The Core Distinction
The most fundamental distinction in pharmaceutical compounding is between sterile and non-sterile preparations. This distinction determines the regulatory standards that apply, the facility requirements, the quality testing protocols, and the clinical applications for which the preparation is appropriate.
Preparations that must be free of viable microorganisms, pyrogens, and particulate matter. Required for any preparation administered by injection, infusion, or instillation into the eye or other sterile body cavities. Governed by USP <797>.
Preparations that do not require sterility — including topical creams, gels, capsules, oral solutions, troches, and suppositories. Governed by USP <795>. Lower facility requirements but still subject to rigorous quality standards.
Sterile Compounding: Requirements and Applications
Sterile compounding is required for any preparation that will be administered in a way that bypasses the body's natural defense mechanisms against microbial contamination. This includes all injectable preparations (intramuscular, subcutaneous, intravenous, intradermal), ophthalmic preparations (eye drops, ointments), intrathecal and epidural preparations, and preparations instilled into the bladder or other sterile body cavities.
USP <797> establishes the standards for sterile compounding. Key requirements include:
ISO-classified cleanroom environments (ISO 5 for direct compounding, ISO 7 buffer area, ISO 8 ante-area)
Personnel training and competency assessment including aseptic technique evaluation
Environmental monitoring (particle counts, viable air sampling, surface sampling)
Sterility testing for preparations with extended beyond-use dates
Endotoxin (pyrogen) testing for preparations administered by injection
Potency testing to confirm active ingredient concentration
Beyond-use dating based on compounding conditions and sterility testing results
Non-Sterile Compounding: Requirements and Applications
Non-sterile compounding encompasses a wide range of dosage forms used in clinical practice. Common non-sterile preparations include topical creams and gels for hormone delivery, dermatology, and pain management; troches and sublingual preparations for hormone therapy; capsules for customized oral medications; oral suspensions for pediatric patients; suppositories for vaginal or rectal delivery; and transdermal preparations.
USP <795> governs non-sterile compounding. While the facility requirements are less stringent than for sterile compounding, non-sterile preparations must still meet rigorous quality standards including:
Appropriate facilities and equipment for the type of compounding performed
Personnel training and competency assessment
Quality control testing including potency, pH, and physical appearance
Proper beyond-use dating based on formulation stability data
Documentation of all compounding activities
Appropriate packaging and labeling
Frequently Asked Questions
Can a non-sterile pharmacy prepare injectable medications?
No. Injectable medications must be prepared under sterile compounding conditions meeting USP <797> standards. A pharmacy that does not have a certified sterile compounding facility cannot legally prepare injectable preparations.
Are topical hormone creams sterile or non-sterile preparations?
Topical hormone creams and gels are non-sterile preparations governed by USP <795>. They do not require sterile compounding conditions because they are applied to intact skin and do not bypass the body's natural defense mechanisms. However, they must still meet quality standards for potency, stability, and physical characteristics.
What is the difference between USP <795> and USP <797>?
USP <795> governs non-sterile compounding standards including facilities, equipment, personnel, formulation, quality controls, and beyond-use dating for non-sterile preparations. USP <797> establishes standards for sterile compounding including cleanroom requirements, environmental monitoring, sterility testing, and beyond-use dating for sterile preparations.