CE Activity Information

1

Update on Sterile Compounding in Health Systems:

Opportunities and ChallengesLouis S. Diorio, RPh, FAPhA

Susan J. SchnieppFred Massoomi, PharmD, FASHP

Supported by an educational grant from PharMEDium Services, LLC.

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CE Activity Information

1.5 contact hours for pharmacists

Proof of completion will be posted to your NABP CPE Monitor profile

Accreditation:

Funding:

This CE activity is supported by an educational grant from PharMEDium Services, LLC.

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3

Faculty

Fred Massoomi, Pharm.D., FASHPSenior Director of Health‐system & Hospital ServicesVisante, Inc.

Louis S. Diorio, RPh, FAPhAPrincipalLDT Health Solutions, Inc.

Mr. Diorio is an employee and shareholder of LDT Health Solutions, Inc. and has served as a speaker for Grifols USA and Spectrum Pharmacy Products. Dr. Massoomi is an employee ‐ consultant for Visante, Inc. and has served as a speaker for Baxter, Equashield, Hospira, and ICU Medical, and as a writer for BD. Ms. Schniepp has served as a consultant for Regulatory Compliance Associates, as an auditor for NSF, and as a consultant for PharMEDium Services, LLC. Content review and conflict resolution conducted by James Dorociak, PharmD, MSc. Dr. Dorociak has no relevant financial relationships to disclose.

Susan J. SchnieppDistinguished FellowRegulatory Compliance Associates, Inc.

Improving the Safety of Compounded Sterile Preparations

USP <797> Changes are coming – How will this impact your practice?

Lou Diorio, RPh, FAPhAPrincipal

LDT Health Solutions, Inc.

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Session Objectives

• Describe the current landscape of the United States Pharmacopeia (USP) Compounding Chapters

• Identify the environmental control requirements for sterile compounding

• Describe batch testing and the role batch testing can play to increase the safety of sterile compounding

• Discuss health system pharmacy accountability related to sterile compounding procedures

• Outline pharmacy leadership strategies for managing the increasing regulated environment while providing optimal patient care services

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The presenter would like to thank the following colleagues for their assistance & guidance in assembling these materials:

• Art Chaput, RPh, PharmD• Patricia C. Kienle, MPA, BS Pharm, FASHP• Eric Kastango, RPh, MBA, FASHP• Dave Thomas, RPh, MBA

Acknowledgements

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How Did We Get Here?

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• The short answer is that there are NO Guarantees!– Constant vigilance is in order!

• Know the limits of your Pharmacy Practice Act.

• Be familiar with all the moving parts:– USP <71> [Sterility Testing]– USP <85> [Endotoxin Testing]– USP <795> [Non-Sterile Compounding]– USP <797> [Sterile Compounding]– USP <800> [Handling of HD in Healthcare Settings]– DQSA [The Drug Quality & Security Act]– NIOSH & OSHA regulation

Can Tragedies Like NECC Be Prevented in the Future?

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9

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Are You Comfortable Knowing How All the Pieces Fit Together?

10

Director of Pharmacy

DOH Compliance

TJC ��& '��#�

DEA Compliance

CMS Compliance

BOP Compliance

FDA

Compliance

Hospital Director of Pharmacy FOCUS

The Balance of Priorities is KEY !

What are the Hospital Administration's

Priorities?

Individual Hospital

Conditions Could Intensify Some of

these Intersections

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Since July 2014 the FDA has issued 27 Guidance documents or Regulatory Policy Statements impacting Pharmacy Practice

Addressing the following topics:• Insanitary Conditions at Compounding Facilities • Pharmacy Compounding of Human Drugs / 503A • 503B Outsourcing Facilities [Registration, Fees,

General Facilities]• Use of Bulk Drug Substances [A / B]• Hospital & Health System Compounding• Compounded Products that are Essentially Copies of

Approved Drug Products [503A / 503B]• Mixing, Diluting, or Repackaging of Biological Products

FDA Guidance onCompounding

http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/PharmacyCompounding/ucm166743.htmhttp://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm452240.htm

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FDA Compliance Program Guidance (CPGs)

– Insanitary Conditions at Compounding Facilities Guidance for Industry – Draft Guidance (8.3.16)

– Pharmacy Compounding of Human Drug Products Under Section 503A of the Federal Food, Drug, and Cosmetic Act - October 2015 -Compounding and Related Documents (Revision 1)

– Sterile Drug Products Produced by Aseptic Processing — Current Good Manufacturing Practice - Guidance for Industry (September 2004)

– Prescription Requirement Under Section 503A of the Federal Food, Drug, and Cosmetic Act - Guidance for Industry - Draft Guidance (04/15/16)

– Hospital and Health System Compounding Under the Federal Food, Drug, and Cosmetic Act - Guidance for Industry (PDF - 81KB) - Draft Guidance (04/15/16)

– Facility Definition Under Section 503B of the Federal Food, Drug, and Cosmetic Act - Draft Guidance (04/15/16)

Relevant FDA Guidance Documents

http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/PharmacyCompounding/ucm166743.htm

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13

When considering FDA Guidance Documents, which statement is TRUE?

A. They do not establish legally enforceable responsibilities

B. They reflect the Agency's current thinking of a topic

C. Unless backed by a specific regulation, they are recommendations

D. All of the above are TRUE

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FDA 503A and 503B Pharmacy Top 25 Observations as of 4/30/2017Observation Occurences

B01

Percentage

1 Aseptic processing areas are deficient regarding the system for monitoring environmental conditions. 59.3%249

2 Aseptic processing areas are deficient regarding the system for cleaning and disinfecting the room and equipment to produce aseptic conditions. 53.8%226

3 Clothing of personnel engaged in the manufacturing, processing, packing, and holding of drug products is not appropriate for the duties they perform. 53.3%224

4 Procedures designed to prevent microbiological contamination of drug products purporting to be sterile are not established, written, and followed. 47.6%200

5 Procedures designed to prevent microbiological contamination of drug products purporting to be sterile do not include adequate validation of the sterilization process. 36.9%155

6 There is no written testing program designed to assess the stability characteristics of drug products. 34.8%146

7 Testing and release of drug product for distribution do not include appropriate laboratory determination of satisfactory conformance to the final specifications and identity 34.3%and strength of each active ingredient prior to release.

144

8 There is a failure to thoroughly review any unexplained discrepancy and the failure of a batch or any of its components to meet any of its specifications whether or not the 33.3%batch has been already distributed.

140

9 Each batch of drug product purporting to be sterile and pyrogen‐free is not laboratory tested to determine conformance to such requirements. 28.8%121

10 Separate or defined areas to prevent contamination or mix‐ups are deficient regarding operations related to aseptic processing of drug products. 20.0%84

11 Aseptic processing areas are deficient regarding air supply that is filtered through high‐efficiency particulate air filters under positive pressure. 16.9%71

12 The labels of your outsourcing facility's drug products do not include the information required by section 503B(a)(10)(A)&(B). 16.0%67

13 Each batch of drug product required to be free of objectionable microorganisms is not tested through appropriate laboratory testing. 15.7%66

14 Aseptic processing areas are deficient regarding systems for maintaining any equipment used to control the aseptic conditions. 15.0%63

15 Equipment and utensils are not cleaned, maintained, and sanitized at appropriate intervals to prevent malfunctions and contamination that would alter the safety, identity, 13.6%strength, quality or purity of the drug product.

57

16 Laboratory controls do not include the establishment of scientifically sound and appropriate sampling plans and test procedures designed to assure that drug products 13.3%conform to appropriate standards of identity, strength, quality and purity.

56

17 Routine calibration and inspection of mechanical and electronic equipment is not performed according to a written program designed to assure proper performance. 11.9%50

18 Batch production and control records do not include complete information relating to the production and control of each batch. 9.5%40

19 Drug product containers and closures were not clean and sterilized and processed to remove pyrogenic properties to assure that they are suitable for their intended use. 8.6%36

20 Buildings used in the manufacture, processing, packing, or holding of a drug product do not have the suitable size, construction, and location to facilitate cleaning, 8.1%maintenance, and proper operations.

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21 There are no written procedures for production and process controls designed to assure that the drug products have the identity, strength, quality, and purity they purport 7.9%or are represented to possess.

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22 Equipment used in the manufacture, processing, packing or holding of drug products is not of appropriate design to facilitate operations for its intended use and cleaning 7.1%and maintenance.

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23 The responsibilities and procedures applicable to the quality control unit are not in writing and fully followed. 6.9%29

24 Buildings used in the manufacture, processing, packing or holding of drug products are not maintained in a clean and sanitary condition. 6.4%27

25 Time limits are not established when appropriate for the completion of each production phase to assure the quality of the drug product.

Facilities: 328 Inspections: 420 Inspectiors: 320 States:

Page 1 of 1

LDT Health Solutions, Inc. www.LDTRx.com Sunday, April 30, 2017

6.4%27

43 20Districts: 6Regions:

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• Since the NECC tragedy the FDA has…

• Visited at least 320 facilities

• Issued 420 FDA Form 483s to those facilities

[From 20 different Field Offices in 43 States!]

FDA by the Numbers(as of 4.30.17)

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• Warning Letters Issued–168 in total

–To 151 different Facilities

• They were issued by FDA–48 days minimum

–368 days on average

–1,249 days maximum!


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• When the FDA walks in the door to inspect your pharmacy, you can expect…– Team will most likely be 2 agents– They will stay about 6.8 days total– They will write up 7.6 observations on the FDA Form

483 they leave behind!• Compounders within the coverage areas of the Dallas,

Los Angeles, Tampa & Nashville FDA Field Offices are more likely to be visited.


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Since Hospitals are registered by their local Boards of Pharmacy, admittance of FDA to the establishment is voluntary.

A. True

B. False

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• Definitions • Responsibilities of compounding personnel• CSP microbial contamination risk levels• Personnel training and evaluation in aseptic manipulation skills• Immediate use CSPs• Single-dose and Multiple-dose containers• Hazardous drugs as CSPs• Radiopharmaceuticals as CSPs• Allergen Extracts as CSPs• Verification of Compounding Accuracy and Sterility • Environmental Quality and Control• Suggested Standard Operating Procedures (SOPs)• Elements of Quality Control• Verification of Automated Compounding Devices (ACDs) for Parenteral Nutrition Compounding• Finished preparation release checks and tests• Storage and beyond-use-dating• Maintaining Sterility, Purity, and stability of Dispensed and Distributed CSPs• Patient or Caregiver training• Patient monitoring and adverse event reporting• The Quality Assurance (QA) Program• Abbreviations and Acronyms• Appendices I-V

USP Chapter <797> Sections

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Which of the following is NOT one of the central themes of USP <797>?

A. Control of the compounding environment

B. Control of the compounding personnel’s actions

C. Control of the compounding process

D. ALL of the above are central safety themes of <797>

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Is about 3 things…

– CONTROL!– CONTROL!

– CONTROL!• Control of the compounding personnel

• Control of the compounding environment

• Control of the compounding processes

USP General Chapter <797>

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Personal Training and Evaluation in Aseptic Manipulation Skills

“Personnel who prepare CSPs shall be trained conscientiously and skillfully by expert personnel and through audio-video instructional sources and professional publications in the theoretical principles and practical skills of aseptic manipulations and in achieving ISO Class 5 environmental conditions before they begin to prepare CSPs.”

1‐USP<797> Pharmaceutical Compounding‐Sterile Preparations Revision Bulletin © USP

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The Responsibility of Compounding Personnel

• The need to maintain high standards for quality & control of processes, components, and environments and for the skill & knowledge of personnel who prepare CSPs.

• The USP is the National Standard, so compounding personnel must understand the legal risks of non-compliance.

– Especially for the Pharmacist-in-Charge / “Manager of Record”

• Focus for now should be USP 39 - NF 34 ! (current chapter)

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Personal Training and Evaluation in Aseptic Manipulation Skills

• Aseptic training in pharmacy schools is inadequate or non-existent.

• Most training occurs “OJT” and by “verbal tradition”

• Training must include didactic instruction in theory and practice of sterile preparation before starting compounding and annually/semi-annually thereafter.

• Evaluations should include a formal written exam, motor-skills assessment and practical evaluation of aseptic technique using growth media.

(c) 2017 LDT Health Solutions, Inc.

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Which of the following is part of a solid program for the provision of CSPs in Health Systems?

A. Solid aseptic training

B. Comprehensive gowning, gloving & garbing processes

C. Standardized cleaning & disinfection of the controlled areas

D. ALL of the above

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Environmental Quality & Control

• Aseptic Processing areas must be of proper design -

– HEPA filtered air introduced at the ceiling

– Low wall returns

– Cleanable surfaces, able to stand up to repeated sanitizations

– Certification of the areas should follow CETA guidance

– Monitoring of Controls (Temperature / Humidity / Pressurization)

• Proper Environmental Monitoring – semi-annually is NOT enough!

• Cleaning cycle must include a sporicidal agent.

• Responses to Viable & Non-Viable contaminations must be appropriate, swift, & measured.

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Cleanroom Cleaning & Disinfecting- for non-HD CSPs[USP <797>]

SWFI70% Sterile

IPA

Quat Ammonium

Cleaner

Sporicidal Agent

2% Sterile Bleach


Per <797> when dissolution of messy spills is in order

Per <797> this is the primary disinfect agent in your cleanroom

Needed when a “soap” is indicated. Sticky spills etc.

FDA is advocating the regular use of a sporicidal agent, regardless of ENV monitoring. POINTS to REMEMBER‐dilution strength & contact time. [as well as residues]

A good economical disinfectant, especially if a large volume of solution is needed. Can be used to remove Sporicidal residues. OSHA‐Corrosive , S Steel could have issues<797> ‐ Primary concern is

Maintaining Sterility

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Risk Levels of USP <797>

“NO” Risk[Low‐Low Risk]

• RTU, Pre‐mixed, or UOU Commercial Doses

Low Risk• “Simple,” single dose compounding

Medium Risk• Using multiple sterile components (i.e. Batch compounding)

High Risk• Beginning from non‐sterile components ORrendering sterile components non‐sterile during manipulations


Are you sure how to categorize any compounded, outsourced or contract compounded CSPs you provide to your patients?

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Beyond-Use Dating

• Applies once a manufacturer's container is opened and the drug product is transferred to another container for dispensing, repackaging, or compounding.

• The USP has developed recommendations for compounders to assign a “BUD” on the label of the new container.

• BUDs cannot exceed the manufacturer's expiration date and often may be much shorter.

• Unlike expiration dating, there is often little scientific basis for the assignment of BUDs.– “Theoretical” dating periods exceeding 30 days must be

supported by appropriate instrumental analysis.

• Compounders must have their BUD policies in writing!

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Finding Balance: Chemical Stability vs Sterility

Chemical Stability of the CSP

Sterility of the Compounded

CSP


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Quality Assurance Program

• Requires formalized policies, controlled processes and clear procedures used in preparing CSPs

• One element of quality that is not routinely performed in pharmacies is documentation, or “written proof” that compounding is occurring properly.


Photos © LDT Health Solutions., Inc.

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Proposed USP <797> Changes

Proposed Major Changes -

3 Risk levels changed to 2 categories distinguished by conditions under which they are made and time within which used

Removal of HD handling section and cross-reference to USP <800>

Quarterly requirement for Personnel Monitoring (visual observation of hand hygiene and garbing, MFT and on-going GFS

Monthly requirement for Viable Air sampling & Surface sampling

BUD and Storage times changes with a maximum BUD of 45 days regardless of sterility testing

Introduction of “In-Use-time” (time before which conventionally manufactured product or compounded dilution bag must be used after it is punctured)

Master formulation and compounding recordswill be required for all batch and non-sterile compounding

New guidance for sterility testing of CSP prepared in batch sizes of less than 40. (10% rule)

New placement requirements on use of isolators Requirement for sterile gloves and sterile sleeves, sterile wipers and cleaning tools that need to be re-sterilized but not sterile disinfectants

CHART © 1999‐2016 Clinical IQ, LLC – All rights reserved – used by permission

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Self-Assessment tools (SAT) or “GAP” Analysis

• Use a SAT or GAP Analysis to identify organizational points of compliance and operational gaps.– High level situational analysis of current state of readiness.– Should address-

• USP <71> <85> <795> <797> <800> • FDA CPGs 503A & Hospital and Health System Compounding• State and Local Regulation

• SAT or GAP Analysis will serve as a placeholder for regulatory and accreditation agencies.– It is only a starting point!– But the best place to start is at the beginning!

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Developing an Action Plan

• Focus should be on:– “Changing the culture”

• Controlled processes and documentation

• Competency Based Training and Education

• Compliance to Local, State, and Federal Regulations

• Patient Safety is always your goal!

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Summary / Conclusions

• There is no substitute for constant vigilance on the part of any professional, compounder, or healthcare provider of CSPs.

• All professionals must be aware of ALL best practices & prevailing regulation!

• A comprehensive situational analysis of the compounders current state of compliance is a good first step in the determination of its long-range compliance plan.

• USP <797> is in place, the time to address the Chapter is NOW !

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Quality Process Courtesy of LDT

• Personnel are capable and qualified to perform their assigned duties.

• Ingredients used in compounding have their expected identity, quality, and purity .

• Critical processes are validated to ensure that procedures, when used, will consistently result in the expected qualities in the finished preparation.

• The engineering controls and production environment is suitable for its intended purpose (addressing such matters as environmental cleanliness, control, monitoring, staff attire, and the setting of action limits, as appropriate).

• There is assurance that processes are always carried out as intended or specified and are under control.

• Appropriate stability evaluation is performed or determined from the literature for establishing reliable expiration dating to ensure that finished preparations have the expected potency, purity, quality and characteristics at least until the labeled expiration date.

• Appropriate release checks or testing procedures are performed to ensure that finished CSPs have their expected potency, purity, quality and characteristics at least until the labeled beyond use date.

• Preparation conditions and procedures are adequate for preventing mix-ups.

• There are adequate procedures and records for investigating the product, correcting failures or problems in preparation, testing, or in the preparation itself.


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Reading List / Bibliography

• General Chapter USP <795> <797> <800> ‐ www.usp.org

• Controlled Environmental Testing Association (CETA) – www.CETAinternational.org

• Centers for Disease Control & Prevention www.cdc.gov

• Pharmacy Purchasing and Products Magazine‐www.pppmag.com

• FDA Website – www.FDA.gov• NECC FDA form 483 ‐

http://www.fda.gov/downloads/AboutFDA/CentersOffices/OfficeofGlobalRegulatoryOperationsandPolicy/ORA/ORAElectronicReadingRoom/UCM325980.pdf

• Drug Quality & Safety Act ‐• http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/PharmacyCompounding/ucm376732.htm

• OSHA / NIOSH Resources –• HD Drug list ‐ http://www.cdc.gov/niosh/docs/2016‐161/default.html

• NIOSH Drug Alert‐ http://www.cdc.gov/niosh/docs/2004‐165/default.html

• Workplace Solutions – PPEs‐ http://www.cdc.gov/niosh/docs/wp‐solutions/2009‐106/pdfs/2009‐106.pdf

• DONNING & DOFFING – (videos) http://www.cdc.gov/vhf/ebola/hcp/ppe‐training/

• CSTD‐ (Draft for comment) ‐http://www.cdc.gov/niosh/docket/review/docket288/default.html


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Reading List / Bibliography

• Pharmacy Purchasing and Products – www.pppmag.com• FDA Website – www.FDA.gov

– NECC FDA form 483 -www.fda.gov/downloads/AboutFDA/CentersOffices/OfficeofGlobalRegulatoryOperationsandPolicy/ORA/ORAElectronicReadingRoom/UCM325980.pdf

– Drug Quality & Safety Act -– http://www.fda.gov/downloads/AboutFDA/CentersOffices/OfficeofGlobalRegulatoryOperationsandPolicy

/ORA/ORAElectronicReadingRoom/UCM325980.pdf– Drug Quality & Safety Act -

• http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/PharmacyCompounding/ucm376732.htm

– Guidance – Pharmacy Compounding –• http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm469119.pdf

– Guidance – Insanitary Conditions – Draft August 2016– http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM5146

66.pdf– Guidance – Aseptic Processing-

• http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm070342.pdf– Guidance-Prescription Requirement Under Section 503A of the Federal Food, Drug, and Cosmetic Act

Guidance for Industry Draft Guidance 04/15/16• http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm496286.pdf

– Guidance- Hospital and Health System Compounding Under the Federal Food, Drug, and Cosmetic Act Guidance for Industry Draft Guidance 04/15/16

• http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm496287.pdf– Guidance- Facility Definition Under Section 503B of the Federal Food, Drug, and Cosmetic Act (PDF -

244KB) Draft Guidance 04/15/16• http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm496288.pdf

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Batch Release TestingWhy do we do it?

What does it mean?

Susan SchnieppDistinguished Fellow

Regulatory Compliance Associates, Inc.

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Batch Release Testing Requirements

Discussion Topics

Regulations

Analytical Chemistry TestingIdentityPotency

Microbiology TestingSterilityEndotoxin

Activities Supporting Batch ReleaseMedia Fills & Smoke StudiesEnvironmental MonitoringGowning Air Quality

Customer ImpactInterpreting the CoA

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Under section 501(a)(2)(B) of the FD&C Act, a drug is deemed to be adulterated if:

the methods used in, or the facilities or controls used for, its manufacture, processing, packing, or holding do not conform to or are not operated or administered in conformity with current good manufacturing practice to assure that such drug meets the requirements of this chapter as to safety and has the identity and strength, and meets the quality and purity characteristics, which it purports or is represented to possess . . . .

Regulations

Food, Drug, and Cosmetic Act

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• Current Good Manufacturing Practice – Interim Guidance for Human Drug Compounding Outsourcing Facilities Under Section 503B of the FD&C Act – July 2014

• Facility Definition Under Section 503B of the Federal Food, Drug, and Cosmetic Act – April 2016

• Insanitary Conditions at Compounding Facilities – August 2016

Regulations (cont’)

Guidance

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• Appropriate specifications must be established for each drug product (see §211.160(b)). Specifications must address those attributes necessary to ensure the quality of the finished drug product (see § 211.160(b)) and should include at a minimum:

– Identity of the active ingredient

– Strength of the active ingredient

– Sterile drug products:

• Limit for visible particles

• Statement of Sterility

• Limit for bacterial endotoxins

Regulations (cont’)

Batch Release Testing Requirements

44

What batch test requirements are measured using chemistry?

A. Identity

B. Potency

C. pH

D. Sterility

E. A and B are both correct

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45

• Potency: Measure of the amount of the active ingredient(s) in a particular dosage form– Typical Specification Range: 90%-110% (USP)

• Identification: Definitive Confirmation of the presence of the active ingredient(s) in the dosage form– Typical Specification: Conforms to Standard

Batch Release Testing

Chemistry Testing

46

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47

What batch test requirements are measured using microbiology?

A. Endotoxin

B. Sterility

C. Environmental Monitoring

D. Media Fills

E. A and B are both correct

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• Sterility: The absence of microbial contamination (pathogens) in the dosage form– Typical Specification: Absence of Salmonella, E. coli,

etc.

• Endotoxin: Identification of the level of fever causing microbial by products present in the dosage form– Typical Specification: < 0.25 EU/mL

Batch Release Testing

Microbiology Testing

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• Media Fills & Smoke Studies – demonstrates the capability of the process to maintain aseptic conditions during manufacturing

• Environmental Monitoring – ongoing assessment of the facility to maintain an environment conducive to product manufacturing

• Gowning Monitoring – ongoing assessment of the human element and their ability to manufacture while maintaining an environment conducive to aseptic processing

• Air Quality – Part of the EM program monitoring viable and non-viable particulates potentially affecting product quality

Batch Release TestingOther Activities Supporting Batch Release

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• Batch release testing reflects a “snapshot” of the quality attributes required for product release

• Although sterility testing is required, the “true” sterility of a batch is assessed through:

– Sound environmental/personnel monitoring program

– Robust cleaning, disinfection & sanitization processes

– Strong manual aseptic processing technique

– Bioburden reduction measures

– Effective gowning procedures

Summary

Hazardous Drug HandlingUSP <800> & Beyond

Fred Massoomi, Pharm.D., FASHP

Senior Director

Healthcare & Hospital Services

Visante, Inc.

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53

Source: LA Times; January 24, 2017

54

Trending Now

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Hazardous Drug Compounding USP <800>

http://www.usp.org/usp-nf/notices/general-chapter-hazardous-drugs-handling-healthcare-settings

First Release March 2014

Comment Due Date July 31, 2014

Second Release December 2014

Comment Due Date May 31, 2015

Approved February 1, 2016

Official Compliance Date July 1, 2018

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

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

Chart Ref: State of Pharmacy Compounding 2017; Pharmacy Purchasing and Products; Supplement April 2017, pg. 35

USP <800> Compliance

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Roadmap 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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Compounding Hierarchy

Food and Drug Administration

United States Pharmacopeia <797> & <795>

State Boards of Health &/or Pharmacy

Industry Best

Practices

ProfessionalBest

Practices

Regulatory Line

United States Pharmacopeia <800>

Centers for Medicaid & Medicare Services


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60

Hazardous Drug SafetyParadigm

USP 797USP 800

FDA Patient Safety

OSHA USP 800

Employee Safety

EPA / DOTPublic Safety


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Surveying Bodies for Compounding• State Boards of Pharmacy• FDA: Food and Drug Administration• CMS: Centers for Medicare/Medicaid Services

• TJC: The Joint Commission• DNV Healthcare• HFAP: AOA’s Healthcare Facilities Accreditation

Program• ACHC: Accreditation Commission for Healthcare

• PCAB: Pharmacy Compounding Accreditation Board


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Inspecting for <797> Compliance

64

Surveying Bodies for Compliance

Physician Owned Offices– If registered as a pharmacy = subject to pharmacy board regulations

– California, Florida & Texas register if they compound sterile drugs


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Introduction & Scope

• Pharmacists, pharmacy technicians, nurses, physicians, physician assistants, home healthcare workers, vets, and vet technicians

• Not listed: Manufacturers; Wholesale personnel; Researchers; Family

http://www.usp.org/usp‐nf/notices/general‐chapter‐hazardous‐drugs‐handling‐healthcare‐settings


66

Which statement best describes the NIOSH hazardous drug list?

A. mirrors the FDA’s list of HD’s

B. is updated approximately every two years

C. is divided into different formulations of drugs

D. includes all research drugs with potential hazards

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67

List of Hazardous Drugs

Must have a list (USP; TJC; NIOSH)– Type of HD:

• antineoplastic; • non-antineoplastic; • reproductive risk

– Risk of exposure


Updated every 2 years

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Types of Exposure

Routes of unintentional entry

–Dermal

–Mucosal absorption

–Inhalation

–Injection

–Ingestion


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Facilities & Engineering Controls

Designated areas must be available for HDs:

•Receipt & unpacking•Storage•Non‐sterile compounding

•Sterile compounding

Example: Signage


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Receipt

HDs must be unpacked in designated area

– Neutral/Negative pressure

Must store in manner to preventspillage/breakage

– Externally vented,

– Negative pressure to ‐.01 to ‐0.03inch column height

– 12 air changes per hour (ACPH)

Storage


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CompoundingContainment Primary Engineering Controls (C‐PEC)

• Biological Safety Cabinet

–Class II BSC types A2 or B2

• Containment Aseptic Compounding Isolator (CACI)


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CompoundingContainment Secondary Engineering Controls (C‐SEC)

• C‐SEC = The Room

– Externally vented

– Physically separated

• Negative pressure

–0.01 and 0.03 inches water column


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74

Close System Transfer Devices (CSTDs) are required for handling hazardous drugs during

A. Pharmacy compounding

B. Nursing administration

C. Both A & B

D. Neither A or B

75

Closed System Transfer Devices CSTDs

Pharmacy Compounding: Should

Nursing Administration:Must

CompoundingSupplemental Engineering Controls


37



CSTD AdoptionAre we all in?

78Source: BD & the Joint Commission Resources; Improving safe handling Practices for Hazardous Drugs. Toolkit 2016

FDA Cleared Closed System Transfer DevicesDevice Manufacturer FDA Cleared FDA

ONBNon-FDA

Type

BD Phaseal™ System Becton Dickenson and Company; Carmel Pharma, Inc. (original)

1998 * Containment

Spiros® ICU Medical, Inc. 2005

Texium™ with SmartSite™

Becton Dickinson and Company; CareFusion, Inc. (original)

2006 Air Cleaning

OnGuard® with Tevadaptor®

B. Braun Medical Inc. (U.S. distributor) TEVA Medical, Ltd. (manufacturer)

2006 * Air Cleaning

ChemoClave® ICU Medical, Inc. 2006 Containment & Air Cleaning

Equashield® Equashield, LLC; Plastmed, Ltd. (original)

2008 Containment

ChemoLock® ICU Medical, Inc. 2013 * Containment & Air Cleaning

ChemoSafety Becton, Dickinson and Company; CareFusion, Inc. (original)

2013 Containment &Air Cleaning

EquaShield II® Equashield, LLC 2014 * Containment

Halo® Corvida Medical 2015 * Containment

38

79

Drug Administration

• Must use CSTDs

• Must pre‐priming IV tubing with non‐HD solution

• Must wear PPE

• Must avoid manipulation

–Splitting, crushing, opening capsules Source: Used with permission

Seth Eisenberg, RN


80

Noted Exposures Nursing Perspective

Source: http://nursing.onclive.com/publications/oncology‐nurse/2017/march‐2017/attitude‐shift‐making‐safe‐handling‐of‐hazardous‐drugs‐a‐priority‐

Table 1. Hazardous Drug Exposure Reported by NursesDrug Safe Handling Program

Frequency Type of Exposure Time Frame

11% - 17% Dermal or eye exposure Previous year

12% - 26% HD spills Previous week –6 months

12% - 24% Took home potentially contaminated clothes

No time frame

6% - 8% Sharps injury involving HDs Previous year

39

81

Non‐sterile Compounding

• Must follow USP <795>

• C‐PEC required for some manipulations– Cutting– Crushing


82

Environmental Quality & Control

• Recommended • BEST PRACTICE every 6 months and following spills


40

84

Personal Protective Equipment

2 pairs

Disposable GownsPolyethylene or laminateClose in the back

2 pairsDon 2 pairs prior to entryRemove outer when leavingAnti-skid

Head coversBeard covers

Eye protection for‐spill protection

Face mask –limited safety

‐N‐95 mask

Powered air‐purifying respirator

‐for spills


Best Practice

85

Personnel & Training

• Must have a designated specialist

• Must be assessed every 12 months

• Must be trained on new HDs and equipment

• Must document competencies


41

86

Labeling, Packaging & Transport

• Labeling

– Precaution clearly labeled

• Transport

– Transport containers

– Must Not transport via pneumatic tubes any liquid HDs


87

Hazardous Waste Management

• Continuous formulary assessment • State and federal regulations

DRUG - GENERIC (BRAND)

CLASS OF MEDICATION

ROUTE/ FORMS COMPANY

PREG CAT MSDS BSC

HAZ CLASS

(1-4)WASTE STREAM

RCRA Y/N

Cyclophosphamide ONCINJ,ORAL Multiple D YES YES Class 1

RCRABLACK Y


42

88

Deactivation, Decontaminating, Cleaning & Disinfecting


89

Spill Control

• Must have proper training for spill management

• Must have spill kits readily available

• Must address size of spills

• Best practice ‐ Date kits


43

90

Nursing report spills occur most frequently in the following scenario?

A. IV port/site leaks

B. Spiking issues

C. Tubing disconnects

D. No spills noted in today's environment

91

Specific Spill ScenariosNursing Perspective


44

92

Specialized Patients & Procedures

• Surgical– Bladder installation

– HOT Chemo Baths

– Ophthalmic surgery = TOPICAL

– Esophageal Strictures = TOPICAL

• Obstetrics– Ectopic pregnancy

• Rheumatology– Rheumatoid arthritis

– Lupus nephritis

• Neurology– Multiple sclerosis

Hyperthermic Intraperitoneal Chemotherapy


93

Future Considerations

• Gene therapy delivery

• Virus & bacterial delivery

• Microrobot delivery of drugs

• Nanotechnology drugs


45

94

Evolution Towards Safety

First and Second Generation Automation


95

Evolution Towards Safety

Third Generation Automation


46

96

Educating Administration

1. USP <797> Pharmaceutical Compounding – Sterile Compounds2. USP <800> Hazardous Drug ‐ Handling in Healthcare Settings3. MM.09.01.01 Antibiotic Stewardship Standard4. 503A & 503B Compounding5. 340B Mega‐Guidance Withdrawn


Questions and Panel Discussion

47

98

Thank you

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