Open Microphone Meeting:

USP General Chapter <797> Pharmaceutical Compounding – Sterile Preparations

October 21, 2015 2:00 p.m. to 4:00 p.m. EDT

Welcome

Overview of USP’s Revision Process

Overview of Revised General Chapter <797> Pharmaceutical Compounding – Sterile Preparations

– Background

– Overview of Revised Content

– Information on How to Submit Comments

Timeline and Next Steps

Question & Answer Session

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Agenda

Overview of the U.S. Pharmacopeial Convention

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Scientific non-profit organization that sets standards for the identify, strength, quality, and purity of medicines, food ingredients, and dietary supplements

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

About USP

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USP Headquarters Rockville, MD

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Chair: Gigi Davidson, B.S. Pharm, DICVP, NC State College of Veterinary Medicine

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2015 – 2020 Compounding Expert Committee

Lisa Ashworth, B.S. Pharm Gus Bassani, Pharm.D. Ruth Ebiasah, Pharm.D. , M.S. Edmund Elder, Ph.D. , B.S. Pharm Ryan Forrey, Pharm.D., M.S. Deborah Houston, Pharm.D. Brenda Jensen, M.A. Patricia Kienle, MPA, B.S. Pharm

Chair: Gigi Davidson, B.S. Pharm, DICVP, NC State College of Veterinary Medicine

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2015 – 2020 Compounding Expert Committee

William Mixon, B.S. Pharm John Musil, Pharm.D. David Newton, Ph.D. Alan Parr, Pharm.D., Ph.D. Abby Roth, B.Sc. Robert Shrewsbury, Ph.D. Connie Rae Sullivan, B.S. Pharm James Wagner Brenda Yuzdepski, B.S. Pharm

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Overview of Development Process

Based on the nature and

significance of the public comments

Forward Ballot Approve

Not approve

Defer

Cancel Proposal re-published for

public comment

Revision proposed by stakeholder,

USP EC, or USP Staff

Proposal published in PF for

90-day public comment

General Chapter <797> Pharmaceutical Compounding – Sterile Preparations

Gigi Davidson, BSPh, DICVP Chair, USP Compounding Expert Committee, 2010-2020

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Chapter History – First Published in 2004 (USP27-NF22)

– First Revised in 2008 (USP 31-NF26 2S)

Purpose of Revision – To reflect new science and evidence based on updated guidance

documents, best practices, and new learnings from investigations

– Respond to stakeholder input received throughout the cycle

– Clarify topics that are frequently queried and misconstrued

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USP <797>: Revision Proposal

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USP <797>: Background

July 2010

<797> subcommittee formed & began work

Early 2013

Collaboration with Microbiology Expert Committee

April 2013

Formed <797> Expert Panel

June 2015

<797> subcommittee completed work

Sept 25 2015

Pre-post <797> for Public Comment

Reorganized chapter – Procedural information placed in Boxes

Categories of CSPs – Collapsed into two categories

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USP <797>: Overview of Major Changes

• BUD ≤ 12 hours at room temperature or ≤ 24 hours refrigerated

• PEC placed in a segregated compounding area

Category 1 CSPs

• BUD > 12 hours at room temperature or > 24 hours refrigerated

• PEC placed in a classified area Category 2 CSPs

Hazardous Drugs – Removed all handling information and replaced with cross-

reference to <800> Hazardous Drugs – Handling in Healthcare Settings

Scope – Administration should follow CDC’s Safe Injection Practices – Reconstitution and dilution strictly in accordance to

manufacturer’s labeling not within scope of chapter – Repackaging must be performed following the requirements in

the chapter – Urgent-Use CSPs (previously termed “Immediate-Use CSPs”)

• Reserved for rare circumstances where a CSP is urgently needed

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USP <797>: Overview of Major Changes

Personnel Qualifications

Personnel Protective Equipment – Based on CSP Category and type of PEC – Requirement for sterile sleeves (or sterile gown)

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USP <797>: Overview of Major Changes

Reevaluation and Requalification Proposed Frequency Visual observation Initially and then quarterly Gloved Fingertip Sampling 3 times initially and then quarterly Media-fill testing Initially and then quarterly

Buildings and Facilities – Primary Engineering Controls (PEC) – new terminology

• Laminar Airflow System (LAFS) • Restricted Access Barrier System (RABS) • Isolator

– Placement of PEC

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USP <797>: Overview of Major Changes

Category 1 CSPs • PEC may be placed in an unclassified Segregated Compounding Area

Category 2 CSPs • LAFS, BSC, and RABs must placed in an ISO Class 7 or better area

• Isolator must be placed in ISO Class 8 area

Environmental controls – Well-lit and comfortable conditions – Temperature 20˚ or cooler – Humidity below 60%

Environmental Monitoring

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USP <797>: Overview of Major Changes

Proposed Frequency Nonviable Air Sampling Every 6 months Viable Air Monitoring Monthly Surface Sampling Monthly

Documentation – Master formulation records – Compounding records

Release Testing – Sterility testing (refers to <71> Sterility Test)

• For batch sizes < 40, number of units to be tested is 10% rounded up to the next whole number

– Endotoxin Testing • Required for Category 2 CSPs prepared from nonsterile

ingredients (except inhalation and topical ophthalmic) • Exception if endotoxin burden is predetermined (i.e.

certificate of analysis)

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USP <797>: Overview of Major Changes

Establishing Beyond-Use Dates Based On –Method of Achieving Sterility –Starting Components –Sterility Testing –Preservative –Storage Conditions

New terminology for In-Use Times

–Time before which a conventionally manufactured product or CSP must be used after it is opened or punctured

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USP <797>: Overview of Major Changes

Roadmap Through Chapter 1. Introduction and Scope 2. Personnel Qualifications—Training, Evaluation, and

Requalification 3. Personal Hygiene and Personal Protective Equipment 4. Buildings and Facilities 5. Environmental Monitoring 6. Cleaning and Disinfecting Compounding Areas 7. Equipment and Components 8. Sterilization and Depyrogenation 9. SOPs and Master Formulation and Compounding Records 10. Release Testing 11. Labeling

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USP <797>: Revision Proposal

Roadmap Through Chapter 12. Establishing Beyond-Use Dates and In-Use Times 13. Quality Assurance and Quality Control 14. CSP Storage, Handling, Packaging, and Transport 15. Complaint Handling and Adverse Event Reporting 16. Documentation 17. Radiopharmaceuticals as CSPs Glossary Appendix 1. Acronyms Appendix 2. Common Disinfectants Used in Health Care for Inanimate Surfaces and Noncritical Devices, and Their Microbial Activity and Properties

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USP <797>: Revision Proposal

General Chapter <797> is posted online at http://www.usp.org/usp-nf/notices/general-chapter-797-proposed-revision

– Download and complete the submission template

– Email submission template to CompoundingSL@usp.org

– Comments due January 31st, 2016

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USP <797>: How to Submit Comments

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USP <797>: How to Submit Comments

Provide comments that do not have any corresponding line numbers.

Provide comments with corresponding line numbers. Include specific

suggestions and rationale.

Provide all information in the event we need to contact you any follow-up

Next steps – Subcommittee will review ALL comments submitted – Comments will be addressed through commentary

posted online

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USP <797>: Timeline and Next Steps

Date Activity

Sept 25, 2015 Revised General Chapter <797> Posted for Public Comment

Sept 25, 2015 through Jan 31, 2016

Open Public Comment Period

Oct 21, 2015 Open Microphone Web Meeting

Jan 31, 2016 Deadline for Submitting Public Comments

Open Microphone Q&A Session

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