USP <797> Overview and Compliance Audit Results. Joseph W. Coyne RPh Director of Field Operations Clinical IQ, LLC

Transcription

1 USP <797> Overview and Compliance Audit Results Joseph W. Coyne RPh Director of Field Operations Clinical IQ, LLC

2 Acknowledgements Many of the slides presented in this program come from the CriticalPoint Live Training/Educational Series. Thanks to Kate Douglass, and Eric Kastango for their expertise in putting together the content. Permission to use the copyrighted slides/images and materials are provided by CriticalPoint, LLC. Use of this educational material by a 3rd party does not constitute endorsement, CriticalPoint or ClinicalIQ

3 Study the past if you would define the future Confucius

4 History of Compounding Pharmacy compounding is simply the art and science of preparing customized medications that are not otherwise commercially available. Compounding is performed by or under the supervision of a pharmacist pursuant to an order from a licensed prescriber for an individual patient. Compounding is an essential element of pharmacy.

5 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:

6 Yesterday

7 Today

8 History of Compounding All states license pharmacists to compound States laws vs. Federal laws (FDA) The federal government, through the FDA, is arguing that patient safety is in jeopardy Each state has varying degrees of regulations and oversight and enforcement of compounding practices 35 states require direct compliance with USP 797 after 14 years Until USP <797>, no consistent and enforceable compounding standard of practice existed

9 Regulatory Status Level by State Direct laws & regulations specifically site USP 797 Indirect do not specifically site USP but sterile compounding laws exist No Reference no laws or regulations

10 The Drug Quality and Security Act (DQSA) Signed into law by President Obama on November 27, 2013 Divided into 2 major sections called Titles Title I Compounding Quality Act Eliminates the unconstitutional provisions of 503A that created uncertainty regarding the laws governing compounding. Requires FDA to engage in two-way communication with state regulators identified as a major deficiency in FDA s response to the meningitis outbreak. Preserve and protect the practice of traditional pharmacy compounding * FDA Guidance for Industry - Interim Product Reporting for Human Drug Compounding Outsourcing Facilities under 503B of FDCA DEC 2013

11 DQSA (continued) Section 503A Pharmacy Compounding State-based regulations State Boards of Pharmacy Traditional, individualized prescriptions Requires compliance with USP chapters on compounding Section 503B 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

12 Outsourcing Facilities Permit entities engaged in compounding of sterile drugs to register as Outsourcing Facilities. Under Section 503B, pharmacy outsourcers to voluntarily register as outsourcing facilities, making them subject to good manufacturing practices, risk-based inspection and other standards

13 Outsourcing Facilities (continued) Retrieved on 8/28/2018 from FDA website on Registered Outsourcing Facilities

14 From October 2012 through September 2014, the FDA performed nearly 150 inspections of compounding pharmacies. In about 90% of those inspections, evaluators identified "objectionable conditions" typically safety and sanitary problems that warranted corrective action. They saw everything from workers wearing soiled gloves to visible mold growth in injectable medications.

15 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 on October 7, 2014.

16 FDA Draft Guidance on Insanitary Conditions Applies to both 503A and 503B facilities Under the FFDCA, any drug, including a compounded drug, that is prepared, packed, or held under insanitary conditions is adulterated. The draft guidance is intended to assist compounding facilities in identifying insanitary conditions so they can implement appropriate corrective actions. It is also intended to assist state regulatory agencies in understanding some examples of what FDA considers to be insanitary conditions.

17 FDA Actions 2012 to guidances on compliance policies 4 regulations addressing products that can/cannot be compounded 1 draft memorandum of understanding (MOU) with the states addressing certain distributions of compounded drugs Almost 500 inspections of 503A and 503B facilities between passage of DQSA and the end of fiscal year 2017 More than 150 recalls of compounded drugs More than 180 warning letters issued 70 referral letters to state regulatory authorities for follow up Examining Implementation of The Compounding Quality Act. Testimony of Scott Gottlieb, M.D., Commissioner of Food and Drugs Before the Subcommittee On Health, House Committee On Energy And Commerce. January 30,

18 Our patients have never had a problem

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20 Evidence of Damage: Pew Charitable Trusts U.S. Illnesses and Deaths Associated with Compounded Medications or Repackaged Medications released 6/2017 Pew reported more than 71 reported compounding errors or potential errors associated with 1416 adverse events including 114 deaths from 2001 to 2017

21 Evidence of Damage: Pew Charitable Trusts

22 Evidence of Damage: Pew Charitable Trusts In 2015 Pew published the National Assessment of State Oversight of Sterile Drug Compounding The Pew Trusts found that only 30% of states (13 of 43 that responded) require sterile compounding pharmacies to report serious adverse events. 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.

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26 NECC Summary

27 Another Event Outbreak of Burkholderia contaminans linked to Intravenous Fentanyl from an Institutional Compounding Pharmacy Occurred at Duke University Hospital from August 31- Sept 6, patients affected Prepared drug from bulk API: High-risk compounding Report published in JAMA Available online: JAMA Intern Med. Published online February 03, doi: /jamainternmed

28 Cost of Just One Event New Jersey Pharmacy Cease and desist issued; pharmacy closed on the order of NJ AG JAMA article detailing the hospital contamination/recall

29 Cost of Just One Event

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31 Traditional BUD Paradigm Assume the compounded preparation is sterile Base the BUD solely on the drug s chemical stability

32 Current <797> BUD Paradigm Recognizes the probability of contamination even under best conditions: Optimal employee performance: 0.1% (1 contaminated dose out of 1,000) Contamination rates in the literature: 0.3% to 16% Based the BUD on the drug s chemical stability in conjunction with microbial limits for patient safety Patient Safety Protect patients from dangerous or even fatal overgrowths of microorganisms that may have been accidentally introduced

33 BUD: Microbiological Limits Most shelf life labels or listed expiration dates are used as guidelines based on normal handling of products. Use prior to the BUD does not necessarily guarantee the safety of the drug. Thus, immediately after the date, a CSP is not always dangerous nor ineffective.* Applied whenever an actual sterility test in accordance with USP Chapter <71> has not been performed

34 Current Beyond-Use-Dating

35 Defining Proposed Category 1 and Category 2 Category 1 Based on facility configuration (SCA/C-SCA) BUD of 12 hours or less at controlled room temperature BUD of 24 hours or less when refrigerated Only if made in accordance with applicable requirements for Category 1 CSPs Category 2 Based on facility configuration (ISO classified ante and buffer rooms) BUD of greater than 12 hours at controlled room temperature BUD of greater than 24 hours when refrigerated Only if made in accordance with applicable requirements for Category 2 CSPs

36 Proposed USP 797: Category 1 CSPs

37 2018 Proposed Revision to 797 Category 2 BUDs

38 Sterility Testing (ST) Performed when Required by Hospitals

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40 Why are Environmental and Personnel Sampling Important? Facilitates early detection of contamination and its source which may include: Personnel Work surfaces Supplies Equipment Failure of engineering controls

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42 Surface Sampling Important component of ensuring 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 Use for evaluating facility and work surface cleaning and disinfecting procedures employee competency in performing work practices USP Chapter <797> requires it to be performed In all ISO classified spaces Periodically

43 Gloved Fingertip Sampling (GFS) Required by the Chapter since the 2008 revision Personnel metric

44 Hospital Compliance with Initial Gloved Fingertip Sampling

45 Overall Self-Reported USP <797> Hospital Compliance by State

46 Comparison of Hospital Compliance with Remedial Action

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48 Self-Reported Compliance with Training Personnel who Clean (all providers)

49 Hospital Compliance with Cleaning and Disinfecting

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51 Quality Release Checks and Tests Documentation Policies and Procedures Master Formulation Records (MFR) Compounding Records/Logs (CL) Accuracy Checks Physical/Visual inspection for: Particulate matterforeign matter Clarity (precipitation, cloudiness, phase changes in PN) Color (unexpected)

52 Quality Release Checks and Tests Qualitative Checks Volume/weight Syringe pull-back-no! Pre and post fill bag weights and use of specific gravity Direct observation-video All staff have authority to stop the line if any questions about CSPs occur (see ISMP guidelines for Safe Preparation of CSPs)

53 Comparison of Selected Non High Risk Hospital Domain Compliance by Year

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57 SOP Gap Analysis Alpha Gap Difference between regulatory requirements and established standards of practice and what is written in SOPs Beta Gap Difference between written SOPs and actual practice in the workplace

58 SOPs must reflect Actual Practice Must involve all employees who will have an effect, contribution or influence over the system Employees must be process owners and buy into the desired state The creation of a shared vision is critical to success Try to identify all the roadblocks to success

59 Comparison of Non High Risk Hospital Domain Compliance for Selected Years

60 Hospital Compliance with Training and Competency Measurement

61 Overall Self-Reported USP <797> Hospital Compliance by State

62 Biggest Current Challenge to Total Compliance with USP Compounding Chapters

63 Most Influential Factor in Hospital Pursuit of USP Compounding Compliance

64 Joseph W. Coyne RPh Director of Field Operations Clinical IQ, LLC Office (224)