Nitrosamine Impurities Affecting Drug-Drug Interaction Studies – Learn More

The Benefits of On-Site Sterile Compounding in a USP Clean Room

Jennifer Moorehead, Pharm D, RP
Clinical Research Pharmacist in Charge, Lincoln, NE

USP <797> refers to chapter 797 “Pharmaceutical Compounding–Sterile Preparations”, in the USP National Formulary. It is the first set of enforceable sterile compounding standards issued by the United States Pharmacopeia (USP).

The intent of USP <797> is to prevent harm and fatality to patients that could result from microbial contamination and bacterial endotoxin. The USP states, “It is the ultimate responsibility of all personnel who prepare CSPs to understand these fundamental practices and precautions, develop and implement appropriate procedures and continually evaluate these procedures and the quality of final CSPs in order to prevent harm and fatality to patients who are treated with CSPs.” USP <797> describes the guidelines, procedures and compliance requirements for compounding sterile preparations (CSPs) and sets the standards that apply to all settings in which sterile preparations are compounded.

The standards in this chapter are intended to apply to all persons who prepare CSPs and all places where CSPs are prepared. This includes hospitals and healthcare institutions, patient treatment clinics, pharmacies, physicians’ practice facilities and other locations or facilities in which CSPs are prepared, stored and transported. USP <797> requirements affect all disciplines involved in sterile compounding, including physicians, nurses, pharmacists and pharmacy technicians.

USP <797> guidelines for low, medium and high risk sterile compounding can be met using a certified clean room. A clean room provides quality air for compounding sterile products. The traditional air environment (where the compounding takes place) of the ISO Class 5 must be surrounded by positive pressure buffer room of ISO Class 7. Furthermore, it is recommended to have an area of ISO Class 8 for gowning, garbing, hand washing and gloving. A clean room consists of a smooth, impervious floor, walls and ceiling with proper vents and doors. The HVAC with HEPA filters control the air pressure, creating the ISO Class 7 during operation. It also maintains the desired temperature and humidity. The HVAC operates itself, making the room clean and simple, and thus an effective way to be compliant and produce safe compounded sterile products.

Non-sterile compounding however does not require a clean room since the final products will not be administered parenterally. These non-sterile formulations can be compounded in a typical pharmacy or lab that has the proper compounding equipment.

Typically, parenterally administered API for clinical studies must be manufactured under GMP conditions. If however reconstitution for injection is performed under USP <797> Clean Room conditions by licensed pharmacists, sterility can be achieved at the clinical site. This potentially reduces the duration of time needed for producing a finished product required to enable dosing. Successfully compounding and filtering a formulation into a sterile intravenous solution is developed in collaboration with the pharmaceutical sponsor and the clinical site pharmacist. Investigational products that can be compounded and filtered into a sterile solution are appropriate for on-site high risk sterile compounding. Sterility can be ensured using mock preparations and labs equipped to validate bacteriostasis, fungistasis, sterility and endotoxin testing.

On-site compounding and sterilization can be used in traditional radiolabelled ADME, micro-tracer and absolute bioavailability studies when an intravenous investigational product is required. This approach is particularly beneficial when an intravenous solution needs to be customized on a single occasion and is not going to be used in further development of the compound.

The approach also allows the API to be introduced to human subjects during the beginning phases of early clinical drug development. Ultimately, sterile extemporaneous compounding allows a flexible alternative to the costly, long development of parenteral investigational products by GMP standards.