October 15th, 2012 by David E. Williams of the Health business blog
Long-time readers of the blog are aware of my ongoing fixation on the repackaging of the colorectal cancer drug Avastin for injection into the eye to treat wet age related macular degeneration. Genentech makes Avastin and the very similar drug Lucentis –which is intended for the eye. Compounding pharmacists figured out that they could split Avastin vials into the much smaller quantities required for the eye and create the equivalent of a $2000 dose of Lucentis for under $100.
Genentech tried to block this practice by not renewing its contracts with compounding pharmacies, but eye doctors kicked up a fuss about it. My principal objection to the practice was (and is) that Genentech should be allowed to get paid based on the value it delivers rather than the size of the dose. Otherwise no one will ever invest the money for eye drugs in the future.
The company was pilloried for being greedy, but I was sympathetic to their other arguments as well. These arguments included concerns about the safety of compounding pharmacies repackaging Avastin for use in the eye. When I interviewed Genentech on November 1, 2007 they noted that FDA had come into the company’s South San Francisco plant and decided to hold the company to the higher ocular standard for particulates rather than the intravenous standard. The argument: Genentech knew compounding pharmacies would be repackaging. As a result Genentech has to destroy a number of lots of the product.
Genentech pointed me to a December 4, 2006 FDA warning letter sent to New England Compounding Center (NECC), the same organization at the center of the ongoing contamination scandal that’s led to several deaths. Item number 3 includes the following:
“FDA is particularly concerned about the manipulation of sterile products when a sterile container is opened or otherwise entered to conduct manipulations. The moment a sterile container is opened and manipulated, a quality standard (sterility) is destroyed and previous studies supporting the standard are compromised and are no longer valid. We are especially concerned with the potential microbial contamination associated with splitting Avastin – a single-use, preservative-free, vial — into multiple doses. When used intravitreaily, microbes could cause endophthalmitis, which has a high probability for significant vision loss. The absence of control over storage, and delays before use after repackaging, only exacerbate these concerns…
“Avastin is approved for use in the treatment of colorectal cancers. The text of your alleged promotional material offers this drug to ophthalmologists . Avastin has no approved indications for use in the eye. As such, your firm is distributing an unapproved new drug in violation of section 505 of the FDCA. Because the product lacks adequate labeling for its intended use (see 21 CFR § 201.128) your firm is also distributing a misbranded drug in violation of section 502(f)(1) of the FDCA (21 U.S.C. § 352(f)(1)). Also, please note that, under section 301(a) of the FDCA (21 U.S.C. § 331(a)), the introduction or delivery for introduction into interstate commerce of any drug that is misbranded is prohibited…
“Further, we have been informed that, although your firm advises physicians that a prescription for an individually identified patient is necessary to receive compounded drugs, your firm has reportedly also told physicians’ offices that using a staff member’s name on the prescription would suffice. Drugs compounded in this manner are not compounded consistent with the CPG, and FDA will not exercise its enforcement discretion regarding those drugs.
The FDA investigation was based on a complaint filed by someone anonymously. Genentech professed ignorance about who that could have been.
In any case, the key concerns that are being publicized in the wake of the current NECC scandal are addressed in that section. Which raises an interesting question: should we be so quick to let Massachusetts regulators off the hook when FDA provided such a stark warning about this very facility years ago? Wouldn’t it have been reasonable for someone to follow up on the simple topic of whether drugs were being compounded for specific patients or shipped in mass quantities?
It seems like FDA went above and beyond the call of duty by going up the chain to Genentech –where the Agency has more authority– and imposing higher standards on them to try to prevent downstream troubles.
FDA should definitely be called upon to police so-called compounding pharmacies that in reality act as drug manufacturers.