Compounding a Sterile Product Without a Beyond-Use Date
A hospital pharmacy prepares a batch of 30 syringes of a compounded antibiotic for immediate use in the operating room. The pharmacy is not a 503B outsourcing facility. The compounder uses a nonsterile active pharmaceutical ingredient (API) and sterile water, prepares the product in a laminar flow hood in a segregated compounding area, and does not assign a beyond-use date (BUD) because the syringes will be used within 4 hours. The pharmacist-in-charge asks whether the batch can be released. The hospital is in California and follows USP <797> and California compounding rules.
1. Can the pharmacy release the batch as prepared? Identify the specific problems.
Read the worked answer
No. There are at least two problems.
First, using a nonsterile API to prepare a sterile compounded preparation is not permitted for a preparation intended for injection unless the API is USP-grade and the preparation is appropriately sterilized. A nonsterile API in a product injected into the body creates an unacceptable risk unless a validated sterilization method is used and verified.
Second, even for immediate-use preparations, the pharmacy must follow USP <797> requirements for the category of preparation. Immediate-use preparations have strict limits (short BUD, preparation in a clean environment, no more than 3 doses, etc.). The pharmacist must determine whether this batch qualifies as immediate use; if it does not, a BUD must be assigned based on the risk level and the environment.
The pharmacist-in-charge should not release the batch until these issues are corrected and documented.
2. What must the pharmacy do to assign a compliant beyond-use date if the product is not immediate use?
Read the worked answer
The pharmacy must classify the preparation by risk level (low, medium, or high) under USP <797> and assign a BUD consistent with that risk level and the compounding environment. If the pharmacy is a conventional (non-503B) facility, the BUD depends on whether the preparation is sterile, the risk level, and the storage conditions. The pharmacy must document the risk assessment and the basis for the BUD. If the pharmacy cannot meet the requirements for a given BUD, it must shorten the BUD or change the process (for example, use a sterile API or a validated terminal sterilization step). The pharmacist-in-charge should also verify that the segregated compounding area meets the required environmental monitoring and that personnel are trained and competent.
3. What should the pharmacist-in-charge do about the 30 syringes already prepared?
Read the worked answer
The syringes should be quarantined and not released for patient use. The pharmacist-in-charge should investigate the deviation, document it, and determine whether any syringes were already used. If any were used, the pharmacist-in-charge should assess patient risk and follow the facility's adverse-event reporting process. The batch should be destroyed or reworked only if reworking is permitted and validated; otherwise it should be discarded. The pharmacist-in-charge should also conduct a root-cause analysis and update procedures to prevent recurrence, including a checklist that requires a BUD and a risk-level determination before release.