May 18, 2015
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Access to compounded medications critical for ophthalmologists, patients

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I strongly believe access to compounded pharmaceutical products is critically important for the ophthalmologist and especially for patients. This is currently an area in flux with significant controversy, and many parties have significant vested interests. The following thoughts are my own, and I would like to disclose that in one form or another, I consult for every level of pharmaceutical product distribution I will discuss in this commentary. When I am sorting out my own personal conflicts of interest, I simply return to a “patient first” prioritization, and it is rare for me to need go any further. So, here are my thoughts as a practicing ophthalmologist treating patients daily and also as a patient on several medications.

I want for my patients and myself broad access to safe and effective drugs. I want them at a reasonable cost, meaning I want a fair value. I am a firm believer that the physician-patient covenant, capitalism, the power of innovation and the free market usually sort out most controversies regarding which product a physician will select in the best interest of the patient. My patients and I want in products the same thing we want in physicians: choice, access and a fair value. Some regulatory oversight is important to assure quality of manufacture for the products we have available for our patients, but overzealous regulatory oversight is usually a catalyst for the law of unintended consequences.

Little of therapeutic value can be accessed with absolutely zero risk. In my opinion, the best outcomes are achieved when a well-trained physician practicing within the centuries-old doctor-patient covenant makes the decision as to what is in each patient’s best interest, one patient at a time. Medical care and treatment must be personalized to be at its best and most effective level. This leads me to want access one way or another to a broad array of medicines and treatments and to be allowed to use them on or off label.

The medicines my patients and I use come from a broad array of sources, and to me, this is good. These include so-called branded, patent-protected drugs that have undergone rigorous FDA clinical trials. Examples in ophthalmology include Eylea (aflibercept, Regeneron), Ilevro (nepafenac ophthalmic suspension 0.3%, Alcon) and Lotemax (loteprednol etabonate ophthalmic gel 0.5%, Bausch + Lomb). These drugs are usually the most carefully evaluated and regulated and therefore the most expensive. In addition, after patents expire, popular branded drugs usually become available in generic forms from several manufacturers. There is no generic example in the anti-VEGF class, but ketorolac and prednisolone acetate are familiar generic alternatives in the NSAID and topical steroid arena. Branded and generic drugs are the two most common channels to access drugs for our patients, but there are several others. These include over-the-counter medications, nutritional supplements and the topic of this issue’s cover story, compounded pharmaceuticals. Finally, in select cases, we find ourselves referring patients abroad for treatments that are not available in the U.S., collagen cross-linking being one example. Each of these classes of therapeutic agent requires some regulatory oversight in regard to quality of manufacture, but it is to me a truism that in regard to drugs and other therapeutics, broad access and choice is in our patients’ best interest.

Now, back to compounded pharmaceuticals. I have used these regularly during my entire career, to the great benefit of thousands of patients. Access has been from hospital pharmacies such as the Phillips Eye Institute Pharmacy and mail-order providers such as Leiter’s and more recently Imprimis. The major disaster with fungal infection after the use of injected methylprednisolone prepared by the New England Compounding Center catalyzed a new set of laws from Congress in 2013. The Drug Quality and Security Act was passed, and the FDA was given increased power to regulate compounding pharmacies. Two classes of compounding pharmacies were created: 503A and 503B. The 503A compounding pharmacy can provide drugs through a prescription written for an individual patient when the 503A pharmacy is also licensed in the individual’s state. The 503B compounding pharmacy, with a higher standard of regulatory oversight, can provide drug in bulk to a physician to dispense from his or her office without a patient specific prescription and can do so across state borders. The FDA is currently working to refine the regulations for these two new classifications of compounding pharmacy.

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The decisions the FDA makes are critical to ophthalmologists and patients, especially in the anti-VEGF category. As I mentioned above, no generic anti-VEGF injectables are available. Lucentis (ranibizumab, Genentech) and Eylea, branded and patent-protected drugs, are excellent therapeutic agents but quite expensive, at approximately $1,100 and $1,800 per treatment. Avastin (bevacizumab, Genentech), shown to have good efficacy for several similar indications, is only available from compounding pharmacies at a price point near $50 per treatment. In the era of high deductible insurance and increasing patient responsibility for the cost of care, this price difference is extremely important for many patients. Loss of this drug would likely result in many patients being unable to afford treatment for potentially blinding conditions such as wet age-related macular degeneration and diabetic macular edema.

Most retina specialists use a treat-and-extend approach with anti-VEGF treatments, meaning they need to see and examine the patient before they know whether the patient will need an injection. A 503A compounding pharmacy approach requiring a patient specific prescription simply will not work in this setting, requiring the patient to return for another appointment for the injection, which is expensive as well as time-consuming for the doctor, patient and patient’s family. This is definitely not in the patient’s best interest. A 503B approach can work, allowing the physician to keep an adequate supply of drug on hand to meet their patients’ needs, but only if the physician has a reasonable number of days to utilize the drug. The currently proposed 5 days is way too short. More reasonable beyond-use dates (BUD) would be, in my opinion, 30 days at a minimum. Of course, 503B compounding pharmacies would need to confirm shelf-life stability and sterility for their products through the BUD period, but the loser will be our patients if unreasonable standards are applied.

So, the biggest elephant in the ophthalmology compounding pharmacy controversy is Avastin, but there are others. As an anterior segment surgeon, I am finding the use of intracameral antibiotics for infection prophylaxis, intravitreal antibiotic/steroid injections for infection/inflammation prophylaxis and treatment, and intracameral epi-Shugarcaine for pupillary dilation to be good options for my patients. Based on significant clinical experience, these compounded drugs appear safe and effective, and they are also a great value when compared with branded or even generic topical therapy alternatives. The 503A patient-specific prescription works, but a 503B outsourcing approach with a month or more to use the drugs would be far superior. Access to topical drops not otherwise available in branded or generic versions is also of great benefit to patients to enhance safety (for example, non-preserved versions of drops such as latanoprost), efficacy (for example, higher concentrations of cyclosporine or unavailable drops such as vancomycin), compliance (for example, commercially unavailable combinations such as a steroid and an NSAID) and of course cost, in which compounded drugs are generally much cheaper than their branded or generic competitors.

My patients and I want broad choice, easy access and a fair value, meaning a reasonable cost. I am hoping the eventual FDA regulations for compounding pharmacies protect these critical issues. We also want reproducible quality assured by current good manufacturing practices (CGMPs), and FDA oversight is important to assure safety and CGMPs. I am hoping the FDA focuses on safety, allowing ophthalmologists and their patients broad access to a wide variety of compounded medications. I am confident we physicians, with extremely rare exception, will only use the therapeutics available to us in our patients’ best interest.