The practice of assigning beyond-use dates for compounded sterile preparations (CSPs) is complicated and often misunderstood. A CSP's beyond-use date identifies the time by which the preparation – once mixed – must be used before it is at risk for chemical degradation, contamination, and packaging permeability.
Pyrogens are a group of fever causing substances. The most widely known pyrogen is bacterial endotoxins.
According to research data from Pew Charitable Trusts, over 50 compounding errors with 1,227 adverse events and 99 deaths have been reported from 2001-2017. Contamination of sterile products was the most common compounding error.
Testing the finished drug product is important to ensure drugs delivered to patients are free of contamination.
USP <797> Pharmaceutical Compounding – Sterile Preparations states that certain compounded sterile preparations (CSPs) must undergo sterility testing prior to being dispensed. This requirement is based on multiple factors, including batch size, risk level, and storage conditions.
A validated sterility test can detect microbial contamination in a drug product.
A media fill test is required by United States Pharmacopeia (USP) and state boards of pharmacy to prove that the aseptic technique process can produce a sterile product without contamination. According to USP <797>, any person engaged in sterile compounding must conduct a media fill test...
Particulate matter contamination in injectable drug products, especially in large numbers, can cause harm to patients. Common particulate sources include: solvent impurities, drug precipitates, dust, glass, rubber, environmental contaminants, fibers and other insoluble materials.
The size of particulate matter is an important factor when considering the potential risk to patients. Particles as small as 2 μm in diameter have been associated with microthrombi formation in patients. Dr. Michael Akers with the Food and Drug Administration notes that the smallest capillary blood vessels are considered to have a diameter of approximately 7 μm. Therefore, all particles having a size equal to or greater than 7 μm can conceivably become entrapped in and obstruct capillaries, increasing the potential for adverse effects. Simple visual inspection, which is required for compounded injections, may be adequate for large particles, but is inadequate for smaller particles. The lower limit of visibility of the naked eye is approximately 40 μm. Specialized testing methods are therefore necessary to adequately assess the total particulate burden of injections.