IV Sterile Compounding Risks and Safety Scarlett S. Eckert, Pharm. - PDF document

1/20/2019 1 IV Sterile Compounding Risks and Safety Scarlett S. Eckert, Pharm. D. 2 Relevant Financial Relationships with Commercial Interests Speaker’s disclosure of any relevant financial relationships with any commercial interest. 1

1/20/2019 3 Objectives Review the severity of IV compounding errors.  Review the New ‘proposed’ USP <797> requirements addressing IV  compounding safety. Review the USP <800> personnel, environment and patient safety  requirements. Describe the components of IV compounding errors.  Identify which risk factors and safety issues can be mitigated.  Discuss how to mitigate risk factors and improve safety of your cleanroom  practices and compounded sterile products. 4 Pre-Test Questions 1. With 100% IV compounding best practice in place 100% of the time, what would be the best accuracy percent you could expect? A. 100 80 B. C. 99.9 D. 75 2. The primary contributing factor of IV compounding errors can be contributed to: Consumable labeling, vials and bags A. Detailed and difficult to follow SOPs B. USP <797> lack of regulatory guidance C. Compounding staff and checking staff D. 2

1/20/2019 5 Pre-Test Questions 3. USP <797> proposed revision does not require visual inspection of Category 1 CSP? True or False 4. USP <800>, allow for Assessment of Risk for compounding drugs on NIOSH table 1, 2 and 3. True or False It is possible to eliminate 100% of the risk associated with manual 5. compounding? True or False 6 Sterile Compounding Safety and Risk What is “Safety”? Condition of being protected from hazards, risks, and harm What is “Sterile Compounding” Performing manipulations of presumed sterile ingredients in a manner which prevents introduction of viable and nonviable contaminants (Proper nomenclature = Aseptic Compounding) 3

1/20/2019 7 What is in the bag? Sterile compounding is the least transparent and most technique-critical process in the pharmacy: Start with sterile drug vial, diluent bags, needles, syringes Accurately manipulate into needed dose and dosage  form Without introducing particulate or viable contaminant  Two potential safety risks that must be mitigated: Accuracy of dose – must have confidence that every  fluid transfer was performed within acceptable tolerance Sterility of finished dose – must have flawless aseptic  technique 100% of the time 8 Sterility Assurance – The Invisible Problem How do we assure sterility ?  Impossible to achieve 100% sterility using aseptic compounding techniques. Even with terminal sterilization, the practical sterility assurance limit is 1x10 -6  With best practices used 100% of the time, the residual risk is 1:1000 for a contaminated dose.  For each contact of the sterile item with a non-sterile object, risk of contamination rises at least 30-fold (contamination recovery rate range 3 - 67%) 4

1/20/2019 9 Contaminated Doses Rate with 99.9% Sterility Rate DOSES PER BED PER DAY BED SIZE 1 2 3 4 5 ANNUALIZED POTENTIALLY CONTAMINATED DOSES 100 37 73 110 146 183 WHEN STERILITY RATE 99.9% 200 73 146 219 292 365 300 110 219 329 438 548 400 146 292 438 584 730 500 183 365 548 730 913 600 219 438 657 876 1095 700 256 511 767 1022 1278 800 292 584 876 1168 1460 900 329 657 986 1314 1643 1000 365 730 1095 1460 1825 10 QUESTION 1  What are two (2) potential CSP safety risks that must be mitigated: A. Accuracy of dose B. Sterility of finished dose C. Timeliness of compounding D. Repetitive Motion Injury 5

1/20/2019 11 QUESTION 1 Answer  What are (2) two potential CSP safety risks that must be mitigated: A. Accuracy of dose B. Sterility of finished dose C. Timeliness of compounding D. Repetitive Motion Injury 12 The Pew Charitable Trusts Pew’s drug safety project has identified more than 71 reported compounding errors or potential errors associated with 1,416 adverse events, including 115 deaths, from 2001 to 2017. However, a 2015 survey found that only 30 percent of states (13 or the 43 that responded) require sterile compounding pharmacies to report serious adverse events. Of the states that require reporting, they type of information that is required to be reported may vary, further contributing to an incomplete picture of adverse events associated with compounded medications. Even in states with strong adverse event reporting requirements, illnesses and deaths caused by compounded drugs are not always linked to the compounding error. Because many such events may go unreported, this chart is likely an underestimation of the number of compounding errors since 2001, Contamination of sterile products was the most common error, others were the result of pharmacist and technicians miscalculation and mistakes in filling prescriptions. 6

1/20/2019 13 Under reported Errors WHY under reported? Lack of recognition   Seeing adverse events and errors as just part of the routine Fear of retribution   You have to feel safe to report someone else’s error, or your own.  “Most hospitals have yet to create a safety culture.” A sense of disbelief   “I remember talking to a hospital CEO once right after the report,” Gibson recalls. “He said that after a significant error, he would get up in the morning and look in the mirror and think, ‘Did this really happen here?’ There’s almost a sense that if you don’t see it, it didn’t exist.” The Hospitalist . 2012 July;2012(7) 14 Under reported Errors  Competing pressures  “ The requirements of healthcare reform have taken up so much time and energy that I fear safety has moved to the back burner”  “Someone in a quality and safety leadership role at one hospital said to me, ‘ Safety was just a fad. We’re not doing that anymore .’”  Productivity demands  “Healthcare’s mantra today has become volume, volume, volume. If you already have an environment that’s not as safe as we would like, and you ramp up the volume so people have to do more in the name of productivity, what’s going to happen?” The Hospitalist . 2012 July;2012(7) 7

1/20/2019 U.S. Illnesses and Deaths Associated With 15 U.S. Illnesses and Deaths Associated With Compounded Medications or Repackaged Medications 16 U.S. Illnesses and Deaths Associated With Compounded Medications or Repackaged Medications 8

1/20/2019 17 U.S. Illnesses and Deaths Associated With Compounded Medications or Repackaged Medications 18 U.S. Illnesses and Deaths Associated With Compounded Medications or Repackaged Medications 9

1/20/2019 Compounded Medications or Repackaged Medications 19 U.S. Illnesses and Deaths Associated With 20 U.S. Illnesses and Deaths Associated With Compounded Medications or Repackaged Medications 10

1/20/2019 21 Studies and Statistics Fl ynn, Pearson, Barker (1997) 9% mean error rate and 2% clinically significant  Essentially 1 out of every 10 sterile preps are flawed  Still quoted to this day by Institute for Safe Medication Practices (ISMP)  Moniz, Chu, Tom, et al (2014) Study of over 425,000 compounded doses  6.8 errors per 1,000 doses - 23% undetectable by inspection  167 of the errors (0.04%) had potential for moderate or severe harm   4/10,000 of all doses compounded Hingl, Deng, Lin (2015) 6 errors per 1,000 doses  22 Studies and Statistics Po ppe, Savage, Eckel (2014)  13% of doses outside acceptable variance (+/- 10%) Reece, Lozano, Roux et al (2016)  7% of doses had error in process  74% would not have been detected by visual inspection 11

1/20/2019 23 United States Pharmacopeia (USP) A scientific nonprofit organization that sets standards for the identity, strength, quality, and purity of medicines, food ingredients, and dietary supplements manufactured, distributed and consumed worldwide. USP’s drug standards are enforceable in the United States by the Food and Drug Administration, and these standards are used in more than 140 countries. USP <797>: Pharmaceutical Compounding — Sterile Preparations (under revision) http://www.usp.org/compounding/general-chapter-797 USP <800>: Hazardous Drugs — Handling in Healthcare Settings http://www.usp.org/sites/default/files/usp/document/our- work/healthcare-quality-safety/general-chapter-800.pdf 24 USP CHAPTER RELEASE DATES 12

1/20/2019 25 USP <797> USP <797>  Guidelines for handling all CSP, personnel, training, compounding, environment, quality assurance and monitoring.  Represent the minimum requirements to be applied in compounding sterile preparations; however, it is always possible to exceed these standards. Major Point: Specific processes for Microbial control . 26 Proposed USP <797>, Changes  Risk Categories:  Low, Medium, High 2 categories  Cleanroom design  Primary Engineering Control (PEC) classification  Sink location options  Environmental monitoring frequency  Personnel monitoring frequency  Personnel Protective Equipment (PPE)  Beyond Use Date  Sterility Testing samples requirement  Action Level for Personnel and Environment samples  In-Use time: addition of compounded source containers 13