Compounded pharmaceuticals are used to treat numerous ophthalmic diseases during both surgical and diagnostic office procedures. Compounding is defined by the US Pharmacopeia (USP) as “the preparation, mixing, assembling, altering, packaging, and labeling of a drug, drug-delivery device, or device in accordance with a licensed practitioner’s prescription, medication order, or initiative based on the practitioner/patient/pharmacist/ compounder relationship in the course of professional practice.”
The Pharmacy Compounding Accreditation Board (PCAB) accredits pharmacies that provide evidence of adherence to quality standards for pharmacy compounding. The PCAB requires proper licensure with state and federal regulatory authorities, appropriate training of personnel, and facilities and methods that permit aseptic compounding of sterile preparations and meet the USP guidelines. Compounding pharmacies are also regulated by state boards of pharmacy and the FDA.
The 2013 Drug Quality and Security Act created a new 2-tiered regulatory structure for compounding pharmacies and the products they distribute. The law defines government oversight authority over large-volume compounding facilities, preserving a pathway for ophthalmologists to access certain compounding drugs for office use. Under the law:
In accordance with section 503A of the Food, Drug, and Cosmetic Act (FDCA), traditional compounding pharmacies require a patient-specific prescription for all drugs compounded. Oversight of these pharmacies remains primarily a state function unless the FDA receives a complaint.
According to section 503B of the FDCA, new outsourcing facilities do not require a prescription, but they must meet higher federal safety, sterility, and quality control standards than conventional drug manufacturing plants, while being subject to similar regular federal inspections.
Although ensuring the safety and sterility of compounded products is important, maintaining practitioner access to essential compounded products for office use is crucial. Unfortunately, the implementation of the new system and its regulation have been uncertain and costly. State rules for 503A compounding pharmacies still prevent some small, local compounders (including hospital pharmacies) from providing ophthalmologists with supplies of fortified antibiotics and other commonly compounded drugs for urgent cases. Shipment of compounded medications across state lines is more difficult because the compounder must have an instate pharmacy license. In addition, costly, extensive baseline testing required for each of the compounded products shortens the compendium list. Finally, although the FDA has dropped its 5-day expiration rule and allows 503B pharmacies to determine the expiration dates on biologics, additional expensive testing regimens are required on the part of compounders to substantiate a longer shelf life on the label.
To help the clinician be proactive about compounding drugs, the American Academy of Ophthalmology (AAO) issued the following recommendations for the sourcing of drugs used in intravitreal injection:
Select a compounding pharmacy that is accredited by the PCAB and adheres to quality standards for aseptic compounding of sterile medications (USP Chapter 797 guidelines; see www.achc.org/compounding-pharmacy.html).
Record the lot numbers of the medication vial and the syringes in the patient record or a log, in case they need to be tracked.
These recommendations were made after the 2011 outbreaks of infectious endophthalmitis associated with compounded bevacizumab. Practicing ophthalmologists should stay up-to-date with current state and federal pharmacy regulations concerning compounding pharmaceuticals. The AAO and many subspecialty societies send e-mail alerts and provide updates on regulations and legislation to their members.
Excerpted from BCSC 2020-2021 series: Section 2 - Fundamentals and Principles of Ophthalmology. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.