Sterile Compounding - 02/23 Exam 1

What occurred in NECC?

Steroid inj contaminated w/ fungus

How were the hospitals complicit with the inappropriate creation of meds by NECC?

Gave fake names so they could get compounded drugs that were cheap

How did NECC purposely avoid the regulations?

Compounding for fake people

Salespeople selling to many people

Cleaning after investigation started

What was the punishment for the supervisory pharmacist at NECC?

8 yrs in prison, 2 yrs of supervised release, restitution

How many people were affected by NECC?

Killed 64

Infected 800ish

What were there problems that NECC RPh overlooked?

Improperly sterilization and verification

Shipped meds w/o test results

Mislabeled drugs

Used expired ingredients

What does the US pharmacopeia do?

Set standards for

Drug products and ingredient quality and purity

Testing and analysis methods

Compounding

What are the USP chapters and which are enforceable?

Nonsterile: 795

Sterile: 797

Hazardous: 800

Chapters under 1000 become part of FDCA by state board, FDA, TJC

What does USP 797 do?

Establish MINIMAL standards to prevent harm from

Contamination

Excessive endotoxins

Variability from strength or correct ingredients

Control people, places, processes

What are examples of CSPs?

Inj

Aq bronchial inhalation

Baths and soaks for live organs and tissues

Irrigations for body cavities

Ophthalmics

Implants

What does USP 797 apply to?

All CSP preparers

All places where CSP are prepared

All employees responsible for ensuring standards are upheld and resolve issues

What is the training required for sterile compounding?

Hand hygiene and garb

Cleaning and disinfectiing

Measuring and mixing

Aseptic tech

Proper cleanroom behavior

Sterilization and depyrogenation methods

Documentation

Understanding direction of HEPA air flow

Proper PECs use

Potential impact of personnel activities

What is the reevaluation that has to be done for sterile compounding?

Written and hands-on every 6 mnths

Visual observation of hand hygiene and garbing

Gloved fingertip sampling

Media-fill test

Cleaning and disinfection

Requalification after pause in compounding

What is the most likely cause of contamination?

Personnel

When should you not compound?

Rash

Sunburn

Sores

Conjunctivitis

Acute resp infection

What are the hygiene and PPE steps required before compounding?

Remove outer garments, cosmetics, jewelry, earbuds

Clean neatly trimmed non-polished nails

Shoe covers

Facial covers, mask, beard cover

Wash hands and forearms w/ water and soap w/ nail picks

Alcohol-based hand scrub w/ persistent activity (chlorhexidine)

Non-lint disposable gown or coverall

Sterile globes and sterile sleeves

What are PECs and examples?

Primary engineering controls (ISO class 5)

Vertical LAFW

Horizontal LAFW

Isolator/restricted access system barrier (RABS)

What is the air movement in LAFWs?

Room air drawn through prefilter on top to get large paricles out

Through 99.99% HEPA filter and projected unidirectionally

Used to minimize cross-contamination in work area and create particulate-free environment

What are the rules of LAWFs?

Run 24/7

If closed, clean thoroughly and run for at least 30min

Draw room air through pre-filter before HEPA filter

Replace HEPA according to manufacturer's recs

What is the direct compounding area?

Critical area w/in PEC where critical sites are exposed to unidirectional air flow

6inch from all sides

What is first air?

Unidirectional air from HEPA filter that shouldnt be blocked

What are the SECs and the classes?

Clean room, buffer room: 7

Ante & prep rooms: 8

What are the other controls in compounding?

Temp: 20 or lower

Humidity: <60%

Pressure: positive for clean rooms, negative for hazardous

Lighting

What does ISO class mean?

Amount of particles allowed in air

Class 3: <35.2

Class 4: <352

Increasing class = 10x amount of particles

What did the particle shedding study show?

Particles generated by humans, clothes, other activities can transport microorganisms to critical sites

What are the types of environmental monitoring for sterile compounding?

Nonviable air: particulate count

Viable air: living contaminates using growth plate

Surface sampling: cleanrooms, hoods, equipment, gowns, work surfaces

How are PECs cleaned?

Use sterile water for inj and sterile low-lint wipes to remove water-soluble residue

Go top to bottom, back to front

Allow surface to dry

What are the cleaning agents used for PECs and why?

SWFI: dissolution of messy spills

70% isopropyl: primary disinfectant

Quat ammonium cleaner: soap for sticky spills

Sporicidal agent: monthly

2% sterile bleach: economic disinfectant that can remove sporicidal residue

What is the minimum freq for cleaning of PECs besides isolators?

Beginning and end of shift

Before each batch

After spill

Suspected contamination

What is the minimum freq for cleaning of isolators?

Every time opened

Once it is closed after each time it has been opened or after each cleaning cycle if cleaning occurs w/o opening

What is the minimum freq for cleaning of work surfaces outside PEC and floors?

Daily

What is the minimum freq for cleaning of walls, ceilings, storage shelving?

Monthly

What is required for components?

Establish, maintain, follow SOPs for selection, receipt, invetory of all components, containers and closure from receipt to consumption

What type of ingredients can you use?

USP/NF when available

APIs from FDA-registered facility w/ CoA

non-APIs need to be verified for identity, strength, purity, quality if not from FDA-registered

Can use chemically pure, analytic reagent grade or ACS grade cautiously

What is required during receipt of components?

Visual inspection

Lot

Evidence of deterioration

Labeling w/ date of receipt, quantity, supplier, exp date, results of testing

CoA which verifies that material met compendium monograph

Reject, label and segregate unacceptable ingredients

What should be done if ingredients dont have vendor exp?

1yr after receipt from facility

What are the sterilization methods and when are they used?

Filtration: 0.2 or 0.22micron sterile, depyrogenated filter, used for ingredients in solution

Steam: autoclave at 121C, 15PSI for 20 to 30min, for heat-stable

Dry heat: 150C for 2.5hr for powders, ointments, oils

What are the types of terminal sterilization?

Steam

Dry heat

Verified w/ biological indicators

How is depyrogenation done?

Utensils and material in direct contact w/ CSP by 250C for 30min

Validate using endotoxin challenge vials: should see >3 log decrease in pyrogens

What are the SOPs required for sterile compounding?

Training and qualifcation

facility design

Cleaning and disinfection

Environmental monitoring

Sterilization and depyrogenation

BUD

Documentation

What do master formulation records include?

Name, strength, dosage form

Physical description of final prep

ID and amounts of all ingredients and approp container-closer system

Complete instructions including equipment, supplies, each step

BUD and storage

Quality control procedures

Sterilization method

Any other info needed to describe operation and ensure repeatability

What do compounding records include?

Name, strength, dosage form

Master formulation record reference

Date and time of prep

Assigned internal ID

Sig or initials of individuals involved in each step

Name, vendor, manufacturer, lot number, exp of each ingredient, container-closer system

Weight or measurement of each ingredient

What are the 2008 USP 797 risk levels?

Immediate use: emergency, immediate admin

Low risk: up to 3 additions using commercially manufactured sterile products

Medium: 1 into many or many into one

High: sterile prep from nonsterile ingredients

What are the 2015 risk levels based on?

Category 1 CSP: not required to be in classified area

Category 2 CSP: in classified area

When is BUD applied?

Manufacturer container opened and drug product transferred to another container

What is the purpose of BUD?

Balancing chemical stability and sterility

What are the current BUD for immediate and low segregated compounding area?

Immediate: 1hr from start of compounding

Low segregated compounding area: 12hrs or less from compounding at RT

What are the current BUD for low risk?

RT: 48hrs

Cold: 14d

Frozen: 45d

What are the current BUD for medium risk?

RT: 30hrs

Cold: 9d

Frozen: 45d

What are the current BUD for high risk?

RT: 24hrs

Cold: 3d

Frozen: 45d

What are the proposed BUD for category 1 CSPs?

RT: ≤12hrs

Fridge: ≤24hrs

What are the proposed BUD for category 2 CSPs aseptically processed and sterility test not done?

One or more nonsterile used

RT: 1 day

Fridge: 4d

Freezer: 45d

All sterile used

RT: 4d

Fridge: 10d

Freezer: 45d

What are the proposed BUD for category 2 CSPs aseptically processed and sterility test done?

RT: 30d

Fridge: 45d

Freezer: 60d

What are the proposed BUD for category 2 CSPs terminally sterilized and sterility test not done?

RT: 14d

Fridge: 28d

Freezer: 45d

What are the proposed BUD for category 2 CSPs terminally sterilized and sterility test done?

RT: 45d

Fridge: 60d

Freezer: 90d

What are the release tests that can be done?

Physical inspection for particulate, defects, cracks

Sterility inspection using USP71 membrane filtration

Bacterial endotoxin using USP85 gel clot

Which release tests are used depending on category of CSP?

Physical: both

Sterility: only category 2 based on BUD

Bacterial: only category 2 if prepared from nonsterile

What does the label on CSP need to have?

Assigned ID

Brand and/or generic or API amounts or concs

Dosage form

Total amount

Storage condition

BUD and in-use time

Single dose or multiple dose

Indication that prep is compunded

Pt name or owner name + species of pt

Route of admin

Special handling instruction

Warning statements

Name, address, contact info of compounder if CSP sent outside facility

What is quality assurance?

Written processes that at minimum verify, monitor, review adequacy of compounding process

Must be formally written down and followed

What is quality control?

Observation of tech and activities that demonstrate reqs are met

Must be formally written down and followed

What needs to be done if storing CSP w/in compounding facility?

Monitor conditions

Check controlled temp area daily

Fluctuations

If temp limits exceeded, discard

What needs to be done in handling CSPs?

Properly

Prevent depression of plunger or dislodging

Prevent attachment of admin set

What needs to be done in packaging CSPs?

Maintain integrity, sterility, stability

Written SOP for containers, insulation, stuffing

Tamper evident closures

Light sensitivity

Coolers

What needs to be done in transporting CSPs?

Delivery to make sure undamaged, sterile, stable

Include specific handling instructions exterior to container

What is the documentation that must be done?

All processes

Training and retraining

Environmental monitoring

Compounding and dispensing

Cleaning and disinfection

Equipment use and maintenance

Complaints and resolution

Release testing

What are the DOs of documentation?

Written policy on good documentation practices

Accurate and clear

Ink

Directly on document

Sign and date

Cross out and initial mistakes

What are the DONTs of documentation?

Document another's work

Assume documentation is complete

Erase, write over, scribble, white out

Ditto marks or arrows

Trust memory

Leave paperwork for next day

When do clean rooms and hoods need to be recertified and what do the tests include?

Every 6 months under dynamic/typical/worst conditions

Airflow volume

ACPH

Room pressurization

HEPA filter leak test

Smoke pattern test

Non-viable particulate count

Viable air and surface count

What are the air pressure relationships in each area?

Ante room to unclassified: positive

Nonhazardous buffer to ante: 0.02 to 0.05

Hazardous buffer to ante: -0.01 to -0.03

What are the air exchanges per hr in each area?

Both 30 APCH

What is nonviable air testing measuring?

Engineering control performance

Number of particles 0.5micrometers or bigger/m3

What is the frequency of non-viable air sampling?

Q6M

What is the nonviable air sampling max for each ISO class?

ISO 5 (PEC): ≤3250

ISO 7 (buffer): ≤325000

ISO 8 (ante): ≤3250000

What does viable air testing measure?

Colony forming units/m3

Measures proper hand hygiene, garbing, aseptic tech, pressure of surface contamination, employee competency

What is the frequency of viable air sampling?

Q6M

What is the viable surface sampling max for each ISO class?

ISO 5 (PEC): ≤3 CFU

ISO 7 (buffer): ≤5 CFU

ISO 8 (ante): ≤50 or 100 CFU

Unless highly pathogenic

What is the frequency of viable surface sampling?

Every month

What is the viable air sampling max for each ISO class?

ISO 5 (PEC): ≤1 CFU

ISO 7 (buffer): ≤10 CFU

ISO 8 (ante): ≤100 CFU

Unless highly pathogenic

What are the highly pathogenic microorganism that require immediate remediation?

Coagulase positive staphylococcus

Gram negative rods

Fungi (yeasts, molds)

What are environmental test results needed for effective ante room?

30 APCH

Positive pressure to pharmacy department

Viable and non-viable tests based on ISO 8

HEPA filter leak test

What are environmental test results needed for effective buffer room?

30 APCH

Nonhazardous: positive pressure to ante room (0.02 to 0.05)

Hazardous: negative pressure to ante room (-0.01 to -0.03)

Viable and non-viable tests based on ISO 7

HEPA filter leak test

What are environmental test results needed for effective PEC?

Viable and non-viable tests based on ISO 7

HEPA filter leak test

Smoke study test

What is the smoke study test?

Tells direction of HEPA airflow

What needs to be done if PEC fails?

Cease to use

Report w/in 48hrs

What are the biannual tests?

Non-viable airborne count

Viable air count

Compounding goods

What are the monthly tests?

Surface sampling

When should temp and humidity be tested?

2x w/in 8hr interval

When should air pressure differential be measured?

Every shift

What is the controlled room temp?

15 to 25C

What is the pharmacy temp?

20 to 25

What is the fridge temp?

2 to 8C

What is the freezer temp?

-25 to -10C

What is the humidity of controlled rooms?

<60%

How often should hood filters be changed?

Prefilter: QM

HEPA: annually

CLOSE HOOD WHILE CHANGING

How many microbes does each person carry?

3 to 5lbs

How many skin cells are shed every day

500milliojn

How many times do people touch face?

23 times/hr

Need to make conscious effort to stop

What do artificial nails and long nails harbor?

Fungus, bacteria

How many particles in makeup and mascara?

5.1 billion

Mascara: 3 billion

What does packaging contaminated with and what are the consequences?

60% bacteria

40% bacterial spores

Need to disinfected before into clean room