DDS Exam 3 Memorization

Sterile Aqueous vehicles

• normal saline, dextrose, lactated ringer’s

• isotonic

Sterile Water Miscible Vehicles

• affect solubility and reduce hydrolysis

• propylene glycol

Sterile non-aqeous vehicles

• oils

• soybean oil

Sterile Preparation Solutes

• antimicrobials

• buffers

• antioxidants

• sodium benzoate

Sterile Antimicrobials

• thimerosal 0.01%

• benzethonium chloride 0.01%

Sterile buffers

• citrates

• acetates

• phosphates

Sterile Antioxidants

• sodium bisulfute 0.1%

Types of containers for sterile preparations

• plastic (polyethylene, polypropylene, polyvinyl chloride)

• glass

• rubber (butyl, silicone, natural rubber)

Type I Glass

• silicon dioxide and boric acid

• low migratory oxides, leaching

• expensive

• preferred (suited for all products)

Type II Glass

• sodium oxide and calcium oxide

• soda-lime glass with HIGH hydrolytic resistance

• melt at lower temps, treated with sulfur dioxide to dealkalize

• best for acidic or buffered solutions

Type III Glass

• sodium oxide and calcium oxide

• soda-lime glass with MODERATE hydrolytic resistance

• highest migratory oxides

• best for dry substances, non-aq. preps

Steam Sterilization

• fast, inexpensive

• use for bulk volumes, solutions in ampules/vials, surgical instruments

• CANNOT use for oily, moisture sensitive preps

• denature and coagulate bacterial proteins

Dry Heat Sterilization

• can use for oily preps

• longer exposure time, higher temp than steam

• use for fixed oils, glycerin, petrolatum, mineral oil, paraffin, glassware, surgical instruments

• dehydration

Filtration Sterilization

• fast for small volumes, relatively inexpensive

• fragile membranes, extensive validation (bubble test), potential to remove drug (if less than 5 mg)

• use for thermolabile, low viscosity solns with more than 5 mg drug

• cellulose acetate, cellulose nitrate membrane filters

Gas Sterilization

• use for thermolabile powders and proteins, medical appliances, surgical supplies, certain antibiotics/drugs

• highly flammable gases, can’t use for solns

• ethylene oxide or propylene oxide gas

• inhibit bacterial cell wall formation

Ionizing Radiation Sterilization

• use for thermolabile powders, antibiotics, hormones, prepackaged disposable items

• expensive equipment, potential radiation risk, limited application

• gamma rays or UV lamp

• destroys vital chemicals/structures

Pyrogens

• lipopolysaccharides on outer cell walls of gram NEGATIVE bacteria

• water soluble

• thermostable

• may survive steam, filtration

• aka endotoxin

USP endotoxin limit

• 5 EU/kg/hr

• INTRATHECAL: 0.2 EU/kg

Pyrogen testing

• Rabbit testing

  • inject into rabbit ear and record temps

• LAL test (more sensitive, used by USP)

  • extract with enzymes that coagulate in presence of lipopolysaccharides

Sterility Testing

• use trypticase soy broth (TSB) and fluid thioglycolate medium (FTM)

• incubate for 14 days

• validate before shipping

• direct inoculation test, membrane filtration, or biological indicator tests

Biological indicator test

• biological indicator/marker: provides info on whether conditions were met to kill specified number of microbes for sterilization process

• use endospores

Stearothermophilus

biological marker for steam, gas, and ionizing radiation

Subtilis

Biological marker for dry heat, radiation

Pumilis

Biological indicator for radiation

USP 797

• min. practice and quality for sterile preps

• enforced by state boards of pharm and FDA

• June 2008

Sterile Preparations

• injections

• ophthalmic drops and ointments

• aqueous pulmonary inhalations

• baths and soaks for live organs and tissues

• irrigations for internal body cavities

• implants

ISO Class 5

• hood (PEC)

• 100 particles in 1 cubic ft

ISO Class 7

• buffer room

• 10,000 particles in 1 cubic foot

ISO class 8

• ante-room

• 100,000 particles in 1 cubic foot

Immediate use sterile preparations

• Class 5 NOT required

• required:

  • aseptic SOPs, process

  • limit to 3 diff sterile products

  • must be labeled UNLESS administered by or witnessed by preparer

• BUD: 4 hours

• ex. epinephrine drip at bedside by nurse for patient w cardiac arrest

Category 1 sterile preparations

• ISO class 5 req

• BUD: 12 hours at room temp, 24 hours in fridge

Category 2 sterile preparations

• compounded in PEC (class 5), within buffer room (class 7), with ante room (class 8)

• BUDs vary

  • higher when terminally sterilized

  • higher when sterility test passed/performed

  • higher when stored at lower temps

  • higher when made from sterile components

Category 3 sterile components

• longest BUDs

  • higher when terminally sterilized

  • higher when stored at lower temp

• additional requirements (more cleaning, more garbing, more viable air)

• sterility testing and endotoxin testing required

• compounded in PEC (class 5), within buffer room (class 7), with ante room (class 8)

Multidose vial BUD

• 28 days

• contain preservative

Single-dose vials BUD

• 12 hours

• ONCE AMPULES OPENED, CANNOT BE STORED

Sources of Class 5 air

• laminar airflow

  • vertical pref for hazardous

• compounding aseptic isolator

Hazardous drug preparation

• class 5 environment in class 7 negative pressure area physically separated from other areas

Sterile 70% isopropyl alcohol must be applied to work surface at least every…

30 min (if activity takes 30 min or less)

Cleaning Frequency is higher for

• cat 3

Sterile compounds that are shipped frozen are stable for…

• 48 hours (room temp)

• 10 days (fridge)

Sterile product labels must have

• preparation name

• strength

• amount of active ingredient

• amount of solvent to add

• route of admin

• storage and expiration

• manufacturer and distributor

• lot number

Handling Hazardous drugs includes

• receipt

• storage

• compounding

• dispensing

• administration

• disposal

• both sterile and nonsterile

Scope of USP 800

all healthcare personnel and entities that store, prepare, transport, or administer HdS

Occupational safety plan must include

• list of HDs

• facility and engineering controls

• competent personnel

• safe work practices

• proper use of appropriate PPE

• policies for HD waste segregation and disposal

List of HDs

• maintained by NIOSH

• reviewed every 12 months

Hazardous drug criteria

• carcinogenicity

• teratogenicity or other developmental toxicity

• reproductive toxicity

• organ toxicity at low doses

• genotoxicity

• new drug with structure and toxicity profile that minics existing HD

NIOSH categories of HDs

• 1: antineoplastic

• 2: non-antineoplastic

• 3: non-antineoplastic with primarily adverse reproductive effects

Assessment of risk determines

• alternative containment strategies and/or work practices

• for anti-neoplastic drugs that do not require any further manipulation other than counting/repackaging and table 2/3 drugs

• some dosage forms may not pose significant risk of direct occupational exposure

  • dust from tablets and capsules may present risk

What HDs must always follow USP?

• HD APIs

• Anti-neoplastic drugs when manipulation required

Assessment of risk must include

• type of HD

• dosage form

• risk of exposure

• packaging

• manipulation

• documentation of alternatives

• reviewed annually, documented

Clomiphene risk assessment

• reproductive hazard

• tablet

• risk: counting

• packaging: use only unit dose blister pack

• containment: dispense in original blister pack

Megesterol (tablet)

• reproductive hazard

• tablet

• risk: counting

• packaging/manipulation: counting may split tablets

• containment: reproductive age does not handle, separate counting tray, gloves

Yaz, Ocella, Yasmin, Drospirenone/Estradiol, Prempro Risk assessment

• non-antineoplastic

• unit dosed tablet

• exposure risk: none

• containment: tablets will not be removed from packaging

Tamoxifen risk assessment

• antineoplastic

• enteric coated tablet

• risk: counting

• containment: dedicated counting tray/spatula, immediately cleaned with alcohol or warm water/soap

Megestrol acetate liquid risk assessment

• antineoplastic

• liquid

• risk: possible spillage

• containment:

  • ATSM chemo gloves

  • plastic backed prep mat

  • alcohol wipe bottles

  • dispose gloves/mat in hazardous waste

  • clean area where worked with alcohol

Topiramate suspension, compunded risk assessment

• reproductive hazard

• risk: crushing tablets to compound suspension

• containment:

  • only non-reproductive age compound

  • chemo gloves and face mask

  • dedicated mortar and pestle

  • no pre-crushing

  • wipe down all drug containers touched with alcohol wipe

  • discard gloves and mask in hazardous waste

  • immediately clean mortar and pestle with soap and water

Progesterone vaginal suppositories

• non-antineoplastic

• compound using first progesterone VGS Vaginal Suppository Kit

  • contains progesterone (API) powder

• containment: no alternative

  • must follow USP 800

  • negative pressure room with at least 12 ACPM

  • appropriate C-PEC

  • appropriate PPE

Types of HD exposure

• dermal and mucosal absorption

• inhalation

• injection

• ingestion

• containers

Designated person

• qualified and trained to be responsible for HD

  • develop and implement procedures

  • oversee entity compliance

  • ensure competency

  • ensure environmental control

  • monitor facility

  • maintain reports

• must understand rationale for risk-prevention, risks, responsibility to report

Designated areas must be available for HD

• receipt and unpacking

• storage of HDs

• nonsterile HD compounding

• sterile HD compounding

Antineoplastic HDs and HD APIs must be unpacked

neutral/normal or negative pressure area

Sterile compounding unpacking must be done in

• outside of sterile compounding area

• in neutral/normal or negative pressure area

Storage of HDs

• Antineoplastic HDs requiring manipulation and HD APIs must be stored separately in negative pressure room with at least 12 ACPH

• exceptions:

  • some can be stored with other drugs

  • must be identifiable

C-PEC

• ventilated device designed to minimize worker and environmental hazard exposure

• CVE: non-sterile powder hoods

• biological safety cabinet: sterile

• compounding aseptic container isolator: sterile, used for cancer drugs

C-SEC

• containment secondary engineering control

• room where C-PEC placed

• may be ISO 7 buffer room with ISO 7 anteroom or unclassified containment segregated compounding area (C-SCA)

• negative pressure and appropriate ACPH

• external ventilation

• room with fixed walls

Containment Supplemental Engineering Controls

• Closed System Transfer Devices (CSTDs)

• provide adjunct controls to offer additional level of protection

• NOT substitute for C-PEC

• MUST be used when administering antineoplastics

Environmental surface wipe sampling should occur

every 6 months

surface wipe sampling should include

• interior of C-PEC and equipment inside

• pass-through chambers

• surfaces in staging or work areas near C-PEC

• areas adjacent to C-PEC

• areas immediately outside HD buffer room or C-SCA

• patient administration areas

Common marker HD

• cyclophosphamide

• measurable levels > 1.00 ng/cm²

• result in uptake of drug in exposed workers

Required HD PPE

• gowns, head, hair, 2 shoe covers, 2 pairs of chemo gloves

• for antineoplastic HDs: 2 pairs of chemo gloves, 2 gowns

Gloves for HD handling

• 2 pairs of powder free gloves

• American Society for Testing and Materials (ASTM) standard D6978

• replace every 30 min

• sterile compounding: outer gloves sterile

Gowns for HD handling

• poly-coated, disposable, close in back

• replace every 2-3 hours

• regular gown under HD gown

Head, Hair, Shoe, and Sleeve covers for HD handling

• full coverage

• 2 pairs of shoe covers

• shoe covers in HD areas must not be worn to other areas

Eye and face protection for HDs

• face shield

• goggles if not in hood (glasses not enough)

Respiratory protection for HDs

NIOSH-certified N95 mask

Hazard Communication program must include

• written plan

• labeled containers of hazards

• SDS for each hazardous chem, readily accessible to personnel

• personnel must be trained

• personnel of reproductive capability must confirm risks in writing

HD Personnel Training

• all personnel

• must occur before independent handling

• must be demonstrated

• reassessed every 12 months

• must be documented

Receiving HDs

• have SOP

• should come from supplier sealed in plastic

• delivered to HD storage area

• must wear PPE

• spill kit accessible

• tiered approach (start with visual exam for damage)

HD Labeling

HDs with special handling precautions must be clearly labeled at all times

Counting HDs

• separate counting tray/spatula

• decontaminate counting tray and spatula after HD use

HDs must be transported in containers that

minimize breakage or leakage

cannot be transported in pneumatic tube

labels must have storage, disposal, and HD cat info

HD disposal

• disposal personnel must be trained

• unused HDs and trace-contaminated PPE disposal must comply with applicable regulations

What HDs can be dispensed without further requirements for containment?

HDs requiring no manipulation other than counting final dosage form

Can automated counting or packaging machines be used for antineoplastic HDs?

NO

can create powder contaminants

HD Compounding

• must be done in proper engineering controls

• use plastic backed prep mat

• us disposable or clean dedicated equipment

• APIs/powders must be handled in C-PEC

• labeling cannot introduce contamination into non-HD areas

Administering HDs

• must be protective medical devices/techs

• must wear PPE

• CSTDs must be used for antineoplastic HDs

• should avoid manipulating HDs

Protective medical devices and techniques for HDs

• needleless and closed systems

• crushing tablets in plastic sleeves/pouches

• spiking/priming of IV tubing with non-HD solution in C-PEC

What should be deactivated/decontaminated/cleaned routinely (USP 800)

• all areas where HD handled

• all reusable equipment/devices

Deactivation

• render compound inert or inactive

• use EPA registered oxidizers: peroxide, sodium hydochlorite

Decontamination

• remove HD residue

• use: water, alcohol, peroxide, sodium hypochlorite

Cleaning

• remove organic and inorganic material

• use: germicidal detergent

Disinfection

• for sterile manipulations

• destroy microbes

• use: EPA-registered disinfectant, sterile alcohol

Spills of HDs must be…

• contained and cleaned immediately

• personnel must wear PPE

• spill kits must be readily available

• when cleaning larger spill: wear goggles, full-face piece, and chemical cartridge-type respirator or powered air-purifying respirator

SOPs for the safe handling of HDs should be reviewed

• every 12 months

• by designated person

• review should be documented

SOPs for HDs should include

• Hazard communication program

• Occupational safety program

• designation of HD areas

• hand hygiene and use of PPE based on activity

• receipt, storage, compounding, use, and maintenance

• deactivation, transport, admin, environmental monitoring

• disposal, spill control med surveillance

HD Medical Surveillance

• goal: minimize adverse health effects in personnel

• useful for identifying gaps in compliance

• provides framework for ongoing eval of exposure control program

HD Medical Surveillance elements

• data collection/documentation

• monitoring

• follow-up plan

  • exposure-related health changes should prompt immediate re-eval of primary prevention measures

  • plan of action to prevent additional exposure

  • confidential communication with employees

  • follow-up med survey

mICROMERITICS

• Science and technology of small particules

• particle size and distribution

• methods of determining particle size

• particle shape and surface area

• derived properties of powders

Particle engineering in tablet manufacturing affects

• downstream processing

• spray drying performance

• bulk density

• particle size

• drug exposure

• flowability

• compaction

Average granule range

1000-3360 mcm