USP Chapters and Special Topics for ...

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USP Chapters <797> and <800>

Special Topics forConsideration for the Pharmacy Professional

Heith A. Crosby, Pharm.D., Ph.D., RCP-SCF

CETA Registered Certification Professional for Sterile Compounding FacilitiesNSF Accredited Biosafety Cabinet Field Certifier

“Under guidelines established by the Accreditation Council for Pharmacy Education, disclosure must be made regarding

financial relationships with commercial interests within the last 12 months”

“I have no relevant financial relationships or affiliations with commercial interests to disclose.”

Financial Disclosure and Resolution

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At the completion of this activity, you will be able to:

1. Identify the updates to the environmental microbiology sampling requirements.

2. Review the personnel competencies required for USP Chapters <797> and <800> compliance.

3. List the updates for beyond use dating (BUDs) for compounded sterile products.

4. Review the minimum requirements for USP Chapter <800> compliance.

Learning Objectives

Pre-Assessment Question 1 - Environmental Sampling

The new USP <797> guidelines for microbiology sampling require that viable air sampling of ISO classed areas must be performed ________.

1. daily2. monthly3. semi-annually4. yearly

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Pre-Assessment Question 2 - Personnel Competencies

The post-aseptic technique gloved fingertip sampling competency must be performed ______.


Pre-Assessment Question 3 - Beyond Use Dating

If outer wrappers are removed, a _____ expiration date must be assigned to the preparation (unless the manufacturer provides evidence that a longer expiration is acceptable).

1. 1-day2. 7-day3. 30-day4. 60-day

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Pre-Assessment Question 4 - USP 800 minimum requirements

Every facility must include any items on the current _____ list of hazardous drugs on the entity list of hazardous drugs.

1. NIOSH2. FDA3. Oklahoma State Board of Pharmacy4. OSHA

Updates to the Environmental Microbiology Sampling Requirements

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What is the purpose of microbiology monitoring?

Purpose of microbiology monitoring

● Determine the quality of the compounding area

● Show environmental quality trends over time

● Identify potential routes of contamination

● Allow for implementation of corrective actions to minimize the risk of CSP contamination

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Goals for the microbiology monitoring program:

● Determine whether contamination is present at unacceptable levels.

● Assess whether proper personnel practices are being followed.

● Cleaning and disinfecting agents are effective.

● Environmental quality is maintained.

Monitoring Requirements

● Collection

● Analysis

● Evaluation

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Sample Collection – When should it be performed?

During dynamic operating conditions to confirm that the required environmental quality in classified areas

is maintained.

Sample Collection - Other Circumstances

● 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 gloved fingertip and thumb sampling results, failed media fill testing, or repeated observations of air or surface contamination).

● In response to changes that could impact the sterile compounding environment (e.g., change to cleaning agents).

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Sample Collection - Training

● The monitoring program must be conducted in a manner that minimizes the chance that the sampling itself will contribute to contamination of the CSP or the environment.

● Personnel must be trained in the proper operation of the air and surface sampling equipment to ensure accurate and reproducible sampling.

● All air sampling devices must be serviced and calibrated as recommended by the manufacturer.

Collection – Type of Samples

● Surface Sampling

● Volumetric Air Sampling (VAS)

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Sample Collection – Timing

● Surface sampling of all classified areas must be conducted at least monthly.

● Surface sampling must be performed at the end of the compounding activities or shift, but before the area has been cleaned and disinfected.

Sample Collection - LocationsSurface sampling for microbial contamination must be performed in all classified areas.

● The interior of the PEC and the equipment contained in it

● Staging or work area(s) near the PEC

● Frequently touched surfaces

● Pass-through chamber(s)

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Sample Collection - Timing and Locations

Volumetric active air sampling using an impaction device must be conducted in each classified area [e.g., ISO Class 5 PEC and ISO

Class 7 and 8 room(s)] during dynamic operating conditions at least every 6 months.

Sample Collection - Quality

When conducting sampling of the PEC, care should be taken to avoid disturbing unidirectional airflow.

A general microbiological growth medium that supports the growth of bacteria and fungi must be used (e.g., TSA medium).

COAs from the manufacturer must verify that the medium meets the expected growth promotion, pH, and sterilization requirements.

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Collection - IncubatorThe microbiological incubator must be placed in a location outside of the sterile compounding area.

Samples must be incubated in a calibrated incubator at temperatures that will promote growth of bacteria and fungi.

The incubator temperature must be monitored during incubation, either manually or by a continuous recording device, and the results must be reviewed and documented.

Sample Analysis - Action LevelsIf levels measured during surface sampling exceed the levels the genus of any microorganism must be identified.

Surface Air

ISO 5 area > 3 CFUs >1 CFUs

ISO 7 area > 5 CFUs >10 CFUs

ISO 8 area > 50 CFUs > 100 CFUs

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Sample Analysis

If levels measured during surface sampling exceed the levels for the ISO classification levels of the area sampled, the cause must be investigated and corrective action must be taken.

Corrective (remediation) action plan

Must be dependent on the CFU count and the microorganism recovered.

The extent of the investigation should be consistent with the deviation and should include an evaluation of trends.

The corrective action plan must be documented.

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Corrective (remediation) action plan

Examples of corrective action:

Process or facility improvements.Personnel training.

Cleaning and disinfecting.HEPA filter replacement and/or repair.

Data Evaluation and Action Levels:

Evaluate cfu counts against the action levels and examine counts in relation to previous data to identify adverse results or trends.

If two devices were collected at a single location, all recovered growth on each is documented and action levels are applied to each device.

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Required Personnel Competencies for USP Chapters <797> and <800>

Compliance

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Competency must be demonstrated in the following:

● Hand hygiene

● Garbing

● Gloved fingertip and thumb

sampling

● Aseptic technique

● Cleaning and disinfection

● Calculations, measuring and

mixing

● Achieving and/or maintaining sterility and

apyrogenicity

● Use of equipment initially● Documentation of the compounding process (e.g.,

master formulation and compounding records) ● Principles of high-efficiency particulate air (HEPA)-

filtered unidirectional airflow within the ISO Class 5 area

● Proper use of primary engineering control (PECs)● Principles of movement of materials and personnel

within the compounding area

USP 800 Personnel Training and Competencies

● Overview of entity’s list of HDs and their risk

● Review of the entity’s SOPs related to handling of HDs

● Proper use of PPE

● Proper use of equipment and devices

● Response to known or suspected HD exposure

● Spill management

● Proper disposal of HDs and trace-contaminated materials

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USP 800 Personnel Training and Competencies

● All personnel who handle HDs must be trained based on their job functions (e.g., in the receipt, storage, compounding, repackaging, dispensing, administrating, and disposing of HDs).

● Training must occur before the employee independently handles HDs.

● The effectiveness of training for HD handling competencies must be demonstrated by each employee.

● Personnel competency must be reassessed at least every 12 months.

● Personnel must be trained prior to the introduction of a new HD or new equipment and prior to a new or significant change in process or SOP.

● All training and competency assessment must be documented.

Updates for Beyond Use Dating (BUDs) for Compounded Sterile Products

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Beyond Use Dates (BUDs) for Compounded Sterile Products (CSPs)

Based primarily on factors that affect the achievement and maintenance of sterility.

● The environment in which the CSP is prepared (e.g., PEC in a cleanroom suite or SCA).

● Aseptic preparation and sterilization method.

● Components and ingredients (e.g., sterile or nonsterile starting ingredients).

● Whether or not sterility testing is performed.

● Storage conditions (e.g., packaging and temperature)

Establishing a BUD for a CSPs

● The BUDs for CSPs are based on the risk of microbial contamination or not achieving sterility despite implementation of the requirements listed in USP chapter <797>.

● It is assumed that the CSP formulation will remain chemically and physically stable, and its packaging will maintain its integrity for the duration of the BUD.

● A shorter BUD is required when the stability of the CSP or its components is less than the hours or days stated.

● The BUD must not exceed the shortest remaining expiration date or BUD of any of the starting components, regardless of the source.

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Establishing a BUD for a CSPs

● BUDs for CSPs must be established in accordance with USP chapter <797> for Category 1 CSPs and Category 2 CSPs

● One day is equivalent to 24 hours.

BUDs for Compounded Sterile Preparations (CSPs) Mixed by Pharmacy

● The shorter stability (established by the manufacturer or listed in a current, authoritative reference) and sterility (USP <797>) shall be used to determine BUD.

● Each CSP label must state the date, or the hour and date, beyond which the preparation must not be used or administration must not begin, and after which time the preparation must be discarded.

● The BUD is determined from the date/time that preparation of the CSP is initiated.

● The BUD is not intended to limit the time during which the CSP is administered (e.g., infused).

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Category 1 CSPs

Storage Conditions

Controlled Room Temperature (20°–25°) Refrigerator (2°–8°)

BUD ≤12 hours ≤24 hours

Preparation

Characteristics

Storage Conditions

Sterilization Method

Sterility Testing

Performedand

Passed

Controlled Room

Temperature (20°–25°)

Refrigerator (2°–8°)

Freezer (−25° to

−10°)

Aseptically prepared CSPs

No Prepared from one or more non-sterile starting component(s):1 day

Prepared from one or more non-sterile starting component(s):4 days

Prepared from one or more non-sterile starting component(s):45 days

Prepared from only sterile startingcomponents:

4 days


9 days


45 daysYes 30 days 45 days 60 days

Terminally sterilizedCSPs

No 14 days 28 days 45 days

Yes 45 days 60 days 90 days

Category 2 CSPs must be prepared in a cleanroom suite

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Beyond Use Dates for Non-Compounded Sterile Preparations.

● Outer plastic wrappers of IV bags must not be removed until immediately prior to use or preparation, if possible.

● If outer wrappers are removed, a 7-day expiration date will be assigned to the preparation (unless the manufacturer provides evidence that a shorter or longer expiration is acceptable).**

● If the outer wrapper is removed prior to use and the IV is not labeled immediately for patient use, the new expiration date shall be affixed to the container.

Beyond Use Dates for Closed Transfer Systems:

● Closed transfer systems that are attached on the floor will have a maximum beyond use date of 24 hours from the time of attaching.

● Closed transfer systems that are attached in a laminar airflow workbench will have the following expiration dates at room temperature:

● Vial-Mate - Viaflex 50 ml containers may be stored for 15 days at controlled room temperature.

● Vial-Mate - Viaflex 100 and 250 ml containers may be stored for 30 days at controlled room temperature

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Minimum requirements for USP Chapter <800> compliance


● Designated Person

● List of HDs

● Facility and Engineering Controls

● Competent Personnel

● Safe Work Practices

● Proper use of appropriate Personal Protect Equipment (PPE)

● Policies for HD waste segregation and disposal

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Designated Person

“Each entity must have a designated person who is qualified and trained to be responsible for developing and implementing appropriate procedures; overseeing entity compliance….”

General Chapter <800> Hazardous Drugs—Handling in Healthcare Settings.

Designated Person

● Create and implement procedures concerning HDs (SOPs).

● Performs a documented annual review of SOPs.

● Ensure worker competency (training).

● Ensures “environmental control” of areas where HDs are found and handled.

● Oversees facility monitoring, managing documentation, acting on results.

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● Entities are required to establish policies and procedures that ensure worker safety during all aspects of HD handling.

● The entity must develop SOPs to ensure effective training regarding proper labeling, transport, storage, and disposal of the HDs and use of Safety Data Sheets (SDS), based on the Globally Harmonized System of Classification and Labeling of Chemicals (GHS).

Elements of the hazard communication program plan must include

A written plan that describes how the standard will be implemented.

All containers of hazardous chemicals must be labeled, tagged, or marked with the identity of the material and appropriate hazard warnings.

Entities must have an SDS for each hazardous chemical they use (29 CFR 1910.1200).

Entities must ensure that the SDSs for each hazardous chemical used are readily accessible to personnel during each work shift and when they are in their work areas.

Personnel who may be exposed to hazardous chemicals when working must be provided information and training before the initial assignment to work with a hazardous chemical, and also whenever the hazard changes.

Personnel of reproductive capability must confirm in writing that they understand the risks of handling HDs.

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List of HDs

● Prepare as a spreadsheet

● Sort into Groups

● Assessments of Risk

● Chart for Handling HDs in Pharmacy

● Chart for Handling - Nursing

Facility and Engineering Controls

● Semi-annual testing

● BSC and/or CACI

● Segregation - Dedicated HD Rooms

● Room Pressure (negative)

● CSTD

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Competent Personnel - Pharmacy

● Core Competencies Training

● Review of the entity's SOPs related to the handling of HDs

● Proper use of PPE

● CSTD

● Proper use of equipment and devices (e.g., engineering controls)

● Response to known or suspected HD exposure

● Spill management

● Proper disposal of HDs and trace-contaminated materials

Competent Personnel - Nursing

• Overview of HDs

• Hazard Communication

• Chart for Handling HDs

• CSTD

• Administering and Disposal of HDs

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Safe Work Practices

Hazard Communication - Labeling of bins and areas where HDs are handled.

Hazard Acknowledgement

CSTD - Training and Assessment

HD drugs labeled

Receiving (training) - HD handling Chart

Storage (training) - HD handling Chart

Spill response (training) - HD handling Chart

CSTD (training)

Policies

Compounding of Hazardous Drugs

• Deactivating, Decontaminating, Cleaning and Disinfecting Compounding Areas and PECs

• Dispensing Final Dosage Forms

• Hazard Communication Program (SDS)

• Receiving Hazardous Drugs

• HD Receipt, Storage and Handling

• Labeling, packaging, transport, and disposal of hazardous drugs (HDs)

• Medical Surveillance

• Spill Control

• Repackaging of non-sterile HDs

• Receiving of Hazardous Drugs

Proper use of appropriate Personal Protect Equipment (PPE)

● Proper use of PPE – Pharmacy

● Proper use of PPE – Nursing

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Policies for HD waste segregation and disposal

● Policies and SOPs

● Designated bins and area(s) for HD waste disposal

● Training

Post-Assessment Question 1 - Environmental Sampling

The new guidelines for microbiology sampling require that viable air sampling of ISO classed areas must be performed ________.


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Post-Assessment Question 2 - Personnel Competencies

Post aseptic technique gloved fingertip sampling must be performed ______.


Post-Assessment Question 3 - Beyond Use Dating

If outer wrappers are removed, a _____ expiration date must be assigned to the preparation (unless the manufacturer provides evidence that a longer expiration is acceptable).

1. 1-day2. 7-day3. 30-day4. 60-day

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Post-Assessment Question 4 - USP 800 minimum requirements

Every facility must include any items on the current _____ list of hazardous drugs on the entity list of hazardous drugs.

1. NIOSH2. FDA3. Oklahoma State Board of Pharmacy4. OSHA

Questions?

USP Chapters <797> and <800> - Special Topics forConsideration for the Pharmacy Professional

Heith A. Crosby, Pharm.D., Ph.D., BCPS, RCP-SCFCETA Registered Certification Professional for Sterile Compounding

FacilitiesNSF Accredited Biosafety Cabinet Field Certifier

[email protected]

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