Skip to Content

Support MinnPost

New regulations of compounded medicines mean fewer options at higher prices

pharma lab
REUTERS/Aly Song
Well-meaning regulations on medicine from compounding pharmacies have had some unintended effects.

Macular degeneration affects more than 2 million Americans, and is especially common in Minnesota due to a higher prevalence in populations of northern European heritage. By serendipity in 2006, a medication originally developed for colon cancer was found to avert blindness in advanced cases of macular degeneration. With monthly injections into the eye, patients may continue to read, drive, and live independently compared to a previous prognosis of eventual blindness. Today, there are three injectable medications available for the treatment of macular degeneration with enormous benefits for a patient’s vision. The three medicines are similar in safety, efficacy, and dosing; however, there is a shocking difference in cost: Avastin costs $50 per dose, while Lucentis and Eylea each cost $2,000.

Geoffrey Emerson
Geoffrey Emerson

Unfortunately, the option to use Avastin has been restricted by the debate on how to regulate medicine from compounding pharmacies. A compounding pharmacy is a pharmacy that offers compounding services were drugs and ingredients are mixed or processed to the specifications of a doctor’s order. Compounding pharmacies can offer a wider variety of mixtures and doses than are available at most pharmacies.

This debate follows the tragic outbreak in 2012 of fungal meningitis linked to tainted steroid from the New England Compounding Center (NECC) that led to 33 deaths. Despite multiple complaints, the Massachusetts Board of Pharmacy (BOP), the licensing agency responsible for the NECC, did not inspect the NECC and failed to correct inexcusable shortcuts in technique and an egregious lack of sterility. The offending pharmacy was closed permanently and the director of the Massachusetts BOP was fired. In an effort to prevent this from occurring again, many states (including Minnesota) strengthened existing requirements necessitating an individual prescription for each dose of medicine before it is compounded.

Avastin is considered a compounded medicine because of a technicality. Avastin is manufactured in larger vials for intravenous infusion in the treatment of cancer, but for macular degeneration, a compounding pharmacy repackages the medication into individual smaller doses. Although Avastin is not mixed, diluted  or altered in the traditional sense of compounding, it is repackaged by a compounding pharmacy and therefore the individual prescription rule now applies to this medication.

This requirement is frustrating to doctors and patients, for several reasons.

First, it is impossible to have Avastin in stock and ready in the clinics where it is used. If a physician wanted to administer Avastin, a prescription would need to be sent to a compounding pharmacy before the dose would be dispensed and shipped back to the clinic. This is inconvenient at a minimum. For some patients with very aggressive forms of retinal disease, the resulting delay in treatment causes unacceptable permanent vision loss. Commercially prepackaged Lucentis and Eylea are stocked in offices and thus immediately available without an intermediary pharmacy or individual prescription. Thus, even though Avastin is the most affordable and has a history of safety and efficacy identical to its counterparts, doctors and patients have little choice due to the limitations of its availability.

Second, the costs implications of these regulations cannot be ignored and should be cause for great concern. Most health insurers cover all three options for macular degeneration. However, for the expensive options, the copay is often $400 every 1-2 months. In 2011, medications for macular degeneration accounted for 16% of the $12 billion total budget for Medicare Part B. This figure is likely to spike if the more expensive medications continue to be substituted for Avastin. Despite physician calls to lower the price of Lucentis and Eylea, the pharmaceutical companies have not, and these new regulations only strengthen their monopoly. This is not responsible stewardship of our Medicare or health care budget.

Most frustrating is that the recent increased regulation does nothing to improve safety or sterility. The root of the fungal meningitis tragedy was a deficiency in NECC’s sterile compounding technique and the State of Massachusetts’ lack of oversight. Absent or inappropriate prescriptions from physicians had nothing to do with the contaminated medicine.

Doctors, state boards of pharmacy and legislators all share a strong desire to improve safety for patients treated with compounded medications. Compounding is an important source of medication for our health-care system. We should focus on oversight of sterile processing at compounding pharmacies, rather than limit the choices available to patients and doctors. The current requirement for an individual prescription has unintended consequences for patients who will now have fewer treatment options at a significantly higher cost.

Geoffrey Emerson, MD, PhD, is an ophthalmologist specializing in macular degeneration at the Retina Center in Minneapolis. He is also vice chair of the Phillips Eye Institute and a member of the board of directors of the Minnesota Academy of Ophthalmology.

WANT TO ADD YOUR VOICE?

Write your reaction to this piece in Comments below. Or consider submitting your own Community Voices commentary; for information, email Susan Albright

Get MinnPost's top stories in your inbox

Related Tags:

Comments (7)

What's YOUR Solution?

Since you do not propose one, I can only suspect that you would like to keep business as usual for "compounding pharmacies."

Which works just fine until people start dying because some of the existing compounding pharmacies have turned themselves into something more akin to large-scale pharmaceutical manufacturing companies,...

while convincing inspectors/regulators that they need little or no oversight because they're just like the pharmacists at small town corner drugstores who used to mix up generic over-the-counter cough syrup for their customers.

If the individual prescription requirement, which seems to be the only change the compounding pharmacy companies were willing to accept, is NOT acceptable to you, (even though it aids in tracking batches and makes it clear to such compounding pharmacies that they can much more quickly and easily be held responsible for lapses in their procedures)

what would YOU propose to do to protect people who will be poisoned and killed because the system is still operating for maximum convenience for itself and the physicians it serves and with FAR LESS concern for the patients who might be injured or killed because corners are being cut in order to maximize those profits and that convenience?

(And you must be kidding if you think we believe it's not possible for Avastin to be contaminated in the process of splitting up large vials into smaller doses. Careless procedures and equipment that is not sterilized often enough - or at all - could EASILY produce such a result.)

Not interested in having fungus injected into my eyball

This is the private sector for you. Apparently there's a consistent demand for smaller doses of Avastin but the manufacturer is incapable of delivering those doses despite the obvious cost effectiveness of doing so. I'm sorry but if all we're doing here is putting Avastin in smaller doses why is exactly is THAT going to cost more with the new regulations? How exactly are the new regulations raising the cost and why? Forgive me for not simply taking a Doctors word for this but we've heard this before.

Pharmacists--and techs-are compounders based on the definition.

Avastin is "compounded" because why? A smaller quantity must be taken from a bigger bottle to fill the order.

Guess what pharmacists--and their techs--do all the time? They take a smaller quantity of something from a bigger bottle to fill the order. Thus, they are all compounders under the law and ALL medications they issue NOT in the 'full manufacturers' packaging' is compounded.

So, how much do you want to pay for each of your "cheap" $4 Rx? $40? $75? $100? They are ALL "compounded", so how do you avoid those high compounder fees and time delays?

This part of the new law is stupid and needs to be revised to define "repackaging" as NOT compounding.

The Difference Between Standard Pill Pushing

and what's happening with shifting Avastin from larger to smaller containers, not to mention what the New England Compounding Center was doing with the products which caused fungal meningitis (because they contaminated them),...

is that both cases deal with INJECTABLE liquids, which require a far higher level of care and represent far more danger to patients when they are contaminated than do the pills and liquids designed to be taken by mouth that the average pharmacist moves form larger containers to smaller.

By the way, Avastin is divided into smaller doses because it's an I.V. chemotherapy drug, and relatively inexpensive. Using it to treat macular degeneration is an "off label" use.

Avastin is very effective, but it was never officially studied or approved for this use, so it's highly unlikely the pharmaceutical company that produces it would feel safe packaging it in doses designed for eye treatments, since they' would likely get in trouble (substantial fines) for PROMOTING an off-label use for their product.

Lucentis and Eylea, the other two products available to treat macular degeneration are almost identical to Avastin, but were tweaked specifically for that purpose as well as being studied and approved by the FDA. Their outrageous prices (around $2000 per dose as opposed to $50 for Avastin) reflect how desperate people are to save their sight.

Although doctors are free to prescribe Avastin for this off label use, the pharmaceutical company that produces it is prohibited from supporting any off label usage,...

as a response to the fact that many pharmaceutical companies have been caught having their reps promote their newest, most expensive drugs to treat anything you can imagine for no other purpose but to maximize their profits for those drugs.

The Difference Between Standard Pill Pushing

and what's happening with shifting Avastin from larger to smaller containers, not to mention what the New England Compounding Center was doing with the products which caused fungal meningitis (because they contaminated them),...

is that both cases deal with INJECTABLE liquids, which require a far higher level of care and represent far more danger to patients when they are contaminated than do the products designed to be taken by mouth that the average pharmacist moves form larger containers to smaller.

By the way, Avastin is divided into smaller doses because it's an I.V. chemotherapy drug, and relatively inexpensive. Using it to treat macular degeneration is an "off label" use.

Avastin is very effective, but it was never officially studied or approved for this use, so it's highly unlikely the pharmaceutical company that produces it would feel safe packaging it in doses designed for eye treatments, since they' would likely get in trouble (substantial fines) for PROMOTING an off-label use for their product.

Lucentis and Eylea, the other two products available to treat macular degeneration are almost identical to Avastin, but were tweaked specifically for eye treatment as well as being studied and approved by the FDA. Their outrageous prices (around $2000 per dose as opposed to $50 for Avastin) reflect how desperate people are to save their sight.

Although doctors are free to prescribe Avastin for this off label use, the pharmaceutical company that produces it is prohibited from supporting any off label usage,...

as a response to the fact that many pharmaceutical companies have been caught having their reps promote their newest, most expensive drugs to treat anything you can imagine for no other purpose but to maximize their profits for those very highest-priced drugs.

Genentech has little incentive to manufacture ophthalmic Avastin

G. Kapphahn raises an excellent point that Genentech, the manufacturer of Avastin, has little incentive to conduct clinical trials or get FDA approval for use of an ophthalmic dose of Avastin in the treatment of macular degeneration. This is partly due to the great expense of a trial and also great expense of the FDA approval process. Genentech also manufactures Lucentis, which may be a further disincentive. Currently Lucentis has FDA approval specifically for macular degeneration while Avastin does not, and some interpret this to mean Lucentis is superior, which confers a market advantage to Lucentis.

Clinical trials are most often funded by the manufacturer, and Genentech has indeed funded several trials showing safety and efficacy for Lucentis. Regeneron, the manufacturer of Eylea, has also done trials that show similar safety and efficacy of Eylea in the treatment of macular degeneration. Neither manufacturer has participated in a trial comparing Lucentis or Eylea to Avastin, even though Avastin was the most common treatment. However, the NIH sponsored the Comparisons of Age-Related Macular Degeneration Treatment Trial (CATT). This randomized, prospective, double-blind trial compared Avastin to Lucentis head-to-head in the treatment of macular degeneration. Two-year results of vision outcomes and safety data were reported in 2012 and showed excellent efficacy and safety for both medications, without significant benefit of one over the other (despite the price difference). Further information on the CATT trial is available on the NIH website.

Is there a way to ensure safety AND availability of Avastin?

I hope so. Many compounding pharmacies set aside a few doses of Avastin for sterility testing when a vial of Avastin is aliquoted into individual doses for ophthalmic use. Then a culture is followed over time to know that occult bacteria or fungus is not growing and that other doses from the same lot continue to be safe until the expiration date of the medication has passed. The lot number is recorded for each patient, so that they could be contacted or treated in case of any issue. It is helpful to have a large enough number of doses from each lot that sterility testing is feasible.

Manufacturers have requirements to test and report sterility of their products and so should compounding pharmacies. But they won’t do it if they are not required, and they won’t do it well if they are not reviewed and inspected. Probably there are some large-scale compounding pharmacies that can do this well, and there are some that can’t or won’t. But under present rules, doctors and patients have a tough time knowing the quality of their compounding pharmacy. As P. Udstrand discusses above, it is a shame that Genentech chooses not to manufacture ophthalmic doses of Avastin. However, until ophthalmic doses of Avastin are available directly from a licensed manufacturer, we are in a quandary. The patients need treatment, but we unable to provide Avastin as quickly as their eye condition requires under the individual prescription rule, and the alternates are too expensive for patients personally or for the health care system as a whole. As suggested by G. Abrahamson above, one possible solution would be for a new type of pharmacy to be defined (“sterile repackagers”) and these pharmacies could be licensed to wholesale repackaged sterile products to qualified facilities (clinics, emergency rooms, and hospitals) if the repackagers meet stringent requirements that include inspections and sterility testing. A third party would need to oversee the sterile repackagers, and possibly the FDA would be more appropriate than state boards of pharmacy, based on the outbreak that occurred under the watch of the Massachusetts Board of Pharmacy. I’m not sure if it will be possible to get the FDA, boards of pharmacy, and legislature to work together on such a change. I am also worried that the reputation of compounding has been damaged so much by the inexcusable practices of the NECC that compounding pharmacies that are doing quality work will not get the trust they deserve.

The thoughtful comments of G. Kapphahn, P. Udstrand, and G. Abrahamson above are sincerely appreciated.