Genentech changes distributers for bevacizumab

November 15, 2007

The retina community is greatly concerned about Genentech Inc.'s decision to embargo sales of bevacizumab (Avastin) to compounding pharmacies, which divide the large vials into single-use injections for off-label use in treating wet age-related macular degeneration (AMD) and additional disorders.

Key Points

The retina community is greatly concerned about Genentech Inc.'s decision to embargo sales of bevacizumab (Avastin) to compounding pharmacies, which divide the large vials into single-use injections for off-label use in treating wet age-related macular degeneration (AMD) and additional disorders.

The announcement has alarmed retina specialists, who fear it will block access for vulnerable elderly patients who might not be able to afford the higher-priced drug. Ranibizumab and its lower-priced relative bevacizumab have been called "miracle drugs" that have halted-and reversed-blinding eye disease in many patients and radically changed retina practices throughout the world, said Julia A. Haller, MD, president of the American Society of Retina Specialists (ASRS).

Genentech informed physicians Oct. 11 that it had decided-after what it described as FDA pressure-no longer to allow compounding pharmacies to purchase bevacizumab from authorized wholesale distributors, effective Nov. 30. That deadline was delayed until Jan. 1 after an Oct. 26 meeting with officials from ASRS and the American Academy of Ophthalmology (AAO).

Company officials also said they would rescind the decision if they receive sufficient FDA clearance to do so.

FDA inspectors subsequently expressed concern that the drug continues to be used for off-label indications, according to Genentech.

"To resolve the concerns raised by the FDA, we destroyed four batches of [bevacizumab] deemed unsuitable for use in the eye due to a higher visual inspection standard. (These lots would have been entirely suitable for its approved use as an intravenous cancer medication.) The action resulted in the loss of more than 350,000 vials of [bevacizumab] with a market value of more than $200 million. The implication of this event was that future supplies of [bevacizumab] would likewise be at risk of having to be destroyed. In our judgment, these FDA actions-and the potential for future similar actions-necessitated a change in our policy toward compounding pharmacies."

If compounding pharmacies cannot order the drug, physicians would be required to order 100- or 400-mg vials from distributors and take them to compounding pharmacies to create the single-use, 1- or 1.25-mg vials for individual injections. Genentech spokeswoman Dawn Kalmar said physicians working with hospital pharmacies would not be affected.

The company said it decided to limit distribution of the drug because the FDA had expressed concerns in a warning letter to a compounding pharmacy about the drug's sterility and repackaging. FDA inspectors, in a routine inspection of the company's South San Francisco manufacturing facility, also had raised concerns that the drug was being used off-label for ocular use, even though the facility was not designed, manufactured, or approved for this use, Kalmar said.