UPFRONT

Trouble Ahead

Peter K. Kaiser, MD

In response to the New England Compounding Center (NECC) fungal meningitis disaster that killed 64 people across 20 states due to contaminated compounded steroids, Congress quickly enacted House Resolution 3204, the Drug Quality and Security Act (DQSA), which President Obama signed on Nov. 27, 2013.

While the goals of the act were laudable, the enactment has produced many unintended consequences that limit our ability to choose the anti-VEGF medication we want to use. As physicians, we all must step up to insure that things are changed.

First, the act requires patient-specific prescriptions for compounded drugs, including Avastin, for “in-office use.” Essentially, this eliminates treating any new patients with Avastin because you wouldn’t have been able to order the drug prior to seeing the patient.

At follow-up visits it becomes easier because you can order the medication ahead of time, but then you cannot bill for the visit because you planned the treatment and weren’t treating as needed. If the patient misses the visit, the drug cannot be used for another patient; it must be destroyed.

The act presents logistical nightmares such that some practices have simply stopped using Avastin for this very reason. To make matters worse, the act does not define “in-office use.” In response, some states have passed legislation allowing in-office use, so patient-specific prescriptions and other aspects of the act are not required. Check with your regulatory officials to see if you’re lucky enough to live in such a state.

More recently, the FDA released draft Interim Guidance for Human Drug Compounding Outsourcing Facilities Under Section 503B, drafted with the assistance of an advisory panel that included anti-VEGF pharmaceutical industry representation and some physicians but no ophthalmologists. This is an important fact given that we are the largest user of compounded medications in the US, and we had no say in the guidelines that mandate its use.

These guidelines cover 503B outsourcing facilities that can compound drugs. The DQSA has brought these pharmacies under FDA supervision, which is a very good thing as oversight was lacking in the past. But the draft guidelines proposed by the FDA have one very serious issue that has to be changed: beyond use dates (BUDs).

The guidelines have proposed BUDs for all compounded drugs, including Avastin, of four hours if no microbial challenge testing is performed, 24 hours if it is, and a maximum of five days after successful container application and “product integrity” testing by the pharmacy. The BUD clock starts when the Avastin vial is opened.

Many current compounding pharmacies perform microbial testing much longer than five days to insure sterility, so this rule effectively requires them to send out the drug before getting back the results of sterility testing. More importantly, the rule is not based on any scientific facts or even in line with previous FDA guidelines.

The FDA allowed a BUD of up to two years (stability testing established an initial six-month shelf life that was gradually extended to two years) for the compounded Avastin used in CATT and Protocol T. This is a big difference. Obviously, a five-day BUD adds another logistical nightmare that further limits our ability to treat patients with Avastin. The guidelines are currently in draft form, so pressure from AAO, ASRS, and you, the end user, is required. Please call, write, and pressure your legislators now.