USP 797 Guide - Impact on Compounding and Equipment

Understanding USP 797 article contents

1. Understanding USP 797: Key Updates and Their Impact on Sterile Compounding
2. Leveraging Traceable Products for USP 797 Compliance in Compounding Pharmacies
3. Defining Non-Compounding Activities Under USP 797 Regulations
4. Key Changes in USP 797 Guidelines: What Pharmacies Need to Know
5. USP 797 Training Requirements: Elevating Pharmacy Compounding Practices
6. Glossary of Terms: Understanding USP 797 Abbreviations and Definitions
7. References

USP 797 key updates

1. Understanding USP 797: Key Updates and Their Impact on Sterile Compounding

Revisions to General Chapter 797 were published on November 1st, 2022, and became official on November 1st, 2023. The purpose of this revision is to establish minimum standards for practitioners when compounding sterile products to minimize harm, including death, to human-animal patients. The scope of this chapter is to ensure that Compounded Sterile Preparations (CSP) maintains its integrity up until the time administration begins.

In Nov 2023, USP 797, was updated to include a new regulation for compounding pharmacies to monitor temperature and humidity in their labs. Active as of Nov. 2023 - According to USP 797, relative humidity (RH) must always be below 60%. Non-hazardous (HD) Drug compounding pharmacies must maintain positive air pressure to keep airborne particulates, contaminants, and dirt from entering through doors, crevices, and ceiling tiles from outside the cleanroom. The chapter provides minimum compounding standards. Compounders can implement more frequent sampling if they deem it appropriate for their facility.

Chapter 797 does not address the use of specific disposable supply items other than to ensure supplies in direct contact with CSP must be sterile and dehydrogenated. It is the responsibility of the facility to determine the appropriateness of specific items, including dispensing pins.

Leveraging Traceable Products for USP 797 Compliance in Compounding Pharmacies

Compound pharmacies are now required to measure temperature, humidity, and changes in pressure. We have Traceable products that can be utilized in this regard. For example:

  1. The Traceable® Thermohygrometer with Alarm and Calibration: Thermohygrometers with alarms are perfect for monitoring critical environments during the day, overnight, and weekends. Alarms sound when humidity or temperature conditions rise above or fall below-programmed set points. If this environment is a clean room, this instrument is manufactured to maintain the sterility of the environment. The Personal Hygiene of the manufacturers is very important. This device is Switchable for °F/°C, so it can be adaptable for the USP-NF requirement, which is in degrees centigrade (Celsius). Each product goes through an intense vetting process before it can carry the Traceable name, thus saving you both time and money by not having to calibrate separately.

  2. Traceable Calibrated Barometric/Temperature/Humidity Wi-Fi Data Logger Compatible with TraceableLIVE® Cloud Service: This instrument can remotely monitor the temperature, humidity, CO2 or barometric pressure levels of your laboratory, warehouse, or greenhouse from your personal devices. Continuous data transmission using Wi-Fi provides a simple and reliable way to monitor the environment wirelessly. You can securely monitor parameters 24/7, control your alarms remotely, view your data logging history, run reports in real-time, and give access to other team members. No local software is required to use the cloud-based data interface. Get mobile push notifications, emails, or texts for out-of-range conditions, connectivity interruptions, low-battery conditions, or if your device is due for calibration. Large triple-line LCD displays current and Min/Max readings

  3. Traceable Excursion-Trac™ Calibrated Thermohygrometer with Barometer: Easily monitor the environment using the data logging meters. The memory capacity is 2 years when set to 2-minute intervals and longer when set to larger intervals. Each device has a unique ID allowing multiple units to be used in the same location. Easily transfer data recorded in a CSV format to any computer via a USB flash drive. No software is required. Simply clear memory after downloading data to a USB drive. The alarm tracking features store each alarm event, detailing which high or low alarm state occurred, when the alarm state occurred, and when the condition returned to normal range. The alarm state indicator includes audio alerts, flashing LCD segments, low battery, full memory, and USB data transfer. Humidity (inside) is for measuring range for the meter; humidity (outside) is for the probe.
    Barometer pressure is measured in mbar (mmHg) only. The measuring range is from 500 to 1030 mbar. Altitude compensation is in meters only. The measuring range is -100 to 2500 m in 10m intervals.

Defining Non-Compounding Activities Under USP 797 Regulations

  1. Preparation of a single dose of a conventionally manufactured sterile product in accordance with approved labeling that includes information about the diluent to be used, the resultant strength, storage strength, and container closure system. These preparations are not subject to the BUD limits stated in this chapter.

  2. Withdrawing a dose from a container of a conventionally manufactured sterile product or spiking an IV bag, without any further manipulation, for immediate administration to a patient.

  3. Pharmaceutical manufacturers do not need to comply with 797; instead, pharmaceutical manufacturers must comply with the FDA’s current good manufacturing practices (CGMP) and/or laws and regulations of the applicable regulatory jurisdiction

Key Changes in USP 797 Guidelines: What Pharmacies Need to Know

  1. This regulation changed the compound sterile preparation (CSP) from a three-term format low-risk, medium-risk, and high-risk format to a category 1, category 2, and category 3 format using the conditions in which they are made and the time within which they are used.

  2. The immediate-use CSPs provision states that the preparation must not involve more than 3 different sterile products. Two or more of the same sterile components (products) may be used if there are not more than three different sterile components (products).

  3. Single-dose containers must not be used for more than 1 patient when used for preparing immediate-sue CSPs.

  4. When sending samples to the laboratory for incubation, samples must be sent as soon as possible (e.g., within 24 hours) for the most accurate results. Samples must be protected from damage and extremes in temperature and humidity during transit. Traceable products can certainly help maintain the temperature of the samples.

  5. The chapter requires removing all hand jewelry that could interfere with the effectiveness of garbing or otherwise increase the risk of contamination of the CSP. Wedding rings may potentially compromise the integrity of the glove (e.g., tearing) and prevent adequate hand hygiene.

  6. Conditions such as dandruff, eczema, or psoriasis could cause someone to be at higher risk for contaminating a CSP or the environment so they must be reported to the designated person(s). The designated person(s) is responsible for evaluating the situation and deciding whether the affected person must be excluded from working in compounding areas until the condition is resolved.

  7. Surface sampling was previously required “periodically”, which was interpreted differently by users (e.g., monthly, quarterly, or biannually). Regular surface sampling provides additional data for trending and allows for monitoring of contamination risks.

  8. After sampling, the sampled area must be thoroughly cleaned and disinfected using a cleaning agent followed by a disinfecting agent or by using a one-step disinfectant cleaner. Additionally, in a PEC, 70% sterile IPA must be applied after cleaning and disinfecting.

  9. If the certifier sends samples to the laboratory for incubation and identification, samples must be sent as soon as possible (e.g., within 24 hours) for the most accurate results. Samples must be protected from damage as well as temperature and humidity extremes during transit.

  10. Once a CSP is dispensed, you should handle this as you would any other medication (manufactured or compounded). Temperature storage conditions in healthcare facilities such as hospitals require the approval of other regulators and accreditors to maintain and document the temperatures of medication storage areas. Generally, this requires at least daily monitoring and documentation.

  11. All monitoring equipment must be calibrated or verified for accuracy as the manufacturer recommends or every 12 months if not specified by the manufacturer.” This statement applies to humidity sensors, pressure monitors, and thermostats.

  12. For the purposes of USP-NF compounded preparation monographs, 0.2 µm, and 0.22 µm filters are interchangeable, as they pass the same performance criteria.

  13. The General Chapter requires a master formulation record for CSPs created for more than 1 patient and CSPs prepared from nonsterile ingredients. If the CSP is created for more than 1 patient, such as repackaging several units, a master formulation record is required.

  14. The opened or punctured conventionally manufactured single-dose containers may be stored outside of an ISO Class 5 PEC. However, the chapter does require that the conventionally manufactured single-dose container be entered or punctured inside an ISO Class 5 PEC. These containers may be used up to 12 hours after initial entry or puncture provided that the storage requirements (e.g., controlled room temperature, cold temperature) are maintained. Opened single-dose ampules must not be stored for any period.

  15. For CSPs prepared from one or more compounded components, the Beyond Use Days (BUD) should generally not exceed the shortest BUD of any of the individual compounded components. However, there may be acceptable instances when the BUD of the final CSP exceeds the BUD assigned to compounded components (e.g., pH-altering solutions). If the assigned BUD of the final CSP exceeds the BUD of the compounded components, the physical, chemical, and microbiological quality of the final CSP must not be negatively impacted.

  16. When using a single-dose vial: “If a single-dose vial is entered or punctured only in an ISO Class 5 or cleaner air, it may be used up to 12 h after initial entry or puncture as long as the labeled storage requirements during that 12-h period are maintained.” The vial of daptomycin mentioned in this example may be used for multiple preparations up to 12 hours after initial entry or puncture provided that the storage requirements (e.g., controlled room temperature, cold temperature) are maintained.
    If reconstituted in advance as a single dose for a single patient, then the daptomycin reconstituted solution may be stored per the approved labeling.

USP 797 Training Requirements: Elevating Pharmacy Compounding Practices

  1. Training and competency assessment requirements are determined by the specific tasks performed and the facility’s SOP and must include aseptic processes to minimize the potential for contact with nonsterile surfaces, introduction of particulate matter or biological fluids, and mix-ups with other conventionally manufactured products or CSPs.

  2. No specific training frequency is identified for training and competency of personnel who perform compounding of immediate-use CSPs.

  3. The written training program must describe the required training and the process for evaluating the performance of personnel, but personnel must both demonstrate knowledge of principles and competency of skill for performing sterile manipulations and achieving and maintaining appropriate environmental conditions as applicable to their assigned jobs.

  4. Personnel who only perform restocking or cleaning and disinfecting duties outside of the primary engineering control (PEC) must be initially trained and demonstrate competency in maintaining the quality of the environment in which they perform their assigned task. At a minimum, these personnel must meet the requirements for personal hygiene and garbing that are described in Personal Hygiene and Garbing. Facility SOPs must outline what initial and ongoing training is required.

  5. Any person entering a sterile compounding area, whether preparing a CSP or not, must meet the requirements on Personal Hygiene and Garbing.

  6. Supervising pharmacists who do not compound must undergo training and evaluation on core skills, garbing competency, and aseptic manipulation.

  7. When specific conditions are met, compounding of CSPs for direct and immediate administration is not subject to the requirements for Category 1, Category 2, or Category 3 CSPs. Personnel must be trained and demonstrate competency in aseptic processes related to assigned tasks and the facility’s SOPs. The competency should include appropriate preparation (e.g., hand washing, cleaning the area that will be used) and technique that is evaluated and approved by a qualified individual.

  8. The chapter requires that each compounding facility develop a written training program that describes the required training, the frequency of training, and the process for evaluating performance. This program must equip personnel with the appropriate knowledge and train them in the required skills necessary to perform their assigned tasks. The facility’s SOPs should specify the training required for such tasks and training and evaluation of personnel must be documented.

  9. Chapter 797 is specific about training for compounding but leaves requirements for other personnel up to the organization. Personnel who receive sterile products and preparations,
    enter orders but do not compound or check CSP preparation, clean compounding areas, transport CSPs, or other activities must have documented competence as defined by the organization.

Glossary of Terms: Understanding USP 797 Abbreviations and Definitions

  1. BUD: Beyond Use Days: The BUD is the date, or the hour and date, after which the CSP must not be used. BUDs apply to CSPs and are not intended to limit the time during which a CSP is administered (e.g., infused).

  2. Hang time: “Hang time” is often used to refer to the amount of time during which a CSP or conventionally manufactured product (e.g., pre-mix, large volume parenteral solution) may be infused before either the tubing or the medication must be changed. The General Chapter does not address administration time (e.g., hang time).

  3. CSP: Compound Sterile Preparation: Sterile compounding is used for preparations that will be administered either through an IV injection or directly into the eyes.

  4. Administration: Modes of treatments.

  5. ISO Class 5: ISO-5 cleanroom classification is a common high-level cleanroom class. The International Organization sets the ISO cleanroom standards for Standardization. It is a private international organization that is a member of 167 national standards bodies.

  6. Primary Engineering Control (PEC): Primary engineering control means a clean room or an apparatus for compounding sterile preparations, including a LAFS, a BSC, a CAI, or a CACI, designed to provide an ISO class five environment for compounding sterile preparations. Just before any item is introduced into the PEC, it must be wiped with sterile 70% IPA using sterile low-lint wipers and allowed to dry before use.

  7. Standard Operating Procedures (SOP): A standard operating procedure (SOP) is a step-by-step process to completing a task. It's a kind of documentation that prevents stress, mistakes, and miscommunication. SOPs ensure reliability, efficiency, and consistently hitting quality standards in regular work activities.

  8. Biological safety cabinets (BSCs): A BSC is a ventilated cabinet that is typically used for compounding hazardous sterile and nonsterile preparations but may be used to compound non-hazardous sterile and nonsterile preparations as well. BSCs are divided into three general classes (Class I, II, and III). Class II and Class III BSCs provide an ISO Class 5 environment, so they are suitable for sterile compounding. Class II BSCs are further divided into types (Type A1, Type A2, Type B1, Type B2, and Type C1). Class I BSCs are suitable for nonsterile compounding only. A BSC used for hazardous drugs must exhaust to the outdoors.

  9. ASHRAE: The American Society of Heating, Refrigerating, and Air-Conditioning Engineers (ASHRAE) is a professional organization that provides certification (including healthcare facility design) and professional development for engineers in this field.

  10. CETA: The Controlled Environment Testing Association is a professional organization for controlled environment certification personnel that provides certification (including Registered Certification Professional – Sterile Compounding Facilities), education, and resources for certification personnel.

  11. Cleaning: Cleaning is the process of removing substances (e.g., organic, and inorganic material) from objects and surfaces, normally accomplished manually or mechanically using water with detergents or enzymatic products.

  12. Disinfecting: Disinfecting is the process of destroying fungi, viruses, and bacteria on inanimate surfaces and objects. A sporicidal disinfectant destroys bacterial and fungal spores and is expected to kill all vegetative microorganisms. In the U.S. disinfectants are registered with the EPA in the USA, and depending on the international location, registered with entities with an equivalent jurisdiction in that nation.

  13. CSP: Compounded Sterile Preparations

  14. USP: United States Pharmacopeia

  15. HD: Hazardous Drugs

  16. NF: National Formulary

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References

https://www.usp.org/compounding/general-chapter-797

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General Chapter 797

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