THE PCCA BLOG

USP 795: Revisions & Impacts, Part 2

Wed, 15 Feb 2023 13:30:23 GMT

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

If you missed Part 1 of our USP 795: Revisions & Impacts, it can be found here.

Beyond Use Dates

The concept of water activity receives significant discussion in the revisions to 795. Water activity is a measure of the water that is unbound and freely available to participate in chemical, biochemical or physicochemical reactions, or provides an environment that supports microbial growth. Compounded preparations with a water activity less than 0.6 are considered anhydrous with extended BUDs because they are less likely to allow degradation of API or microbial growth. Discussions on water activity were expanded in 795 revisions and examples of the water activity of various dosage forms were added to the chapter (USP 1112 also discusses water activity).

The maximum potential BUDs that can be assigned to compounded nonsterile preparations without additional stability testing has changed. Nonaqueous topicals, suppositories and troches are now preparations that allow up to 180-day expanded BUDs. Nonaqueous oral preparations can be assigned up to a 90-day BUD. Aqueous dosage forms are separated based on whether or not they have a preservative: non-preserved aqueous dosage forms may be given up to a 14-day BUD when stored at refrigerated temperature; preserved aqueous dosage forms may be given up to a 35-day BUD at room temperature or under refrigeration.

BUDs may extend up to 180 days with a stability study (published or unpublished) using a stability-indicating assay for the API(s), CNSP and type(s) of container closure used. If the BUD of an aqueous preparation is extended, the formulation must also be tested for the performance of the preservative, known as antimicrobial effectiveness testing, according to USP Chapter 51. Revisions to Chapter 795 also permit use of bracketing for stability studies and antimicrobial effectiveness testing. Bracketing is performing tests on a low concentration and a high concentration of API(s). If the formulation passes the tests at both concentrations, the data can be applied to all strengths that fall between the two that were tested.

PCCA has developed over 200 FormulaPlus^™ formulas tested with stability-indicating assays and USP 51 antimicrobial effectiveness (when applicable) for extended BUDs. Some of these are bracketed formulations to help PCCA members address the variety of strengths prescribed by practitioners. FormulaPlus^™ formulas meet all requirements in USP 795 revisions.

THE DESIGNATED PERSON(S)

Responsibility for the performance of the compounding operation created a new role, called the “designated person(s) (DP),” which holds one or more people responsible and accountable for the performance and operation of the facility and personnel preparing CNSPs. The DP(s) is tasked with over 20 areas of responsibility. Note a pharmacy can have one or several persons as the designated person(s), hence the “(s).” These responsibilities can therefore be divided among team members who are appropriate for each responsibility. A few DP(s) key responsibilities are training, documentation and quality control/assurance. While training was discussed above, it is imperative to highlight documentation, including:

Personnel training, competency assessments and qualification records, with corrective actions for any failures
Equipment records (e.g., calibration, verification and maintenance reports)
Certificates of analysis and all documentation required for components not conventionally manufactured
Receipt of components
Standard operating procedures, master formulation records and compounding records
Release-inspection and testing records
Information related to complaints and adverse events, including corrective actions taken
Results of investigations and corrective actions
Records of cleaning and sanitizing the designated compounding area
Temperature logs
Accommodations to personnel compounding CNSPs
Any required routine review (e.g., yearly review of quality assurance and quality control programs, yearly review of chemical hazard and disposal information)

USP 795 references USP 1163 on quality assurance, which can be a helpful resource in developing the required formal written quality assurance and quality control program. This program should establish a system of:

Adherence to procedures
Prevention and detection of errors and other quality problems
Evaluation of complaints and adverse events
Appropriate investigations and corrective actions, such as:

Determining when recalls must be initiated, including procedures to immediately notify the prescriber of a failure of specifications with the potential to cause patient harm (e.g., strength, purity or other quality attributes)
Determining the distribution of any affected CNSP, including other affected lots, and the date and quantity of distribution
Identifying patients who received the CNSP
Recalling any unused dispensed stock and quarantining any remaining stock
Disposing of the recalled CNSP and documentation

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.

Look for USP 797: Revisions & Impacts, Part 1 Blog, on March 1.

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.

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.

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.