lab - USP 795

Question 1

Terminology

Answer 1

API (Active Pharmaceutical Ingredient)

• Added substances (excipients).
• BUD (Beyond Use Date).
• Compounding: the preparation, mixing, assembling, altering, packaging and labeling of a drug, drug delivery device in according with a licensed practitioner’s prescription, medication order, initiative based on the practitioner/patient/pharmacist/compounder relationship in the course of professional practice.
• Manufacturing: The production, propagation, conversion, or processing of a drug or device.

Question 2

Personal Hygiene and Garbing
1. PersonnelPreparation

Answer 2

Before compounding, remove any items are not easily cleanable and might interfere with garbing:
a. Remove personal outer garments (i.e. coats, hats).
b. Remove all hand, wrist, and other exposed jewelry including piercings that could interfere with barbing or hand hygiene (i.e., watches, rings).
c. Remove earbuds and headphones.

Question 3

Personal Hygiene and Garbing
2. Hand Hygiene

Answer 3

Personable must perform procedures necessary for appropriate hand hygiene when enter the compounding area.
a. Wash hands with soap and water for at least 30s
b. Dry hands with disposable towels
c. Don gloves

Question 4

Personal Hygiene and Garbing
3. Garb and Glove Requirements

Answer 4

a. Gloves must be worn for all compounding activities.
b. Other Garb (e.g. show covers, hair covers, facial hair covers, face masks, and gowns) should be wear as needed for the protection of personnel from chemical exposures and for prevention of CNSP contamination.
c. Garb must be replaced immediately if it becomes visibly soiled.
d. Garb should be removed when leaving compounding area and discarded (except for gown).

Question 5

Buildings and Facilities

Answer 5

1. Compounding area
   a. An area must be designated for nonsterile compounding. Other activities mist not be occurring in the compounding area at the same time as compounding.

b. Must be well-lit, and maintained in a clean orderly and sanitary condition.

c. No carpet in the compounding area.

d. Must provide orderly placement of equipment and material to prevent mix-ups among components, containers, labels and in-process material.

Question 6

Buildings and Facilities

Answer 6

2. Storage area
   a. Temperature monitoring at least once daily.
   b. All CNSPs, components, equipment, and containers must be stored off the floor.
3. Water Sources
   a. A source of hot and cold water and an easily accessible sink must be available.
   b. Purified water should be used for rinsing equipment and utensils.

Question 7

Cleaning and Sanitizing

Answer 7

1. Nonsterile compounding working surfaces:
   a. at the beginning and end of each shift on days when compounding occurs
   b. after spills, and when surface contamination (e.g., from splashes) is known or suspected.
   c. Between compounding CNSPs with different components.

Question 8

Equipment

Answer 8

a. Equipment surface that contact components must not be reactive, additive or sorptive.
b. Equipment must be stored in a manner that minimizes the risk of contamination.
c. Equipment and devices used in the compounding must be inspected prior to use.
d. After compounding, equipment must be cleaned to prevent cross-contamination for the next preparation.

Question 9

Components Selection

Answer 9

1. APIs
   a. Must comply with the criteria in the USP-NF monograph if one exists.

b. Must have a COA that includes specifications and test results that the API meets the expected quality.

c. In the US, must be manufactured by an FDA-registered facility.

d. Outside the US, must comply with the laws of the applicable regulatory jurisdiction.

Question 10

Components Selection

Answer 10

2. All other components
   a. Should be accompanied by a COA that verifies it meets the criteria in USP –NF monograph if one exists, and any additional specification.
   b. In the US, should be manufactured by an FDA-registered facility. If not available, the designated person must select a component suitable for the intended use.
   c. Outside the US, comply with law/regulation of applicable regulatory jurisdiction.
3. Water: purified water or better quality.

Question 11

Grade designations for ingredients

Answer 11

USP/NF: the ingredient is certified to meet or exceed the specifications edition of the USP/NF.

• FCC: the ingredient is certified to meet or exceed the specifications listed in the current edition of Food Chemical Codex.
• ACS: the ingredient is certified to meet or exceed the specifications listed in the current edition of Regent Chemical (published by the American Chemical Society).
• AR: analytical regent grade, assigned to chemicals of high purity that are suitable for analytic laboratory work.
• CP: chemically pure, is applied to chemicals that are more refined than technical grade, but only partial analytic information is available.
• Technical: commercial grade for industrial quality.
• Food grade: chemicals that have clearance for use in foods.
• Cosmetic grade: chemical approved for use in cosmetics.

Question 12

Master Formulation Records

Answer 12

Name, strength or activity, and dosage form of the CNSP

• Identities and amounts of all components (including
  particle size, salt form, purity grade, solubility)
• Container closure systems
• Complete instructions for preparing the CNSP including equipment, supplies, and description of compounding steps
• Physical description of the final CNSP
• BUD and storage requirements
• Reference source to support the assigned BUD
• Calculations to determine and verify quantities/concentrations of components and APIs.
• Labeling requirement (i.e., shake well)
• Quality control procedure (i.e., pH testing, visual inspection) and expected results

Question 13

Compounding Record

Answer 13

• Name, strength or activity and dosage form of the CNSP
• Date and time of preparation of CNSP
• Assigned internal ID number (prescription or lot number)
• Individuals involved in the compounding process
• Name, manufacture, lot number, expiration date of each component
• Weight or measurement of each component
• Total quantity of CNSP compounded
• Assigned BUD and storage requirements
• Calculations to determine the quantities of components and strength of APIs
• Physical description of final CNSP
• Results of quality control procedure (pH, visual inspection)
• MFR reference for the CNSP

Question 14

Labeling

Answer 14

1. On each container of prepared CNSP
   – Assigned internal identification number
   – Active ingredients and their strengths
   – Storage conditions
   – BUD
   – Dosage form
   – Total amount or volume
2. On the dispensed CNSP
   – Route of administration
   – Indication that the preparation is compounded
   – Any applicable special handling instruction
   – Any warning statements
   – Compounding facility name and contact information

Question 15

Quality Control

Answer 15

Final check on preparation

• Pharmacist must evaluate
  – finished preparation
  – compounding procedure
• Discrepancies should be noted & evaluated
• Patient Counseling
  – important with all medications
  – correct use, storage, beyond-use date, evidence of instability in compounded medication

Question 16

Final Check

Answer 16

The pharmacist is responsible for checking final prep – weight variation
– proper mixing – odor
– color
– consistency
– pH if appropriate

Pharmacist signs & dates prescription
– documenting/ensuring quality

Question 17

Establish Beyond USE Date (BUD)

Answer 17

• Chemical and physical stability properties of the API and added substances
• Compatibility of the container with the finished preparation (leachable, interaction)
• Degradation of container closure system
• Potential of microbial proliferation in CNSP
• Significant deviation from essential compounding steps and procedures.

Question 18

CNSP Requiring Shorter BUDs

Answer 18

The BUD of the CNSP must not exceed the shortest remaining expiration date of any commercially available starting components

• BUD should not exceed the shortest BUD of any individual compounded components (except pH-altering solution).

Question 19

there’s a whole bunch of charts

Answer 19

look at it from time to time I guess

Question 20

Extending BUDs for CNSPs

Answer 20

• CNSPswithaUSP-NFmonograph: When compounding from a USP-NF compounded preparation monography, BUD should not exceed the BUS specified in the monograph.
• CNSP with stability information: if there is a stability study using a stability-indicating analytic method for the APIs, CNSP formulation, and material of composition of the container closure that will be used, the BUD indicated by the study may be used up to a max of 180 days.
• If BUD is extended, aqueous CNSP must be tested for antimicrobial effectiveness.

Question 21

797
CSP Categories

Answer 21

Category 1 CSPs: compounded under the least controlled environmental condition.

• Category 2 CSPs: require more environmental controls and testing than category 1.
• Category 3 CSPs: undergo sterility testing, supplemented by endotoxin testing when applicable, and have more requirements than category 2 for personnel qualification, use of sterile garb, use of sporicidal disinfectants, frequency of environmental monitoring, and stability determination.

Question 22

where to prepare Category 1 CSPs and Category 2 CSPs

Answer 22

category 1 CSPs
- may be prepared in a PEC located in an unclassified segregated compoudning area
- assigned a BUD of < 12 hours at controlled room temp. or < 24 hours when refrigerated

category 2 CSPs
- must be prepared in a cleanroom suite
- assigned a BUD of > 12 hours at controlled room temp. or > 24 hours if refrigerated

Question 23

more charts………..

Question 24

Sterilization

Answer 24

• Terminal sterilization (steam, dry heat, or irradiation) is the preferred method unless the CSP or container closure system cannot tolerate terminal sterilization.
• Steam sterilization is not an option of moisture, pressure, or temperature used would degrade the CSP.
• Filtration may not be an option for some compounded preparations with suspended drug particles or emulsions.

Question 25

Sterilization

Answer 25

• Sterilizing filters must be sterile, depyrogenated, and have a nominal pore size of 0.22 μm or smaller. Filtration is not a terminal sterilization method.
• When steam sterilization, all items must be directly exposed to steam (e.g. 20 -60 min at 121oC at a pressure of 15 PSI).
• Dry heat sterilization is performed in an oven designed for sterilization at 160 oC or higher.

Question 26

Depyrogenation

Answer 26

• Dry heat depyrogenation must be used to render glassware, metal, and other thermostable containers and components pyrogen-free.
• The depyrogenation process operates at a range of temperatures from 170 oC- 400 oC.
• Items that are not thermostable must be depyrogenated by multiple rinses with sterile, nonpyrogenic water

Question 27

Facilities and Equipment

Answer 27

Primary Engineering Control (PEC)—A device or room that provides an ISO Class 5 environment for the exposure of critical sites when compounding CSPs.

Such devices include, but may not be limited to,
– laminar airflow workbenches (LAFWs),
– biological safety cabinets (BSCs),
– compounding aseptic isolators (CAIs), and
– compounding aseptic containment isolators (CACIs).

Question 28

types of hoods

Answer 28

laminar airflow workbenches (LAFWs)

biological safety cabinets (BSCs)

compounding aseptic isolators (CAIs)

compounding aseptic containment isolators (CACIs)

Question 29

Facilities and Equipment

Answer 29

Direct Compounding Area (DCA)—A critical area within the ISO Class 5 primary engineering control (PEC) where critical sites are exposed to unidirectional HEPA-filtered air, also known as first air.

Question 30

Responsibility of Compounding Personnel

Answer 30

• CSPs are accurately identified, measured, diluted and mixed, and are correctly purified, sterilized, packaged, sealed, labeled, stored, dispensed, and distributed
• Maintaining appropriate cleanliness conditions and providing labeling and supplementary instructions for proper clinical administration of CSPs.

Question 31

Gloves

Answer 31

• Intermittently sterilize gloves with isopropyl alcohol 70%
• Change glove when torn, punctured, or contaminated

Question 32

Environment Control ISO Class

Answer 32

• International Organization of Standardization (ISO) Classification of particulate Matter in Room Air (Air Cleanliness)
  – LAFWs/DCA- ISO Class 5
  – Buffer/Clean Room - ISO Class 7
  – Ante Room – ISO Class 7 or 8
  – Measuring, weighing, mixing, and other manipulation of non-sterile in-process CSP are performed in air quality of at least ISO Class 8

Question 33

USP and ISO Limits in Controlled Environments (Air Quality)

iso class 5

iso class 7

iso class 8

Answer 33

iso class 5
- US customary ft^3: 100
- non-viable m^3: 3,530
- CFU/m^3: <3
- CFU/ft^3: <0.1

iso class 7
- US customary ft^3: 10,000
- non-viable m^3: 353,000
- CFU/m^3: <20
- CFU/ft^3: <0.5

iso class 8
- US customary ft^3: 100,000
- non-viable m^3: 3,530,000
- CFU/m^3: <100
- CFU/ft^3: <2.5

Question 34

Personnel Training

Answer 34

• Personnel who prepare CSPs must be provided with appropriate training from expert personnel, audio-video instructional sources, and professional publication skills of aseptic manipulations before they begin to prepare CSPs
• Training techniques include the following:
  – Handling sterile materials
  – Moving deliberately
  – Keeping the body out of the path of first air
  – Approaching a necessary manipulation to prevent product compromise
  – Maintaining proper gown control
  – Safety

Question 35

Why are people the greatest source of contamination?

Answer 35

• People shed skin
• People create aerosols
• Personal hygiene