What Air Filter Professionals Should Know About USP <797>

1. What Air Filter Professionals Should Know About USP <797> NAFA September 22, 2005 By Linda Renninger Filtech, Inc.

2. What is USP <797>? • US Pharmacopeia • General Chapter <797>

3. US Pharmacopeia • “The United States Pharmacopeia (USP) is the official public standards-setting authority for all prescription and over-the-counter medicines, dietary supplements, and other healthcare products manufactured and sold in the United States.” • USP is an independent, science-based public health organization. • Prescription and over-the-counter medicines available in the United States must, by federal law, meet USP's public standards, where such standards exist.

4. Chapter numbers • 1-999 – are considered to be U.S. medication standards and are therefore enforceable by the FDA under the Federal Food, Drug and Cosmetics Act. • 1000-1999 – are considered to be advisory or informational. Non mandatory issued for guidance purpose. • 2000 + - apply to nutritional supplements.

5. USP <797> • USP 797 is considered to be an official minimum standard for pharmacy sterile compounding, and it is therefore enforceable by the Food and Drug Administration (FDA), state boards of pharmacy, boards of health, and other regulatory agencies. • Including JCAHO!!!

6. Joint Commission on Accreditation of Health Care Organizations • Has published a document detailing time table for completing the various sections of USP Chapter <797>.

7. Joint Commission on Accreditation of Health Care Organizations -TIMELINE • Section that deals with - CSP Work environment • Appropriate solid surfaces • Limited (but necessary) furniture, fixtures, etc. • Anteroom • Buffer zone Approved facility renovation plan by January 2005 for completion in 3 years. Interim safety measures required by July 2005.

8. USP <797> • Mandatory • Applies to all practice settings where compounded sterile products ( CSP) are prepared and stored (Health care institutions, pharmacies, physician practices, and other facilities)

9. USP <797> • The Intent of this chapter is “to prevent patient harm and fatality from microbial contamination (non-sterility), excessive bacterial endotoxins, large content errors in the strength of correct ingredients.” • Increase quality of patient care.

10. USP <797> - 13 major sections • Responsibility of Compounding Personnel • CSP Microbial Contamination Risk Levels • Verification of Compounding Accuracy and Sterilization • Personnel Training and Evaluation in Aseptic Manipulation Skills • Environmental Quality and Control • …Etc.

11. CSP Microbial Contamination Risk Levels • Low-risk CSP’s • Medium-risk CSP’s A majority of the hospital pharmacy practices fall under this risk level • High-risk CSP’s Nonsterile bulk chemicals used to compound

12. Engineering controls for USP 797 • Primary – point of use • Secondary – facility design

13. Primary Engineering Controls

14. Secondary Engineering Controls

15. Engineering controls • Engineering controls employed in sterile compounding applications use High Efficiency Particulate Air (HEPA) filters supplying airflow to create air of appropriate Cleanliness Classification. Filtration Airflow Cleanliness Classification

16. Filtration • HEPA filters HEPA filters allow control of the airborne particulate level entering the work zone or cleanroom.

17. Filtration • HEPA filters Type C filters per IEST-RP-CC001.3 Tested for overall penetration and have been leak tested. The minimum filter efficiency of the filter is 99.99% on 0.3 micron particle.

18. Airflow • Airflow quantity • Airflow patterns

19. Airflow • Airflow Quantity Air changes per hour Room velocity Clean zone velocity

20. Airflow • Airflow patterns Unidirectional – sweeps contaminates out of zones. Non-Unidirectional – dilutes contaminates by mixing the air.

21. Cleanliness Classification • Defined by ISO 14644-1

22. Engineering Controls Requirements • USP Chapter 797 • “Sterile product preparation facilities utilize laminar airflow workbenches (LAFWs) to provide an adequate critical site environment” • “Primary engineering controls…include horizontal flow clean benches, biological safety cabinets, and barrier isolators” • “Primary environmental control must provide at least ISO Class 5 quality air”

23. Primary Engineering ControlsLaminar Air Flow Workbench (LAFW) • Offer product protection only • Provide ISO Class 5 (class 100) conditions • Approximate velocity across the workspace is 90 + 10 fpm. • Air is directed across the workspace toward the user. • Does not provide any protection to the user from materials being handled.

24. Primary Engineering ControlsLaminar Air Flow Workbench (LAFW)

25. Primary Engineering ControlsBiological safety cabinet(Chemo hood)

26. Biological Safety Cabinet(Chemo hood)

27. Primary Engineering ControlsBarrier Isolators

28. Secondary Engineering Controls • Facilities • CSP must be manipulated in ISO class 5 environment. ISO class 5 environment must be located in a buffer area that is ISO class 8* * Will be changing to ISO class 7 (class 10,000)

29. Secondary Engineering Controls • Cleanroom for low & medium risk level

30. Secondary Engineering Controls • Cleanroom for high risk level

31. Cleanroom Design Considerations • HEPA filtration • Although USP 797 does not specifically require or mention HEPA filters or HEPA filtration, future revisions will.

32. Secondary Engineering Controls • Airflow quantity – air changes per hour recommendations DESIGN GUIDE FOR CLEANROOMS

33. Secondary Engineering Controls • Airflow patterns • Unidirectional flow – Typically addressed in terms of velocity (feet per minute) • Non-unidirectional (turbulent) flow – Typically addressed in terms of air changes per hour.

34. Secondary Engineering Controls • Airflow patterns • Must be carefully considered as air flow patterns are required to “sweep” contaminates out of the buffer area. • Low side wall returns, carefully laid out, are critical. Return locations are probably more important than supply air locations.

35. Secondary Engineering Controls • Pressurization • Insures airflow is from cleanest area to less clean areas. Buffer room → ante room → unclassified areas. • FDA aseptic processing guide 0.04” – 0.06” wg. • ISO 14644-4 5 pa. (0.02”) to 20 pa. (0.08”)

36. Secondary Engineering Controls • Temperature • Operator comfort • Product consideration • Typical temperature range 66°F - 72°F

37. Secondary Engineering Controls • Humidity • Issues • Microbial growth • Affect on product and processes • Worker comfort • Static electricity Typical range 30% RH to 60% RH

38. Secondary Engineering Controls • Cleanroom construction considerations • Walls • Epoxy coated gypsum board • Interlocking walls made with cleanroom compatible materials • Avoid horizontal surfaces that can collect dust like large window sills and ledges.

39. Secondary Engineering Controls • Cleanroom construction considerations • Ceilings • Epoxy coated gypsum board • Anodized aluminum tee bar grid, with cleanroom grade ceiling tiles. • Tiles should be caulked to tee bar, in a manor to facilitate service and replacement when necessary.

40. Secondary Engineering Controls • Cleanroom construction considerations • Lights – light lenses should be smooth surface to facilitate cleaning.

41. Secondary Engineering Controls • Cleanroom construction considerations • Flooring • Sheet vinyl flooring with heat-welded seams. • Flooring material coved up wall 4”. • Flooring must stand up to cleaning and disinfecting agents. • No crevices in floor for microorganisms to grow • NO FLOOR DRAINS

42. Secondary Engineering Controls • Cleanroom construction considerations • Pass throughs • Great for moving items in and out of cleanroom. • Consider one for moving carts also.

43. Secondary Engineering Controls • Cleanroom design considerations • Sinks • Stainless steel • Hands free – good feature • Hand drying • Hand dryers or lint free wipes

44. Proposed Revisions and Clarifications • Proposed revisions and clarifications have been published. Until the revision process is completed – probably in 2006 – the current USP chapter <797> remains official.

45. Proposed Revisions and Clarifications • Some proposed changes • The buffer area should be ISO class 7 • New section on hazardous drugs • An “immediate use” exemption from ISO class 5 is proposed. • Barrier isolator usage – The proposed revision will clarify that barrier isolators should be used according to manufacturer’s recommendations. There are a variety of barrier isolators currently on the market and the requirements vary among manufacturers.

46. Summary • Web site for additional information: www.ashp.org/SterileCpd