Summary of USP 797 for Compounding Sterile Preparations

1. Summary of USP 797 for Compounding Sterile Preparations Presented at: HFMADV Meeting February 3, 2009 Presented by: Tom N. Petersen, P.E. Environmental and Engineering Solutions, Inc. www.eesolutions.net Copyright Environmental and Engineering Solutions, Inc. 2009

2. Purpose of U.S. Pharmacopeia (USP) 797 • For pre-administration phase of sterile preparations - Reduces the potential for contamination caused by unclean environment, pharmacist error, lack of quality control, incorrect beyond-use dating and other factors. • Joint Commission requires a gap analysis and action plan for USP 797 compliance.

3. Overview of New USP 797 (6/1/08 Update) • Introduction and Organization of the Chapter – (direct contact is principal source of contamination) • CSP Microbial Contamination Risk Levels • Single–Dose v. Multiple Dose Containers • Hazardous Drugs as CSPs • Radiopharmaceuticals as CSPs • Allergen Extracts as CSPs • Sterilization Methods – three methods were revised and a new section on depyrogenation (removal of pyrogens – endotoxins or exotoxins) added

4. Overview of New USP 797 (6/1/08 Update) - continued • Environmental Quality and Control • Exposure of Critical Sites – exposure to “first air” from HEPA • Placement of Primary Engineering Controls • Additional Personnel Requirement • Personnel Cleansing and Garbing • Disinfectant and Cleaning • Five Appendices – shall vs. should, checklists, suggestions for garbing

5. PA State Board of Pharmacy’s Position • USP 797 Special Notice on the web site: • “…provisions of the USP are not part of the Pharmacy Act’s substantive sections or Board regulations.” HOWEVER… • “Section 5(a)(12) of the Pharmacy Act provides that the departure from, or failure to conform to, the standards of acceptable and prevailing pharmacy practice is grossly unprofessional conduct.”

6. Compounding Sterile Preparations (CSP) Microbial Contamination Risk Levels • Immediate Use CSPs – for non-haz only, 1 hr. after start of preparation must be administered • Low-Risk Level • Low-Risk Level w/12 hour or less Beyond Use Date (BUD) – subsection of low risk, designed for facilities with no ISO 7 secondary control clean room • Medium-Risk Level • High-Risk Level • Responsibility of personnel to determine level

7. Single–Dose vs. Multiple Dose Containers • Single dose vials (SDV) – if opened or punctured in ISO 5 area may be used for up to 6 hours. • Single dose ampuls must be discarded and not stored • MDV – 28 day BUD

8. Protecting the workers from exposure to certain drugs during preparation References NIOSH Alert regarding choosing the appropriate Primary Engineering Control (PEC) Recommends PEC that do not recirculate air Biological safety cabinets (BSC) or Compounding Aseptic Containment Isolator (CACI) should be vented to the outside Locate in separate negative pressure ISO Class 7 with ISO Class 7 ante area Disposal of waste according to state and federal regulations Equipment High Risk Immuno- compromised Patients Infection Control Risk Assessment (ICRA) Immunocompromised Patients Inpatient Invasive Imaging Procedure Room Non-Aspirating Diffuser Protective Environmental Room Triage Hazardous Drugs as CSPs

9. Radiopharmaceuticals as CSPs • Must be prepared in an ISO 5 containment device in an ISO 8 environment or cleaner • Principals of ALARA followed (As low as reasonably achievable) • Allowance for preparation of radiopharmaceuticals under the Low-Risk Level with 12 hr BUD – hot labs in hospitals have better chance of compliance as long as they have ISO Class 5 PEC

10. Allergen Extracts as CSPs • Unpreserved allergen extracts must fully comply with 797, but most allergen extracts are highly preserved. • Exempt from certain aspects under certain conditions: • Hand hygiene • PPE used • Simple aseptic transfer • Contain effective amount of preservative • Single patient only • Gloves are disinfected with IPA • Vial stoppers disinfected • Labeling requirements • Exemption granted based on a study with 27,000 subjects and no infections.

11. Environmental Quality and Control • Laminar air flow workbenches (LAFW), BSC, CAI, CACI • ISO Class 5 sources, buffer areas and ante areas – there is a circular diagram conceptual representation of the layout – concentric circles of control • Secondary engineering controls for buffer area and ante area and have HEPA filtered air sources • The recirculating ISO Class 5 devices count towards the overall 30 air changes per hour for the buffer Class 7 area • Airflow and balance testing required at installation site • There is an exception for CAI’s related to providing isolation from the room – if secondary engineering control ISO 7 not available

12. Environmental Quality and Control - continued • Environmental Sampling • Designed to demonstrate a suitable environment for aseptic compounding • Electronic measurement of the total number of airborne particles • Certification of ISO 5, 7, and 8 environments • Volumetric air sampling of viable microorganisms • Glove fingertip monitoring • Surface sampling

13. Additional Personnel Requirement • Training requirements – • Classroom instruction and written exam plus observational evaluation • Garbing • Aseptic work practices • Maintaining ISO Class 5 environment • Media-fill testing of aseptic work skills • Outside support personnel must also be trained properly

14. Personnel Cleansing and Garbing • Remove outer garments and jewelry, makeup, including earbuds and headsets • Garb from dirtiest to cleanest parts of body • Shoe covers, hair covers, beard covers and face masks, even if have no hair • Hand/arm hygiene • Disposable non-shedding gowns • Sterile powder-free gloves compatible w/ IPA • Repeatedly apply IPA to contact areas of gloves • Immediate use provision (emergency situation) does not have garbing requirements

15. Disinfectant and Cleaning • Maintenance of compounding areas is overlooked and this was an extensively updated portion of USP 797. • Designed to reduce bioburden in compounding areas • Use sterile 70% IPA and germicidal detergent • To be performed in ISO 5 environment very frequently • Clean from cleanest to dirtiest • Use dedicated mops and cleaners

16. Questions? • For questions or assistance with regard to indoor air quality and infection control for hospitals, contact Tom Petersen, P.E. at 215-881-9401, or by email at tom@eesolutions.net.