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BUDs may extend up to 180 days with a stability study (published or unpublished) using a stability-indicating assay for the API(s), CNSP and type(s) of container closure used.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)

• 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:

1. 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)

2. Determining the distribution of any affected CNSP, including other affected lots, and the date and quantity of distribution
3. Identifying patients who received the CNSP
4. Recalling any unused dispensed stock and quarantining any remaining stock
5. 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.