Implementation of a Personnel Training and Assessment Program for the Compounding of Sterile Preparations

1. Implementation of a Personnel Training and Assessment Program for the Compounding of Sterile Preparations Philip Trapskin, PharmD Pharmacy Practice Management Resident KSHP 2005 Spring Meeting May 19th, 2005

2. Review of the USP 797 standards related to personnel training and assessment Describe the personnel training and assessment program at the University of Kentucky Chandler Medical Center Discuss practical approaches and provide take home materials for the development and implementation of a training and assessment program at your institution Objectives

3. True Story 5-11 Betamethasone (BM) inj. compounded 6-7 Swabs taken at pharmacy grow Serratia 5-31 More BM injs. given 6-2 Second pt. dies 6-8 38 pts. treated with antibiotics; 10 hospitalized; 3 deaths 5-29 14 pts. receive BM inj. for back pain 6-6 Autopsy finds fist pt. died of Serratia meningitis; state board of pharmacy notified and pharmacy is inspected 5-30 First pt. dies

4. More Publicity • 2002 “Painkiller suspected in fourth N.C. meningitis case.” • 2003 “Enterobacter cloacae bloodstream infections in pediatric patients traced to a hospital pharmacy.” • 2004 “Stirring Debate: As druggists mix customized brews, FDA raises alarm; ‘Compounders’ often meet special needs, but industry falls in regulatory gap; rare fungus in steroids.” • 2005 “Safety concerns grow over pharmacy-mixed drugs.”

5. Why might contamination happen? • Quality assurance for sterile preparations incurs costs. • Adequate quality assurance requires time and effort … essential quality assurance functions for sterile preparation may not be performed adequately. • Not all pharmacists believe in necessity of strict standards… “We have always done it this way”… • Most pharmacists have not been adequately trained in the theory and practice of sterile product preparation. Training is often on the job and of uncertain adequacy… Trissel. Am J Health-Syst Pharm 2003;60:432

6. What level of regulation is necessary? • Lack of evidence for sterile-product preparation guidelines • Reports of contamination in the literature lack relevance • “Are pharmacists unconcerned about their patients’ safety or just not convinced of the need for sweeping changes” • Education and training… more important than garb… Kopcha. Am J Health-Syst Pharm 2004;61:1445-46

7. Where was the profession in 2002? • National Survey of Quality Assurance Activities for Pharmacy-Compounded Sterile Preparations • Written questionnaire to pharmacy directors • Survey sample of 600 hospitals in the U.S. • 182 (30.3%) of hospitals returned surveys • Survey designed to measure compliance with 2000 ASHP Technical Assistance Bulletin Compounded Sterile Products (CSP) Morris et al. Am J Health-Syst Pharm 2003;60:2567-76

8. Which Guidelines are Used to Develop CSP Policies and Procedures Morris et al. Am J Health-Syst Pharm 2003;60:2567-76

9. Which staff receive CSP training? Morris et al. Am J Health-Syst Pharm 2003;60:2567-76

10. What methods are used to train staff in CSP preparation? Morris et al. Am J Health-Syst Pharm 2003;60:2567-76

11. What areas are covered in training of CSP preparation? Morris et al. Am J Health-Syst Pharm 2003;60:2567-76

12. What methods were used to assess CSP skills? Morris et al. Am J Health-Syst Pharm 2003;60:2567-76

13. United States Pharmacopeia Chapter <797>

14. Selected Sections of Chapter <797> • Personnel cleansing and gowning • Responsibilities of compounding personnel • Risk level classification of Compounded Sterile Products (CSP) and quality assurance • Verification of accuracy and sterilization • Personnel training and assessment • Environmental quality and control • Equipment • Storage and beyond-use dating

15. Personnel Training and Assessment “Personnel who prepare CSPs must be provided with appropriate training from expert personnel, audio-video instructional sources, and professional publications in the theoretical principles and practical skills of aseptic manipulation before they begin to prepare CSPs.”

16. Personnel Training and Assessment • Compounding personnel shall perform didactic review, and pass written and media-fill challenge testing initially and: • Annually for personnel preparing low and medium-risk level products • Semi-annually for personnel preparing high-risk level products • Media-fill tests must simulate the most challenging and stressful compounding products and conditions

17. Personnel Training and Assessment • Media-fill challenge • Sterile bacterial culture medium transferred via a variety of aseptic manipulations • Products are monitored for microbial growth indicated by visual turbidity for 14 days • Failure to successfully complete all components of the assessment requires re-instruction and re-evaluation before personnel are permitted to compound sterile products

18. Steps for Implementation • Create training and assessment curriculum for your institution • Obtain necessary references and materials • Create a system to document and track personnel training status • Identify personnel that require training and assessment • Train and assess personnel as part of an on-going quality assurance process

19. UKCMC Training and Assessment Program • Didactic Lectures • Instructional Video • Computer based learning modules • Proctored media-fill challenge test and assessment of aseptic technique

20. Didactic Lectures • Instructors • Pharmacist • Technician Supervisor • Review of theoretical principles of aseptic technique and sterile compounding • Review of practical skills of aseptic technique with hands-on simulations of common aseptic manipulations • Provided over 3 separate 1-hour sessions

21. Available from ASHP Selected sections are viewed and associated workbook chapters are completed Instructional audio-video

22. Computer Based Learning Modules • Administered via NetLearning® Software (Knoxville, TN) • Personnel can access PowerPoint slide lectures via the internet • Content created by UKCMC staff • Pre and post-test capabilities allow for the assessment of learners and documentation via an electronic transcript

23. Computer Based Learning Modules • USP <797> CBL curriculum includes: • Aseptic manipulations • Review of definitions and theoretical principals and practical skills of aseptic manipulations • Pharmacy Calculations • Review of definitions, common abbreviations and common math calculations • USP chapter <797> standards • Review of background for creation and overview of the standards • CBL slides are available at the UK Pharmacy Services Website www.hosp.uky.edu/pharmacy/

29. P<0.05 P<0.001

30. Media-Fill Challenge Test • Proctored by one of two pharmacists • Assessment checklist developed to standardize assessment • Simulated products included: • Ampule to minibag • Vial to minibag • Vial to minibag via mini-spike • Syringe dilution • Total number of manipulations >25

31. Media-Fill Challenge Test • Soybean-Casein Digest Medium • Aerobic bacteria and fungi • Incubate at room temperature for 14 days • Vendors • QI Medical http://www.qimedical.com/ • Valiteq http://www.valiteq.com/

32. * *Micrococcus and Bacillus spp

33. Limitations • Relatively small sample size for media-fill challenge tests • Testing conditions for practical exam may bias (underestimate) true contamination rate • Attention bias or Hawthorne effect • Testing was scheduled not by surprise

34. Low-Risk-Level Contamination Rate • Use of medium-fill simulation to simulate low-risk-level compounding • 1035 1-ml TB syringes filled with 0.9ml of medium • Performed by 2 CPhT in ISO 5 conditions • No bacterial growth was detected in any of the 1035 syringes • Contamination rate concluded to be <0.1% Trissel. Am J Health-Syst Pharm 2003;60:1853-55

35. Medium-Risk-Level Contamination Rate • Use of medium-fill simulation to simulate medium-risk-level compounding • Reconstitution of dry growth medium • Withdrawals from vials ampuls with syringes, needles, a dispensing pin, and a filter straw • Transfers of the growth medium into an empty plastic bag • Of 539 evaluations over 2 years, 28 (5.2%) yielded microbial growth Trissel. Am J Health-Syst Pharm 2005;62:800-03

36. Conclusions • Training and assessment program successfully developed and implemented to meet USP standards • CBLs able to teach key concepts and document understanding • Lack of standard practice in aseptic manipulation techniques observed during assessments • Media-fill growth rate for medium risk level preparations consistent with other reports in the literature • Contamination rate of 5% would be unacceptable if extrapolated to all CSPs

37. Summary • Focus on the basics • Training and assessment of aseptic manipulations should be ongoing • Don’t reinvent the wheel • A good program does not need to break the bank