Inspections and End Product Evaluations

The compounded formulation should be inspected for:

• container integrity or leaks in flexible containers
• cracks or leaking stoppers in glass containers
• particulate material properties such as color, odor, fill volume, consistency, etc.
• unexpected precipitation, crystallization, or other physical property

Preparations in flexible containers should be squeezed to ensure the absence of unintended holes and slits. Glass bottles should be examined for cracks and leaking stoppers.

Visual inspection will show two of the six characteristics of parenteral solutions: (1) particulate material and (2) stability if such stability is physically characterized by precipitation or crystallization. The presence (or absence) of particulate material is best determined when the parenteral is held against an illuminated light/dark background.

Formulation properties should be known before hand and documented on the formulation record. The compounded product should be compared to these standards.

The pharmacist should also verify that the product was accurately prepared with respect to:

• ingredients (check used vials, ampules, diluents)
• quantities (check syringe volumes used)
• containers (check final solution container)
• instrumentation (check calibration and settings on repeat or automated dispensing devices)

During compounding, volumes of additives in syringes should be examined to confirm accurate measurements. The volumes of solutions remaining in vials and ampules should be determined to compare to the theoretical volumes required to make the formulation. A mass balance of materials should be evident. Also additive containers and syringes should be available (not discarded in the trash) until the product checks are completed. These inspections should be performed after each individual preparation is completed. Preparations that are not distributed promptly should be inspected again before leaving the pharmacy, the purpose of which is to check for defects such as precipitation, cloudiness, and leakage that may have developed during storage.

Formulations should be subjected to quality control tests as outlined in the formulation records and compounding records. These are generally the physical tests that can be conducted within the pharmacy and may involve weight variation, specific gravity, pH, filtration membrane integrity, etc.

A quality assessment review could involve the review of many items or steps, so it is important to focus on those items that may have significant impact on the entire compounding operation. Examples are:

1. Evaluate the compounding operation with the GMPs.
2. GMPs require information about "method suitability," which assures that the test being conducted either in-process or at the completion of operations will provide a true outcome. For example, many compounded sterile preparations contain antibiotics and preservatives which could lead to false negative of a sterility test's results.
3. Evaluate the effectiveness of the current microbiological applications in the compounding operation to a compliant microbiological program that is in compliance with USP-NF General Chapter <1116> Microbiological Control and Monitoring of Aseptic Processing Environments.
4. Preservatives such as antioxidants, antimicrobials, and antifungals often are added to the preparations to improve stability or to protect them from microbial contamination so evaluation of the effectiveness of the preservatives is important in those formulations.

Formulations that are not distributed promptly should be inspected again before leaving the pharmacy. The purpose of the pre-distribution inspection is to check for defects such as precipitation, cloudiness, and leakage which may have developed during storage.