Am J Health Syst Pharm. 2008; 65:

13 Measuring the particles released Expect zero here (why?) Measure particulate from open packaging here Expect zero or close to zero here (why?) Measure particulate burden in buffer area Kastango, ES, Wagner JT, Kastango KB, Kastango NE, and Wagner TJ. Generation of particulate matter during handling of needle and syringe packaging. Am J Health Syst Pharm. 2008; 65:

14 Peel & Present: always lower particle counts than Pop Through... 40,000 Average Particle Count For Two Methods of Opening particle es per cubic fo oot (ppcf) 35,000 30,000 25,000 20,000 15,000 10,000 5, ,243 Peel and Present Pop Thru 17,937 17,222 6,230 4,182 4,512 5,713 2,472 2, BD Tyco Terumo BD Tyco BD Tyco BD Tyco Terumo 18g needle 1mL syringe 60mL syringe 10 ml/12 ml syringe Kastango, ES, Wagner JT, Kastango KB, Kastango NE, and Wagner TJ. Generation of particulate matter during handling of needle and syringe packaging. Am J Health-Syst Pharm. 2008; 65:

15 Principle of First Air Good aseptic technique in sterile compounding requires the understanding andproper use of First Air : First air zone is in the direct path of the HEPA filter discharge. Unidirectional air stream Virtually free of particulate contaminants. All critical manipulations must be carried out in the unobstructed First Air zone Proper product and process 2006, Clinical IQ, LLC and Controlled Environment Consulting placement with respect to the supply and discharge will provide Zone of first air a contamination free compounding area. Simulated with smoke to show airflow 14

16 Direct Compounding Area (DCA) DCA First Air 2006, Clinical IQ, LLC and Controlled Environment Consulting The DCA is only the portion of the ISO Class 5 device dedicated to the task of aseptic manipulation. 15

17 Environment vs. Personnel It is dangerous to assume that the use of a cleanroom will independently improve the quality of patient care by eliminating contamination. Once a baseline environmental quality (class 100 LAF hood) is established, admixture quality assurance efforts should focus on other critical factors Thomas M, Sanborn M, Couldry R. I.V. admixture contamination rates: Traditional practice site versus a class 1000 cleanroom. Am J Health Syst Pharm 2005;62:

19 Facility construction=compliance There are three broad areas that contribute to meeting the objectives of USP <797> Contamination Control Address particulate sources people, products, process Create a clean environment where aseptic compounding will take place Training and Documentation Compounding personnel are skilled, educated and trained Operator testing for proficiency Written policies, procedures Document training CSP Checks and Tests Reduce occurrence of contamination Verify the process produced correct CSPs Use the same process each htime If contamination or error happens, detect it and take action 2009 Clinical IQ, LLC. All rights reserved 18

23 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. ThomasM M, SanbornM M, CouldryR R. IV I.V. admixture contamination rates: Traditional practice site versus a class 1000 cleanroom. Am J Health Syst Pharm 2005;62: Clinical IQ, LLC. All rights reserved 22

25 Outsourcing shifts our risk National, regional and local providers of outsourcing services Parenteral nutrition Cardioplegia SVPs Anesthesia syringes PCA syringes Significant advantages to outsourcing CSPs 24

26 Outsourcing shifts our risk Caveat Emptor ( Buyer Beware ) If non patient specific (NPS) medications are provided by vendor: 1. They should be registered with the FDA as a manufacturer 2. How do they ensure the sterility of their CSPs? 3. How do they ensure the content accuracy of their CSPs? 4. How do support their beyond use dates? Is this data available for review 25

27 Outsourcing shifts our risk In lieu of a detailed ANDA or NDA submission to the FDA, outsource vendors are expected by the FDA to have the ability to link its CSPs to specific patient to whom the CSPs are ultimately dispensed*. Do you have the necessary controls to link outsourced CSPs by lot or control number to specific patients in the event of a recall? * p// / / g_ / /g p 26

28 Outsourcing shifts our risk Customer Responsibilities Customer shall be responsible for determining whether any compounded solution provided under this XXX Services Agreement is clinically correct, appropriate or accurate for prescribing to any particular patient and for any particular disease or condition, and for determining and recording the individual id patients that receive the medications. i 27

30 My state board doesn't reference <797>, so I don't need to be in compliance In addition to State Board of Pharmacy, are there other legal or regulatory/accreditation issues you need to consider? 29

31 Compliance optional The Joint Commission (TJC) Standard MM Elements of Performance for MM The hospital collects data on the performance of its medication management system. (See also PI , EPs 14 and 15) 4. The hospital reviews the literature and other external sources for new technologies and best practices. 5. Based on analysis of its data as well as review of the literature for new technologies andbestpractices practices, the hospitalidentifies identifies opportunities for improvement in its medication management system. 6. The hospital takes action on improvement opportunities identified as priorities for its medication management system. 7. The hospital evaluates changes to confirm that they resulted in improvements for its medication management system. 8. The hospital takes action when planned improvements for its medication management processes are either not achieved or not sustained. 30

32 Compliance Optional Warranties of a compounding pharmacist David B. Brushwood and W. Thomas Smith Am J Health Syst Pharm. 2009; 66:

33 Compliance optional Introduction to the Law It has become commonplace in American commerce to expect that a purchased commodity will bring with it a warranty, in the absence of an expressed disclaimer. A warranty indicates that a commodity is free ofdefect and that statements made about the commodity are complete and truthful. A breach of warranty may serve as the basis of litigation against the provider of the commodity if harm has occurred to the user of the commodity. A recent case before the Court of Appeals for the Fifth District of Florida reviewed exposure to liability of a pharmacy that had compounded an allegedly defective drug product (contaminated TPN). In this case, the court distinguished between liability under the law of warranty and liability under the law of negligence, gg or strict liability. Warranties of a compounding pharmacist. Brushwood DB, Smith WT, Am J Health Syst Pharm. 2009; 66:

34 Conclusion Compliance optional In protecting themselves and their institutions from liability: pharmacists must be mindful not only of the standards of care they must meet...but also the expectations patients will have of pharmacists and the warranties that may result from these expectations. Having: clear policies and procedures, thorough training and supervision of pharmacy technicians adequate documentation of what was done in the preparation of a prescription order for a patient will provide the evidence necessary to demonstrate compliance with an implied warranty. Warranties of a compounding pharmacist. Brushwood DB, Smith WT, Am J Health-Syst Pharm. 2009; 66:

36 Is having a gap analysis enough? USP <797> Compliance Process Overview Planning to Change and Changing Action planning and implementation against identified gaps bring compliance! State of Compliance (point in time) Understand Regulation Assess Risk Level Perform Gap Analysis Develop Action Plan Implement Compliance Plan Control Identifying What to Change Gap analysis is an important activity to identify areas requiring improvement (people, process, facility) Ensuring Changes are Permanent Control measures ensure changes stick and help identify further improvements. 35

37 Baseline Measure of Current Performance Pe ercent Shoe Hair Face Wash to Gown Hand Gloves Spray Cover Cover Mask elbows Sanitizer Gloves Slide courtesy of J. Kacmarcik, JHHMC Baseline N= 66 (5/12 5/29)

38 Repeated educational and audit cycle results Baseline N = 66 (5/12-5/29) Cycle 1 N = 48 (5/30-6/5) Cycle 2 N = 44 (6/6-6/12) Cycle 3 N = 52 (6/13-6/20)

40 Compounding

41 Inherent Particles Present in Cleanrooms Activity Person emits during garmenting process Particles 0.3 μm 3,000,000/min Cleanest skin (hands) 10,000,000/ft 2 Employee street clothes 10,000,000 30,000,000/ft 2 Floor and bench surfaces > 10,000,000/ft 2 Garments supplied by cleanroom laundry 1,000,000/ft 2 Kastango ES, Bradshaw, B, AJHP, vol 61: Sep 15, 2005

42 Sources of Microbial Contamination in Aseptic Processing* Source Ranks Personnel 1 1 Human error 2 2 Aseptic assembly 4 3 Non routine activity 3 4 Mechanical failure 5 5 Airborne contaminants 7 6 Improper sanitization 6 7 Surface contaminants μm filter failure 8 8 HEPA failure 9 9 *AgallocoJ, Akers J, Madsen R. Aseptic Processing: A Review of Current Industry Practice. Pharmaceutical Technology. 2004; 28(10, Oct):128.

43 Compounding Personnel Hair net Beard cover and face mask Gown Nonsterile Gloves Sterile Shoe covers

44 Employee hand hygiene and garbing: Unacceptable practices

45 Intrinsic vs. Extrinsic Contamination "Intrinsic contamination occurs during the manufacturing process, either via the introduction of contaminant or the failure to inactivate contaminants that are present in the raw ingredients." (e.g., High risk compounding scenario) "Extrinsic contamination occurs after manufacturing, generally after the product's container has been opened for use." (e.g., a failure of following good aseptic technique.) 44

46 Outbreaks caused by multiple dose vials from 1983 through 2002 Propofol Propofol Propofol Propofol Propofol Medication Pathogen Infection Patients Death Evidence of relatedness Propofol Propofol Saline Saline Saline Saline and anesthetic Saline Epoetin alfa Vaccine DT Vaccine DTP Heparin Heparin Heparin and saline solution Dextrose (NICU) TPN Anesthetic; not specified Distilled water Bupivacaine Methyl-prednisone Iomeprol Not specified Not specified E Cloacae S marcescens S aureus S aureus S aureus, C albicans, Moraxella, osloensis, E agglomerans, S marcescens K pneumoniae HCV HCV A xylosoxidans HCV S aureus HBV S liquefaciens Streptococci, group A Streptococci, group A B cepacia Plasmodium falciparum HCV E cloacae and P aeruginosa C albicans HBV P pickettii HBV S marcescens P aeruginosa HIV HCV, wound infection Wound infection Nosocomial infections Hepatitis C Hepatitis C Hepatitis, Abscess Hepatitis Abscess Abscess Malaria Hepatitis Hepatitis Hepatitis Arthritis Meningitis AIDS Hepatitis Epidemiologic, molecular biological Epidemiologic, molecular biological Molecular biological Epidemiologic, molecular biological Epidemiologic, molecular biological Microbiological Epidemiologic, molecular biological Epidemiologic, molecular biological Microbiologic Molecular biological Molecular biological Molecular biological Molecular biological Microbiologic Microbiologic Epidemiologic, i i molecular l biological i l Epidemiologic Epidemiologic, molecular biological 6 Epidemiologic, molecular biological 8 2 Molecular biological 2 3 Epidemiologic, molecular biological Microbiologic Epidemiologic, serotyping Microbiologic Molecular biological 2 Epidemiologic, molecular biological Epidemiologic, molecular biological Year Reported Abbreviations:, bloodstream infection; DT, diphtheria and tetanus toxoids; DTP, diphtheria and tetanus toxoids and pertussis; HBV, hepatitis B virus; HCV, hepatitis C virus; NICU, neonatal intensive care unit; TPN, total parenteral nutrition. Bacterial contamination of multiple-dose vials: A prevalence study, Mattner, F., Gastmeier, P., Amer. J. Infection Control, vol. 32, no. 1, February 2004, pp

47 Outbreaks Associated with Contaminated Medications by Contaminant Name, 2001 Contaminant Clinical Syndrome Medication Intrinsic or Extrinsic Gram-negative bacteria Acinetobacter calcoaceticus PR Peritonitis Heparinized saline Peritoneal dialysate Extrinsic Extrinsic Burkholderia cepacia Enterobacter cloacae RTI Sterile water Multidose dextrose Albuterol Fentanyl Human albumin Multidose dextrose Intrinsic Extrinsic Extrinsic Intrinsic Intrinsic Extrinsic Klebsiella pneumoniae Pseudomonas aeruginosa Ralstonia picketii Serratia marcesens Serratia liquefaciens Serratia odorifera Mixed gram-negative Gram-positive bacteria Bacillus cereus Staphylococcus aureus Staphylococcus saprophyticus Group A Streptococcus Mycobacteria Mycobacterium abcessus Mycobacterium chelonae Fungi Candida albicans Candida parapsilosis Virus HIV HBV HCV Multiple organisms Endotoxin Gram-positive toxins UTI, colonization RTI/colonization, PR Abcesses Abcesses Abcesses Abcesses, disseminated Endophthalmitis Transmission Transmission Transmission Transmission, SSI, fever Sterile peritontitis Fever/hypotension Parenteral nutrition Ultrasound coupling gel Multidose dextrose Sterile water, injection Fentanyl Sterile saline, respiratory Fentanyl Epoetin alfa Parenteral nutrition Parenteral nutrition Calcium gluconate DTP vaccine Parenteral nutrition DTP vaccine Adrenal cortical extract Multidose lidocaine Parenteral nutrition Parenteral nutrition Balanced salt solution Hemodialysis flush solution Multidose saline Multidose local anesthetic Multidose saline Propofol Peritoneal dialysate Polygeline Extrinsic Extrinsic Extrinsic Intrinsic Extrinsic Intrinsic Extrinsic Extrinsic Intrinsic Extrinsic Intrinsic Extrinsic Extrinsic Extrinsic Intrinsic Extrinsic Extrinsic Extrinsic Intrinsic Extrinsic Extrinsic Extrinsic Etrinsic Extrinsic Extrinsic Intrinsic Intrinsic Abbreviations: PR, pyrogenic reaction;, bloodstream infection; RTI, respiratory tract infection; UTI, urinary tract infection; DTP diphtheria-tetanus-pertussis; HIV, human immunodeficiency virus; HBV, hepatitis B virus; HCV, hepatitis C virus; SSI, surgical site infection. Seminars in Infection Control, vol. 1, no. 2, June 2001

48 Outbreaks Associated with Intrinsic* Contaminated Medications by Contaminant Name, 2001 Contaminant Clinical Syndrome Medication Gram-negative bacteria Burkholderia cepacia Sterile water Fentanyl Enterobacter cloacae Ralstonia picketii Serratia odorifera RTI/colonization Human albumin Sterile water, injection Sterile saline, respiratory Parenteral nutrition Gram-positive bacteria Bacillus cereus Mycobacteria Mycobacterium abcessus Fungi Candida parapsilosis Endotoxin Gram-positive toxins Abcesses Endophthalmitis Sterile peritontitis Fever/hypotension Calcium gluconate Adrenal cortical extract Balanced salt solution Peritoneal dialysate Polygeline Abbreviations: PR, pyrogenic reaction;, bloodstream infection; RTI, respiratory tract infection; UTI, urinary tract infection; DTP diphtheriatetanus-pertussis; HIV, human immunodeficiency virus; HBV, hepatitis B virus; HCV, hepatitis C virus; SSI, surgical site infection. Seminars in Infection Control, vol. 1, no. 2, June *Intrinsic = introduced at the type of manufacture/medication preparation 47

49 Evidence based science An Intervention to Decrease Catheter Related Bloodstream Infections in the ICU. N Engl J Med 2006;355: The average infection rate fell from 7.7/1,000 central line catheter days to 1.4/ 1,000 central line catheter days after 18 months. 'More than half the hospitals (103) in this study were able to report that they had ZERO infections after implementing the program,' Consistent and vigilant work practices were key factor: Assuring that participants ii wash their hihands bf before the procedure. Assuring full barrier protection a sterile bed sheet rather than just keeping the insertion site sterile, Staffwear sterilegloves gloves, gowns, hairnets and masks. Cleansing the skin surface with chlorhexidine. 48

50 Proper employee hand hygiene and garbing: Cii Critical lpatient Safety Sf Initiative i i 49

51 Any Questions? Access to USP <797> info: FAQs to be published on USP website shortly Information on State Board of Pharmacy s requirements regarding USP<797>: Mycontact information: Eric S. Kastango, MBA, RPh, FASHP [email protected] 50