Sterile Compounding Inspections

Transcription

1 Disclosure The following slides were developed for a presentation to the Kentucky Board of Pharmacy at the 2015 Board Retreat. Parts of the presentation have been edited due to usage agreements. These slides refer to some requirements of USP 797 but are not all inclusive. The slides have been made available at individual request.

2 Sterile Compounding Inspections THE KENTUCKY BOARD OF PHARMACY SERVES THE COMMONWEALTH TO PROMOTE, PRESERVE, AND PROTECT THE PUBLIC HEALTH, SAFETY, AND WELFARE THROUGH EFFECTIVE REGULATION OF THE PRACTICE OF PHARMACY.

3 Objectives Brief History of USP 797 Inspector Training and Inspection Form Observations Facility Controls Personnel Matrix Documentation

4 Objectives Clarifications Facility Controls Design Certification and Testing Surface Sampling Documentation Record Retention Stability References Sterility Testing Compound Record Personnel Matrix Supervision

5 Objectives Where do we go from here? Communications with pharmacists Future Board Meeting updates Future clarifications Nuclear pharmacies Regulation update Report care Out of State permits Non-sterile compounding USP 795

6 Brief History of USP 797 Published November 2003 Became official January 2004 First major proposed revision December 2007 Became official June 2008 Second major proposed revision September 2015 Comment period November 2, 2015 to January 31, 2016 Becomes official???

7 Kentucky Statute KRS (31) Official compendium means the official United States Pharmacopoeia, official homeopathic pharmacopoeia of the United States, official national formulary, or any supplement to any of them. July 2008 Board Meeting, the Board clarified low volume for hazardous drugs to be an average of 5 hazardous compounds/2 week period.

8 Inspectors Trainings Critical Point Continuing Education Boot Camp Inspector Training

9 Inspection Form Previously 10 questions on hospital, organized healthcare facility or infusion pharmacy inspection form, none on community/retail pharmacy inspection Updated form 16 pages, universal not practice site specific Addresses requirements of USP Chapter 797 also incorporates 201 KAR 2:076 Parenteral Pharmaceutical Compounding Divided into sections based on chapter headings and compounding types

10 2013 Compounding Survey In-State Pharmacy Permit Holders Response Rate: 1306/1341 (97%) Performing Sterile Compounding: 195 (15% of responders) High Risk: 33 (17% of sterile compounders or 3% of responders)* 1346 current in-state pharmacy permit holders (as of 8/5/15) Out-of-State Pharmacy Permit Holders Response Rate: 451/466 (97%) Performing Sterile Compounding: 170 (38% of responders) High Risk: 82 (48% of sterile compounders or 18% of responders) 669 current out-of-state pharmacy permit holders (as of 8/5/15) * May not be true representation some confusion with hazardous drug compounding

11 2013 Compounding Survey In-State Sterile Compounders by Permit Type: Hospital and Hospital/Ambulatory: 114 High Risk: 9 Reality: 2 Community Independent: 36 High Risk: 18 Reality: 14 (5 veterinarian only) Infusion: 23 High Risk: 5 Reality: 0 Long Term Care: 16 High Risk: 1 Reality: 0 Nuclear: 6

12 Inspection Observations Facility Controls Personnel Metrics Documentation

13 Facility Controls Design Workflow Hazardous Rooms Cleaning/Maintenance Documentation Environmental Services ISO Classification Consistent certification Environmental Sampling Re-sampling Sampling plan

14 Personnel Metrics Garbing/Hand Hygiene Minor differences Aseptic Technique Supervision Cleaning Documentation Equipment Training

15 Documentation Policies & Procedures Formulaic Personnel Training Observations, Written tests, Media fill, Gloved Fingertip Sampling Facility Conditions Temperature, Pressure Cleaning Logs Daily, Monthly Environmental Sampling Surface Sampling Equipment Maintenance Calibration, Depyrogenation Compounding Record Sterility Results Extended BUD Endotoxin Results

16 National Hospital Compliance 2015 Most compliant practice setting Home infusion 92.65% Hospital 79.9% 80% wear sterile gloves 76% on-going and annual training and competencies 28% perform sterility testing when it is required 68% daily air pressure/velocity documentation 57% line of demarcation 48% initial gloved fingertip sampling 39% on-going gloved fingertip sampling

17 National Hospital Compliance % initial and on-going media fill testing 62% remedial action when action levels triggered 58% Quality Assurance program specific to CSPs 63% training and competencies in cleaning 37% written hazardous drug confirmation of risk 72% all elements of environmental sampling 31% report using 0.22 micron filter to sterilize solution (high risk) 10% report performing high risk compounding

18 National Hospital Compliance 2015 Link to survey results:

19 Points of Clarification Facility Controls Facility Design ISO Certification Non-viable air sampling Viable Air Sampling Surface Sampling Documentation Record Retention Stability References Sterility Testing Compound Record Personnel Metrics Supervision

20 Facility Design Current Areas of Concern Lack of ante room or ante room not properly used Incomplete segregation of compounding rooms Wood/laminate shelving, doors and accessories [ENVIRONMENTAL QUALITY AND CONTROL: Facility Design and Environmental Controls] Proposed Clarifications (USP 797 proposed revision published 9/2015) Creates 2 categories of compounding dependent on room design Segregated area, restricted BUD Distinct rooms, longer BUD [4. BUILDINGS AND FACILITIES: 4.2 Facility Design and Environmental Controls]

21 Facility Design Current Concern: Hazardous Drugs Lack of negative pressure compounding room [HAZARDOUS DRUGS AS CSPs] Proposed Clarification: USP 800 Hazardous Drugs Hazardous compounding must be done under negative pressure [Chapter 800 HAZARDOUS DRUGS - HANDLING IN HEALTHCARE SETTINGS: 5.3 Compounding]

22 ISO Certification Nonviable Air Sampling Current Areas of Concern Proposed Clarifications (USP 797 proposed revision published 9/2015) ISO Classified Areas: Certification performed every 6 months and when PECs relocated or rooms altered ISO Classification below standard ACPH below standard Required pressure differential not met [ENVIRONMENTAL QUALITY AND CONTROL] PEC not at ISO 5 cannot be used for compounding Ante/buffer rooms not at appropriate ISO level, BUD is limited to Category 1 CSP (12 hr room/24 hr refrigerated) [5. ENVIRONMENTAL MONITORING: 5.2 Monitoring Air Quality for Nonviable Airborne Particles: DATA EVALUATION AND ACTION LEVELS]

23 Viable Air Sampling Current Areas of Concern Proposed Clarifications (USP 797 proposed revision published 9/2015) ISO Classified areas: Viable air sampling performed every 6 months as part of re-certification Action levels exceeded investigation, eliminate, clean and resample Highly pathogenic microorganisms immediately remedied [ENVIRONMENTAL VIABLE AIRBORNE PARTICLE TESTING PROGRAM] ISO Classified areas: Viable air sampling performed monthly using medium for both microbial and fungal Trend data Action levels meet or exceed corrective actions taken including resample Highly pathogenic microorganisms immediately remedied [5. ENVIRONMENTAL MONITORING: 5.3 Monitoring Air Quality for Viable Airborne Particles: DATA EVALUATION AND ACTION LEVELS]

24 Surface Sampling Current Areas of Concern Surface sampling shall be performed in all ISO classified areas on a periodic basis Most pharmacies are performing at least semiannually [ENVIRONMENTAL QUALITY AND CONTROL: Personnel Training and Competency Evaluation of Garbing, Aseptic Work Practices, and Cleaning/Disinfection Procedures: SURFACE CLEANING AND DISINFECTION SAMPLING AND ASSESSMENT] Proposed Clarifications (USP 797 proposed revision published 9/2015) Surface sampling shall be performed at multiple locations in all ISO classified areas at least monthly Trend data Specified areas to sample PEC exceeding action levels cannot be used to compound Ante/Buffer rooms exceeding action levels, BUD is limited to Category 1 CSP (12 hr room/24 hr frig) [5. ENVIRONMENTAL MONITORING: 5.4 Sampling Surfaces for Contamination: DATA EVALUATION AND ACTION LEVELS]

25 Record Retention: Personnel Training Current USP 797 Proposed Clarifications (USP 797 proposed revision published 9/2015) Retained for as long as compounded personnel employed Silent on how long to retain if personnel no longer employed Maintained to provided a permanent record and long-term assessment of competency At least 3 years or as required by state laws [2.2. Competency Testing in Garbing and Hand Hygiene, 2.3 Competency Testing in Aseptic Technique and 16. DOCUMENTATION]

26 Record Retention Other Issues Current USP 797 Silent on: Cleaning Equipment Maintenance Temperature Pressure Room/Hood Certifications Environmental Sampling Compounding Records Batch and Compounding Records Sterility and Endotoxin testing Proposed Clarifications (USP 797 proposed revision published 9/2015) Facility Design and initial qualifications for as long as facility operational All other records at least 3 years or as required by state law [16. DOCUMENTATION] Kentucky typically 5 years on record retention when addressed

27 CSP Stability Current Areas of Concern BUD based on chemical and physical stability and sterility: seeing 180 days on high risk preparations Stability data obtained from: Manufacturer Published literature Stability indicating tests Formulas from API distributor (PCCA, Medisca) Proposed Clarification (USP 797 proposed revision published 9/2015) BUD is capped Stability of all components and devices must be considered when assigning BUD [12. ESTABLISHING BEYOND-USE DATES AND IN- USE TIMES: 12.2 Critical Parameters to Be Considered in Establishing a BUD and 12.3 Establishing a BUD for a CSP]

28 Sterility Testing Current USP 797 Required for: All extended BUDs regardless of risk level High risk CSPs prepared in groups 25 single dose or multi-dose vials for multiple patients High risk CSPs exposed to warm temperature for extended period of time [FINISHED PREPARATION RELEASE CHECKS AND TESTS: Sterility Testing] Proposed Clarifications (USP 797 proposed revision published 9/2015) Sterility testing of Category 2 CSPs will allow for a longer BUD [12. ESTABLISHING BEYOND-USE DATES AND IN- USE TIMES: 12.3 Establishing a BUD for a CSP]

29 Sterility Test Current USP 797 Proposed Clarification (USP 797 proposed revision published 9/2015) Shall meet USP Chapter 71 Sterility Test or a method not described in USP may be used if verification results demonstrate that the alternative is at least as effective and reliable as USP 71 USP days Rapid Scan 3 days (non USP) Bioluminescence 7 days (non USP) [FINISHED PREPARATION RELEASE CHECKS AND TESTS: Sterility Testing] Must be performed in a manner consistent with USP 71, with the exception to batch size requirements in USP 71 [10. RELEASE TESTING: 10.2 Sterility Testing]

30 Proposed BUDs Category 2 CSPs (USP 797 proposed revision published 9/2015) Preparation Characteristics Method of Achieving Sterility Sterility Testing Performed Preservative Added Storage Conditions Room Temp C BUD Aseptically Prepared No No 1 or more nonsterile starting component 4 days BUD Aseptically Prepared No No Only sterile components 6 days Refrigerator 2-8 C 1 or more nonsterile starting component 7 days Only sterile components 9 days Freezer C At least 1 nonsterile starting component 45 days Only sterile components 45 days BUD Aseptically Prepared No Yes 28 days 42 days 45 days BUD Aseptically Prepared Yes No 28 days 42 days 45 days BUD Aseptically Prepared Yes Yes 42 days 42 days 45 days BUD Terminally Sterilized No No 14 days 28 days 45 days BUD Terminally Sterilized No Yes 28 days 42 days 45 days BUD Terminally Sterilized Yes No 28 days 42 days 45 days BUD Terminally Sterilized Yes Yes 42 days 42 days 45 days

31 Compounding Record Current USP 797 Referenced multiple times but not defined Current practice: Infusion and Community have compound record Hospital Batch Records Certain preparations (TPN, Chemotherapy) [FINISHED PREPARATION RELEASE CHECKS AND TESTS: Inspection of Solution Dosage Forms and Review of Compounding Procedures] Proposed Clarification (USP 797 proposed revision published 9/2015) Master Formula for CSPs batched or prepared from nonsterile ingredients Compound Record required for every CSP prepared [9. SOPs AND MASTER FORMULATION AND COMPOUNDING RECORDS]

32 Proposed Master Formulation Record Requirements (USP 797 proposed revision published 9/2015) Name, strength, and dosage form of the CSP Physical description of the final preparation Identities and amounts of all ingredients and appropriate containerclosure systems Complete instructions for preparing the CSP, including equipment, supplies, and a description of the compounding steps BUD and storage requirements Quality control procedures (e.g., ph, filter integrity, and visual inspection) Sterilization method, if applicable (e.g., filter, steam or dry heat) Any other information needed to describe the operation and ensure its repeatability (e.g., adjusting ph and tonicity and temperature) [9. SOPs AND MASTER FORMULATION AND COMPOUNDING RECORDS: 9.2 Creating Mater Formulation Records]

33 Proposed Compounding Record Requirements (USP 797 proposed revision published 9/2015) Name, strength, and dosage form of the CSP Master Formulation Record reference for the preparation, when used Date and time of preparation of the CSP Assigned internal identification number (e.g., prescription or lot number) Signature or initials of individuals involved in each step (e.g., technician or pharmacist) Name, vendor or manufacturer, lot number, and expiration date of each ingredient and container closure system Weight or measurement of each ingredient Documentation of the calculations made to determine and verify quantities and/or concentrations of components, if appropriate Documentation of quality control procedures in accordance with the SOP (e.g., filter integrity, ph, and visual inspection) Any deviations from the Master Formulation Record, if used, and any problems or errors experienced during the compounding of the CSP Total quantity compounded Assigned BUD Duplicate container label if prepared in a batch [9. SOPs AND MASTER FORMULATION AND COMPOUNDING RECORDS: 9.3 Creating Compounding Records]

34 Stock Solution/Pharmacy Bulk Package Current Chapter Pharmacy Bulk Package bear a statement limiting the time frame in which the container may be used once it has been entered Single-Dose Container no preservative; vials exposed to ISO Class 5 air may be used up to 6 hours after initial needle puncture [DEFINITIONS and SINGLE-DOSE AND MULTIPLE- DOSE CONTAINERS] Proposed Revision (USP 797 proposed revision published 9/2015) In-Use Time the time before which a conventionally manufacturer product or a CSP must be used after it has been opened or needle punctured (e.g., after a container closure of a vial has been penetrated) Compounded stock solution in-use time is 6 hours [12.4 Establishing In-Use Times]

35 Supervision KRS (1) No owner of a pharmacy who is not a pharmacist shall fail to place a pharmacist in charge of his pharmacy or shall permit any person to compound or dispense prescriptions, drugs, medicines, or pharmaceuticals, in his place of business except in the presence and under the immediate supervision of a pharmacist KRS (11) Immediate Supervision means under the physical and visual supervision of a pharmacist KRS (25) Supervision means the presence of a pharmacist on the premises to which a pharmacy permit is issued, who is responsible, in whole or in part, for the professional activities occurring in the pharmacy

36 Supervision Proposed revision: Supervisors of compounding personnel should observe compounding activities on a daily basis [2. PERSONNEL QUALIFICATIONS TRAINING, EVALUATION AND REQUALFICATION] Training of compounding personnel Some facilities have technicians training compounding personnel Some facilities do not have any training on pharmacists Will perform compounding Will check/supervise compounding

37 Future Meetings Communication with sterile compounders Updates to Board Further areas requiring clarification Nuclear pharmacies Regulation update Require continuing education Report cards Out of state permits Non-sterile compounding USP 795

38 Requested Guidance Cessation of compounding Retesting of room Compound record