Current Regulatory Landscape for Sterile Compounding: Part ...

Current Regulatory Landscape for Sterile Compounding: Part 1PharMEDium Lunch and Learn Series

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ProCE, Inc.www.ProCE.com

Current Regulatory Landscapefor Sterile Compounding: Part 1

June 8, 2018

Featured Speaker: Fred Massoomi, PharmD, FASHPSenior Director of Health‐system & Hospital ServicesVisante, Inc.Omaha, Nebraska

LUNCH AND LEARN

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ProCE, Inc. (Pharmacist and Tech CE)

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Funding: This activity is self‐funded through PharMEDium.

It is the policy of ProCE, Inc. to ensure balance, independence, objectivity and scientific rigor in all of its continuing education activities. Faculty must disclose to participants the existence of any significant financial interest or any other relationship with the manufacturer of any commercial product(s) discussed in an educational presentation. Dr. Massoomi does not have any relevant commercial and/or financial relationships to disclose.

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© Copyright Visante, Inc. All rights reserved | www.visanteinc.com

Current Regulatory Landscape

Sterile Compounding: Part 1Fred Massoomi, Pharm.D., FASHP

Senior Director; Hospital and Health‐system Services


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© Copyright Visante, Inc. All rights reserved. | www.visanteinc.com7

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-Describe oversight of sterile compounding standards and regulations

-Review USP inaugural meeting on sterile compounding

-Compare cGMP to USP and the necessary integration of standards

-Review FDA activity for sterile compounding oversight

-Identify key FDA guidance documents for sterile compounding for 503A and 503B facilities

-Theorize immediate future expectations for safe sterile compounding


Collaboration of Standards?


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USP Announcements

Source: usp.org/compounding/updates-on-standards


USP Compliance Timelines

Source: usp.org/compounding/updates‐on‐standards

NOTE: Individual states may require compliance sooner


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Regulatory Activity

NOTE: Not listed FDA activity on healthcare facilities

Source: Pharmacy Purchasing and Products; State of Pharmacy Compounding 2018; 11th Annual: April 2018

© Copyright Visante, Inc. All rights reserved | www.visanteinc.com 12

Compounding Inspections

CMSHospitalsClinics

State Board of PharmacyHospitals

Retail Pharmacy’sCompounding Pharmacy’s

FDA


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Surveying Bodies for Compounding

• TJC: The Joint Commission

• DNV Healthcare

• HFAP: AOA’s Healthcare Facilities Accreditation Program

• ACHC: Accreditation Commission for Healthcare

• PCAB: Pharmacy Compounding Accreditation Board

13© Copyright Visante, Inc. 2017 | www.visanteinc.com


Source: https://www.jointcommission.org/certification/mdccert.aspx

The Joint Commission


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• FDA Policy goals• Public health concerns• Provide clarification• Decrease regulatory burden

• 3 policy types• Access• Auality• Necessity; must use FDA approved drugs

• FDA voluntary top recalls• Sterility assurance• Potency• Labeling

• FDA Civil and Criminal Enforcement• Medistate July 2017• Pharmakon pharmaceuticals 2017

• Compounding Risk Alert System• 2017 eye injection of a compounded drugs 43 patients; combo issues by a Texas compounding facility• ‐017 one illness and one death turmeric and curium; non‐FDA USP registered products

• Finalization of cGMP for Outsourcing Manufacturers

FDA Update @ USP


PDA Update FDA Activities• 503A 4500+ • 503B 73 Registered

– ALL have 483’s– 9 warning letters– 1 Consent Decree

• August 2016 to October 2017– 63 warning letters– 4 injunctions

• #1 Insanitary Conditions• #2 Lack of sterility assurance

Source: http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Pharmacy Compounding/ucm535968.htmSource: PDA News UPDATE November , 2107; Lachman Consults.com(http://www.lachmanconsultants.com/2017/11/compunding-pharmacies-still-in-fdas-crosshairs/)


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Sterile Compounding Compliance

18© Copyright Visante, Inc. 2015 | www.visanteinc.com

Current Perception of Compliance

63% Not in full compliance



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Construction For Compliance



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Source: http://www.usp.org/compounding/general‐chapter‐797


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Sterile Compounding Evolution


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Compounding Standards

1975 20001980 1985 1990 1995 20102005 2015

NCCLVPRecommendations

USP <1074> Dispensing Practices for Sterile Drug Products Intended for Home Use

ASHP TAB“Quality Assurance for Pharmacy‐

Prepared Sterile Products”

NAPB “Model Rules for Sterile Pharmaceuticals”

USP <1206> Sterile Drug Products for Home Use

USP <800> Hazardous

Drugs Handling in Healthcare

Settings

USP <797> Pharmaceutical Compounding – Sterile Preparations

Drug Quality & Security Act

Federal Standards

2004

Best Practice Recommendations


Differing Standards?

This interim guidance reflects FDA’s intent to recognize the differences between compounding outsourcing facilities and conventional drug manufacturers…….

Maintaining the minimum standards necessary to protect patients from the risks of contaminated or otherwise substandard compounded drug products.


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Differences between cGMP & USP <797>

• Crosswalk of USP Chapter <797> and cGMP (21 CFR 211):

– 187 individual cGMP requirements specifically examine

– 20 are fully covered in USP Chapter <797>

– 127 requirements of cGMP are not covered by USP Chapter <797>


Key Revisions to USP 797

• Compounded Sterile Products Categories nomenclature

– OLD: Immediate use; Low-risk; Medium-risk; High-risk

– NEW: Urgent use; Category 1; Category 2

– REMOVAL of hazardous drugs section= USP 800

– REMOVAL of Radiopharmaceuticals = USP 825

– In-Use-Time = time a CSP must be used after it has been opened or punctured

• Sterility testing sampling for batching <40 (Test 10% of the batch size)

• Allergens no longer exempted

Proposed revision to USP 797 is a complete re-write of 2008 chapter

Source: http://www.usp.org/usp-nf/notices/general-chapter-797-proposed-revision


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Monthly viable air sampling Was every 6 months

Monthly viable surface sampling Was periodic

Quarterly media fill test Was annually

Quarterly finger glove tip test Was annually

Room temperature 20° C or cooler

Humidity Below 60% at all times

Key Revisions to USP 797

Proposed revision to USP 797 is a complete re-write of 2008 chapter

• Garbing and Cleaning- Sterile gloves and sterile sleeves or gowns- Sterile wipes and cleaning equipment

Source: http://www.usp.org/usp-nf/notices/general-chapter-797-proposed-revision



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29© Copyright Visante, Inc. 2015 | www.visanteinc.com 29

Hazardous Drug HandlingUSP <800> Handling Hazardous Drugs in Healthcare Settings

BTW: Also, includes 503B Facilities


Current Perception of Compliance

92% Not in full Compliance



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Source: http://www.usp.org/compounding/general‐chapter‐hazardous‐drugs‐handling‐healthcare

NOTE: Individual states may require compliance sooner‐Washington‐California‐North Carolina‐New Jersey


Road Map to Safety

• Introduction and scope

• List of Hazardous Drugs

• Types of exposure

• Responsibilities of handling HDs

• Facilities and engineering controls

• Environmental quality and control

• Personal protective equipment

• Hazard communication program

• Personnel training

• Receiving

• Labeling, packaging, transport & disposal

• Dispensing final dosage forms

• Compounding

• Administering

• Deactivating, decontaminating, cleaning, & disinfecting

• Spill Control

• Documentation and standard operating procedures (SOPs)

• Medical surveillance


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Scope


The Source

Photo: Firouzan Massoomi, Pharm.D, FASHP

Source: http://www.pharmaceuticalonline.com/doc/reducingtherisksofparticlesontheoutsideofvials0001?sectionCode=Editorial&templateCode=Single&user=31…

NEVER touch boxes or vials with bare hands!


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Types of Exposure

– Dermal

– Mucosal

– Inhalation

– Injection

– Ingestion


List of Hazardous Drugs

• Must have a Hazardous Drug list– USP 800– The Joint Commission– Occupational Safety & Health Admin.

• Type of Hazardous Drugs • antineoplastic• non‐antineoplastic• reproductive risk

• Risk of exposure considerations• Continual and annual update


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Risk Stratifying Handling


Facilities & Engineering Controls

Must Have Designated Areas

• Receipt & unpacking

• Storage

• Non‐sterile compounding

• Sterile compounding

Example: Signage


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Receiving & Storage

• Must be unpacked in marked area– Neutral/Negative pressure

• MUST

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• CLEANABILITY


Personal Protective Equipment

Disposable GownsPolyethylene or laminateClosed in the back

Shoe Covers: x 2

Head coversBeard coversEye protectionFace mask

ASTM 6978


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Personnel & Training

• All personnel who handle HDs must be trained based on their job functions

• Must be assessed every 12 months

• Must be trained on new HDs and equipment

• Must document competencies


DeactivationBreaking chemical bonds

2% Sodium Hypochlorite

CleaningRemove dirt, oils, residue, etc.

Tri or Quadra-valent detergent

5 –cidal notably: Sporicidal

DecontaminationPhysical wiping of surfacePeroxide RTU

DisinfectingReduce bioburden

Sterile Isopropyl Alcohol 70%

UV-C light


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These Do Not Clean Hazardous Drug Spills

© Copyright 2017 Firouzan Massoomi, Albarello, LLC. All Rights Reserved.


Safe Disposal of Waste


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Outsourcing


Drug Quality and Security Act 2013

• The Drug Quality and Security Act (DQSA) signed into law on November 27, 2013

– Public Law 113-54

– New Law Consists of Two Sections

• Title I: Compounding Quality Act

• Title II: Drug Supply Chain Security Act

– Drug pedigree through distribution channel

– Manufacturer to the pharmacy


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Compounding Quality Act FDA

Pharmacy Compounding

Under Section 503A

Per prescription

Guidance for Industry

Current GMP

Compounding Outsourcing Facilities

Under Section 503B of the FD&C Act

• State Boards of Pharmacy

• CMS

• FDA

• USP 797 + 503A + State Regulations + FDA Guidance

• Food & Drug Administration

• State Boards of Pharmacy

• Current cGMP

• Section 211 + FDA Guidance

1. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM469119.pdf Accessed 11/23/162. http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm403496.pdf Accessed 11/23/163. 2016 GAO report: Drug Compounding: FDA has taken steps to implement compounding law, but some states/stakeholders reported challenges

Hospitals and Clinics Outsourcing ManufacturersVoluntary


Source: http://www.pewtrusts.org/~/media/assets/2014/11/drug_compounding_infographic_final.pdf?la=en


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• Licensed pharmacist has direct oversight

• Compound only drugs from bulk ingredients that appear on a list developed by the Secretary

• Register as an outsourcing facility

• Report to the Secretary upon registering, every 6 months

• Be inspected by FDA

• Report serious adverse event experiences within 15 days

• Label products with a statement identifying it as a compounded drug

• Source: Public Law 113‐54. ‘‘Drug Quality and Security Act”. www.gpo.gov/fdsys/pkg/PLAW‐ 113publ54/pdf/PLAW‐113publ54.pdf. Accessed May 15, 2015

Outsourcing Facility Requirements


• An outsourcing facility MUST NOT:

• Compound drugs removed from the market for safety and effectiveness reasons

• Compound copies of marketed FDA‐approved drugs except in the case of a drug shortage

• Sell to Wholesalers/Distributors, and all must be labeled “not for resale.”

• Source: Public Law 113‐54. ‘‘Drug Quality and Security Act”. www.gpo.gov/fdsys/pkg/PLAW‐ 113publ54/pdf/PLAW‐113publ54.pdf. Accessed May 15, 2015

Outsourcing Facility Requirements


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Accountability 2017



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Reliance On Outsourcing



Outsourced Compounding

Looking forward, most facilities expect to continue outsourcing much of the same product mixThat they currently rely on their vendors to supply.

State of Pharmacy Compounding. Pharm Purch Prod.2018.


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Outsourcing Assessment

From a legal and The Joint Commission perspective Hospitals are responsible for the services provided to patients from an outsourced vendor


Key Safety Elements

People

Skills set

Aptitude

Training

Math skills

Environmental monitor

Clean environment

Ingredient standards

Trustworthy

Reliability

Processes

Compounding skills

Continuous education

Consistency

Documentation of processes

Documented training

Operator testing

Re-training process

Products

Stability

Sterility

Labeling

Appropriate dating

Reduce contamination

Consistency

Recall process

VALIDATION


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Proper Room for Compounding


Proper Room Controls

TemperatureHumidity

PositivePressure

ISO 7: HEPA Ceiling


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The Proper Work Area

ISO 5 laminarFlow Cabinet

ISO 5 CompoundingAseptic Isolator

ISO 5 HEPACompounding Space


Effective Training?


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Acceptable?

Source; E.Kastango

Source; F. Massoomi

Source; F. Massoomi



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Proper Technique


Proper Cleaning


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Source: http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/PharmacyCompounding/ucm389118.htm Accessed May 15, 2015

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Checking Outsourcing Compliance


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Understanding Outsourcing Issues


Evaluating Product Safety

• Safety of Intravenous Drug Delivery System

• Participants ranked products based on safety –(highest=7 lowest=1):

–Manufacturer ready-to-use (6.0)

–Point-of-care activated (4.6)

–Outsourced ready-to-use (4.5)

–Pharmacy compounded (4.2)

–Non-pharmacy compounded at point of care (1.8)

Sanborn MD, Moody ML, Harder KA et al. Second Consensus Development Conference on the Safety of Intravenous Drug Delivery Systems 2008. Am J Health-Syst Pharm. 2009; 66:185-92.

2nd Consensus Development Conference


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ISMP Sterile Compounding Summit

• ISMP Summit 2011

– When available• commercially manufactured

• premixed IV products

– Use over manually compounded sterile products

Source: Guidelines for the Safe Preparation of Sterile Compounds: Results of the ISMP Sterile Preparation Compounding Safety Summit of October 2011. Rich S, et al. Hosp Pharm 2013;48(4):282–294,301.


Missing in the Equation


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Seeing the Unseen

G. L. Shearer, “Taking a Closer Look at Parenteral Contaminants," Pharmaceutical Technology 40 (9) 2016.

Glass CoringPrecipitant Filaments

© Copyright Visante, Inc. All rights reserved | www.visanteinc.com

Thank you.

Fred Massoomi, Pharm.D., FASHPSenior DirectorVisante, Inc.

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