CE Activity Information & Accreditations3.proce.com/res/pdf/PharMEDium2018Dec.pdf · • Compounding using bulk drugs • Compounding ‘essentially copies’ of approved drugs •

503B Outsourcing Facilities: Health-System Evaluation Strategies and An Update on FDA GuidancePharMEDium Lunch and Learn Series

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503B Outsourcing Facilities: Health‐System Evaluation Strategies and An Update on FDA Guidance

December 14, 2018

Featured Speaker: Kevin Hansen, PharmD, MS, BCPSAssistant Director of PharmacyCone Health, Moses H. Cone Memorial HospitalGreensboro, North Carolina

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503B Outsourcing Facilities:Health‐SystemEvaluationStrategiesandanUpdateonFDAGuidance

Kevin Hansen, PharmD, MS, BCPSAssistant Director, PharmacySterile Products, Special Formulations, Perioperative ServicesMoses H. Cone Memorial Hospital | Cone HealthGreensboro, North Carolina



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• I have no relevant financial relationships to disclose with regards to this presentation

•The views/opinions expressed in this presentation are of my own and not that of my employer

Disclosures

88

Technicians1. Outline the impact regulatory systems and changes may have on

sterile compounding practices2. Identify insanitary conditions in compounding facilities3. Discuss importance of proper training and competency programs

Pharmacists1. List Food, Drug and Cosmetic (FD&C) Act exemptions for 503A,

503B, and manufacturing facilities2. Outline the impact regulatory systems and changes may have on

sterile compounding practices3. Describe evaluation strategies to outsource to a 503B facility4. Discuss importance of proper training and competency programs

Learning Objectives



99

• ANDA: Abbreviated New Drug Application

• API: Active Pharmaceutical Ingredient• BUD: Beyond Use Date• CGMP: Current Good Manufacturing Practices

• COA: Certificate of Analysis• EM: Environmental Monitoring• FDA: Food and Drug Administration• FD&C: Food, Drug, and Cosmetic Act• HRO: High Reliability Organizations• ISMP: Institute for Safe Medication Practices

• ISO: International Organization for Standardization

• MOU: Memorandum Of Understanding

• NDA: New Drug Application• QA: Quality Assurance• QC: Quality Control• REMS: Risk Evaluation and Mitigation Strategies

• SBOP: State Board of Pharmacies• USP: United States Pharmacopeia

Abbreviations

1010

• Contaminated methylprednisolone acetate injections

• Resulted in fungal meningitis

• 76 deaths

• > 800 sickened

Compounding Tragedies: Contamination

Photo credit: https://www.cdc.gov/media/releases/2012/images/dpk‐meningitis‐3A_0982‐B.jpg

Fungal infection of brain tissue

Kastango, ES. JCHP. 2013;66(3):152‐153.

• Contaminated parenteral nutrition solution

• 9 patients died

• Compounding amino acids using non‐sterile ingredients

Serratia marcescens

• Contaminated intraocular injections of Avastin® (bevacizumab)

• Repackaged for off‐label eye injections

• 16 people were infected

• Resulted in blindness for some

• Contaminated heparin/saline flush

• Resulted in 36 cases of Pseudomonas fluorescens bloodstream infections

• Concentrated heparin solution made from heparin powder

• Added to bags of saline, and syringes were prepared from bag

2005 2012

Photo credit: https://commons.wikimedia.org/wiki/File:Serratia_marcescens.jpg



1111

Insanitary Conditions

FDA Human Drug Compounding Progress Report 2017

Visible rust Unsealed ceiling tile Visible mold Visible mold

Visibly dirty Vermin Exposed ceiling

1212

“Unfortunately, there are too many people in health care who feel that if it hasn’t happened to them, the

adverse experiences of others do not apply.”‐ Michael Cohen, MS, FASHP (ISMP)

V(value)

Q(quality)

S(service)

$(cost)

=+

The traditional ‘Value Equation’ does not put quality at the forefront for patient care

Require more strict regulation that demands a focus on quality

AccessAchievable

Strict Compounding Regulations

Considerations:1. Science/evidence based2. Standardized3. Accountability4. Doesn’t restrict patient access5. Achievable or scalable to

different practice settings



1313

• Address manufacturing standards for outsourcing facilities

• Regulate compounding from bulk drug substances

• Restrict compounding of drugs that are essentially copies of FDA‐approved drugs

• Solidify the FDA’s partnership with state regulatory authorities

• Provide guidance on other activities that compounders undertake

• Aims to protect patients from unsafe, ineffective, and poor quality compounded drugs, while preserving access to lawfully‐marketed compounded drugs for patients who have a medical need for them.

FDA 2018 Compounding Policy Priorities Plan


1414

•Main Priorities• Patient safety (principle focus)• Insanitary conditions• Contamination• Product and manufacturing quality

• Goals• Preserve patient access• Protect consumers• Make it more feasible for compounding pharmacies to become outsourcing facilities

FDA 2018 Compounding Policy Priorities Plan




1515

503A 503B Manufacturing

Exemptions:• CGMP [501(a)(2)(B)]• Labeling with adequate directions for use [502(f)(1)]• NDA/ANDA [505]

Exemptions:• Labeling with adequate directions for use [502(f)(1)]• NDA/ANDA [505]• Track and trace [582]

NO EXEMPTIONS

Conditions:• Prescription for individual patients• Pharmacist / licensed physician• State licensed pharmacy or federal facility• Limited quantities before receipt of prescription• USP compliance• Specific bulk drug substances (503A list)• No drugs that have been withdrawn/removed from market• Limited compounding of ‘essentially copies of commercially

available drug products’• No compounding of ‘demonstrable difficult to compound’

drugs• Limited distribution• State with memorandum of understanding (MOU) with

FDA

Conditions:• Reporting drugs compounded, adverse events to FDA• Specific bulk drug substances (503B list)• Ingredients must meet certain requirements• No drugs that have been withdrawn/removed from market• No compounding of ‘essentially copies of commercially

available products’• No compounding of ‘demonstrable difficult to compound’

drugs• Demonstrate REMS requirements for applicable drugs• Drugs not sold or transferred by other entities (other than

outsourcing facility)• Paid all applicable establishment and reinspection fees• Specific labeling requirements• All drugs compounded must be in accordance with 503B• CGMP

FD&C Act: Exemptions and Conditions

FDA Guidance Public Docket 3/6/2015 ‐https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/PharmacyCompounding/ucm435070.htm

FD&C Act

1616

In Between Similar to manufacturingSimilar to 503A

Compounding Spectrum

503A 503B Manufacturing

Compounding Manufacturing

Limited Mass scale

Preparation

Production

Risk‐Based TestingQA

Yes NoPrescriptions

Limited BroadDistribution

SBOP FDAOversight

USP, SBOP CGMP, FDAStandards

No YesFDA Drug Approval

Infrequent RoutineQC

Minimum FullLabeling

Where does 503B fit in?



1717

FDA Compounding Guidance Documents

Draft Final

503A

• Memorandum of understanding (revised)• Hospital and health system compounding

• Compounding under 503A• Compounding using bulk drugs• Compounding ‘essentially copies’ of approved drugs• Compounding and repackaging of radiopharmaceuticals• Prescription requirements

503B

• CGMP (revised)• Evaluation of bulk drugs

• 503B Registration• Fees for 503B• Considerations for registering as a 503B• Adverse event reporting• Electronic drug product reporting• Compounding using bulk drugs• Compounding ‘essentially copies’ of approved drugs• Facility definition• Compounding and repackaging of radiopharmaceuticals

Both

• Insanitary Conditions (revised) • List of drugs that have been withdrawn/removed from market

• Repackaging of certain drugs• Mixing, diluting, repackaging biologic products

https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/PharmacyCompounding/ucm166743.htm Accessed: 12/11/2018

1818

• 21 CFR Parts 210 and 211 outline ‘full’ CGMP regulations

• FDA guidance document (draft) indicates:“FDA Intends to promulgate more specific CGMP regulations for outsourcing facilities. Until final regulations are promulgated, this guidance describes FDA's expectations regarding outsourcing facilities and the CGMP requirements in 21 CFR parts 210 and 211 during this interim period.”

• Focus: sterility assurance, strength, labeling, preventing drug mix‐ups

• CGMP / USP <797> Chapter Cross Walk: http://www.clinicaliq.com/images/stories/ciq_gmp‐797_crosswalk.pdf

CGMP ‘Lite’



1919

503B CGMP Guidance (Revised)

FDA’s Proposed Current Good Manufacturing Policies for Outsourcing Facilities• Revised draft guidance released on 12/10/2018

• Update from the 2014 draft guidance• Public meeting: 5/21/2019• Submit electronic or written comments on this public meeting by 6/21/2019

• Link: https://www.regulations.gov/document?D=FDA‐2014‐D‐0779‐0023

https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM403496.pdf

2020

• Under section 501(a)(2)(B), a drug is deemed to be adultered if:“[T]he 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 [Act] as to safety and has the identity and strength, and meets the quality and purity characteristics, which it purports or is represented to possess…”“… the term “current good manufacturing practice” includes the implementation of oversight and controls over the manufacture of drugs to ensure quality, including managing the risk of and establishing the safety or raw materials, materials used in the manufacturing of drugs, and finished drug products”

• The revised guidance provides these same principles of CGMP, however in a risk‐based approach. The most critical aspects of ensuring quality of drug products include:

• Control of raw materials

• Facility design and maintenance

• Production techniques and controls

• Personnel practices





2121


Compounding ActivitiesLower Risk Higher Risk

• Lower production volumes• Non‐sterile production• Use of automated equipment

• Higher production volumes• Sterile production• Manual manipulations


2222

Aggregate Batch Size (over 6‐month reporting period)

Default BUD (no testing)

BUD Based on Limited Stability Testing

≤ 1,000 units Default BUD, which may be further limited by literature or other scientific information. See Appendix B for the conditions that must be met.

Data‐driven stability program. See Appendix B for the conditions that must be

met> 1,000 units N/A. Default BUDs are notapplicable to larger aggregate batch sizes.

503B CGMP Guidance (Revised): Stability/Expiration Dating for Compounded Drug Products




2323

503B CGMP Guidance (Revised):Default BUDs

Processing Conditions Contains a Preservative?

Controlled Room Temperature

Refrigerator Freezer

• Finished drug product is aseptically processed; and

• A sterility test has not been completed before release

No 6 days 9 days 45 days

Yes 28 days 42 days 45 days

• Finished drug product is terminally sterilized;

• A validated sterilization cycle that uses physical, chemical, or biological indicators is employed; and

• A sterility test has not been completed before release



• Finished drug product is aseptically processed or terminally sterilized and has a completed, passing sterility test before release



1.) Default BUD (No Testing) for Sterile Drug Products(Aggregate Batch Size ≤ 1,000 units) 2.)

3.)

Literature or other scientific information, including relevant commercially available product labeling for a similar drug (i.e. components, dosage form, route of administration, primary container‐closure type), does not indicate that the drug product may not be physiochemically stable over the time period listed

The BUD is used as the expiration date.


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503B CGMP Guidance (Revised):Batch Release Testing

Conditions Iden

tity

Strength

Sterility

Endotoxin

pH

Color

Clarity

Visible

Particulates

Subvisible

Particulates

Other

1. Batch size ≥ 60 units or once 60 units are produced Y Y Y Y Y Y Y Y Y Y

2. Batch size < 60 units, if omitted tests are performed once 60 units are produced

Y Y Y Y

3. Batch <10 units compounded pursuant to prescription for single patient and label bears BUD per ‘Default BUD’, if omitted tests are performed once 60 units are produced

Y Y Y

Other conditions listed, including:• Potency method used• Solutions and TPNs• Terminal sterilization




2525

FDA Guidance: Insanitary Conditions (503A/503B)Examples(non‐exhaustive list)

Sterile/Non‐Sterile: Vermin, visible microbial (i.e. mold) and non‐microbial (i.e. rust, hair) contamination, cross‐contamination with beta‐lactams, hazardous drugs, or highly potent drugs, production during adjacent construction without adequate controlsSterile: improper gowning, failing to disinfect/change gloves frequently, non‐sterile gloves, exposed hands, wrists, legs, hair, or mouth; manipulations outside of ISO 5 area, movement of personnel in/out of cleanroom, moving too quickly, blocking first air, non‐sterile tools, touch contamination outside ISO 5 area, unsealed ceiling tiles, leaking HEPA filters, presence of sinks/drains in cleanrooms, non‐sterile disinfecting agents, infrequent use of sporicidal agent, insufficient disinfectant dwell time, frequent pressure reversals from areas of less clean air to areas of higher cleanliness

Identification • Conduct routine environmental monitoring• Certify the ISO 5 area every 6 months• Measure pressure differentials during operations• Conduct media fill studies to closely simulate aseptic operations (worst‐case)

Corrective Actions Certain insanitary conditions deemed to be particularly serious requiring ceasing sterile operations and recall of purportedly sterile drugs until the conditions have been corrected (see red text above).


2626

Compounding from bulk drug substances involves more complexand numerous interrelated manipulations by the compounder compared to compounding only using FDA‐approved drug products.

Compounding from Bulk Drug Substances

Risks associated with compounding with bulk drug substances:

• Bulk drug substances are not FDA‐approved products

• Compounder must address risks related to ingredient quality

• Bulk drugs are non‐sterile

• Will require sterilization steps if producing sterile drugs as final form

• Terminal sterilization may impact potency and impurities

• Increases potential for errors and mix‐ups

• Need to consider powder flow properties, hygroscopicity, and liquid viscosity for handling/weighing

• Cross‐contamination more likely

Bulk Drug Substance / Active Pharmaceutical Ingredient (API)

“any substances that is intended for incorporation into a finished drug product and intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of a disease, or to affect the structure or any function of the body”




2727

• Category 1: under evaluation, sufficient information, do not appear to present a significant safety risk

• Category 2: raise significant safety risks [not eligible]

• Category 3: nominated without adequate support [not eligible, unless re‐submitted with supporting information]

Compounding from Bulk Drug Substances (503B)

• Bulk drug substances with ‘clinical’ need:• There is a clinical need to compound using bulk drug

substance• The drug product must be compounded using the bulk

drug substance• Can compound category 1 bulk drug substances if conditions

are met:• Appears on category 1 list for specific registration (503A vs

503B)• Original manufacturer of bulk drug substance is registered

under section 510 of the FD&C Act• Substance is accompanied with a valid COA• Complies with USP or NF monograph (if applicable)• Drug product compounded is in compliance with all other

provisions of registration (503A vs 503B)


2828

Category 2 Substance Registration Notes Safety Risks

Domperidone 503A Used by lactating women to enhance breast milk production and for severe gastrointestinal motility disorders. Not FDA approve drug. Available in other countries.

Serious risk of life‐threatening cardiac arrhythmias and sudden cardiac death in all populations, including healthy lactating women.

Quinacrine HCl for intrauterine administration

503A Used for female sterilization. Banned in many countries due to concerns about lack of informed consent and long‐term safety. Not FDA approved drug. Benefits do not outweigh risks.

A known mutagen and associated with serious adverse reactions such as aplastic anemia, hepatitis, severe dermatitis, exacerbation or worsening psoriasis, and psychosis. Increased risk for life‐threatening reproductive tract malignancies.

Cesium chloride 503A Used by cancer patients seeking alternative treatment. Not FDA approved drug.

Poses significant safety risks and is potentially associated with death. Can cause arrhythmias and hypokalemia.

Germanium sesquioxide

Both Used in the treatment of cancer and chronic illnesses. Not FDA approved drug. Delaying treatment with FDA‐approved products with well‐established safety/efficacy raises significant patient safety concerns.

Likely to be contaminated with highly toxic inorganic forms of germanium salts which can be toxic to the kidneys. Has resulted in nephrotoxicity and death, even at recommended levels.

Bulk Drug Substances that Pose Safety Risks

Domperidone: https://www.fda.gov/drugs/developmentapprovalprocess/howdrugsaredevelopedandapproved/approvalapplications/investigationalnewdrugindapplication/ucm368736.htmQuinacrine: https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/PharmacyCompoundingAdvisoryCommittee/UCM490729.pdfCesium: https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/PharmacyCompounding/ucm614211.htmGermanium: https://wayback.archive‐it.org/7993/20170723121621/https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/PharmacyCompoundingAdvisoryCommittee/UCM465542.pdf



2929

Registered Outsourcing Facilities (503B)

73 FacilitiesAs of 11/23/2018

https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/PharmacyCompounding/ucm378645.htm

3030

503B Registration and Inspections

Initial Registrationas of 11/23/2018

Other Actions Taken


66FDA Form 483’s issued during most recent

inspection



3131

503B Registered Facilities

Was a form FDA‐483 issued?

Intends to compound sterile drugs from bulk

drug substances?


3232

• Compounding before receipt of a valid prescription order• Based on history of prescriptions (average 30‐day period over the past year)

• Holds for distribution no more than 30‐days supply of a particular compounded drug product

• Need to consider the days supply limitation for beyond‐use date application

• For ‘office use only’ is not allowed

503A Prescription Requirements




3333

503B Facility Definition

The section 503A establishment may be located near the outsourcing facility or in the same building, provided the compounding in the outsourcing facility is completely segregated from compounding by the section 503A establishment.

Conditions:1. Do NOT share any common rooms2. Do NOT share any fixed equipment or

supplies for use in compounding3. Have separate entrances and exits4. Do NOT share an internal pass‐through5. Separated by permanent physical barriers


3434

Guidance in Whether to Register as a 503B Outsourcing Facility

• ALL drugs compounded at outsourcing facility must be in accordance with section 503B

• Must engage in compounding of STERILE human drugs• FDA compounding definition does NOT include REPACKAGING• Does NOT include BIOLOGICS (under Public Health Service Act)

Important to know scope of compounding at the facility and any other activities that may be occurring in or adjacent to facility




3535

• For‐cause• Serious adverse events• Quality or facility concerns• Complaints• State request for assistance

• Surveillance• Risk‐based model; history• Routine risk‐based (503B)• Limited risk‐based (503A)

• Follow‐up• Corrective actions implemented after prior FDA inspection or regulatory actions

FDA Inspections

503A 503B

• Determine current operational status:

• Qualifications of exemptions under 503A

• Sterile and non‐sterile product production practices and facility conditions

• Assess conformance with applicable standards for producing compounded drugs

• Prevent production/distribution of drugs produced under conditions that may present significant risk to patient safety

• Evaluate compliance with conditions of 503B (including labeling, adverse event reporting, etc.)

Inspection Objective

https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/PharmacyCompounding/UCM546560.pdf

3636

FDA Inspections

“…everything the inspectors observe may be evidence that can be used against the pharmacy and individuals present in the pharmacy, and may result in civil, criminal, and administrative fines, penalties, and/or possible jail time”

Kulkarni, D. IJPC Sep/Oct 2013: 358‐362



3737

FDA 483: Top Inspection Observations and Actions

Rank Short Description

1 Procedures not in writing, fully followed

2 Scientifically sound laboratory controls

3 Investigations of discrepancies, failures

4 Absence of written procedures

5 Written procedures not established/followed

6 Testing and release for distribution

7 Computer control of master formula records

8 Procedures for sterile drug products

9 Calibration / inspection / checking not done

10 Lack of written stability program

Top Inspection Observations (503A/503B)FDA Actions

Advisory Actions Warning Letters

Recalls Voluntary Recall (potency, labeling, sterility assurance)

Enforcement Actions Civil injunction, Criminal actions

State Referrals For 503A facilities

Policy / Procedure

Analytical Testing

https://www.fda.gov/ICECI/Inspections/ucm589892.htm#Drugs

3838

• FDA form 483: issued to firm/company management at the conclusion of an inspection when an investigator has observed any conditions that may constitute violations of the FD&C Act

• Observations are based on investigators judgement

• Not all‐inclusive; only responding to what they saw

• Corrective action planning and implementation required

• FDA Warning Letter:• FDA officials reviewed observation and determined a serious violation may exist

• Often cite ‘insanitary conditions’

• Must respond within 15 days• Both are public information

FDA Form 483 and Warning Letters

483



3939

• How to access?• FDA.gov > Home > Drugs > Guidance, Compliance & Regulatory Information > Compounding > Compounding: Inspections, Recalls, and other actions

• What to do with them?• Evaluate observations and severity of findings• Insanitary conditions are significant findings

• What next?• Review written response letter from firm’s to determine if observations are adequately addressed

• Review ‘close‐out’ letter (if applicable) to see if the FDA was satisfied with the firms response and demonstration of corrected actions

FDA Form 483 and Warning Letters


4040

How can health‐systems evaluate 503B Outsourcing Facilities• ASHP Outsourcing Vendor Assessment Tool• Regulatory and quality document review• Outsourcing policies and procedures• Physical on‐site assessment• Formulary generation• Periodic re‐assessment



4141

High Reliability Organizations are those that operate in complex, high‐hazard domains for extended periods without serious accidents or catastrophic failures.

High Reliability Organizations

?

Weick et al 2007; Hines et al 2008; Chassin et al 2013; Rochlin 1999

https://www.maxpixel.net/Aircraft‐Commercial‐Airplane‐Flight‐Airline‐Jet‐1995432 https://www.maxpixel.net/Nuclear‐Nuclear‐Reactor‐Nuclear‐Power‐Plant‐744424 https://www.maxpixel.net/Train‐Railway‐Station‐Rail‐Traffic‐Railway‐Ice‐426425

4242

Preoccupation with Failure

Reluctance to Simplify

Sensitivity to Operations

Deference to Expertise

Commitment to Resilience

High Reliability Organizations: Characteristics

1

2

3

4

5

Preoccupation with Failure• Aware and thinking about potential for failure

• Know that new threats emerge regularly• Alert to small signs of potential problems• Near misses viewed as opportunities to learn• Absence of accidents leads to heightened sense of vigilance for next possible failure




4343







1

2

3

4

5

Reluctance to Simplify• Resist understanding of how/why things succeed or fail in the environment

• Understand the work is complex/dynamic• Seek underlying rather than surface explanations

• Recognize value of standardization of workflows to reduce variation

• Appreciate complexity inherent in teams, processes, and relationships involved in daily operations


4444







1

2

3

4

5

Sensitivity to Operations• Strive to maintain high awareness of operational conditions

• “Big picture understanding” / “Situational Awareness”

• Know how the current state supports or threatens safety




4545







1

2

3

4

5

Deference to Expertise• Appreciate that people closest to the work are the most knowledgeable about the work

• Highest knowledge may not be the person with the highest status/seniority

• De‐emphasis on hierarchy in favor of learning about potential safety threats

• Expectation to share concerns with others in a climate that all staff are comfortable speaking up regarding safety problems


4646







1

2

3

4

5

Commitment to Resilience• Assume the system is at risk for failure• Practice performing rapid assessments of and responses to challenging situations

• Teams cultivate situation assessment and cross monitoring to identify potential safety threats quickly

• Response before safety problems cause harm or mitigate seriousness of safety event




4747

Are sterile drug compounders considered as high reliability organizations?

Photo Credit: https://www.flickr.com/photos/fdaphotos/5434295204

Since the 2012 outbreak of fungal meningitis, the FDA has overseen more than 200 recalls conducted by compounders, most as a result of FDA inspectional

findings indicating lack of sterility assurance.

https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm621600.htm

4848

The Four Abilities of Resilient Organizations

Resilient organizations have the ability to:

Hollnagel E., Woods D.,Leveson N., Eds., Resilience engineering, concepts and precepts. Qual Saf Health Care. 2006 Dec; 15(6): 447‐448.

Respond Prepared, reduction of risk, prevention, quick recovery

Monitor Identify variation, Key Performance Indicators (KPI), recognize early warnings

Anticipate Front line staff sufficiently competent and empowered to take action, ability to influence, real‐time information

Learn Learn from failures, inadequacies, misunderstandings in communication, overconfidence in safety systems, successes



4949

Outsourcing Vendor Assessment Tool

http://www.ashpfoundation.org/MainMenuCategories/AdvancingPractice/SterileProductsTool

Health‐Systems should take a comprehensive and organized approach to appropriate vendor selection.

Focus of assessment:• Regulatory compliance• Quality and patient safety measures• Medication administration safety features• Service excellence

Part 1: Minimum Requirements for a Vendor (not scored)Part 2: Vendor Assessment (scored)

• Label features and packaging• Product availability and breadth of line• Ease of ordering and turnaround• Storage, space, and service considerations

Current as of June 2015

5050

90 – 100% (Excellent)

Meets most of the organization’s outsourcing needs

80 – 89%(Good)

Meets many of the organization’s outsourcing needs

70 – 79% Meets some of the organization’s outsourcing needs

Less than 69% Does not meet of the organization’s outsourcing needs

Outsourcing Vendor Assessment Tool

Scoring

Vendor AssessmentMinimum Requirements

Green Consistent with applicable federal and/or patient safety standards

Yellow Investigate further. Inspection findings that are serious deficiencies/issues that can be quickly/easily resolved

Orange Obtain additional information prior to considering vendor

Red Non‐compliant with applicable federal regulations and/or standards

Categories

Example Questions• Is vendor registered with FDA as a 503B outsourcing

facility?• Has the facility recorded a Form FDA‐483?• Has the facility had a product recall within the past year

due to sterility assurance concerns or other issues that could pose risks to patients?

Example Questions• Does the vendor use drug name differentiation in the form

of TALL MAN lettering for sound‐alike and look‐alike drugs?• Does the vendor’s labeling provide total drug amount and

concentration? (i.e. mg/mL)• Does the vendor bar code labeling include the lot number

and expiration date?• Does the vendor compound products in the dosages and/or

concentrations needed by my institution?

http://www.ashpfoundation.org/MainMenuCategories/AdvancingPractice/SterileProductsTool



5151

Regulatory and Quality Document Review

483 Warning Letters

VENDOR

Response Letters

Inspection Reports

Quality Documents

5252

• Formulate a Pharmaceutical Compounding Advisory Counsel (PCAC)• Clinical Pharmacists, Pharmacy Leadership, Infection Prevention Specialist, Quality, Physician Champion

• Create policy for Procurement of Compounded Medications• 503B Outsourcing Facilities• 503A Outsourcing (retail/community compounding pharmacy)

• Policy includes:• Vendor assessment• Minimum qualifications• Documents to request/review• On‐site inspection requirements• Vendor status: expedited, full• Approved institutional vendor list• Approved institutional list of products• Re‐assessment periods

Outsourcing Policies and Procedures



5353

What to look for during an on‐site assessment:• FDA insanitary conditions• Flow of product (unidirectional ideal)• Flow of people (unidirectional ideal)• Aseptic technique of staff performing admixing• What is stored in the cleanroom• Use of automation and technology• Proper garb/attire• Observation / verification methods of products

Physical On‐Site Assessment of Outsourcers

5454

• How do pilots get trained?• Certifications

• Practical exams

• Training on specific type of aircraft

• Virtual flight trainers

• Obtain certain number of hours in specific type of aircraft

• Maximum hour requirements

Training and Competency for Sterile Compounding

• What if we applied same methodology to training sterile compounding?

• Certifications

• Practical exams

• Training on specific type of dosage forms (syringes, bags, epidurals, etc.)

• Virtual compounding labs

• Obtain certain number of hours compounding certain dosage forms

• Maximum hour requirements



5555

• The National Institutes of Health (NIH) Competencies Proficiency Scale

• Used to measure one's ability to demonstrate a competency on the job

Training and Competency for Sterile Compounding

Fundamental Awareness Basic Knowledge Common knowledge or understanding of basic techniques/concepts

Novice Limited Experience Experience in classroom and/or experimental scenarios or as a trainee on‐the‐job. Needs help performing this skill

Intermediate Practical Application Able to successfully complete tasks as requested. Help from expert may be required from time‐to‐time, but usually independent

Advanced Applied Theory Performs skill without assistance. Recognized as ‘person to ask’ when difficult questions arise

Expert Recognized Authority Known as expert in this area. Can provide guidance, troubleshooting, and answer questions related to this skill

https://hr.nih.gov/working‐nih/competencies/competencies‐proficiency‐scale

5656 Graphic by K.Hansenhttps://hr.nih.gov/working‐nih/competencies/competencies‐proficiency‐scale

NIH Proficiency Scale

0 – N/A1 ‐ Fundamental Awareness2 – Novice3 – Intermediate4 – Advanced5 ‐ Expert

Competency

Knowledge

Abilities / Traits

Attitudes / Behaviors

Skills

Competency Assessment Methods

Physical ModelsJob SimulationJob Sample

Written/Computer Based Examination

Knowledge Skills/Abilities

Record Review



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