Sterility and Beyond Use Dating

free from viable microorganisms

sterility

Factors that impact sterility

1. compounding personnel

2. Environment

3. Use of multiple-dose vials

4. Open systems

5. Aseptic processing and sterilization methods

6. Starting components

7. Sterility testing

__________ who compound exert the greatest influence on sterility

Personnel

____________ contamination is the #1 source of contamination

Touch

The ___________ of the environment in which a CSP is prepared can affect sterility

air quality

MDV are entered multiple times and stored between uses which represents an __________________________

increased risk of contamination

Open systems like ___________ are more prone to contamination due to contact with air

ampules

Mode of processing sterile pharmaceutical medical products into separate sterilized packaging. Must occur in ISO Class 5 conditions

Aseptic Processing

Compound with sterile and/or non-sterile starting ingredients → sterilization to achieve probability of < one in one million nonsterile unit (dry heat, steam, irradiation)

Terminal Sterilization

Using one or more ______________ starting components to compound CSPs introduces risk of contamination to the preparation

nonsterile

By _____________ a CSP, compounding personnel provide added assurance that there is no product contamination

sterility testing

If a unit passes a sterility test, this in and of itself does not guarantee the ____________________

sterility of the entire batch

Keeping CSPs in _______________, such as in a refrigerator or freezer, assists with the slowing of microbial growth, but Not all CSPs can be stored under these conditions

cold storage conditions

Designated person is responsible for assigning ___________ because professional judgement required

BUD

The time after which the product should not be used (regardless of whether the product was opened or unopened) because the strength, quality, and purity of the shelf‐life can no longer be guaranteed. Based on extensive testing done during FDA approval

Expiration date

expiration date is determined by

manufacturer

The date or time after which a CSP may not be stored or transported. Based on available data from direct testing, literature or other sources

BUD

BUD is determined by

compounder

characteristics showing evidence of stability

1. Nature of the drug

2. Container in which it is packaged

3. Expected storage conditions

4. Expected length of the course of therapy

when establishing stability

1. direct testing

2. Primary literature

3. Manufacturer recommendations

USP <797> provides guidance based on ___________

risk level

Risk levels depends on

1. Product ingredients

2. Type of aseptic manipulations performed

3. Compounding environment

BUD limits based on:

1. Risk of microbial contamination

2. Not achieving and maintaining sterility despite implementation of the requirements in the chapter

CSP formulation must remain ___________________

chemically and physically stable

_______________ must maintain its integrity for duration of BUD

Packaging

Preparations compounded in a segregated compounding area or cleaning suite

Category 1 CSPs

BUD for Category 1 CSPs at room temp

≤ 12 h

BUD for Category 1 CSPs in refrigerator

≤ 24 h

Preparations must be compounded in a clean room suite

Category 2 CSPs

Category 2 CSPs: Aseptically processed CSPs with no sterility testing and one or more nonsterile starting component(s) are prepared at room temp

1 day

Category 2 CSPs: Aseptically processed CSPs with no sterility testing and only sterile starting components prepared at room temp

4 days

Category 2 CSPs: Aseptically processed CSPs with sterility testing and at room temp

30 days

Category 2 CSPs: Aseptically processed CSPs with no sterility testing and one or more nonsterile starting component(s) are prepared in the refrigerator

4 days

Category 2 CSPs: Aseptically processed CSPs with no sterility testing and sterile starting component(s) are prepared in the refrigerator

10 days

Category 2 CSPs: Aseptically processed CSPs with sterility testing and prepared in the refrigerator

45 days

Category 2 CSPs: Aseptically processed CSPs with no sterility testing and one or more nonsterile starting component(s) are prepared in the freezer

45 days

Category 2 CSPs: Aseptically processed CSPs with sterility testing and are prepared in the freezer

60 days

Category 2 CSPs: Terminally Sterilized CSPs with no Sterility Testing and at room temp

14 days

Category 2 CSPs: Terminally Sterilized CSPs with sterility testing and at room temp

45 days

Category 2 CSPs: Terminally Sterilized CSPs with no sterility testing and refrigerated

28 days

Category 2 CSPs: Terminally Sterilized CSPs with

sterility testing and refrigerated

60 days

Category 2 CSPs: Terminally Sterilized CSPs with

no sterility testing and in freezer

45 days

Category 2 CSPs: Terminally Sterilized CSPs with

sterility testing and in freezer

90 days