6.6 Compounding: Sterile, Nonsterile & Hazardous

Compounding Under PA and Federal Law

PA compounding is governed by 49 Pa. Code §§ 27.601–27.606 (finalized June 22, 2019), the federal FDCA § 503a, and the current USP chapters. PA's 2019 rulemaking modernized compounding to align with the Drug Quality and Security Act (DQSA) of 2013 and current USP standards. The framework distinguishes who can compound, what records must be kept, how sterile vs nonsterile vs hazardous drugs are handled, and the line between traditional compounding and outsourcing-facility manufacturing.

FDCA § 503A vs § 503B

Section 503A (traditional compounding) covers pharmacists compounding patient-specific preparations under a prescription, or in limited anticipatory quantities. 503A compounders are exempt from new drug approval, Adequate Directions for Use, and track-and-trace requirements, provided they meet the statute's conditions: patient-specific compounding (or limited anticipatory), no compounded drug that is essentially a copy of an approved drug, and no third-party resale of compounded products.

Section 503B creates the outsourcing facility — a facility that compounds drugs without patient-specific prescriptions and is registered with FDA, inspected on a risk-based schedule, and subject to current Good Manufacturing Practice (cGMP). Outsourcing facilities can ship interstate to hospitals and pharmacies. PA pharmacies that buy from a 503B facility must verify the facility is FDA-registered.

Anticipatory vs Patient-Specific Compounding

Patient-specific compounding is the preparation of a drug for an identified patient pursuant to a prescription. Anticipatory compounding is preparing a limited quantity in advance of a prescription based on a documented history of prescriptions. PA permits anticipatory compounding in limited quantities consistent with USP and federal rules; excessive anticipatory compounding without dispensing history looks like manufacturing and falls outside 503A.

USP Chapters

Sterile Compounding Categories

USP <797> defines risk levels based on the source of the starting material and the manipulations:

• Immediate-use CSPs: simple preparation intended for immediate administration, no storage beyond 4 hours (or 12 hours if started from commercially available sterile components with simple aseptic transfer)
• Low-risk CSPs: made from commercially available sterile components with simple aseptic manipulations in an ISO 5 environment; BUD typically 48 hours refrigerated or longer per USP
• Medium-risk CSPs: multiple sterile components, complex manipulations, or batch-prepared; longer BUDs permitted with stability data
• High-risk CSPs: made from nonsterile components or exposed more than 6 hours to ISO 5 air before sterilization; requires terminal sterilization

Beyond-Use Dating

A beyond-use date (BUD) is not the same as an expiration date. The BUD is the date after which the compounded preparation should not be used, derived from USP criteria (stability, sterility, container, storage). BUDs for compounded sterile preparations (CSPs) depend on risk level and storage temperature; high-risk CSPs have the shortest BUDs. As default examples under USP <797> (when stability data does not support longer), low-risk CSPs may be stored 48 hours at room temperature, 14 days refrigerated, or 45 days frozen; medium-risk 30 hours at room temperature, 9 days refrigerated, or 45 days frozen; high-risk 24 hours at room temperature, 3 days refrigerated, or 45 days frozen. Each compounded preparation must be labeled with a BUD; BUDs must not exceed the shortest expiration date of any component, the container's durability, or the documented stability data.

Hazardous Drug Handling

USP <800> became effective November 2023 and is enforced by PA. It applies to hazardous drugs (e.g., antineoplastics, hormones, certain antivirals) identified on the NIOSH list. Required engineering and practice controls: a negative-pressure compounding room, a biological safety cabinet (BSC) or compounding aseptic containment isolator (CACI) as the primary engineering control, personal protective equipment (PPE), medical surveillance for personnel, spill kits, and segregation from non-hazardous compounding. Final products must be labeled as hazardous and dispensed in protective packaging. USP <800> applies to receiving, storage, compounding, dispensing, and administration — not only the compounding step.

Compounding Records

PA requires compounding records be retained for 2 years, including the formula, components and their quantities, lot numbers, BUD, and the name of the pharmacist or technician who compounded. Records must be available for Board inspection. Compounding records are part of the pharmacy's recordkeeping under 49 Pa. Code Chapter 27.

Traps

• A 503B outsourcing facility is not a traditional pharmacy and is not required to be licensed as a PA pharmacy — but the buying PA pharmacy must verify FDA registration before purchasing.
• Anticipatory compounding of an essentially-a-copy of an approved drug is prohibited; e.g., compounding a commercial oxytocin preparation when the commercial product is available.
• USP <800> applies to receiving, storage, compounding, dispensing, and administration — even repackaging a hazardous drug triggers <800>.
• A pharmacist must not compound a drug that has been withdrawn from the market for safety reasons.
• A patient-specific compound for a hospital inpatient may still be 503A; batch-produced sterile products for hospital stock without patient-specific prescriptions come from a 503B outsourcing facility.