BCSCP Prep

What is total body water dependent on and what is the percent in males and females?

% TBW depends on weight, age, sex, and body fat % - Average adult male: 60% - Average adult female: 50%

C to F converstion

(0 C x 9/5) + 32 = F

F to C converstion

(0 F -32) x 5/9 = C

Occupational exposure to hazardous drugs can result in what three effects?

(1) acute effects, such as skin rashes; (2) chronic effects, including adverse reproductive events; and (3) possibly cancer

Quality Assurance program should be clearly defined and implemented and should include which of the following nine separate but integrated components (USP 116?

(1) training; (2) standard operating procedures (SOPs); (3) documentation; (4) verification; (5) testing; (6) cleaning, disinfecting, and safety; (7) containers, packaging, repackaging, labeling, and storage; (8) outsourcing, if used; and (9) responsible personnel.

Hazardous buffer room requirements

(C-SEC) - ISO 7 air or cleaner (ISO 8 if using isolator), contains C-PEC. Not <30 ACPH. Pressure -0.01 to -0.03 to anteroom, Exhausts outside, enter through anteroom (If non-HD buffer room, then line of demarcation in C-SEC for garbing / de-garbing).

According to USP 71 how many units are required to be tested for non-parenterals (eye drops, inhalation, etc.)?

- < 200 containers, test 5% or 2 containers, whichever is greater - 200 or more containers, test 10 containers - If products are packaged in unit doses, refer to SVP

Define U-Listed RCRA hazardous waste and six examples of common medications on the list?

- Additional twenty-one medications noted for their toxicity profile - No concentration or dilution limits to handle waste as hazardous - Empty containers dispose in traditional waste stream. - Example agents: Chloral hydrate, cyclophosphamide, mephalan, mitomycin C, uracil mustard, warfarin <0.3%

Controlled cold temperature excursion limits?

- Allows for excursions between 0 C and 15 C - Spikes to 25 C are permitted for < 24 hours

Controlled room temperature excursion limits?

- Allows for excursions between 15 C and 30 C ' - Spikes to 40 C are permitted for < 24 hours

Microbial excursions from norm should prompt investigational review of what process and operational areas?

- Area maintenance documentation; - Sanitization/decontamination documentation; - Occurrence of nonroutine events; - Environmental temperature and relative humidity changes; - -- Training status of personnel.

What are six requirements required by FDA 503a for non-sterile to sterile compounding?

- Bulk drug from FDA-registered establishment - Bulk drug substances with valid COAs - Ingredients that comply with USP-NF monographs - Not using drugs withdrawn or removed from the market for being unsafe or not effective - Not using drugs identified by FDA as having demonstrable difficulties for compounding - Not making copies of commercially available drugs

What are common disposal bin strategies for hazardous waste?

- Bulk hazardous waste (black bin) - Unused or partially used hazardous vials, syringes, or IV bags - Spill cleanup materials - Trace hazardous waste (yellow bin) - Empty hazardous drug vials, syringes or IV bags - PPE used during drug preparation or administration

The method of suitability test will determine what 5 specific methodologies?

- CSP method of preparation - filter used - diluent used - recovery medium used - microorganisms used

Normal daily macronutrient PN dosing requirements (Calorie, Glucose, Fat, Protein, Fat:

- Calories (20-30 kcal/kg/day) - Glucose (S/M: 4-5, CI: <4, M: 4-5 mcg/kg/min or 7g/kg/d) - Fat SO 1, CI: <1: OO, SO ILE 1-1.5, SO, OO, MCT, FO 1.2 g/kg/d - Protein S: 0.8-1.5, CI: 1.2-2.5 g/kg/d.

What are the 4 types of 3:1 TPN instability?

- Creaming: accumulation of triglyceride particles at the top of the emulsion - Aggregation: clumping of triglyceride particles within the emulsion - Coalescence: fusion of small triglyceride particles into larger particles - Cracking: separation of the oil and water components of the emulsion

Calories/Kilogram - equation for energy requirements.

- Easiest 20 - 30 kcal/kg/day

Risk of calcium phosphate precipitation may be reduced by?

- Final AA conc at 2.5% or greater - Maintain a final pH of 6.0 or lower - Infusion solution within 24 hours of preparation - Use calcium gluconate instead of calcium chloride - Avoid mixing Ca and Phos in close sequence - Keep calcium:phosphorus ratio greater than 1:2 - Keep total amount of Ca and Phos < 45 mEq/mL - Keep the calcium:phosphorus solubility product < 150 - Add cysteine to the amino acids

Percentage of glucose to fat nonprotein calories?

- Glucose 70-85% - Fat 15-30%

The retina is subject to the risk of drug-induced toxicities owing to its rich blood supply, complex neuro-retinal organization and lifelong exposure to light rays. multifactorial toxicities. What factors can cause toxicities?

- High concentration of drug • Narrow range between therapeutic and toxic doses - Presence of preservatives • Benzyl alcohol has been implicated - Osmolarity and pH changes • Avoid extremes

What additional hazardous characteristics are subject to EPA disposal guidelines?

- Ignitability - Corrosivity - Reactivity - Toxicity - Primarily non-medical use chemicals.

How should supply waste be handled (i.e. needles and sharps)?

- Items prone to cause needle sticks should be disposed in dedicated sharps container (needles, broken vials or ampules, syringes with attached needle) - Vendors handling sharps waste typically can only handle infectious waste - Maintain separate sharps containers for hazardous drugs and RCRA hazardous waste - Educate staff on appropriate sharps disposal stream based on drug used

What TPN factors may reduce risk of destablization?

- Keeping the final amino acid concentration at 2.5% or greater - Maintaining a final pH of 5.0 of above - Keeping the final dextrose concentration at 3.3% or greater - Avoiding trivalent cations (i.e. iron dextran) - Avoiding mixing dextrose and lipid directly

According to USP 71 how much volume needs to be tested for small volume parenterals?

- Less than < 1 mL total volume: entire volume - 1 - 40 mL total volume: 50% of total volume, minimum of 1 mL - 41 - 100 mL total volume: 20 mL - > 100 mL total volume: 10% of volume but at least 20 mL

What are the considerations for manual visual inspection (MVI)?

- Light intensity: NLT 2,000 - 3,750 lux - Background contrast: Black / White backgrounds (matte) - Rate: 10 seconds per container (5 seconds white + 5 seconds black) - Movement: careful swirl or inversion of contents - Magnification: not recommended

What are the three sterility assurance levels?

- Low-level disinfection (10-3): 1 nonsterile unit in 1 thousand - High-level disinfection (10-4): 1 nonsterile unit in ten thousand - Pharmaceutical sterilization (10-6): 1 nonsterile unit in 1 million

What are the voluntary versus mandatory ADEs reporting requirements and the systems available to report ADEs?

- Mandatory: • Distributors, importers, manufacturers - Voluntary: • Patients, consumers, healthcare providers - MedWatch: * VAERS: Vaccine Adverse Event Reporting System * FAERS: FDA Adverse Event Reporting System - TJC Sentinel Event Reporting System

What is estimated fluid requirements based on age and weight, for most adults, older adults and elderly?

- Most adults (18-55 yrs): 35 mL/kg/day - Older Adults (56-75 yrs): 30 mL/kg/day - Elderly (> 75 yrs): 25 mL/kg/day

Normal daily electrolyte PN dosing requirements:

- Na, K = 1-2 mEq/kg - Cl, acetate = as needed acid-base balance (= amts Na or K) - Phos = 20-40 mmol - Ca = 10-15 mEq (gluconate perferred) - Mg = 8-20 mEq

ASHP Guidelines on Compounding Sterile Products eight label requirements?

- Name and amount of active ingredients - Total volume of preparation - Route of administration - BUD - Date and time dose prepared - Special storage requirements - Unique identification number - Positive ID of compounding and checking personnel

How should healthcare facilities handle non-RCRA pharmaceutical waste?

- Non-RCRA pharmaceutical waste should be handled as solid waste - Waste stream dictated by federal, state, and local regulatory bodies - New RCRA Management Standards allows healthcare facilities to choose how to handle non-hazardous waste - Separate from RCRA hazardous waste for disposal - Combine with RCRA hazardous waste for disposal - Many agents not covered by RCRA exhibit characteristics of hazardous waste

What are 4 primary sources of contamination their percent contribution.

- People-75% - Ventilation-15% - Room structure-5% - Equipment-5%

What are ISMP labeling best practices?

- Strategic use of BOLD to highlight important label components: patient name, generic drug name, dose - Generic drug name should be printed in all lowercase -If using brand name, use all CAPITAL letters to differentiate - Use tall-MAN lettering for look-alike, sound-alike drugs. - Font San Serif 10-12 points, adequate spacing - Avoid dangerous abbrev. and use USP stand abbrev (ex mL) - Always use leading zero, never trailing zero

What are the three types of drug information references and examples of each?

- Tertiary - interpretation of primary data, generally well-accepted (review articles, guides, textbooks, encyclopedias, drug databases, package inserts) - Secondary - Resource that guides one to primary and tertiary literature (abstracting databases, e.g., PubMed, Medline) - Primary - Primary research (case reports, clinical trials)

Normal daily B-vitamins PN dosing requirements:

- Thiamine (B-1) = 6 mg - Riboflavin (B-2) = 3.6 mg - Niacin (B-3) = 40 mg - Folic acid = 600 mcg - Pantothenic acid = 15 mg - Pyridoxine (B-6) = 6 mg - Cyanocobalamine (B-12) = 60 mcg

What are the principles for compounding for CNS injections.

- Use strict adherence to aseptic technique - Use preservative-free medication formulations - Perform accurate calculations and measurements - Filter per your institution's policy - Remove air from epidural infusion containers - Label all containers clearly with the route of administration

How should hazardous pharmaceutical waste not on RCRA list be handled?

- Waste associated with medications on NIOSH Hazardous Drugs List - Only nine NIOSH hazardous drugs are also RCRA Hazardous - Limited to agents on market when RCRA established - Exhibit characteristics similar to P- and U-listed hazardous waste - Should be disposed of as RCRA hazardous waste - Recommendation from OSHA, NIOSH, ASHP

Mifflin-St Jeor - equation for energy requirements.

- currently most recommended Women = -161 + (10×Weight (kg)) + (6.25×Height (cm)) - (5×Age (yr)) Men = 5 + (10×Weight (kg)) + (6.25×Height (cm)) - (5×Age (yr))

Freezing temperatures (C & F)

-25 to - 10 C -13 to 14 F

What are 6 common conditions used in forced degredation?

-Acidic pH (hydrochloric acid) - Neutral pH (phosphate buffer) - Basic pH (sodium hydroxide) - Oxidation (02 or H2O2) - Photolysis (UV, fluorescence) - Temperature / humidity (thermostatic and humidity-controlled ovens)

Normal daily vitamin A, C, D, K PN dosing requirements:

-Ascorbic acid = 200 mg -Vitamin A = 1 mg (3300 IU) -Vitamin D = 5 mcg (200 IU) -Vitamin E = 10 mg (10 IU) -Vitamin K = 150 mcg

Define P-Listed RCRA hazardous waste and eight examples of common medications on the list?

-Considered acutely hazardous under RCRA - Oral lethal dose is less than 50mg/kg - Includes full, partial and empty containers -Current eight P-listed medications: Arsenic trioxide, epinephrine base, nicotine, nitroglycerin, phentermine, physostigmine, physostigmine salicylate, warfarin >0.3%. (NTG, Epi formulations used in hospital excluded)

What are techniques for managing dead space in syringe and needles?

-Use a new syringe and needle for each step of the preparation - Mix ingredients in a sterile empty vial before withdrawing the final dose - Individual ingredients often can first be drawn into separate syringes and then injected into a larger syringe by insertion of the needles into the needle/free tip of the larger syringe - Prime needles after changing from a filter needle before taking the final measurement.

What is the maximum endotoxin limit in preparations for intrathecal use.

0.2 USP endotoxin units/kg/hr

Recommended filter size for PN without lipid (2:1)?

0.2 micron filter

Common aqueous isotonic vehicles used in sterile preparations.

0.9% sodium chloride (NS), Ringer's injection, dextrose 5% and lactated Ringer's injection.

Common calculation conversions (household):

1 cup = 8 fluidounces 2 cups = 1 pint 2 pints = 1 quart 4 quarts = 1 gallon

What is the correlation between Urinary Urea Nitrogen and lean tissue loss?

1 g of Urinary Urea Nitrogen represents the loss of 30 g of lean tissue. - 24-hr Urinary Urea Nitrogen excretion • 15 g equivalent to ~ 0.5 kg lean body mass/day • Post-surgery: 0.64 kg lean body mass lost/day • NPO for 5 to 7 days = 2.5 to 3.5 kg lean body mass loss

Metric relationship between volume, distance and mass for 1 ml water?

1 ml water = 1 cubic centimeter = 1 gram

The intent of 797 chapter to prevent harm, including death from what five risks?

1) microbial contamination [nonsterility], 2) excessive bacterial endotoxins, 3) variability from the intended strength of correct ingredients, 4) physical and chemical incompatibilities, 5) chemical and physical contaminants, and/or 6) use of ingredients of inappropriate quality.

ASHP compounding 4 key guidance documents?

1. 1993-Technical Assistance Bulletin on Quality Assurance for Pharmacy-Prepared Sterile Products (TAB) 2. 2000-ASHP Guidelines on Quality Assurance of Pharmacy-Prepared Sterile Products -TAB update 3. 2014-ASHP Guidelines on Compounding Sterile Preparations 4. 2018-ASHP Guidelines on Handling Hazardous Drugs

Designated person(s) must ensure that the facility has formal, written QA and QC programs that establish a system of what 4 things?

1. Adherence to procedures 2. Prevention and detection of errors and other quality problems 3. Evaluation of complaints and adverse events 4. Appropriate investigations and corrective actions

USP 797 2022 (4.1.2) describes what key facility design requirements to maintain air quality?

1. Anterooms to positive pressure buffer rooms are min. ISO 8. 2. Anterooms to negative pressure buffer rooms are min. ISO 7. 3. Buffer room must meet ISO 7. 4. Cat. 1, 2, 3 must be compounded in ISO 5 or better. 5. If only Cat. 1 PEC may be in unclassified SCA.

Name 5 sources of pyrogens in sterile preparations.

1. Aqueous vehicles, 2. Equipment, 3. Containers and closures, 4. Chemicals used as solutes, 5. Human touch.

Immediate-Use CSP's Requirements 2022 (7 requirements)?

1. Aseptic techniques, processes, and procedures are followed, (written SOPs in place). 2. Personnel are trained and demonstrate competency. 3. Evidence-based information for physical and chemical compatibility (e.g., approved labeling, stability and compatibility studies). 4. The preparation involves not more than 3 different sterile products. 5. Unused starting component from a single-dose container must be discarded and not be used for more than one patient. 6. Administration begins within 4 h following the start of preparation, or else promptly discarded. 7. Unless directly administered or witnessed by the preparer, the CSP must be labeled (names, amounts of all active ingredients, name or initials of preparer, 4-h BUD)

What are the two basic types of air handling systems and the key diffrences.

1. Central HVAC - powerful remote custom unit with prefilter, extensive ductwork. 2. Ceiling distributed - fan filter units (FFU) pushing air through HEPA, HVAC feeds neg. pres. plenum above room (not custom), returns go to plenum.

FDA under 503A defines compounding using bulk drug substances can only be done if what 5 criteria are met?

1. Comply with USP-NF monograph if one exists, and the USP chapter on pharmacy compounding; 2. components of FDA-approved drug products if an applicable USP or NF monograph does not exist; or 3 appear on FDA's list of bulk drug substances that can be used in compounding (the 503A bulks list) if such a monograph does not exist and the substance is not a component of an FDA-approved drug product. 4. accompanied by a valid COA. 5. manufactured by an establishment registered with FDA under section 510 of the FD&C Act

What are the 5 factors described in USP 797 (2022) that affect microbial risk?

1. Conditions of environment where CSP is prepared. 2. Aseptic processing and sterilization method. 3. Starting components. 4. Sterility testing. 5. Storage conditions.

The goals of a microbiological air and surface monitoring program is to determine what 4 environmental control elements?

1. Contamination is present at unacceptable levels. 2. Assess whether proper personnel practices are being followed. 3. Cleaning and disinfecting agents are effective 4. Environmental quality is maintained.

FDA conditions required for repackaging to avoid compliance actions with FDCA 501(a)(2)(B)

1. Drug product is approved 505 FDCA 2. Appears on drug shortage list 506E (must be distributed during shortage or during 30 days following) 3. State licenced, Federal, outsourcing facility. 4. Under licensed RPh supervison. 5. Distributed only after receipt of valid prescription. 6. Does not conflict with approved drug product labeling (except SDV labeling on original package). 7. Container is suitable throughout BUD. 8. Includes storage and handling instructions as approved labeling. 9. BUD is appropriate for in use time, 503b and 503a (797,795) requirements. 10. Not on list of withdrawn or removed /unsafe/ineffective. 11. Not transferred or sold by other entity. 12. Distributed in states licensed by facility.

Steam sterilization documentation should be completed when and requirements include?

1. Each sterilization run or load. 2. Biological indicators (i.e., Geobacillus stearothermophilus or, physicochemical indicators). 3. Temperature and pressure, using calibrated data recorder or chart. 4. Date, run, and load numbers of the steam sterilizer used to sterilize a CSP must be documented in the CR.

What are the key 3 Federal regulations that apply to compounding?

1. FDA Compounding Regulations (FD&C Act) - Section 503A,- Section 503B 2. OSHA - 29 CFR 1910.1020: Access to employee medical and exposure records - 29 CFR 1910.1200: Hazard communication standard 3. EPA - RCRA of 1976

What are the three techniques for using LAL as a test reagent?

1. Gel-clot where gel clot is formed in presense of endotoxin. 2. Turbidimetric where the presense of turbidity is observed. 3. Chromogenic where a color change is observed.

When should testing occur for a CSP with extended BUD and rational for each.

1. Initial testing - To determine CSP potency & stability over time, appropriate storage container, sterility of CSP overtime, 2. Testing of each batch / lot - To detect potential issues in method of preparation or sterilization that could result in unsafe product 3. Ongoing testing for BUD maintenance (Occasionally) • To defend extended BUD • Must be done anytime there is a change to components, container closure, or process.

USP 797 2022 EM excursion investigational requirements (5 listed)?

1. Investigate, take corrective action, and review effectiviness. 2. Corrective action plan based on CFU # & microorganism. 3. Extent of investigation based on deviation. 4. Document corrective action plan. 5. ID growth to genus if ID exceeded (microbiologist assist). **No more mention of "highly pathogenic organisms"**

USP 797 2022 indicates that complaint handling must document at minimum the following 7 items?

1. Name of the complainant or other unique identifier. 2. Date the complaint was received. 3. Nature of the complaint. 4. Response to the complaint. 5. name and strength of the CSP (if known). 6. Assigned internal identification number (e.g., prescription, order, or lot number), if known. 7. Investigation and follow up.

What is the minimum documentation requirements for garbing and aseptic manipulation competencies (USP 797 2022 section 2)? What are the requirements for microbial identification?

1. Name of the person evaluated. 2. Evaluation date and time. 3. Media and components used including manufacturer, expiration date, and lot number. 3. Starting temperature for each interval of incubation. 4. Dates of incubation 5. Results and identification of the observer and personnel reading and documenting the results. Microbial identification of the colony-forming units (cfu) is not required for gloved fingertip and thumb sampling, or media fill.

Non-ISO5 (outside PEC) room minimum cleaning frequencies stated in USP 797 2022?

1. Pass-throughs, work surfaces, floors: • Cleaning and Disinfecting - Daily - compounding days • Sporicidal - Monthly (Cat. 1 &2) - Weekly (Cat. 3) 2. Walls, Ceilings, Storage shelves/bins, equipment: • Cleaning and Disinfecting - Monthly • Sporicidal - Monthly 3. Sinks (surfaces): • Cleaning and Disinfecting - Daily - compounding days • Sporicidal - Monthly

What are top 10 sources of microbial contamination with aseptic processing?

1. Personnel contaminants, 2. Human error, 3. Aseptic assembly, 4. Nonroutine activity, 5. Mechanical failure, 6. Airborne contaminants, 7. Surface contaminants, 8. Failure of 0.2 micron filter, 9. Failure of HEPA filter, 10. Improper sterilization

When is preparation of conventionally manufactured product considered out of scope of USP 797 (2022)? (name 3 requirements)

1. Prepared as a single dose. 2. For a single patient. 3. Approved labeling specifies the diluent, the resultant strength, the container closure system, and the storage time.

What does a method of suitability for sterility testing prove and determine? How often is it performed for a formulation? What control is required?

1. Proves that microorganisms can be recovered in the presence of the drug product. 2. Determines if membrane filtration or direct inoculation and if filtered the numaber for times rinsed. Only need to be performed once. Requires negative control.

USP 797 2022 (4.3.1) Describes what conditions for easy cleaning?

1. Smooth, impervious, free from cracks and crevices, and nonshedding. 2. Resistant to damage (rust) by cleaning agents. 3. Juctures of ceiling/walls and wall/floor sealed, caulked or coved. 4. Inlaid ceilings caulked. 5. Walls durable material (epoxy painted or heavy-guage plymer). 6. No dust-collecting overhangs, utility pipes or easily cleanable. 7. Lights smooth, flush mounted and sealed.

When selecting the sterilization method for CSPs prepared from one or more nonsterile starting components or using nonsterile supplies or devices, personnel must take into consideration what 3 criteria? (USP 797 2022 section 10)?

1. The nature of the component(s), 2. Their physical and chemical properties, 3. The intended container closure system.

The standards for compounding allergenic extracts, which are described in USP 2022 section 21. Compounding Allergenic Extracts, are applicable only when what 2 criteria are met:

1. Transfer via sterile needles and syringes of conventionally manufactured sterile allergen products and appropriate conventionally manufactured sterile added substances; and 2. Manipulations are limited to penetrating stoppers on vials with sterile needles and syringes and transferring sterile liquids in sterile syringes to sterile vials.

USP 797 2022 (4.2) describes what other controls related to lighting, temp, humidity and control requirements.

1. Well lighted and comfortable. 2. Temperature of 20 C or cooler. 3. Relative humidity 60% or below. 4. Temp and humidity must be monitored on compounding days (document daily or continuous recording device). 5. Must control by HVAC (no free-standing units) 6. Temp and humidity devices calibrated every 12 months.

Four criteria for dispensing before sterility results received? What 3 areas should be investigated?

1. Written procudure, 2. daily observation specimens, 3. immediate recall if growth, 4. notify patient and physician of risk if growth. Investigate: 1. technique, 2. environment, 3. other sterility assurance controls.

Pharmacy bulk package label shall state what three criteria?

1. state prominently ―"Pharmacy Bulk Package—Not for Direct Infusion", 2. contain or refer to information on proper techniques to help ensure safe use of the product, and 3. bear a statement limiting the time frame in which the container may be used once it has been entered, provided it is held under the labeled storage conditions.

What filter should be used for lipids and why?

1.2 micron - risk of lipid emboli.

What is the distribution of total body water in the body?

1/3 Extracellular - Interstitial 3/4 - Intervascular 1/4 2/3 Intracellular

Microbial organisms are typically associated with what size particles?

10-20 micron

What is the calorie provided by soybean oil fat and what is the alternative?

100% soybean oil - 20% oil-in-water ILE • 1 g provides 10 kcal - Fat provides 9 kcal/g plus energy from glycerin (for osmolarity) - Alternative ILEs: - 30% soybean oil, 30% MCT oil, 25% olive oil, 15% fish oil - 80% olive oil, 20% soybean oil • 20% oil-in-water ILE - 1 g provides 10 kcal - Maximum of ILE: 60% of total calories or 2.5 g/kg/day

Squamous cells are normally shed from the human body at a rate of ___________, and those skin particles are ____________________.

10^6 or more per hour, laden with microorganisms

If a single-dose vial is entered or punctured only in an ISO Class 5 or cleaner air, it may be used up to ______ h after initial entry or puncture as long as the labeled storage requirements during that period are maintained.

12 hours

What are the NaCl mEq equivalents in 1000ml of 0.9%, 0.45% and 0.2% NaCl respectively? What is mEq equivalent for concentrated 23.4% NaCl?

154 mEq, 77 mEq, 38.5 mEq, 4 mEq

Dry heat common temperatures and times for sterilization.

180 °C for 30 min or 170 °C for 1 hr 160 °C for 2 hr

What is minimal grams of dextrose /kg/day needed for protein-sparing effect with TPN.

2 g dextrose/kg/day

Controlled Cold Temperature

2 to 8 C with mean kinetic 8 C 36 to 46 F

According to USP 71 how many units are required to be tested for large volume parenterals?

2% or 10 containers, whichever is less

Common calculation conversions (cm-in, kg-lb, g-lb, g-oz, ml-pint):

2.54 cm = 1 inch 1 kg = 2.2 pounds (lb) 454 g = 1 lb 28.4 g= 1 ounce (oz) (usually rounded to 30 g) 473 ml = 1 pint (usually rounded to 480 ml)

When using a syringe for measuring, maximum accuracy and reproducibility, the smallest volume measured should be what percentage for the syringe capacity.

20 % , for example the smallest volume that can be measured accurately on a conventional 1mL tuberculin syringe is 0.2mL (1mL x 20% = 0.2mL)

Controlled room temperature

20-25 C 68-77 F mean kinetic temp 25 C

What is maximum concentration of aluminum in PN?

25 mcg/L

Once initially entering or puncturing the multiple-dose container, the multiple-dose container must not be used for more than ______ day unless otherwise specified by?

28 days, the manufacturer on the labeling.

When BET limit (TPD) is not referenced in USP-NF monograph, what are the limits defined in USP <85>?

5 EU/kg/hr is the TPD for (IV) or (IM). 0.2 EU/kg/hr for (IT), radiopharmaceutical, K = 175 EU for non-intrathecal routes of administration and 14 EU for intrathecal administration.

The business plans support that a new facility requires selling of non-patient-specific compounded preparations to others, what type of registrant should be pursued?

503(b)

Controlled cool temperatures

8 to 15 C (46 to 59 F)

What is maximum osmolarity of PPN.

900 mOSm//L

Hyperglycemia more common in hospitalized patients receiving PN with what dextrose infusion rate?

> 4 mg/kg/minute of dextrose

When is compounding record (CR) required and what is the one situation where a CR is NOT required?

A CR is required for ALL category 1, 2 and 3 preparations. A CR is not required for immediate use preparations compounded for a single patient.

Viable sampling media includes:

A general microbiological growth media that supports the growth of bacteria and fungi must be used (e.g., TSA) or TSA and fungal media (e.g., malt extract agar [MEA] or Sabouraud dextrose agar [SDA]).

How does USP 797 2022 define Critical sites?

A location that includes any component or fluid pathway surfaces (e.g., vial septa, injection ports, and beakers) or openings (e.g., opened ampules and needle hubs) that are exposed and at risk of direct contact with air (e.g., ambient room or HEPA filtered), moisture (e.g., oral and mucosal secretions), or touch contamination.

Name a scenarios where the Centers for Disease Control and Prevention (CDC) safe injection practices guidance on single-dose vials apply?

A nurse compounding a sterile emergent medication from a multidose vial in the patient care area

What is quality assurance?

A system of procedures, activities, and oversight that ensure the compounding process consistently meets quality standards.

What are requirements for depyrogenation by dry heat?

A typical cycle would be 170-400 C (ie, 30 minutes at 250°). Document temp, times, effectiveness of cycle verified using endotoxin challenge vials (ECV) initially and annually or if change. Endotoxin test on ECV to verify 3-long reduction.

Chemotherapy gloves must be tested to what standard?

ASTM standard D6978

Why is cysteine used in parenteral nutrition.

Added to PN for pediatric and neonatal, to enhance solubility of calcium and phosphate which would normally precipitate.

CMP normal ranges.

Albumin: 3.4 to 5.4 g/dL (34 to 54 g/L) Alkaline phosphatase: 20 to 130 U/L ALT (alanine aminotransferase): 4 to 36 U/L AST (aspartate aminotransferase): 8 to 33 U/L BUN (blood urea nitrogen): 6 to 20 mg/dL (2.14 to 7.14 mmol/L) Calcium: 8.5 to 10.2 mg/dL (2.13 to 2.55 mmol/L) Chloride: 96 to 106 mEq/L (96 to 106 mmol/L) CO2 (carbon dioxide): 23 to 29 mEq/L (23 to 29 mmol/L) Creatinine: 0.6 to 1.3 mg/dL (53 to 114.9 µmol/L) Glucose: 70 to 100 mg/dL (3.9 to 5.6 mmol/L) Potassium: 3.7 to 5.2 mEq/L (3.70 to 5.20 mmol/L) Sodium: 135 to 145 mEq/L (135 to 145 mmol/L) Total bilirubin: 0.1 to 1.2 mg/dL (2 to 21 µmol/L) Total protein: 6.0 to 8.3 g/dL (60 to 83 g/L)

Viable surface sampling requirements and frequency include?

All ISO classified areas on a periodic basis, contact plates or swabs, conclusion of compounding, locations defined in plan, plate size (24-30cm^2), neutralizing agent.

Opthalmic eye medications considerations.

All eye preparations must be sterile - Eye preparations must be prepared in an ISO Class 5 environment Accuracy in calculations and measurements - A fresh needle and syringe should be used for each preparation step to prevent errors caused by dead space or residual volumes - Dilutions should be made if less than 0.2mL volume is required Eye injections should be compounded from preservative-free and additive-free dosage forms if possible

Bacterial Endotoxin (Pyrogen) Testing needs to occur when?

All high-risk level CSPs (except inhalations and opthalmics) that in groups > 25 identical individual single-dose packages or in multiple-dose vials (MDVs) for administration to multiple patients OR that are exposed > 12 hours at 2° to 8° and longer than 6 hours at warmer than 8° before they are sterilized.

Gloves used with HD must meet what standard? How often do they need to be changed?

American Society for Testing and Materials (ASTM) standard D6978 (or its successor). Must be powder free. Every 30 minutes unless manufacture specifies other and if torn, punctured or contaminated.

When USP-NF compendial monograph ingredients are not available, what other sources may be acceptable.

Another high-quality ingredient source, eg (certified analytical reagent) certified by the American Chemical Society or Food Chemicals Codex grade.

What is the dextrose cutoff for peripheral PN?

Approximately 12.5% due to phlebitis.

How many ACPH must be supplied by the room HVAC system?

At least 15 ACPH of the 30 ACPH must be supplied by the room HVAC system.

Body mass index formula?

BMI (kg/m^2) = weight (kg)/[height (m)]^2 if Ht in cm /100. Lbs & in = 703 x Wt (lb)/[Ht (in)]^2

BSA formula in meter squared.

BSA = square root of height (cm) * weight (kg) /3600

What are components of eye irrigations and storage requirements?

Balanced salt solution plus - glucose and glutathione which are both necessary to protect the corneal epithelium - It must be used within 6 hours after reconstitution Storage and temperature - Glass bottles are preferred over bags. Storage in bags leads to bubble formation which can damage the corneal epithelium and obscure the surgeon's view - Irrigations for the eye are used at room temperature.

What is Baricity

Baracity compares the density of a medication to the density of CSF (with both at 37ºC which is body temperature) - Addition of glucose to the formulation will make a solution hyperbaric • A hyperbaric solution is heavier than CSF - An isobaric solution has the same density as CSF -Baracity determines the spread of the drug in the intrathecal space - Hyperbaric solutions will flow in the direction of gravity

Compounding equipment such as ACD when must accuracy test be performed, how is precision monitored and what is documentation requirement (USP 2022)?

Before initial use and each day equipment is used. Based on an assessments of day to day variations in accuracy measures. Must maintain daily record of accuracy check on days used.

What are the most common ophthalmic preservatives?

Benzalkonium chloride (0.004-0.02%) - most common. Other preservatives include: phenylmercuric acetate and nitrate (0.001- 0.01%), phenyl-ethanol (0.5%), parabens (0.1%), and chlorobutanol (0.5%).

Commonly used preservatives in injectables.

Benzyl alcohol (usually 0.9%) and the parabens (methyl 0.18% combined with propyl 0.02%).

What is the smallest size particle detected by visual eye? What device can be used to improve detection and down to what size particle.

Best observations will detect 20-50 µm diameter. Light obscuration particle sizer is the ideal as it can detect fine precipitates that may occlude small blood vessels (4-9 µm in diameter).

Warm temperature definition?

Between 30° and 40° (86° - 104° F).

What is used to validate effectiveness of dry heat sterilization?

Biological indicators of Bacillus atrophaeus spores and other temperature-sensing data loggers for each cycle.

Examples of RABS and their placement?

CAI, CACI, pharmacy robotic IV systems. Cat. 1 may be SCA Cat. 2 or 3 must be cleanroom suite. • Requires dynamic smoke study every 6 months. • Must document manf. recovery time and internal procedures

Administering and with drawing final doses of are out of scope of USP <797>, what reference is commonly used for guidance on administration?

CDC's Safe Injection Practices to Prevent Transmission of Infections to Patients

What is the definition of contamination recovery rates (CRR) and how does it compare to identification of CFU counts.

CRR is the rate at which environmental samples are found to contain microbial contamination, for example incident rate of 1% would mean that only 1% of the samples taken have any contamination regardless of colony number. In other words, 99% of the samples taken are completely free of contamination. Recovery rates are a more useful measure of trending results than is focusing on the number of colonies recovered from a given sample.

According to USP 797 (2022) which CSPs are required to have endotoxin testing?

CSP that are compounded from nonsterile ingredients and are assigned a BUD date that requires sterility testing.

Revised 797 indicates a master formula is required in which situations?

CSPs prepared from nonsterile ingredients or prepared for more than one patient.

Written procedures for equipment should outline what requirements?

Calibration, annual maintenance, monitoring for proper function, use of the equipment, and frequency of these activities. Reports kept life time of equipment. Training, including identifying proper functioning.

When considering TPN sterility, what fungi proliferate in AA based solutions and what steps should be taken?

Candida albicans, proliferate in amino-acid based solutions (even within a brief period of 24 hours) Should be immediately refrigerated after preparation. For 3:1 TPN a 1.2 micron filter should be used (removes C. Albicans , but not S. epidermidis) For 2:1 use a 0.22 micron filter (bacteria retentive).

What conditions if any can a BUD be extended past those listed in the tables of USP 797 (2022)?

Cannot be extended based on SIM performed by organization or peer reviewed literature. Can be extended based on based on USP-NF monograph if followed exactly with tests that are required.

What are the frequency and requirements for INITIAL garbing and hand hygiene competencies (USP 797 2022 - 2.2)?

Cat. 1 ,2, 3 Initial: • Before beginning to compound or have direct oversight. • No fewer than 3 consecutive times • Consists of visual observation and gloved fingertip and thumb sample (GFT) of both hands. • Following separate, complete hand hygiene garbing. • Failure indicated by visual and/or exceeded sample action limit (>0 cfu) • Do not apply sIPA to gloves before sample. • Document: Personel evaluated, date/time, media/components (manuf, lot, exp), starting incubation temp, incubation dates, results, indentification of observer and reader.

What are the frequency and requirements for ON-GOING garbing and hand hygiene competencies (USP 797 2022 - 2.2)?

Cat. 1 and 2 on-going: at least every 6 months. Cat. 3: at least every 3 months. Direct Oversight Person: 12 months (same garbing as personnel they oversee). Cannot compound unless complete above requirements).

CAIs and CACIs shall be placed in an ISO class environments based on Category?

Category 1 CSPs, the ISO in an unclassified SCA. Category 2 or Category 3 CSPs, the RABS must be cleanroom suite with an (ISO 7 or better buffer room, ISO 8 or better anteroom).

USP 797 2022 Media Fill Frequency

Category 1 and Category 2 CSPs, the aseptic manipulation competency must occur initially and at least every 6 months thereafter. Category 3 CSPs, the aseptic manipulation competency must occur initially and at least every 3 months thereafter.

Viable Air Sampling Frequency USP 797 2022

Category 1 and Category 2 CSPs, this must be completed at least every 6 months. Category 3 CSPs, this must be completed within 30 days prior to the commencement of any Category 3 compounding and at least monthly thereafter regardless of the frequency of compounding Category 3 CSPs.

What is the measurement used for viscosity?

Centipoise - LA low centipose will flow and move asily and fast. A higher centipoise will flow much slower. Water is 1.

What certification guidelines should be used for a non-sterile containment ventilation enclosure and what should be used for a BSC?

Certifier should use ASHRAE 110, which is the performance test for laboratory fume hoods. Certification of BSCs must include compliance with NSF-ANSI 49.

Normal daily trace elements PN dosing requirements:

Chromium = <= 10 mcg Copper = 0.3-0.5 mg Manganese = 55 mcg (Caut. with incr. Bilirubin - neuro toxic) Zinc 3-5.0 mg (requir. increase with GI output). Selenium 60-100 mcg (indicated LT care & crit. ill) Iron = not routinely added (long term PN prone to def.)

What precautions should be taken when manipulation of a patient's blood-derived or other biological material (e.g., radiolabeling a patient's or donor's white blood cells) during compounding?

Clearly separated from routine material-handling procedures and equipment used in CSP preparation activities, and they shall be controlled by specific SOPs in order to avoid any cross-contamination.

Compounding definitions (FDA).

Combine, mix, or alter ingredients of a drug to create a medication tailored to the needs of a patient. - Requires a material change to drug product - Does NOT include: • Mixing • Reconstituting • Repackaging • Otherwise preparing per manufacturer instructions

What factors effects calcium and phosphorus solubility?

Concentrations of Ca/Phos, conc and distribution of AA, Dex and Mag, temp of PN storage and admin, final pH, sequence components added.

Individuals with what kinds of conditions, may have a higher risk of contaminating the CSP and environment? How should these conditions be reported and the decision made to exclude them from compounding?

Conditions: • personnel with rashes • recent tattoos • oozing sores • conjunctivitis • active respiratory infections) Must be reported to the designated person(s), who is responsible for evaluating whether these individuals should be excluded from working in compounding areas.

What is the longest permitted BUD for Category 1? What environment can Category 1 be compounded?

Controlled Room Temperature (20°-25°) <=12 h, Refrigerator (2°-8°) <= 24h. SCA or Cleanroom suite.

What are the longest permitted BUDs for Category 2 CSPs ASEPTICALLY prepared from one or more NONSTERILE starting component(s), when sterility testing is NOT performed?

Controlled Room Temperature (20°-25°): 1 day Refrigerator (2°-8°): 4 days Freezer (−25° to −10°): 45 days

What are the longest permitted BUDs for Category 2 CSPs that have been terminally sterilized, but sterility testing is NOT performed?

Controlled Room Temperature (20°-25°): 14 days Refrigerator (2°-8°): 28 days Freezer (−25° to −10°): 45 days

What are the longest permitted BUDs for Category 2 CSPs ASEPTICALLY prepared, when sterility testing is performed and passed?

Controlled Room Temperature (20°-25°): 30 days Refrigerator (2°-8°): 45 days Freezer (−25° to −10°): 60 days

What are the longest permitted BUDs for Category 2 CSPs ASEPTICALLY prepared from only STERILE starting component(s), when sterility testing is NOT performed?

Controlled Room Temperature (20°-25°): 4 days Refrigerator (2°-8°): 10 days Freezer (−25° to −10°): 45 days

What are the longest permitted BUDs for Category 2 CSPs that has been terminally sterilized and a sterility testing is performed and passed?

Controlled Room Temperature (20°-25°): 45 days Refrigerator (2°-8°): 60 days Freezer (−25° to −10°): 90 days

What are the longest permitted BUDs for Category 3 CSPs that has been ASEPTICALLY processed, sterility tested, and passing all applicable tests for Category 3 CSPs?

Controlled Room Temperature (20°-25°): 60 days Refrigerator (2°-8°): 90 days Freezer (−25° to −10°): 120 days

What are the longest permitted BUDs for Category 3 CSPs that has been terminally sterilized, sterility tested, and passing all applicable tests for Category 3 CSPs?

Controlled Room Temperature (20°-25°): 90 days Refrigerator (2°-8°): 120 days Freezer (−25° to −10°): 180 days

What trace elements should be reduced in severe hepatic dysfunction or cholestasis?

Copper and Manganese

Repackaging definitions (FDA, USP).

Current USP silent on repackaging. FDA repacking - transfer of drug product from original manufacturer container int a different container without further manipulation of the drug.

What does the D value represent in sterilization?

D-value is the time (customarily in minutes) or radiation dose (customarily in kiloGrays) required to reduce the microbial population by 90% or 1 log10 cycle (i.e., to a surviving fraction of 1/10) and must be associated with the specific lethal conditions at which it was determined.

For incubators, what is the frequency of temperature monitoring, cleaning and calibration?

Daily, monthly, annual

What refrigerators are allowed in C-SEC? What is prohibited?

Dedicated refrigerator (consider installing refrigerator exhaust), refrigerated pass through prohibited in C-SEC

What are the optimal final concentrations of Dex, AA and IL in 3:1 TNA formulation for stability?

Dex >= 10% AA >= 4% and ILE >= 2%

What are water-miscible solvents used for and 3 common examples?

Dissolve drugs with low water solubility. e.g., ethyl alcohol, liquid polyethylene glycol, propylene glycol. Usually IM injection (some vitamins, antihistamines and cardiac glycosides)

What elements must be evaluated in assessment of risk (AOR) for a HD drug and what three categories of drugs for which an AOR cannot be performed?

Drug, Dosage form, Risk of exposure, Packaging, Manipulation, And document alternative containment strategies and work practices. Cannot use AOR for API, raw powder of any HD on NIOSH list, Table 1 antineoplastic that are manipulated, items that don't fit your AOR.

What are the growth promotion test requirements for the two media used in <71> sterility testing, name organisms and incubation requirements?

Each lot must pass growth promotion test, by being inoculated with 100 cfu of required microorganisms to validate it is suitable for growth. TSB (Bacillus subtilis, Candida albicans, Aspergillus brasiliensis) - 3 days , 5 days (20-25); FTM (Clostridium sporogenes, Staphylococcus aureus, Pseudomonas aeruginosa) - not > 3 days (30-35)

What is the NIOSH hierarchy of controls from the most to least effective?

Elimination Substitution Engineering Controls Adminstative Controls PPE

1906 Pure Food and Drugs Act

Enforced USP & NF standards for strength, quality, and purity, first legal recognition of USP standards in the US.

What do chelating agents do and what is most common used?

Enhance effectiveness of antioxidants, by forming complexes with heavy metals eliminating catalytic activity. Edetate disodium.

When considering lipid emulsion stability what properties do they have in regards to growth and what are CDC recommendations?

Excellent medium for growth of gram-positive, gram-negative, and fungal species at room temperature and after refrigeration - CDC recommends preparation container / tubing used to infuse fat emulsion / containing preparations be changed within 24 hours of initiating infusion.

What are exotoxins? Can they be detected by LAL test?

Exotoxins are polypeptides produced by both Gram positive and Gram negative bacteria. They are excreted by living cells and have specific actions such as blocking neural transmission or inhibiting protein synthesis. Limulus Amoebocyte Lysate (LAL) cannot detect.

CFU counts give a specific measure of the environmental bioburden - T/F

F - gives an approximate measure.

Garbing and gloving requirements are not required for CAI & CACI-T/F

F- Requirements are same as other ISO, unless the isolator manufacturer can provide written documentation based on validated environmental testing that any component(s) of PPE or personnel cleansing are not required.

A drug with a name recognized in USP-NF must comply with the current version of USP compendial standards or would be considered? Cite FDCA and FDA regulations.

Failure to comply risks being deemed adulterated, misbranded, or both • FDCA 501(b) and 502(e)(3)(b) • FDA regulations 21 CFR 299.5(a&b) Drugs in USP-NF must also comply with standards for strength, quality, and purity - FDCA 501(b) - 21 CFR 299.5(c)

T/F - Using potency over time study is appropriate method to determine extended stability BUD.

False - need to include additional tests and forced degradation (stress testing).

It is acceptable to withdraw two identical doses into the same syringe - T/F?

False - reduces accuracy.

What are the three macronutrients in PN?

Fat, Protein, Carbohydrate (Dextrose)

Nonaqueous vehicles

Fixed oils. USP specifies must be vegetable (metabolizable), odorless, no rancid odor or taste. Peanut, cottonseed, corn and sesame. (vitamins, hormones). Emulsified oils (soybean, safflower) as liposomes mimic natural chylomicrons. (propofol, amphotericin, EFA-lipids).

What are the sterility test by filtration rinse fluids and why are they used?

Fluids A, D and K. Wet the filter prior to filtering. Rinse the canisters after filtering to remove residue and preservatives.Determined by meth.of suit. No more 5x100ml rinses.

What are the three USP standards structures and ranking?

General Notices (Basic assumptions) < Chapters (Establish procedures, methods and practices) < Monographs (Provide specific formulations and/or quality standards)

USP 800 describes what PPE must be used for sterile and non-sterile compounding?

Gowns, head, hair, shoe covers, and two pairs of chemotherapy gloves.

What are the two phosphate anions and their two calcium salts that could be found in PN? What are their solubility differences and what main factor effects their formation?

H2 PO4 ^- Monobasic phosphate, dihydrogen phosphate HPO4 ^2- Dibasic phosphate, monohydrogen phosphate Ca[H2 PO4 ] 2 Monobasic calciumphosphate, calcium dihydrogen phosphate (solubility 18 mg/ml) CaHPO4 Dibasic calcium phosphate, calcium monohydrogen phosphate (solubility 0.3mg/ml) The greater pH is below 7.2, the more percentage of monobasic phosphate.

What steps should be recommended for SEC down time < 1 hour before resuming compounding?

HVAC fully restored, PECs operational, vacate room and allow sufficient ACPH; re-enter when temperature, humidity, pressure, particles are at normal levels, perform full daily cleaning activity - sporicidal agent & SIPA disinfection, viables at end of the day.

What steps should be recommended for SEC down time > 1 hour before resuming compounding?

HVAC fully restored, PECs operational, vacate room and allow sufficient ACPH; re-enter when temperature, humidity, pressure, particles are at normal levels, perform triple clean all SEC surfaces (ceiling, walls, floor, all surfaces, furniture, equipment)- 1x germicidal detergent, 2x sporicidal agent then SIPA disinfection, PEC clean germicidal or sporicidal agent then SIPA,viables at end of the day.

What other ingredients are added to TPN?

Heparin (thought to prevent thromboembolism, not recommended due to interaction with fat and lack of evidence) H-2 blocker - ranididine, famotidine Insulin Carnitine

What are the most common degradation reactions that result in loss of active drug?

Hydrolysis, Oxidation, Photochemical decomposition.

Ideal body weight (female) formula?

IBW (kg) for females = 45.5 kg + 2.3(inches over 5')

Ideal body weight (male) formula?

IBW (kg) for males = 50 kg + 2.3(inches over 5')

Hazardous anteroom requirements

ISO 7 air quality. positive pressure > 0.02 wc (anteroom may be a non-hazardous buffer room), not < 30 ACPH.

Presterilization procedures for high-risk level CSPs, such as weighing and mixing, shall be completed in what environment? What must be done to minimize risk of contamination?

ISO Class 8 or better environment (e.g., anteroom or buffer room). Procedures must be performed in single-use containment glove bags, containment ventilated enclosures (CVEs), BSCs, or CACIs. If performed ISO-7 must not occur during sterile compounding and PEC at least 1 m apart.

Air Sampling Microbial Action Levels 2022

ISO-5 is > 1, ISO-7 is > 10, ISO-8 or worse is > 100 (CFU /cubic m [1000 liters] air/plate).

What are the ideal minimal final amino acids, dextrose and ILE concentrations needed for TNA stability?

Ideally final amino acid ≥ 4% + dextrose ≥ 10% + ILE ≥ 2%

CSP Label Requirements listed in USP 797 20222

Identification number (e.g., barcode, Rx, order, or lot number) • Active ingredient(s) and amount(s), activity(ies), or concentration(s) • Storage conditions if other than controlled room temperature • BUD • Dosage form • Total amount or volume if it is not obvious from the container • If it is a single-dose, a statement stating such if space permits • If it is a multiple-dose container, a statement stating such • Route(s) of administration • Special handling instructions • Warning statements •Facility name, contact information if sent outside of the facility •The labeling SHOULD indicate preparation is compounded.

USP 797 (2022) provides guidance on the number of units required to be sterility tested for smaller batches, what is the number of units that meet this requirement and how many units need to be tested? If the the number of units are greater what guidelines need to be followed?

If batch is 1-39 units then 10% rounded to the next whole number may be tested. If 40 or more units require sterility testing then refer to tables 2 and 3 in USP 71.

USP 797 2022 Media Fill Incubation temperatures, durations and order of incubation?

Incubate the final containers at 20°-25° and 30°-35° for a minimum of 7 days at each temperature band to detect a broad spectrum of microorganisms. The order of the incubation temperatures must be described in the facility's SOPs.

What is the difference between a physiochemical indicator and a physiochemical integrator?

Indicators show at least one parameter of the cycle is met Integrators show all the parameters of the cycle are met

Core competencies should be completed how often and consist of at least what 11 areas (USP 2022)?

Initially and at least every 12 months in at least the following: • Hand hygiene • Garbing • Cleaning and disinfection • Calculations, measuring, and mixing • Aseptic technique • Achieving and/or maintaining sterility • Use of equipment • Documentation of the compounding process (e.g., MFR, CR) • Principles of HEPA-filtered unidirectional airflow in ISO 5 area • Proper use of PECs • Movement of materials/personnel within compounding area

Use of a rusty pair of scissors in the ISO classified space would be considered?

Insanity conditions by FDA.

The decision is made to remain under section 503(a) for compounding to limit liability and costs for the health system. What primary regulatory body remains a consideration?

Inspection by the state pharmacy regulatory authority

What is the qualification approval testing done by construction vendor for a new cleanroom.

Installation qualification: No equipment or personnel, correct install, Operational qualification: all equipment, no personnel, Performance qualification: equipment and personnel present met USP <797> and CETA.

What standard specifies requirements for classified areas?

International Organization for Standardization (ISO) Standard 14644-4

Through which of the following mechanisms can the FDA influence 503(a) compounding practices even if 503(a) compounders do not register with the agency?

Issuing Guidance for Industry documents on the Federal Food, Drug, & Cosmetic (FD&C) Act, including insanitary conditions

What is the formula for calculating an endotoxin limit in parenterals and what do the variables stand for?

K/M, where K = the Threshold Pyrogenic Dose (TPD) and M is the dose of the drug in units/kg/hr. TPD = levels of endotoxin activity that it takes to induce a fever in a rabbit.

What is Limulus Amoebocyte Lysate (LAL) and what is it used for?

LAL is an extract of blood cells (amoebocytes) from the horseshoe crab, which reacts with bacterial endotoxins (lipopolysaccharides). Used in assays to detect endotoxins.

What may cause undetectable damage to filter integrity and shrinkage of microorganisms to sizes smaller than filter nominal pore size?

Large deviations from usual or expected chemical and physical properties of CSPs (e.g., water-miscible alcohols).

The risk of, or potential for, critical sites to be contaminated with microorganisms and foreign matter increases with what factors?

Larger the area of the critical sites, the density or concentration of contaminants, and exposure duration to worse than ISO Class 5, type of surface-rough, permeable surface (elastomeric) vs smooth (glass).

ISO 5, 7, 8 Particle requirements and sample volumes?

Limits 0.5 µm and larger per m3, ISO 5: 3,520; ISO 7: 352,000; ISO 8: 3,520,000. Minimum of 1 minute sample time and 2 liter volume of air.

Endotoxin limits for CSP?

Limits defined in USP offical monograph, in absence should not exceed USP Endotoxin Units/hr/kg or bsa m^2 defined in USP 85

What are endotoxins?

Lipopolysaccharides that are part of cell wall of Gram negative bacterial. Released under bacterial stress, cell death or proliferation.

Requirements for all components OTHER THAN API selection (4 listed USP 797 2022)?

MUST comply with USP-NF monograph, if one exists MUST have documentation (COA, labeling) that includes the specifications (e.g., compendial requirements for quality) and that test results for the component show that the API meets expected quality. • In US, SHOULD be manufactured by an FDA-registered facility. If not FDA-registered facility, DP MUST select acceptable/reliable source, est. identity, strength, purity, quality by reasonable means (visual, COA, Analytical). Outside US, MUST comply with the laws and regs of jurisdiction.

What is the MW of NaCl, the valence and the number of species?

MW = 58.5 g/L Valence = 1 Species = 2

Two media used specifically for fungi? What is used for bacteria?

Malt extract agar (MEA) and sabouraud dextrose agar (SDA) are frequently used for testing yeast and mold growth, and tryptic soy agar (TSA) is a general purpose culture medium commonly used in testing for bacterial growth

What 2018 RCRA guidance provided clarification for healthcare facilities?

Management Standards for Hazardous Waste Pharmaceuticals and Amendment to the P075 Listing for Nicotine Final Rule - Final rule signed in December 2018 - Clarifies RCRA for healthcare facilities - Prohibits disposal of hazardous waste down the drain - Exempts healthcare facilities from many requirements for large quantity generators of hazardous waste.

Method of choice for sterility testing and alternative method?

Membrane filtration where feasible (compatible with membrane). Alternatively USP Direct inoculation of culture medium.

Considerations for dosing weight in PN for obese and patients under IBW.

Methods for adjusting IBW have been suggested but not validated = [(Actual Wt- IBW) x 0.25] + IBW if > 130% IBW. Use actual body weight if below IBW.

Which of the following was the first document to recommend that pharmacy oversee the compounding of sterile medications?

Mirror to Hospital Pharmacy

What are three common types of filter material and what they are best suited to filter?

Mixed cellulose esters (MCE) - Used for filtering aqueous solutions - Do NOT use to filter proteinaceous solutions (binds proteins) - Do NOT use to filter 98% ethanol Polyethersulfone (PES) - High flow rates - Moderate to low adsorption of proteins - Limited solvent compatibility Polyvinylidene fluoride (PVDF) - Used for filtering aqueous or proteinaceous solution or solvents - May be used with ethanol, formaldehyde and phenol - Higher cost.

What are the most common antioxidants and what determines which is used? What are other antioxidants?

Most common are Na, K salts of metabisulfite and sulfite ions. Choice based on pH of system to be stabilized. Low-metabisulfite, Intermed.- bisulfite, High- sulfite. Acetone metabisulfite, ascorbic acid, cysteine hcl.

How do you determine osmolarity of a final TPN using percentages?

Multiply dextrose by 50, AA by 100, ILE contributes 15 mOsm/L per 1% concentration, electrolytes 1 mOsm per 1 mEq of total electrolytes added.

What quality assurance documentation is required for a sterilizing grade filter?

Must be qualified by the manufacturer to meet ISO 9001 Quality Systems Standards and documented in the filters certificate of performance or certificate of quality. Sterile and pyrogen free.

What should the DP do if components cannot be obtained from an FDA registered facility? USP 2022

Must establish the identity, strength, purity, and quality of the ingredients obtained from that supplier by reasonable means. Reasonable means may include but are not limited to visual inspections, evaluation of a COA supplied by the manufacturer, and/or verification by analytically testing a sample to determine conformance with the COA or other specifications.

How much dead space is in syringes and needles? When and why is it important to account for dead space?

Needles vary from 0.01 to 0.06 ml. Syringe 0.07 to 0.2 ml. Important to account for dead space when measuring small volumes < 1ml, mixing 2 drugs in a single syringe, diluting a drug in a single syringe. May overdose first drug and underdose second.

Ziconotide use, degradation and initial order considerations.

Non-opioid analgesic approved for IT administration Susceptible to degradation more than opioids due to peptide structure - Oxidation when exposed to air - Thermal degradation when exposed to body temperature - Deamidation of the C-terminal cysteine caused by exposure to titanium oxides on new pump surfaces Initial orders for ziconotide - Use only the undiluted 25 mcg/mL formulation for naïve pump priming - Rinse internal surfaces of the pump with 2 mL of ziconotide at 25 mcg/mL - Repeat twice for a total of three rinses.

Who requires material safety data sheets and what is standard information they contain?

OSHA requires employers to provide access to SDS for all chemicals and compounds (29 CFR 1910.1200). They contain properties of each chemical, first-aid, fire-fighting, accidential expsure information, safety precautions for handling, storing and transporting, disposal information.

Personnel who transport, compound or adminster HD's must document training according to?

OSHA standards (see OSHA Standard 1910.120 Hazardous Waste Operations and Emergency Response) and other applicable laws and regulations.

What is the regulation that oversees respiratory protection?

Occupational Safety and Health Administration (OSHA) respiratory protection standard (29 CFR 1910.134).

Apothecary conversions still used grain and dram?

One grain represents ~ 60 mg for most medications (e.g., thyroid, phenobarbital). However, 1 grain of aspirin is 65 mg, so 5 grains is 325 mg and 10 grains is 650 mg. One dram is used to represent 5 mL or 1 teaspoon.

Syringes generally measure accurately to what faction of their calibration marks?

One-half, ie 20ml syringe can measure accurately 18.5ml but not 18.25ml.

What type of insulin can be added to TPN and what dosing guideline should be used based on dextrose?

Only add Regular Human Insulin which is solution. NPH is suspension. 1 unit Insulin for every 10 g of Dextrose if serum glucose > 180mg/dL 1 unit Insulin for every 15 g of Dextrose in underweight patients.

Sterility testing by direct inoculation? When would it be used, 2 examples and imitations.

Only recommended for use when CSP is not able to be filtered (certain suspensions, oil-based samples), limitations for milky or non-clear fluids require subculture. Lack of sensitivity. Test volume <=10ml.

When should sterilization by dry heat be use?

Only those materials that cannot be sterilized by steam, when either the moisture would damage the material or the material is impermeable. Also to render glassware or containers such as vials free from pyrogens. NOTE—Dry heat sterilization may be performed at a lower temperature than may be effective for depyrogenation.

What is the difference between Osmolality and Osmolarity

Osmolality = mOsm/Kg Osmolarity = mOsm/L

When are Point-of-care systems (like addEASE, ADD-Vantage, Mini-Bag Plus) considered out of scope and when are they considered in scope of USP 797 (2022)? What determines BUD dates when they are in scope?

Out of scope when docked and activated for immediate administration according to manufacturer instructions. In scope when docked for future activation and administration - considered compounding and must follow 797 except for BUD dates which default to manufacturer's labeling.

What are the leading causes of emergency department visits for ADEs?

Overall: Anticoagulants, antibiotics, diabetes drugs, and opioid analgesics - Among children and adolescents (<=19 yo): Antibiotics - Among adults 20-64 years old: - Antibiotics - Among older adults (65 +): Anticoagulants &diabetes drugs

Immediately before filling ampuls and vials that will be steam sterilized, solutions are?

Passed through a filter having a nominal pore size not larger than 1.2 µm for removal of particulate matter

What is difference between the three IV complications, phlebitis, infiltration and extravasation?

Phlebitis - chemical irritation of the inside of blood vessels; Infiltration - Leakage of medication into surrounding tissue. Extravasation - infiltration leads to tissue or nerve damage.

What electrolytes shift intracellularly when administering TPN due to the dextrose?

Potassium, phosphorus, magnesium (principle intracellular electrolytes) will shift due to insulin release from dextrose.

What effects can particulates cause in eye CSP and what measures should be taken to reduce risks?

Preparations must be free of particulate matter. - corneal epithelium damage leading to infection /scaring. - particles in/on intraocular tissue may cause inflammation, granulomas, increase intraocular pressure. Filter reconstituted powders - 5 micron filter needle Many institutions filter all eye injections - 0.22 micron.

Opthalmic considerations for CSP used in surgery?

Preparations used during surgery or in a traumatized eye must be preservative-free Preservative-free preparations should be packaged in single dose containers

What is PNSU and SAL definition?

Probability of a non-sterile unit (PNSU) or sometimes referred to as a sterility assurance level (SAL). The probability of a non-sterile item making it through the sterilizaiton process.

Macronutrients and electrolyte standard intake requirements?

Protein (AA) 0.8 - 2 g/kg Total Calories 20 - 30 kcal/kg Volume 30 - 40 mL/kg Sodium 1 - 2 mEq/kg Potassium 1 - 2 mEq/kg Magnesium 8 - 20 mEq Phosphate 20 - 40 mmol* Calcium 10 - 15 mEq* * Based on compatibility limits

What is the biggest microbe concern with sterile ophthalmic preparations, what preservative is effective against it?

Pseudomonas aeruginosa; however, no preservative is 100% effective against all strains of it.

Achieving and maintaining sterility and contamination free CSP'S is dependant on?

Quality of components incorporated, process utilized, personnel performance and environmental conditions.

Room air change per hour formula

RAER (ACH) = (Total Supply Air/CFM) x (60 min/hr.) --------------------------------------- (Room Volume/ cubic feet)

Radiopharmaceuticals are out of scope of USP 797 and needs to meet which requirements?

Radiopharmaceuticals—Preparation, Compounding, Dispensing, and Repackaging <825>

Exceeded viable cfu counts requires ________ and can include following _____causes?

Re-evaluation personnel work practices, cleaning procedures, operational procedures, and air filtration efficiency, causes can include HVAC systems, damaged HEPA filters, and changes in personnel garbing or work practices. Gloved FT exceed count review hand hygiene and garbing and sIPA disinfecting practices. Eliminate cause, clean, resample.

1938 FD&C Act

Recognized USP & NF standards for strength, quality, purity, packaging, and labeling. USP-NF as the "official compendium".

1994 Dietary Supplement Health Education Act (DSHEA)

Recognized USP standards for dietary supplements

1848 Drug Import Act

Recognized USP standards to stop the dumping of drugs by Europeans

2010 Affordable Care Act

Recognizes USP Model Guidelines to assess coverage of Essential Health Benefits

2013 DQSA

Recognizes USP monographs for bulk drug substances and USP chapters on pharmacy compounding

What personal items need to be removed before entering the ISO environment.

Remove personal outer garments (e.g., bandannas, coats, hats, jackets, scarves, sweaters, vests); all cosmetics, all hand, wrist, and other visible jewelry or piercings (e.g., earrings, lip or eyebrow piercings). Artificial nails or extenders.

HEPA filtering efficiency rating?

Removes 99.97% of 0.3 micron particles.

What is FDA guidance on repackaging?

Repackaged drugs are subject to FD&C Act -Treated similar to drugs produced in commercial, 503B setting - Adulteration, misbranding, and approval requirements - cGMP production standards FDA released Repackaging of Certain Human Drug Products by Pharmacies and Outsourcing Facilities - Final guidance published in January 2017 Exempts repackaged products from certain requirements of FD&C Act.

2003 Medicare Modernization Act

Requested USP to develop and revise the Model Guidelines for Medicare Formularies

Hazardous segregated compounding area (C-SEC) requirements

Requires structural, but not ISO air requirements. Temp 20⁰ C/68⁰ F, hum <60%, 12 ACPH, neg press 0.01 - 0.03, externally HEPA vented, sink 1 m from C-PEC. Only cat 1 (Immediate Use)

What are HD gown requirements? When should they be changed?

Resist pearmeability - polyethylene-coated polypropylene. Must close in the back, long sleeved, closed cuffs. Sealed seams. Changed per manufacturer's information, or if not available every 2-3 hours or after spill or splash.

Sterilizing Grade Membrane Requirement

Retain 100% of cultures of 10^7 Brevundimonas (Pseudomonas) diminuta /sq cm of surface under not less 30 psi (1 bar). 0.2-0.22 µm

Surface Sampling Microbial Action Levels 2022

SO-5 is > 3, ISO-7 is > 5, ISO-8 or worse is > 50 (CFU /plate).

What elements should a viable sampling plan contain?

Sample location, method of collection, frequency of sampling, volume of air sampled, and time of day as related to activity in the compounding area and action levels.

What is the preferred method to terminally sterilize aqueous preparations that have been verified to maintain their full chemical and physical stability?

Saturated steam under pressure, or autoclaving; 121° under a pressure of about 1 atmosphere or 15 psi, usually 20 to 60 minutes + time allowance to reach 121.

1997 FDA Modernization Act

Sec. 503A stated that compounding must comply with USP-NF standards and chapter on pharmacy compounding

What is the performance recommended accuracy for an ACD?

Should be accurate within 5% of the amount programmed.

What is the approximate amount of days peripheral PN can be used and why?

Should not be more than 7 days due to risk of thombophlebitis.

What are the two growth media used for sterility testing <71>?

Soybean Casein Digest Medium (SCDM), also known as TSB (Tryptic Soy Broth), which is medium for both aerobic bacteria as wel as fungi. FTM (Fluid Thioglycollate Medium) is primarily for anaerobic bacteria, however will detect aerobic bacteria.

Category 3 BUD date must be supported by what type of stability data? What are the four elements of stability requirements according to USP 797 (2022)

Stability data using a stability-indicating method (SIM), that distinguishes active ingredients from degradants and impurities. Four elements: 1. Exact formulation from which stability data is derived. 2. Same storage & container closure material composition as study. 3. Validated analytical method as described in <1225> 4. Facility must have documentation of study, including methodology, validation of method, SIM and results.

What is a SIM test?

Stability indicating Method - A validated analytical procedure that accurately and precisely measures active ingredients (drug substance or drug product) free from potential interferences like degradation products, process impurities, excipients, or other potential impurities.

What are buffering systems formulated to do?

Stablize an aqueous solution against chemical degradation. Limit use of sod. bicarb. forms gas. Use lowest conc. needed to avoid distrubing body pH. Common acid salts - citrates, acetates, phosphates.

What water should be used for parenteral products and which ones should not.

Sterile water for injection USP, cannot use sterile water for inhalation or irrigation.

Rapid Microbiological Method (RMM) sterility test use.

Sterility test alternative if validated to demonstrate as good or better than compendial. Extremely difficult. USP Chapter 1223 Validation of Alternative Microbiological Methods.

What are the three skin injection types and volume limits?

Subuctaneous, Intradermal, Intramuscular. Adults limited to 3ml.

What types of preservatives must be avoided in injectables for intrathecal administration?

Surfactant-based preservatives.

Symptoms from exposure to pyrogens?

Symptoms of a pyrogenic reaction may include chills, rigors, nausea, vomiting, and hypotension. Possible organ failure and death.

Toxic anterior segment syndrome

TASS- terile inflammatory reaction that can occur after cataract surgery - May lead to permanent corneal edema and glaucoma TASS has been linked to: - Preservatives • Benzalkonium chloride, bisulfite, metabisulfite - Particulates - Additives made to balanced salt solutions • Antibiotics • Epinephrine with preservatives or antioxidants

Viable surface plate handling, sampling and incubation requirements, plate labeling (USP 2022)?

TSA incubated 30° to 35° for no less than 48 h, then 20 - 25 C for no less than 5 additional days (lids secured, inverted). • Alternatively, two samples can be incubated concurrently. Either two TSA or one fungal MEA or SDA. • Label - sample type "surface", location, date. • Raised, convex surface. • Neutralizing additives (lecithin and polysorbate 80). • Must clean and disinfect following surface sample. • Count total number cfu / device. • Record results on form based on sample type, location and date.

What are the incubation requirements for sterility testing <71> media?

TSB is incubated at 20 to 25 C. FTM is incubated at 30 to 35 C. Both types of media are incubated for a total of 14 days.

The Drug Quality and Security Act of 2013 was an attempt by the U.S. Congress to prevent pubic harm from poor compounding practices. What was the impetus for this legislation?

The New England Compounding Center (NECC) fungal meningitis outbreak

What type of filter can reduce endotoxins in solution?

The Pall Posidyne ELD filter which is a 0.2 micron positively charged.

Beyond-Use-Date (BUD) as described in USP 797? How is this time determined?

The date, or hour and the date, after which a CSP must not be used, stored, or transported. BUD is determined by the date and time from which the CSP compounding started.

Required garbing order USP 797 2022

The required garb, manner of storage, and order of garbing must be determined by the facility and documented in the facility's SOPs.

What is quality control?

The sampling, testing, and documentation of results that, taken together, ensure that specifications have been met before release of the CSP.

What are the biosafety levels and risk statifications.

There are 4 BL risk levels. BL - 1 microbes not consistently known to cause disease PPE . BL-2 moderate risk PPE-face sheild +BSC,. BL-3 exotic, severe, respirator, BL-4 most severe, few labs.

What are Biosafety Levels (BSLs)?

There are four biosafety levels. Each level has specific controls for containment of microbes and biological agents. The primary risks that determine levels of containment are infectivity, severity of disease, transmissibility, and the nature of the work conducted. Origin of the microbe, or the agent in question, and the route of exposure are also important.

Opthalmic routes of administration.

Topical - Drops, ointments Periocular Injection - Subconjunctival - Retrobulbar - Subtenons - Peribulbar Intraocular Injection - Intravitreal - Intracameral

Those CSPs that are not immediately distributed are stored in an appropriate location as described in the written procedures - T/F

True

Written procedures for double-checking compounding accuracy shall be followed for every CSP during preparation and immediately prior to release. - T/F

True

What are the different classes of USP glass used for containers and which type should be used by pharmacists?

Type I (borosilicate glass), Type II (soda-lime-treated glass), Type III (soda-lime glass), or NP (soda-lime glass unsuitable for parenteral container. Pharmacists should only use type I.

What is fat (ILE) adult percent of total calories and dose for critically ill vs non critically ill patient? What are EFAD requirements?

Typical adult approximately 15-35% of total calories - With 100% soybean oil ILE < 1 g/kg/day in critically ill patients is recommended. 0.8 - 1.2 g/kg/day is typical for non-critically ill patients - Essential fatty acids required: LA (1-4%) & ALA (0.25-0.5%) - Minimum to prevent EFAD with PN - 54% LA & 7% ALA • 100 g/week of 100% soybean oil as 20% oil-in-water ILE

What are typical aduld carbohydrate intake requirements?

Typical adult carbohydrate intake is approximately 50% of total calories - Minimum: 50 g/day to avoid ketone production Carbohydrate in PN provided as dextrose (most common) or glycerol - 1 g of dextrose monohydrate provides 3.4 kcal Maximum: 7 g/kg/day - 1 g of glycerol provides 4.3 kca

Protein requirements based on conditions?

Typical adult protein approximately 15-20% of total calories - Minimum: 0.8 g/kg/day - Stable: 0.8 - 1 g/kg/day - Critically ill: 1.2 - 2 g/kg/day - Obesity: 2 - 2.5 g IBW/kg/day - Maximum: 2.5 g/kg/day - CRRT - Protein in PN as crystalline AAs - 1 g of N = 6 g of protein (e.g., 15 g Nitrogen = 90 g Protein) - Provides 4 kcal/g

What is the history of USP compounding chapters?

USP <1206> Sterile Drug Products for Home Use -1995 informational. USP Chapter <797> Pharmaceutical Compounding— Sterile Preparations -2004 enforceable, revised: 2008,2019,2022 USP Chapter <795> Pharmaceutical Compounding-Nonsterile Preparations 2014 - revised from USP <1161> USP <800> Hazardous Drugs—Handling in Healthcare Settings-2016; official 12/1/19.

What are the 7 common tests for CSP used for stability indicating studies and what are there applicable USP chapter numbers?

USP <621>: Assay (stability indicating method) USP <71>: Sterility tests USP <85>: Bacterial endotoxin test USP <791>: pH USP <1790>: Visual inspection (appearance) USP <788/789>: Particulate matter Container / closure integrity

Scales are addressed in what USP chapters? Calibration needs to be done when, how and within what % accuracy?

USP Chapters <41> Balances, <1176> Prescription Balances and Volumetric Apparatus Used in Compounding, and <1251> Weighing on an Analytical Balance., Calibration: accuracy within 0.1% of test weight. Installation, when moved, after maintenance, annually with NIST weight, daily before use.

What is the USP standard for assay testing and what is chapter reference? What is the generally accepted criteria range in monographs?

USP Standard: USP <621>: Chromatograph; +/- 10%

Your facility wants to start compounding sterile sodium bicarbonate injection using nonsterile ingredients due to a shortage of the sterile product. A USP monograph for this preparation will be followed. What reference should be used for BUD?

USP monograph beyond-use date (BUD)

Sterility testing <71> by membrane filtration method, when would it be used. Filter size and requirements.

USP preferred method. Filter having nominal pore size not greaterthan 0.45 micron. Compatible with drug and all components sterile.

The failure to wear sterile gloves raises legal concerns because it violates standards for compounding sterile preparations. What references would you cite to your risk management department in support of the need to wear sterile gloves to meet legal requirements while compounding sterile preparations?

United States Pharmacopeia (USP) chapter <797> Pharmaceutical Compounding—Sterile Preparations

Drug Quality and Security Act (DQSA) four significant changes for compounded drugs.

Updates to the Federal Food, Drug and Cosmetic Act (FD&C), eliminated provisions concerning advertising of compounded drugs, 503a conditions CSP exempt from FD&C approval prior to marketing, cGMP, labeling with addequate directions for use., pt specific. Added section 503b, outsourcing facilities.

When using syringes to obtain a precise measurement of small dose, what process should be employed?

Use two syringes of appropriate size rather than read between calibration lines.

Careful consideration and evaluation of nonsterile ingredient sources is especially warranted when the CSP will be administered into the __________?

Vascular system, central nervous system, or eyes.

Intrathecal injections are usually what volumes

Very small, Usual range: 0.5mL to 5mL.

What 12 release quality metrics that shall be performed include?

Visually (white/black), Rx orders, written compounding procedure, preparation records, expended materials used for accuracy, identities, amounts of ingredients, aseptic mixing, sterilization, packaging, labeling, expected appearance, before admin or dispensed.

What are micronutrients used in PN?

Vitamins - A, B, C, D, E, K (2 Vls, short stability after mixed) Trace Elements - copper, selenium, zinc, chromium, manganese. Electrolytes - Na, K, Ca, Phos, Mg, Acetate, Cl

What thickening agents are added to ophthalmic preparations to increase viscosity and why is viscosity important?

Water dispersible polymers, e.g., methylcellulose, carboxy methylcellulose, hydroxypropyl cellulose, and polyvinyl alcohol. Viscosity extends contact between the solution and the eye.

Component requirements for API selection (4 listed USP 797 2022)?

When APIs are used: • MUST comply with USP-NF monograph, if one exists • MUST have a COA that includes the specifications (e.g., compendial requirements for quality) and that test results for the component show that the API meets expected quality. • In US, MUST be manufactured by an FDA-registered facility • Outside United States, MUST comply with laws/regulations jurisdiction.

When is a MFR and CR required for immediate use?

When prepared for more than one patient.

Creatinine clearance formula

[[140 - age(yr)] x weight(kg)] --------------------------------------- (x 0.85 for women) [72 x serum Cr(mg/dL)]

When CSPs contain excessive bacterial endotoxins they are potentially most hazardous to patients when administered what space?

central nervous system

Milliequivalents (mEq) is product of what componets?

mEq = mmol x valence mEq = [(mg of substance)/MW] x valence mg = (mEq x MW)/valence mg/ml = (mEq/ml x MW)/valence

mOsm equations:

mOsm = mmol x number of species mOsm/L = (mEq/L) /valence x number of species mOsm/L = [conc. of substance (gm/L)]/ MW (g/mol) x number of species x 1000

Common drugs that leach into DEHP containers?

nitroglycerine, diazepam, vitamin A, insulin, sufentanil, filgrastim, calcitriol, lorazepam, aldesluekin

Harris Benedict - equation for energy requirements.

oldest for estimating basal energy expenditure (usually × 1.2) • Women = 655 + (9.6×Weight (kg)) + (1.7×Height (cm)) - (4.7×Age (yr)) • Men = 66 + (13.7×Weight (kg)) + (5×Height (cm)) - (6.8×Age (yr))

What is the pH and tonicity of lacrimal fluid? What tonicities can the eye tolerate without minimal irritation. How are ophthalmic solutions adjusted to proper tonicity?

pH 7.4, tonicity similar to aqueous sodium chloride 0.9% solution, Eye tissue can tolerate tonicities of 0.5-1.8%. Freezing-point depression (FPD) (lacrimal fluid lowers the freezing point of water by 0.52 °C). Proportion 0.52C/0.9% = Opth. drug FPD)/X

Preservatives with innate toxicity with concentrations used.

phenylmercuric nitrate 0.01%, benzalkonium chloride 0.01%, and phenol 0.5% - mostly used in Opthalmics and MDV for IM/SQ

Common Roman numerals for 1/2, 1, 5, 10, 50, 100, 1000

ss = 1/2, I or i = 1, V or v = 5, X or x = 10, L or l = 50, C or c = 100, M or m = 1000

CSP should be discarded if known to be exposed to which temerpature conditions, when unable to confirm using direct assay?

temperatures warmer than the warmest labeled limit or to temperatures exceeding 40°for more than 4 hours

Specifications for sterilization by gamma irradiation.

~25 kGy; requires very high radiation to be effective.

BSC CLASS II TYPE B2

• 100% externally exhausted (No recirculated air inside cabinet or return into room). • Contaminated ducts and plenums under negative pressure. • Must be connected to buildings exhaust system. • Provide HEPA filtered down-flow air and HEPA filtered exhausted air. • Excellent for volatile chemicals.

BSC CLASS II TYPE A2

• 70% HEPA filtered air recirculated as vertical, unidirectional airflow in DCA, • 30% HEPA filtered air is exhausted, • Neg. pressure therefore suitable for trace volatile compounding and proper external exhaust canopies. • Most commonly used BSC for most known HDs.

BSC CLASS II TYPE A1

• 70% HEPA filtered air recirculated as vertical, unidirectional airflow in DCA. • 30% HEPA filtered air is exhausted. • Pos. pressure therefore not suitable for volatile compounding.

BSC CLASS II TYPE B1

• 70% externally exhausted and 30% recirculated air within the cabinet. • Contaminated ducts and plenums under negative pressure. • Must be connected to buildings exhaust system. • Provide HEPA filtered down-flow air and HEPA filtered exhausted air.

According to USP 71 how many units are required to be tested for small volume parenterals?

• < 100, test 10% or four units, whichever is greater • 100 up to 500, test 10 units • more than 500, test 2% or 20 units, whichever is less

USP 800 indicates that an entity's health and safety management system must, at a minimum, include:

• A list of HDs • Facility and engineering controls • Competent personnel • Safe work practices • Proper use of appropriate Personal Protective Equipment (PPE)

What are patient-related risk factors for ADEs?

• Age • Gender • Maternity status • Renal function • Allergies • Body weight • Ethnicity

What are social related risk factors for ADEs?

• Alcohol consumption • Smoking status

Viable AIR sampling timing and location requirements include (USP 2022)?

• All classified areas ISO- 5 PEC, ISO -7, 8 rooms (MUST) • Impact volumetric sampler • Dynamic operating conditions. • Category 1 and 2 CSPs - minimum every 6 months. • Category 3 CSPs - within 30 days prior to start, then at least monthly thereafter regardless of the frequency of compounding Category 3 CSPs.

Viable SURFACE sampling timing and location requirements include (USP 2022)?

• All classified areas ISO- 5 PEC, ISO -7, 8 rooms (must) • Pass-through chambers (must) • Equipment in PEC (should) • Staging or work area near PEC (should) • Frequency touched surfaces (should) • DCA in conjunction with media fill testing. • End of a compounding activity or shift, before cleaning • Category 1 and 2 CSPs - minimum Monthly. • Category 3 CSPs - prior to assigning BUD > table 13 and at least Weekly (regardly frequency of Cat. 3 compounding). Additionally, in PEC following batch (unless robotic device, then daily at end of operation); before cleaning and disinfecting.

Minimum cleaning frequency of ISO5 PEC in USP 797 2022?

• Cleaning and Disinfecting - Daily - interior surfaces, equipment when compounding occurs and when surface contamination is known or suspected. • Cleaning and Disinfecting of work surface of tray daily and underneath Monthly. • Sporicidal - Monthly (Cat. 1 &2) - Weekly (Cat. 3) • Sporicidal - Monthly. - work surface of tray and underneath surfaces. • Additionally, sIPA must be applied after disinfectant or sporicial for residue removal. • During compounding sIPA must be applied horizontal work surface, removable work trays, at least every 30 min if the compounding process takes 30 min or less (> 30 min following).

What are treatment options for ADE's?

• Discontinuation of the offending agent • Supportive Care (Corticosteroids, Antihistamines)

In addition to routine required frequencies, viable sampling MUST be performed in which circumstances (USP 2022 6.1)

• In conjunction with the certification of new facilities and equipment • After any servicing of facilities or equipment • In response to identified problems (e.g., positive growth in sterility tests of CSPs) • In response to identified trends (e.g., repeated positive GFTs, failed MF, or repeated observations of air or surface contamination) • In response to changes that could impact the sterile compounding environment (e.g., change in cleaning agents)

CSPs in scope in USP 797 2022?

• Injections, including infusions • Irrigations for internal body cavities (i.e., any space that does not normally communicate with the environment outside of the body, such as the bladder cavity or peritoneal cavity). [NOTE—Irrigations for the mouth, rectal cavity, and sinus cavity are not required to be sterile.] • Ophthalmic dosage forms • Aqueous preparations for pulmonary inhalation. [NOTE—Nasal dosage forms intended for local application are not required to be sterile.] • Baths and soaks for live organs and tissues • Implants

What are preventative strategies to avoid ADE's?

• Medication histories • Documentation • Drug interaction review • Pretreatment for high-risk therapies

What is the required pressure differential for a nonhazardous cleanroom suite and the monitoring requirements?

• Minimum 0.020-inch wc • Between ISO classified spaces and classified and non-classified. • Monitoring device must be used to continuously monitor. • Review/document results DAILY - compound days • No pressure differential is required between the SCA and the surrounding area. • No open architecture allowed for Cat 1 or 2.

Compounding records includes at least what minimal 14 information elements (USP 797 2022)?

• Name, strength or activity, and dosage form of the CSP • Date and time of preparation of the CSP • Assigned internal identification number (Rx, order, lot #) • Identify of individuals compounding and final verification. • Name of each component • Vendor, lot number, exp date for each component for CSPs prepared for more than one patient and for CSPs prepared from nonsterile ingredient(s) • Weight or volume of each component • Strength or activity of each component • Total quantity compounded • Final yield (e.g., quantity, containers, number of units) • Assigned BUD and storage requirements • QC results (visual inspection, filter integrity, pH) • MFR reference for the CSP • Calculations for quantities and/or conc. of all components

Master formulation includes at least what minimal 9 information elements (USP 797 2022)?

• Name, strength or activity, and dosage form of the CSP • Identities and amounts of all ingredients • Type and size of container closure system(s) • Complete instructions for preparing (equip, supplies) • Physical description of the final CSP • BUD and storage requirements • Reference source to support the stability of the CSP • Quality control (QC) procedures (pH testing, filter integrity) • Other information needed to ensure process/repeatability (adjusting pH, tonicity; sterilization method)

What are drug-related risk factors for ADEs?

• Polypharmacy • Drug dosing & frequency

What is a pharmaceutical isolator and comprises its 4 elements? Where can an isolator be placed?

• Provides isolation from the surrounding area, maintains ISO 5 dynamic operating conditions. (Not a CAI or CACI) Isolator four elements: 1. Controlled workspace 2. Transfer device(s) 3. Access device(s) 4. Integral decontamination system Placement: Cat. 1 can be SCA. Cat. 2 or 3 must be ISO 8 or better (anteroom not required). • Requires dynamic smoke study every 6 months.

What are USP 797 2022 SOP requirements?

• SOPs for compounding process and support activities (must) • Include types of categories compounded • DP must ensure SOP implemented, training and competency • DP corrective action for deviations, failures - documented • Staff trained to recognize problems, failures - report to DP • SOPs reviewed initially and at least every 12 months - docum. • Revisions communicated and acknowledgement docum.

Viable air plate handling and incubation requirements, plate labeling (USP 2022)?

• TSA incubated 30° to 35° for no less than 48 h, then 20 - 25 C for no less than 5 additional days (lids secured, inverted). • Alternatively, two samples can be incubated concurrently. Either two TSA or one fungal MEA or SDA. • Label - sample type "viable air", location, date. • Count total number cfu / device (record cubic m air) separately. • Record results on form based on sample type, location and date.

Air sampling device requirements:

• Test at least 1 cubic meter or 1000 L of air from each location sampled • Calibrated and serviced per manufacturer guidelines

Microbiological air and surface monitoring program include what general requirements (USP 797 2022) - MUSTS

• Viable volumetric air sampling and surface sampling • Regular sample data review and trending (documented) • Results reviewed in conjunction with personnel data • Corrective actions taken, documented and validated effectiviness. • Performed initialing to establish baseline • Program described in SOP (diagram, procedures, frequency, size, time of day, action levels) • Personnel trained and competent. (Not listed as MUST) • Sampler service and calibrated.