THE PCCA BLOG

USP 797: Revisions & Impacts, Part 2

Wed, 08 Mar 2023 12:00:00 GMT

by Matt Martin, PharmD, BCSCP, PCCA Director of Clinical Services

If you missed Part 1 of USP 797: Revisions & Impacts, it can be found here.

ENVIRONMENTAL MONITORING

Personnel compounding Category 3 sterile preparations are required to perform media fills with glove fingertip sampling and surface sampling of the direct compounding area at least every three months, compared to at least every six months for those compounding Category 1 or 2 sterile preparations.

Pharmacies compounding Category 3 sterile preparations also require more frequent monitoring. Thirty days prior to starting to compound any Category 3 batches, viable air sampling must be conducted. Viable air sampling using an impaction device must be completed for each classified area monthly for facilities preparing Category 3 sterile preparations, compared to every six months for facilities preparing Category 1 or 2 preparations.

Surface sampling is required weekly for Category 3 sterile preparations and must be performed in the ISO 5 with each batch of a Category 3 CSP unless using a self-enclosed robotic device. By contrast, for Category 1 or Category 2 preparations, surface sampling is required monthly. Surface sampling must be done in all classified areas and pass-throughs. The sampling must include:

Each classified area, including each room
The interior of each ISO Class 5 primary engineering control (PEC)
Pass-through chambers connecting to classified areas
Equipment contained within the PEC
Staging or work area(s) near the PEC
Frequently touched surfaces

Pharmacies must also conduct viable air sampling and surface sampling:

When new facilities and equipment are certified
After servicing any facility or equipment (see Section 4, Facilities and Engineering Controls)
After identifying any problem (e.g., microbial growth in preparation sterility tests)
After identifying any problematic trends (e.g., failed fingertip/thumb sampling results, failed media-fill testing, or repeated air or surface contamination)
Any changes are made to the facility or processes that could impact the compounding environment (e.g., change in cleaning agents)

Pharmacies must also conduct total airborne particle-count testing in all classified areas during dynamic operating conditions at least every six months for all categories of sterile preparations.

CLEANING AND SANITIZING

Cleaning and sanitizing procedures also changed in Chapter 797 revisions. Pharmacies must clean surfaces prior to disinfecting them unless they use EPA-registered (or equivalent outside the U.S.) one-step disinfectant cleaners that simultaneously clean and disinfect with an appropriate contact time specified by the product.

In a PEC, after cleaning and disinfecting, pharmacies must apply sterile 70% isopropyl alcohol (IPA) to remove any residues of the product(s). Sterile 70% IPA must also be applied immediately before initiating compounding.

Another significant difference exists in the frequency of sporicidal application between Categories 1 and 2 and Category 3 preparations. When pharmacies create Category 3 preparations, they must apply a sporicidal agent to the PEC, including the removable work tray (if applicable), the equipment and work surfaces outside the PEC (pass-throughs and floors) at least weekly. Compounding Categories 1 and 2 preparations require monthly application of a sporicidal agent to all areas.

Along with these changes, the process for cleaning and disinfecting the PEC received more detailed directions. Compounders must:

If necessary, remove visible particles, debris or residue with an appropriate solution (e.g., Sterile Water for Injection or Sterile Water for Irrigation) using sterile, low-lint wipers.
Use a sterile low-lint wiper, apply a sterile cleaning agent followed by a sterile EPA-registered disinfectant, or apply a sterile EPA-registered (or equivalent for entities outside the U.S.) one-step disinfectant cleaner to equipment and all PEC interior surfaces.
Ensure the contact time specified by the manufacturer is achieved.
Use a sterile low-lint wiper, apply sterile 70% IPA to equipment and all PEC interior surfaces.
Allow the surface to dry completely before beginning compounding.

WHAT COMES NEXT

USP 795 and 797 are official and possibly enforceable in your state on November 1, 2023. Revisions to USP 795 and 797 also make USP Chapter 800, Hazardous Drugs — Handling in Healthcare Settings, “compendially applicable” (USP term) and possibly enforceable in many states on November 1, 2023. For more information on Chapter 800, visit pccarx/USP Update/800.

PCCA offers resources to help pharmacies navigate the changing compounding standards and regulatory environment, including our blog on FDA Insanitary Conditions and limited USP training courses at eLearning Compounding Training.

PCCA offers additional resources to our members, including all courses offered in our eLearning Compounding Training, multiple online webinars and training sessions and, for members with Clinical Services, Speakers Bureau to guide, assist and educate compounding pharmacy staff. Members with Clinical Services may also contact our Clinical Services team for help with formulas and other compounding concerns.

The complete version of this article originally appeared in PCCA’s members-only magazine, the Apothagram.

USP 795: Revisions & Impacts, Part 1

Mon, 06 Feb 2023 14:33:14 GMT

by Matt Martin, PharmD, BCSCP, PCCA Director of Clinical Services

On November 1, 2022, the United States Pharmacopeia (USP) published revisions to General Chapter 795, Pharmaceutical Compounding — Nonsterile Preparations (CNSPs), which becomes official and possibly enforceable in your state on November 1, 2023. The date also triggers potential enforcement of USP 800, which addresses CNSPs using hazardous drugs.

For access to USP 795 revisions, USP offers two purchase options: the USP Compounding Compendium or the full USP-NF. Purchase of the USP Compounding Compendium grants access to more than 40 USP General Chapters, including 795, 797 and 800. Although purchase of the full USP-NF costs more, access includes USP chemical and product monographs, which are useful in determining how to use data from certificates of analysis.

USP 795 Revisions

USP offers a number of tools, including:

USP 795 FAQs
USP 795 Commentary
USP 795 Open Forum Presentation presented and recorded on November 8, 2022
USP 795 Open Forum Slides presented on November 8, 2022
Adding Flavor to Conventionally Manufactured Nonsterile Products

Training

Revisions to USP 795 emphasize certain subtopics: specifically, a significant expansion and emphasis on training, including knowledge in and demonstration of core competencies. A trainee must show their ability to read and understand concepts and demonstrate their knowledge and ability to perform tasks, with documentation of all trainings and demonstrations.

Core competencies include:

Hand hygiene
Garbing
Cleaning and sanitizing
Handling and transporting components and CNSPs
Measuring and mixing
Proper use of equipment and devices selected to compound CNSPs
Documentation of the compounding process (described in Section 7 of the chapter, Master Formulation and Compounding Records)

In addition, training must include:

Ability to understand USP 795 requirements
Ability to understand and interpret safety data sheets (SDSs) and, if applicable, certificates of analysis (COAs)
Read and understand procedures related to their compounding duties

Hand hygiene, garbing, cleaning and sanitizing are cited as significant core competencies for nonsterile compounding. While some may consider the purpose of garbing and personal protective equipment (PPE) is to protect compounders, the garbing process and PPE are significant tools that reduce skin cells shed and the microbes they can carry from potentially contaminating the compounded medication. In other words, properly donned PPE protects the compounder from chemicals and protects the compounded medication from potential contamination.

Cleaning and Sanitizing

Table 1 in the USP 795 revisions define minimum schedules for cleaning and sanitizing nonsterile compounding area surfaces. USP has multiple chapters on microbial limits for nonsterile preparations, including USP 61 and USP 62. These chapters contain total microbial contamination limits and specific objectionable microorganisms prohibited in nonsterile compounds. The FDA also focuses on the quality of the compounding environment for CNSPs in their guidance, Insanitary Conditions at Compounding Facilities.

Beyond-Use Dates

Beyond-use dates (BUDs) are always of significant interest to compounders because they affect patient care opportunities. When considering BUDs, it is common to look at the chemical and physical properties of an active pharmaceutical ingredient (API). The revisions to USP 795 also focus on the container closure system used for final formulations, including how the container closure may interact with CNSP API(s). Visually inspecting the integrity of the container closure after packaging and prior to release, as well as considering the possible container closure degradation over time, are all valuable. The integrity of the container closure is important because an improperly sealed, cracked or degraded container closure can potentially lead to microbial contamination or a loss of potency.

Part 2 of USP 795: Revisions & Impacts can be found here.

The complete version of this article originally appeared in PCCA’s members-only magazine, the Apothagram.