by Melissa Merrell Rhoads, PharmD, PCCA Director of Formulations

The revised USP Chapter 795 will become official on November 1, 2023. This chapter describes the full guidelines for pharmaceutical compounding of nonsterile preparations (CNSPs). Specifically looking at the revisions related to the beyond-use date (BUD), we will be updating all PCCA formulas for compliance.

USP states the BUDs presented “are based on the ability of the CNSP to maintain chemical and physical stability and to suppress microbial growth.” The dosage forms are described as aqueous and nonaqueous based on water activity (a_w or Aw). An aqueous preparation is one that has an a_w ≥ 0.6 (e.g., emulsions, gels, creams, solutions, sprays or suspensions). Nonaqueous dosage forms have an a_w < 0.6 and are separated into two categories: “nonaqueous oral liquid” and “other nonaqueous dosage forms” (e.g., capsules, tablets, granules, powders, nonaqueous topicals, suppositories, and troches or lozenges).

Below are the revised BUDs and notes that will be added to all nonsterile formulas.

Non-preserved aqueous (PF) – 14 days refrigerated

Note: According to USP guidelines, “in the absence of a USP-NF Compounded Preparation Monograph or CNSP-Specific Stability Information,” the maximum BUD for a CNSP that is a non-preserved aqueous dosage form with a water activity (Aw) of >/= 0.6 is 14 days stored in a refrigerator, unless such storage affects the physical or chemical properties of the CNSP.

For more information, refer to current USP Chapter 795.

Preserved aqueous – 35 days

Note: According to USP guidelines, “in the absence of a USP-NF Compounded Preparation Monograph or CNSP-Specific Stability Information,” the maximum BUD for a CNSP that is a preserved aqueous dosage form with a water activity (Aw) of >/= 0.6 is 35 days.

For more information, refer to current USP Chapter 795.

Nonaqueous (anhydrous) oral liquid – 90 days

Note: According to USP guidelines, “in the absence of a USP-NF Compounded Preparation Monograph or CNSP-Specific Stability Information,” the maximum BUD for a CNSP that is a nonaqueous oral liquid dosage form with a water activity (Aw) of < 0.6 is 90 days.

For more information, refer to current USP Chapter 795.

Nonaqueous (anhydrous) excluding nonaqueous oral liquids – 180 days

Note: According to USP guidelines, “in the absence of a USP-NF Compounded Preparation Monograph or CNSP-Specific Stability Information,” the maximum BUD for a compounded CNSP that is a nonaqueous dosage form (excluding nonaqueous oral liquids) with a water activity (Aw) of < 0.6 is 180 days.

For more information, refer to current USP Chapter 795.

Additional notes are also being added to the formulas to bring awareness to some of the guidelines that the USP Chapter 795 now requires during the compounding process. The notes below are not all encompassing of the chapter requirements, so we recommend that you become familiar with the chapter and that you are in compliance with all requirements.

Component evaluation before use

Note: USP Chapter 795 states guidelines regarding “component evaluation before use.” “Compounding personnel must visually re-inspect all components to detect any container breakage, looseness of the cap or closure, or deviation from the expected appearance or texture of the contents that might have occurred during storage.”

Visual inspection

Note: USP Chapter 795 states guidelines regarding “visual inspection.” After the completion of compounding, the preparation must be visually inspected to determine whether the physical appearance is as expected. The inspection must also include visual inspection of container closure integrity.

Establishing and extending BUD

Note: USP Chapter 795 sets forth parameters to consider when establishing a BUD and states, “BUDs for CNSPs should be established conservatively to ensure that the preparation maintains its required characteristics to minimize the risk of contamination or degradation.” Stability testing may be performed by a FDA-registered laboratory using a stability-indicating assay to extend the BUD.  An antimicrobial effectiveness test (see USP Chapter 51) must also be performed by a FDA-registered laboratory when extending the BUD of an aqueous CNSP.

PCCA Members with clinical services may contact our Clinical Services Team for additional information on PCCA Formulas and other compounding concerns.

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