2008 ASHP Summer Meeting Seattle, Washington Educational Session Abstracts

Transcription

1 2008 ASHP Summer Meeting Seattle, Washington Educational Session Abstracts 116 USP <797> Update 2008 and Personnel-Related Environmental Sampling Trissel, L.A. TriPharma Research, P.O. Box 265, Cashiers, NC 28717, USA. Kastango, E.S. Abstract: The United States Pharmacopeia (USP) has published revisions to USP Chapter <797>, the national quality standards for sterile compounding. The revised quality standards become the current standard as of June, This presentation provides an overview of the content of the USP Chapter <797> with a focus on the new and changed standards to aid practitioners in understanding and interpreting the needed quality assurance measures to protect patients from erroneous and contaminated sterile compounded preparations. Chapter <797> contains standards that begin with defining the responsibilities of compounding personnel. The Chapter also includes discussion and description of various quality assurance steps involving environmental control and monitoring, quality testing of compounded dosage forms, personnel aseptic technique evaluation, determination of product risk, storage and beyond use dating, topics for standard operating procedures, and more. The presentation will focus on these quality assurance components that need to be considered and addressed to safely provide compounded sterile products for use in patient care. Learning Objectives: 1. Outline recent revisions of USP Chapter <797> requirements. 2. Explain the rationale for many of the changed standards. 3. Explain the implications for pharmacists of changes in USP chapter <797> standards. 4. Describe five principal new sections of USP Chapter <797> needed to achieve USP chapter <797> compliance for compounding sterile preparations. Self-Assessment Questions: 1. The revisions to the quality standards of USP Chapter <797> are few in number and minor in nature. a. True

2 2008 ASHP Summer Meeting Seattle, Washington Educational Session Abstracts b. False 2. Sterile drugs compounded according to the Immediate Use category requirements: a. Allow home care pharmacies get around the quality requirements of <797>. b. Are for use within 1 hour after the start of compounding. c. Eliminate the need for a laminar airflow hood or isolator for compounding parenteral nutrition (TPN and TNA) admixtures. d. May not be stored overnight for use the next day after compounding. e. Both b and d. 3. For hazardous drugs, such as cancer chemotherapy: a. Compounding must be performed in biological safety cabinets or compounding aseptic containment isolators vented to the outside and located in a separate negative airflow ISO 7 buffer room. b. Closed-system vial transfer devices provide a suitable substitute for biological safety cabinets and compounding aseptic containment isolators. c. The requirements of <797> for hazardous drugs are to be followed no matter how few doses are compounded. d. Personal protective garb is not needed if a biological safety cabinet is used. 4. USP Chapter <797> specifies the cleaning and disinfection frequencies of sterile compounding facilities. Which of these cleaning and disinfection frequencies is incorrect? a. Floors daily. b. Biological safety cabinets, laminar airflow workbenches, and compounding aseptic isolators daily. c. Work counters daily. d. Walls and storage shelves monthly. e. Ceilings monthly. 5. For compounding aseptic isolators (CAIs), which of the following are correct? a. Placement in an ISO class 7 buffer room may be needed depending on the CAI design and functionality. b. Personnel protective garb may be required unless the CAI manufacturer has proven that the garb is unnecessary.

3 2008 ASHP Summer Meeting Seattle, Washington Educational Session Abstracts c. CAIs must be validated at the use site to maintain an ISO class 5 environment under dynamic (in-use) working conditions. d. CAIs must maintain unidirectional airflow at the critical sites. e. All of the above Answers: 1. b; 2. e; 3. a; 4. b; 5. e

4 ASHP 2008 Summer Meeting Seattle, WA 10 June, 2008 Understand the personnel-related changes of the revised USP Chapter <797> Eric S. Kastango, MBA, RPh, FASHP Clinical IQ, LLC Florham Park, NJ Disclaimer Although I am a member of the USP Sterile Compounding Committee, I am speaking in my individual capacity and not as a member of the Committee or as a USP representative. The views and opinions presented are entirely my own. They do not necessarily reflect the views of USP, ASHP or any other organization, nor should they be construed as an official explanation or interpretation of <797>.

5 Systems Thinking It must be remembered that there is nothing more difficult to plan, more doubtful of success, not more dangerous to manage than the creation of a new system; for the initiator has the enmity of all who would profit by the preservation of the old institution and merely lukewarm defenders in those who would gain by the new one. Machiavelli The Prince 1513 Leadership Responsibilities Pharmacy is a profession. Despite the challenges to professionalism presented by changes in healthcare, pharmacists must embrace the responsibilities that stem from their profession s guiding principles. ASHP Statement on Professionalism. Am J Health-Syst Pharm. 2008; 65:172-4 Believe in what is expected from employees and ensure that employees understand what is expected of them from you! Being a change agent is one of the most difficult thing you can be asked to do. The principles of USP <797> is not difficult, changing peoples attitudes and beliefs about compounding what is hard and requires great leadership.

6 Leadership Responsibilities Examine the system and monitor for failures Audit critical activities Remove the system failure in order to uncover the human errors Provide feedback Find employees doing things right Address deviations in the process or procedure Retrain Discipline Action Attitude Attitude towards compliance, following the rules and being vigilant will ultimately determine the success or failure of any program, especially aseptic compounding Regardless of Primary and Secondary Engineering Controls used, inappropriate and improper employee work practices and activities can result in contaminated CSPs

7 Responsibility of Compounding Personnel Compounding personnel are: Adequately skilled, educated, instructed, and trained to correctly perform and document the following activities in their sterile compounding duties Perform antiseptic hand cleansing and disinfection of nonsterile compounding surfaces Select and appropriately don protective garb Responsibility of Compounding Personnel Maintain or achieve sterility of CSPs in ISO Class 5 primary engineering devices and protect personnel and compounding environments from contamination by radioactive, cytotoxic, and chemotoxic drugs. Identify, weigh, and measure ingredients. Manipulate sterile products aseptically, sterilize high risk level CSPs, and label and quality inspect CSPs.

8 Hand Hygiene Hand washing is defined as the vigorous, brief (30 seconds) rubbing together of all surfaces of lathered hands, followed by rinsing under a stream of water. Hand washing suspends microorganisms and mechanically removes them by rinsing with water. The fundamental principle of hand washing is removal, not killing. Single most important way to reduce the risks of transmitting germs. Even after using anti-microbial soap, there is still about 20,000 microbes per sq mm.

9 Definitions Hand hygiene Performing handwashing, antiseptic handwash, alcohol-based handrub, surgical hand hygiene/antisepsis Handwashing Washing hands with plain soap and water Antiseptic handwash Washing hands with water and soap or other detergents containing an antiseptic chemical agent Alcohol-based handrub Rubbing hands with an alcohol-containing preparation Surgical hand hygiene/antisepsis Handwashing using an alcohol-based surgical scrub with persistent activity (Sterile compounding of preparations and the performance of a surgical procedure are considered in the same league together) Guideline for Hand Hygiene in Health-care Settings. MMWR 2002; vol. 51, no. RR-16. Hand hygiene 1 is paramount to safety, as this agar imprint of an unwashed hand shows E Larson. Am J Nurs, AJN. July 1989:935.

10 Efficacy of Hand Hygiene Preparations in Killing Bacteria Good Better Best Plain Soap Antimicrobial soap Alcohol-based handrub Ability of Hand Hygiene Agents to Reduce Bacteria on Hands % 99.9 Time After Disinfection log minutes 3.0 Bacterial Reduction Alcohol-based handrub (70% Isopropanol) Antimicrobial soap (4% Chlorhexidine) Plain soap Baseline Adapted from: Hosp Epidemiol Infect Control, 2 nd Edition, 1999.

11 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. I.V. admixture contamination rates: Traditional practice site versus a class 1000 cleanroom. Am J Health- Syst Pharm 2005;62: Compounding Personnel A human person in a cleanroom is considered a broad spectrum particle generator enclosed by inefficient mechanical filters which may also be sources of particles The human body harbors an average of different classes of bacteria Hands have an average of 100,000 organisms / sq mm The body sheds 5 grams of skin fragments each day along with shedding 1 layer of skin every 5 days (size range 10 to 300 micron 1000 th of a mm) Our greatest asset and also our biggest liability!

12 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 Sept 15. Sources of Microbial Contamination in Aseptic Processing* Source Personnel Human error Aseptic assembly Non-routine activity Mechanical failure Airborne contaminants Improper sanitization Surface contaminants 0.2 μm filter failure HEPA failure Ranks *GallocoJ, Akers J, MadsenR. Aseptic Processing: A Review of Current Industry Practice. Pharmaceutical Technology. 2004; 28(10, Oct):128.

13 Garbing requirements Garb requirement Immediateuse Low Risk (12 hr) Med Risk High Risk Makeup/Jewelry restrictions N Hand washing Hair/facial cover N Shoe covers N Low-shed gown N Sterile Gloves N Masks N

14 Employee hand hygiene and garbing Unacceptable practices Employee hand hygiene and garbing Unacceptable practices

15 Employee hand hygiene and garbing Proper Gowning Guidelines Dress from head down Dirty to Clean (head, face and feet) Wash Hands Gown Persistent Antimicrobial Hand Scrub Sterile Gloves and Sterile Alcohol Understand garment design Know how to seal gaps between clothing (closed at the neck and elastic cuffs) Perform final inspection (in mirror or others) Minimize motion Walking in street cloths generates millions of particles

16 Compounding Personnel Hair net Beard cover and face mask Gown Nonsterile Gloves Sterile Shoe covers Aseptic Technique Most critical element to prevent CSP contamination is directly related to employee aseptic technique and proper disinfection practices

17 USP 797 and Particulates Why such an emphasis? Dust Particles Breach of Aseptic Technique Contamination + = Microbes ride dust and particulates Particles with microbes infiltrate CSP Microbes grow within CSP Implication 2: Since you never get 0 particulate, proper aseptic technique controls the rest of contamination risk Implication 1: Control particulate, you reduce downstream contamination risk substantially Images courtesy ClinicalIQ, LLC. Principle of First Air Good aseptic technique in sterile compounding requires the understanding and proper use of First-Air. First-Air is the air exiting the HEPA filter in a unidirectional airstream and is virtually free of particulate contaminants. All critical manipulations must be carried out in the unobstructed first air zone in the direct path of the HEPA filter discharge. Proper product and process placement with respect to the supply and discharge will provide a contamination free compounding area. 2006, Clinical IQ, LLC and Controlled Environment Consulting Zone of first-air Simulated with smoke to show airflow

18 Direct Compounding Area (DCA) First Air 2006, Clinical IQ, LLC and Controlled Environment Consulting The DCA is only the portion of the PEC dedicated to the task of aseptic manipulation. Second Air 2006, Clinical IQ, LLC and Controlled Environment Consulting Improper hand placement disrupts first air

19 First Air 2006, Clinical IQ, LLC and Controlled Environment Consulting Proper hand placement permits first air Training and Evaluation Compounding personnel shall perform didactic review and pass written test and media-fill testing of aseptic manipulative skill initially. At least annually thereafter for low- and medium-risk compounding. At least semiannually for high-risk level compounding. Consider performing routine observational audits of employee work practices Document observational audits

20 Evidence-based science An Intervention to Decrease Catheter-Related Bloodstream Infections in the ICU. N Engl J Med 2006;355: An evidence-based intervention resulted in a large and sustained reduction (up to 66%) in rates of catheter-related bloodstream infection that was maintained throughout the 18- month study period. The average infection rate fell from 7.7 percent to 1.4 percent 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 wash their hands before the procedure. Assuring full barrier protection -- a sterile bed sheet rather than just keeping the insertion site sterile, Staff wear sterile gloves, gowns, hair nets and masks. Cleansing the skin surface with chlorhexidine. Environmental Sampling Environmental Sampling Task Dilemma: One of the most contentious section of USP Chapter <797> Since 1970 s, the US Centers for Disease Control (CDC) has not advocated routine viable environmental monitoring The US Food and Drug Administration requires sterile processing operations to perform daily monitoring of viable air, surface and personnel glove fingertip samples

21 Environmental Sampling Routine Viable Microbial Environmental Monitoring (EM) None Daily US Centers for Disease Control US Food and Drug Administration Environmental Monitoring None Routine Viable Microbial Environmental Monitoring (EM) USP 797 Daily US Centers for Disease Control US Food and Drug Administration

22 Environmental Monitoring Environmental Monitoring section has been separated into a facility-related performance metric and a personnel related performance metric Facility-related Environmental Sampling Viable air samplingvia volumetric method (impaction) to occur at least every 6 months Personnel-related Environmental Sampling Personnel fingertip sampling during initial training, with media fills and as a competency assessment tool Surface sampling for viable microorganisms Environmental Sampling: Viable Air Sampling Collection method via electric volumetric sampler (impaction preferred method) Gravimetric methods (e.g., plates or paddles) are not permitted Growth media: TSB and MEA (when high-risk compounding) Sampling plan developed and based on a risk assessment of compounding activities Sampling locations to include: Each ISO Class 5 Engineering Control Area in ISO Class 7 and 8 and segregated areas and around ISO Class 5 area at greatest risk (e.g., pass-thru, labeling, staging, gowning areas)

23 Environmental Sampling: Viable Air Sampling Sampling plan to include: Method of collection (Impaction preferred method) Frequency of testing Volume of air sampled ( L) Time of day and activity of compounding CFUs action levels Frequency of testing Initial facility commissioning At least every six months during recertification of facility and engineering controls of all areas Reference: USP <1116>: Microbiological Evaluation of Clean Rooms and Other Controlled Environments Environmental Monitoring Viable Air Sampling Gravimetric vs. Volumetric Sampling Courtesy of MSI, Inc. Houston, TX (

24 Environmental Sampling: Employee-centric Activities The risk of contaminating a CSP prepared under low-risk level and medium-risk level conditions is highly dependent on: Proper hand hygiene and garbing practices, Compounding personnel aseptic technique, and Presence of surface contamination Assumes all work is performed in a certified and properly functioning ISO Class 5 Environmental Sampling: Employee-centric Activities Compounding personnel shall: Complete didactic training, Pass written competence assessments, Undergo skill assessment using observational audit tools (see Appendices III V) Garbing and Gloving Competency Evaluation Aseptic Manipulation Competency Evaluation Cleaning And Disinfecting Competency Evaluation Successfully complete aseptic media fill testing

25 Environmental Sampling: Gloved Fingertip Sampling Initial training assessment with audit tool Successful gloving with three-time fingertip sampling with ZERO CFUs Annually re-assessment for low and medium-risk compounding operations Semi-annual re-assessment for high-risk compounding operations During any media fills Environmental Sampling: Surface Surface Cleaning and Disinfection Sampling and Assessment Surface sampling is an important component of the maintenance of a suitable microbially controlled environment Transfer of microbial contamination from improperly disinfected work surfaces via inadvertent touch contact by compounding personnel can be a potential source of contamination of CSPs It is useful for evaluating facility and work surface cleaning and disinfecting procedures and employee competency in work practices such as disinfection of component/vial surface cleaning.

26 Environmental Sampling: Surface Surface Cleaning and Disinfection Sampling and Assessment Sampling of all ISO classified areas will occur on a periodic basis at the end of compounding Contact plates (plate size cm 2 ) Swabs (defined template) Plates to have a neutralizing agents (lecithin and polysorbate 80) Environmental Sampling: Cleaning Cleaning And Disinfecting Competency Evaluation Compounding personnel and other personnel responsible for cleaning shall be visually observed during: Performance of cleaning and disinfecting procedures During initial personnel training on cleaning procedures During changes in cleaning staff, At the completion of any media-fill test procedure Visual observation documented on Sample Form (Appendix V)

27 Integration of Policy into Practice Where do we begin? How do we begin? How do we ensure success? How do we measure success? Integration of Policy into Practice Where do we begin? Identify the desired state of being What is driving this desired state of being? Resources (Fiscal, Human or other) Regulatory In response to an event What do want our process to look it but more importantly What is our desired outcome from our policy?

28 Integration of Policy into Practice How do we begin? Must involve all employees who will have an affect, contribution or influence over the system Employees must be process owners and buy into the desired state The creation of shared vision or model is critical Try to identify all the roadblocks to success Optimize the system! Termite Hill Can t be reduced to the termites Statistically emergent from termite By the way there is no CEO termite or DOP termite etc., just termites that all know their places and tasks in the system We establish order and control through actions of a few top people in the organization this may be the biggest factor holding back innovation and progress in our organizations

29 Integration of Policy into Practice How do we measure success? Look carefully for workarounds, shadow aids, and other deviations Indicators of attempts to bridge gaps in performance Non-threatening observations of real work give voice to the unvoiced Give feedback (positive and negative) and demonstrate leadership People respect what we inspect! Try not. Do, or do not. There is no try. -Master oda