The USP has recently published a revised version of general chapter <797> Pharmacy Compounding — Sterile Preparations addressing sterile compounding.¹ This chapter provides guidance on requirements for the compounding of safe, sterile pharmaceutical dosage forms in the pharmacy, as opposed to the controlled pharmaceutical manufacturing environment.

This chapter was prompted by concerns over the quality of drugs produced in the growing arena of pharmacy compounding laboratories.² This was not the first USP chapter to provide guidance in this area. Previously, USP published chapter <1074>, Dispensing Practices for Sterile Drug Products Intended for Home Use in an attempt to address this concern. This chapter was not as effective as originally hoped.³ To this end, USP <797> was created. While the FDA is charged with enforcing USP, there is some leeway in enforcement practice at the pharmacy level. However, many state boards and professional associations have adopted the provisionsof the USP chapter in their expectations.⁴

This chapter has generated a great deal of interest in the compounding pharmacy. Among the provisions of the chapter, the compounding pharmacy is expected to:

• Have written quality procedures with allowance for in-process checks on compounding,
• Establish accuracy and precision of measuring and weighing,
• Observe the requirement for sterility,
• Qualify methods of sterilization and purification,
• Establish safe limits and ranges for strength of ingredients, bacterial endotoxins, particulate matter, and pH,
• Ensure labeling accuracy and completeness,
• Ensure beyond-use date assignment, and
• Establish packaging and storage requirements

To help with the microbial risk level, there are three categories of productsdescribed in the current <797>:

1. Low Risk Medications – “The CSPs are compounded with aseptic manipulations entirely within ISO Class 5 (see Table 1 [in Guidance Document) or better air quality using only sterile ingredients, products, components, and devices. The compounding involves only transfer, measuring, and mixing manipulations with closed or sealed packaging systems that are performed promptly and attentively. Manipulations are limited to aseptically opening ampoules, penetrating sterile stoppers on vials with sterile needles and syringes, and transferring sterile liquids in sterile syringes to sterile administration devices and packages of other sterile products. For a low-risk preparation, in the absence of passing a sterility test, the storage periods cannot exceed the following time periods: before administration, the CSPs are properly stored and are exposed for not more than 48 hours at controlled room temperature (see General Notices and Requirements), for not more than 14 days at a cold temperature (see General Notices and Requirements), and for 45 days in solid frozen state at –20 °C or colder.”

2. Medium Risk Conditions exist when the medication is compound under aseptic conditions as above, and any of the following additional conditions exists –
a. “Multiple individual or small doses of sterile products are combined or pooled to prepare a CSP
(compounded sterile product) that will be administered either to multiple patients or to one patient on multiple occasions.
b. The compounding process includes complex aseptic manipulations other than the single-volume transfer.
c. The compounding process requires unusually long duration, such as that required to complete dissolution or homogeneous mixing.
d. The sterile CSPs do not contain broad-spectrum bacteriostatic substances, and they are administered over several days (e.g., an externally worn or implanted infusion device).
e. For a medium-risk preparation, in the absence of passing a sterility test, the storage periods cannot exceed the following time periods:

i. before administration, the CSPs are properly stored and are exposed for not more than 30 hours at controlled room temperature (see
General Notices and Requirements),
ii. for not more than 7 days at a cold temperature (see General Notices and Requirements), and
iii. for 45 days in solid frozen state at –20 °C or colder.”