USP Releases Major Updates to Chapter <797> Pharmaceutical Compounding of Sterile Preparations. Are You Ready?
On November 1, 2022 the United States Pharmacopeia (USP) published the final revision to General Chapter <797> Pharmaceutical Compounding of Sterile Preparations. Compounding pharmacies must clearly understand how the new standards affect their compounding operations and take proper steps to comply.
The revised chapters clarify misunderstood topics, and include input from more than 1,400 comments from 328 commenters encompassing healthcare practitioners, regulators, academicians, and industry. Most of the changes were made because of the advancing practice of compounded medicine and current scientific evidence, according to USP.
Changes Become Official on Wednesday November 1, 2023
Organizations first need to comprehend how the updated standards apply to their sterile compounding operations, then prepare to update existing SOPs or create new operational processes and conduct training. Home infusion pharmacies, hospitals, and sterile compounders may also need to make certain facility or equipment enhancements to meet the new minimum compliance standards.
“The revisions to <795> and <797> will significantly advance compounding quality, accounting for the realities of pharmacy practice and the needs of patients. Some specific updates to chapter <795> include recommendations and requirements for facilities and equipment, minimum frequencies for cleaning, and more information about the protective garb that personnel wear. Among the changes to chapter <797>, there are updates to labeling requirements and the frequency of surface contamination testing based on the products being compounded,” USP said in an interview with Pharmaceutical Technology.
A robust scientific and risk-based approach to the assignment of beyond-use dates (BUD) for compounded medicines is included the revised <797> chapter. BUD is the date after which a compounded medicine cannot be used, according to USP.
“This approach allows for longer beyond-use dates under certain circumstances, while still aiming to protect patients from the potentially dangerous consequences when ingredients breakdown or harmful microbials emerge over time,” USP went on to say.
The updated chapters include <795> Pharmaceutical Compounding - Non-sterile Preparations and <797> Pharmaceutical Compounding - Sterile Preparations.
USP’s updated chapters are available on their website only to those who subscribe to the USP Compendium. Several proposed revisions from the 2019 draft remain.
USP Has Been Working on the Revision For Years
The USP’s revision work on <797> has taken place over a ten-year span. Upon its debut, USP issued a commentary, FAQs, and a beyond-use date (BUD) summary page with scientific rationale for changes to BUDs to help providers better understand the updated requirements.
The most recent chapters have been out for three rounds of public comments. During the public comment periods, the USP Compounding Expert Committee collaborated to review comments, provide feedback and make amendments where necessary.
The latest proposed revision was released in September 2021. It was followed by public comment, which ended on March 17, 2022. During the April 19, 2022 meeting, the Committee concluded the comment review, therefore advancing it to make it official.
Pushback From Pharmacy Leaders
The Alliance for Pharmacy Compounding, APC, and others have argued against beyond-use date caps and batch size limits for compounded sterile preparations (CSPs) because they feel the restrictions were not based on scientific evidence.
APC’s President Dave Miller said, “We’re disappointed but not surprised at the restrictions in <797>. It was clear throughout the process that USP’s Compounding Expert Committee was pursuing arbitrary restrictions on BUDs and batches. What no one has been able to demonstrate, though, is how patients are made safer by these restrictions.”
Summary of Major Changes
Substantial Changes Include: Beyond-use dating (BUD) for Categories 1, 2, and 3 compounded sterile preparations (CSPs), requirements for cleanroom personnel qualification and evaluation, the need for a person designated to validate the quality of sterile environments, environmental monitoring details, and increased testing and cleaning.
Cleaning and Disinfection: Sterile products must be used in the primary engineering control (PEC) and sporicidal agent use is required.
Beyond-Use Dates (BUDs): Category 1 and Category 2 will remain with some minor concessions within dating. Category 3 is new and was introduced to provide a framework for the longest BUDs allowed under the new USP <797> standards.
Category 3 Compounding Includes: More frequent cleaning, additional environmental monitoring, supplementary competency assessments, sterility testing, and a batch size limited to 250 units. Also, Category 3 sterile preparations may have longer BUDs versus those within Category 1 and Category 2.
This is huge for combining sterile preparations because facility design is key to achieve a state of control and subsequently achieving this through preparation during the compounding process.
There are also several changes with respect to the frequency and type of environmental monitoring, as well as additional information concerning the core competencies for personnel training and competency evaluation.
There are areas within the standards where the facility is left to develop standard operating procedures (SOPs) that would detail specifics for compliance, leaving flexibility for organizations to design processes like garbing or material transfer that will meet their unique needs and workflow.
Changes to <797> Pharmaceutical Compounding – Sterile Preparations
There are a number of changes throughout the chapter, mainly in two areas around facility design.
The two major changes are:
1. Facilities and equipment section
2. Minimum frequencies for cleaning
The USP website states, “The requirements in this chapter must be followed to minimize harm, including death, to human and animal patients that could result from 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.”
Bullet Points of the Revised USP <797> Standards, as Written by the USP:
1. CSP
1.1 Sterility of CSPs
1.2 Demonstrate knowledge and competency of core skills
1.3 Includes repacking, allergenic extracts, hazardous drugs, blood-derived and biological material, sterile radiopharmaceuticals and personnel settings.
1.4 Preparation per approved labeling
1.5 CSP Categories
1.5.1 Category 1, 2 and 3 CSPs are assigned BUDs
Note: Immediate-use CSPs can be prepared outside of emergency situations and can be used within 4 hours of preparation instead of 1 hour. Some FDA-approved drugs and biologics can be prepared without complying with requirements for Category 1, 2 and 3 if conditions are met. Examples include single patient dose with labeling about diluent, final strength and storage time. BUDs should be assigned conservatively by Category.
2. Personnel training and evaluation
2.1 Demonstrate knowledge and competency of core skills
2.2 Competency in garbing and hand hygiene
2.3 Competency testing in aseptic manipulation
Note: Categories 1 and 2 must undergo garbing, hand hygiene and aseptic manipulation competency testing initially and at least every 6 months. Incubation from gloved fingertip testing (GFT) will be a 2-stage process.
3. Personal hygiene and garbing
3.1 Personnel preparation
3.2 Hand hygiene
3.3 Garbing requirements
Note: Jewelry that cannot be removed will be allowed in the cleanroom but must be covered and cannot interfere with compounding. New changes disallow brushes, hand dryers, and refilling of disposable soap containers. Facilities can define the garbing order based on their sink locations.
4. Facilities and engineering controls
4.1 Protection from airborne contaminants
4.1.1 Design requirements to maintain air quality. Includes anterooms, buffer rooms, and PECs.
4.2 Facility design and environmental controls
4.3 Creating areas to achieve easily cleanable conditions
4.4 Water sources
4.5 Placement and movement of materials
Note: Facilities must spell out the procedures for collection, define frequency of sampling, collection and action levels.
5. Certification and recertification (e.g., airflow, HEPA filter integrity, total particle count, dynamic airflow smoke test)
5.1 Total airborne particle sampling
Note: No tacky mats are permitted in ISO-classified areas. Facilities must have a defined buffer room and anteroom, pass-through doors can’t be opened at the same time and must be interlocking, access doors should be hands free. Must monitor temperature and humidity every day.
6. Microbiological air and surface monitoring
6.1 General monitoring requirements
6.2 Monitoring air quality for viable airborne particles
6.3 Monitoring surfaces for viable particles
7. Cleaning, disinfecting and applying sporicidal disinfectants in compounding areas
7.1 Cleaning, disinfecting, and applying sporicidal disinfectants
7.2 Cleaning supplies
7.3 Cleaning, disinfecting and applying sporicidal disinfectants in compounding areas
Note: Spraying is no longer adequate and materials and equipment must be wiped with one of the chapter solutions after dwell time has been met. The revision outlines agents that can be used.
USP <797> requires that facilities have a written quality program in place that is reviewed every 12 months by a designated person and includes SOPs.
The chapter online document includes an A to Z glossary to help explain terminology.
Changes in the Pharmacy May Not Be Easy, But are Necessary to Stay Compliant
Recently in a poll of 227 users of Wolters Kluwer’s Simplifi 797 solution had considerable concerns with the finalized USP updates. Thirty-four percent of participants placed the difficulty of making changes between 8 and 10.
For USP <797> Category 2 facilities (including many hospitals), the impact may be a tall order. Many facilities previously considered medium risk will now need to implement cleanroom standards because environmental monitoring is key to ensuring specific conditions are met.
503A pharmacies and hospitals should be aware of USP <797>’s requirement to record temperature in any CSP storage area, and those devices must be verified for accuracy annually. Anterooms and storage areas should use continuous environmental monitoring to keep conditions within acceptable ranges and prohibit microbial growth.
Cross-contamination in cleanrooms are prevented in part by appropriate HVAC engineering and proper airflow dynamics, therefore tracking differential pressures of these areas is critical. Per USP <797>, quantitative results from pressure monitoring must be reviewed and documented each day compounding occurs.
Continuous environmental monitoring systems can provide an uninterrupted assessment into environmental restrictions, thereby supporting compounding areas to operate within optimal temperature and relative humidity limits, which reduces the proliferation of airborne microbiological particles. Thermal mapping may help find areas where excursions like hot spots or humidity issues may occur, and prevent expensive loss or non-compliance in the future.
The USP Compounding Expert Committee
The USP was formed in 1820 when a “small group of physicians came together to protect patients by forming the U.S. Pharmacopeia (USP), an independent, scientific, non-profit organization dedicated to improving public health. USP published the first edition of a national, uniform set of guidelines for the best understood medicinal substances and preparations of the day.”
The current compounding expert committee consists of 15 members from various disciplines, that include health care practitioners with knowledge in sterile and non-sterile compounding, veterinary compounding, aseptic technique, microbiology, environmental engineering, and analytical testing.
The committee also includes six government liaisons who are non-voting members. There are currently four representatives from the FDA, and two from the CDC.
USP has been a global leader in medicines, supplements and foods for setting standards to ensure quality and safety, and to help reduce the risk of sterile compounded medication contamination, infection, or incorrect dosing, and deals specifically with compounded sterile preparations including injections, infusions, implants, and pulmonary inhalation preparations.
Training and Resources
USP’s Third Annual Compounding Implementation Workshop includes <797> changes. Click here.
USP will host a virtual and in-person compounding workshop for implementation on February 7 to 8, 2023. In-person attendees will attend training at the USP headquarters in Rockville, MD.
E-learning training, click here.
You can contact Selma Mitiche, Scientific Liaison and part of the Expert Committee CMP 2020 Compounding at Selma.Mitiche@usp.org for questions on USP <797> Sterile Preparation Changes.
Stay informed on USP Compounding Standards and associated initiatives and educational materials by signing up for USP Healthcare Quality and Safety updates.
Reach out to USP at CompoundingSL@USP.org to reach their Healthcare Quality and Safety team.
Reminder: The changes become official one year from the final revision publication. Log into the USP website to obtain the official copy of the revised and final chapter <797>, which has more detailed information. This article is an overview of major changes and does not cover all changes and updates.
Compliance Target Date: November 1, 2023
Where Does Your Facility Stand?
If you’re looking to become compliant with the new USP requirements or if you wonder how you measure up, let consultants at Restore Health Consulting LLC perform a USP 797 gap analysis to assess your pharmacy or hospital compliance status against the new minimum standards and lead remediation planning if needed.
References:
20 Best Practices to Apply When Upgrading Your Pharmacy to USP 797 and 800 Standards
Chapter <797> includes BUD, batch size restrictions
Infusion Magazine Volume 28 Number 6 Technology in Health Care
Updates to USP General Chapters <795> and <797>
USP <795> and <797> FACT Sheet
USP <795> and <797> Revisions: What Compounders Should Know
USP Expert Discusses Revisions to Compounding Chapters <795>, <797>
USP Revises Drug Compounding Chapters
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