As the role of compounding pharmacies grows, these key questions will help to evaluate whether the facility’s products meet the necessary standards.
Compounding pharmacies have become an essential part of ophthalmic practice, and while they can fill critical gaps when commercially available medications are unavailable, inaccessible, or prohibitively expensive, it is essential that we properly evaluate these facilities and their products to protect our patients and our practices.
Here, I’ll provide a brief overview of compounding pharmacies, as well as some advice on how to assess them.
What is a compounding pharmacy?
Unlike traditional drug manufacturers that mass-produce FDA‑approved drugs, compounding pharmacies prepare individualized or small‑batch formulations of medications that address patient needs. Examples include preservative‑free eyedrops for glaucoma patients, post-operative combination drops that reduce the complexity of regimens, or intracameral antibiotics for cataract surgery.
Note that compounded drugs are not FDA-approved, meaning they undergo less manufacturing scrutiny and clinical testing compared to those that receive FDA approval.1
There are two main types of compounding pharmacies:1
- 503A: These produce medications on a patient‑specific basis. States primarily regulate them and require a valid prescription to prepare a drug.
- A classic example in ophthalmology is the use of fortified antibiotics compounded locally for a corneal ulcer. The trade-off with this model is that it cannot batch-produce or ship medications across state lines for office use.
- 503B: These are more comparable to traditional manufacturers. They are subject to FDA inspection and must comply with current Good Manufacturing Practices (cGMP).
- Facilities under the 503B designation are permitted to manufacture batches in advance, ship across state lines, and provide medications directly for office stock. This includes medicines used routinely in the peri-operative period.
Both types of pharmacies play essential roles. 503A pharmacies remain invaluable for urgent or uniquely tailored needs, while 503B facilities are typically the more practical choice for routine or intraocular applications.
Lessons learned from the past
In 2012, a fungal meningitis outbreak occurred due to contaminated preservative-free methylprednisolone acetate injections compounded by the New England Compounding Center (NECC) in Framingham, Massachusetts.2 The outbreak resulted in more than 750 cases of illness across 20 states and 64 deaths.
The following year, Congress passed the Drug Quality and Security Act, which created a new section 503B in the Federal Food, Drug, and Cosmetic Act.3
This section outlined that a compounder could become an outsourcing facility only if it:4
- Complies with cGMP requirements
- Undergoes FDA inspections according to a risk-based schedule
- Meets other conditions, such as reporting adverse events and providing the FDA with certain information about the products they compound
Table 1: Comparison of 503A and 503B compounding facilities.4
| 503A Compounding Pharmacy | 503B Outsourcing Facility | |
|---|---|---|
| Intended use of medication | Patient specific | Patient specific or stocked by healthcare facility |
| Main regulatory body | State pharmacy board | FDA |
| Regulatory standards | US Pharmacopeia (USP) standards such as 795 and 797 | Certain USP standards and cGMP (21 CFR Part 210 and 211 and related FDA guidance) |
| Reporting | Varies by state | Must report product list and adverse events to FDA |
| Inspection | State inspections | Mandatory FDA inspections and state inspections |
| Requirement for environmental monitoring | Based on USP | cGMP standards such as every production shift in primary compounding areas; weekly in secondary compounding areas |
Table 1: Courtesy of Blake Williamson, MD, MPH, MS.
What are the benefits of using compounding pharmacies?
Ophthalmology relies on compounding for several important reasons, including:
- Addressing drug shortages
- Delivering preservative‑free or personalized therapies tailored to patients
- Streamlining post-operative regimens with combination drops
- Ensuring continuity of care when commercial products are discontinued
Cost is another major factor; compounded medications provide therapeutic benefits while dramatically reducing cost and improving compliance. Commercial post-operative regimens can add up to hundreds of dollars per bottle, at times exceeding the Medicare reimbursement for cataract surgery.
Which ophthalmic medications are most often produced by compounding pharmacies?
Over the last decade, I have seen compounded products make high-quality post-operative care more affordable and accessible, while also driving innovation across our field. For instance, intracameral antibiotics for cataract surgery and oral sedation first gained momentum in the compounding space before progressing toward FDA approval.
Additional ophthalmic medications that are often prepared by compounding pharmacies include:
- Antibiotics
- Anti-inflammatories
- Autologous serum eye drops
- Mitomycin-C
- Fortified antibiotics
- Anti-fungals
- Anti-parasitic
- Intravitreal injections
- Glaucoma medications (both single and fixed combination)
- Oral sedation mydriatics
Access to these customized formulations enables ophthalmologists to address a wide range of clinical needs, improve patient convenience and compliance, and maintain continuity of care when commercial products are unavailable or do not provide the required dosing or delivery options.
Getting started with compounding pharmacies
For those beginning their search, I recommend starting with professional networks, local and national ophthalmic societies, and peers who can share their experiences. Specialty meetings and trade events are also excellent opportunities to learn about reputable compounding pharmacies.
From there, evaluating partners based on regulatory compliance, accreditation, ophthalmic expertise, and service capabilities will help identify the right fit for each practice. In my own practice, we rely on ImprimisRx, which has been a trusted partner for our ophthalmic compounding needs.
Though this tool is geared towards patients, the Alliance for Pharmacy Compounding has a “Find a compounding pharmacy” directory that can be helpful for finding local pharmacies.
Careful evaluation of compounded pharmacies is essential
As the role of compounding pharmacies expands, ophthalmologists have an increasing responsibility to evaluate the facilities with which we partner carefully.
Ophthalmic medications, especially those used intraocularly or peri-operatively, have no margin for error in terms of safety. Therefore, ophthalmologists must carefully vet any compounding pharmacy before partnering with it.
9 questions to ask your compounding pharmacy
To determine whether a compounding pharmacy meets the necessary safety standards, I recommend asking the following questions:
- Where are your formulations made, and does the company own and manage those facilities? Direct ownership and oversight often correlate with stronger quality control. Knowing exactly who is responsible for facility management and production can help reduce variability and avoid potential liability gaps.
- How long has the pharmacy been producing these formulations? Certain compounds, especially combination antibiotic‑steroid‑NSAID drops or intraocular medications, are technically complex. A pharmacy with years of experience delivering these products is less likely to experience any missteps when it comes to quality control.
- Are all formulations tested in an FDA‑registered laboratory, and does the pharmacy adhere to cGMP standards? FDA registration and compliance with cGMP ensure that compounded medications are held to the same standards as those that regulate commercial drugs.
- Is every batch tested for potency, sterility, and endotoxins, and will I receive a report? All batches of compounded medications should undergo testing, not occasional or monthly spot checks. In ophthalmology, where endotoxin contamination can be devastating, batch‑specific testing is non‑negotiable. Also, to ensure transparency, the pharmacy should send documentation with each shipment that confirms the testing.
- Is the beyond‑use date (BUD) based on validated stability‑indicating studies from an FDA‑registered lab? When a BUD is established with validated methods, it assures that the drug will maintain potency and sterility for the labeled period. This helps to reassure us that the medication will have a long shelf life and that we can rely on the BUD.
- Does the pharmacy test the active pharmaceutical ingredients (APIs) before preparing new batches of medication? Changes in raw material quality can have downstream consequences. In ophthalmology, we have seen how manufacturing changes can compromise outcomes, as evidenced by a recent link between an intraocular lens and outbreaks of toxic anterior segment syndrome. The same principle applies here to safeguard our patients.
- Are finished products stored in validated warehouses? Ophthalmic medications are sensitive to temperature and storage conditions. When a compounding pharmacy stores medications in a validated warehouse, it ensures that proper conditions are maintained throughout the distribution process.
- Can I maintain an in‑office inventory for immediate use? For urgent scenarios, having medications in the office is essential. For example, some fortified antibiotic/steroid combinations are designed to be kept on hand for timely access.
- Does the pharmacy participate in the FDA's MedWatch reporting program? Through the MedWatch program, compounding pharmacies report adverse events, product quality issues, or use errors to the FDA. This is mandatory for 503B outsourcing facilities. Their participation in MedWatch enables the detection and addressing of any potential safety concerns.
Conclusion
Compounding pharmacies have transformed ophthalmology by reducing costs, enhancing compliance, and providing access during times of shortage. But with their growing role comes an obligation to assess their safety and quality.
For medications as sensitive as those given intraocularly or peri-operatively, the risk of devastating outcomes is too high for us not to do our due diligence. By asking the right questions and ensuring clear, documented answers, ophthalmologists can partner only with compounding pharmacies that meet the highest standards.
