I interviewed Genentech spokeswoman Dawn Kalmar today to get some more details on the company’s decision to stop distributing Avastin to compounding pharmacies. For background please see my prior posts: Avastin update: Still seeking answers and Latest developments in the Avastin/Lucentis saga raise new questions.
- In its inspection of Genentech’s manufacturing site, FDA objected to the level of particulates in Avastin, holding Genentech to the higher ocular standard rather than the intravenous standard
- Genentech is hopeful that it won’t have to make Avastin to the ocular standard on an ongoing basis, but isn’t certain
- Genentech doesn’t know who filed the complaint against New England Compounding Center that led to a Warning Letter against that compounding pharmacy for repackaging Avastin
- Genentech seems unlikely to seek FDA approval to continue supplying Avastin to compounding pharmacies
In my view, this isn’t turning out too well for Genentech.
- Avastin repackaging will continue to stunt Lucentis sales
- FDA may force Genentech to make Avastin to ocular standards on an ongoing basis
- Ophthalmologists are unhappy with Genentech rather than grateful to it for the efficacy of Lucentis
Here’s the transcript of the interview:
David Williams (Health Business Blog): What specific concerns did the FDA raise in its inspection of Genentech’s South San Francisco plant? What is meant by a “higher visual inspection standard”?
Dawn Kalmar (Genentech): When we make a drug to ocular standard, like Lucentis, it undergoes a visual inspection, where –literally in a room that has little booths that are specially lit– our inspectors lift up the vial to the special light to see whether or not there are any impurities, particularly any particulate matter in those solutions. They hold them up to that light and they spend hours looking at these vials and making sure that all the vials that leave our site are meeting the ocular standard.
That type of inspection is not undergone for Avastin or drugs that are designed to meet the USP intravenous standards. So, it’s an additional step that’s taken for a drug to meet ocular specs. And the USP specs are different for intravenous versus ocular… The major difference is the ocular grade has less particulate matter.
When the FDA came and conducted this routine inspection of Avastin, they performed a visual inspection on the Avastin despite the fact that that is typically reserved for an ocular grade drug.
David: Since you supply Avastin to compounding pharmacies you have to assume some will be used for ocular use. Is that the issue?
Dawn: Right. The implication was that if they were performing this type of inspection of Avastin and if they did ask about the ongoing ocular use of Avastin and we said, “Well of course we don’t make it to ocular grade because that’s not what it’s designed to do,” and they [would say], “Yes but you know that it’s being used in the ocular setting.” And so the implication as the letter describes is that this type of inspection and potentially having to destroy lots of Avastin would continue.
David: The American Academy of Opthalmology letter indicates that Genentech has agreed not to impede physicians or other legal agents, such as group purchasing agents, from ordering Avastin or using compounding pharmacies after the embargo is in place. Is that your understanding?
Dawn: Yes. It was not our intent to block the use or stop the use of Avastin in the eye. It was simply our intent that we would no longer have agreements with compounding pharmacies that would allow them to purchase from distributors. Once our drug goes from the distributor directly to the physician or from the distributor to the hospital pharmacy it is in the market and is available for physicians to prescribe as they deem appropriate. We would not interfere with that. That’ part of the practice of medicine. We don’t get involved at that level.
David: Is that change in distribution important to the FDA? Can’t they come back and say you know it’s still going to be used in the eye?
Dawn: Compounding pharmacies are not part of how we distribute any of our intravenous drugs. In April of 2006 we made changes to how we distribute all of our infused oncology products: Rituxan, Herceptin and Avastin. And those changes were made to reduce the number of distributors, primarily for security reasons given anti-counterfeiting concerns and the value of these drugs to the company. One of the channels that… was an obvious choice for us [to eliminate] in the oncology setting was compounding pharmacies. Because compounding pharmacies are not a necessary route for the drug to get from us through the distributor and ultimately to an oncologist.
We made the decision to remove compounding pharmacies from our distribution model. When we made that public, the retina specialists raised significant concerns, much in the same way they’re doing now, and they said, “Look, we’re at a time where we know you’ve got Lucentis coming. We’re still waiting for FDA approval. We need Avastin and we need ready access to it given the unmet patient need that’s out there.” And so we evaluated the decision and in our October 11 letter we outline that we continued to permit compounding pharmacies even after that global change to our infused oncology model went into place in ’06. We decided to continue to allow compounding pharmacists to purchase Avastin, given the unmet need.
What enabled that was contracts that were in place with compounding pharmacies. Those contracts were one-year contracts, and they began to expire in June and continue to expire through November. And so our date of November 30 wasn’t an arbitrary date. And what we decided was knowing that it would have a significant impact on the ophthalmology community we decided to allow the seven weeks notice, so that they would know that as of November 30 no longer would Genentech have these contracts because we were not going to renew them. And that was based on our assessment of the situation that is described in the October 11 letter –of primarily FDA approval of a drug so it’s a different situation than in 2006, and our commitment and confidence in our access programs that patients will not have to go without an approved therapy.
David: Let’s say I’m an FDA inspector and come back to your South San Francisco plant. I take the Avastin and want to hold it up to the light, because I know Avastin is still being used in the eye. Will the Genentech people at the facility say, “That’s an unreasonable standard. You can’t hold us to that because we no longer distribute Avastin directly to compounding pharmacies?”
Dawn: I can’t speculate on what the future will hold. We are doing our best to make sure that the drug is delivered appropriately and that it gets to where it needs to go for its approved indication; we don’t regulate beyond that. Now what’s going to happen in the future we can’t predict.
David: Do you think you’ll have to make Avastin to an ocular standard in the future?
Dawn: Our judgment based on these FDA actions [was] that there was a potential for future similar actions and that that necessitated our change in policy.
David: In your open letter you refer to an FDA Warning Letter that was sent to a compounding pharmacy. Is that the December 4, 2006 letter that was sent to New England Compounding Center?
Dawn: That’s correct.
David: Do you know who filed the complaint against them?
Dawn: We do not.
David: Your open letter says “Genentech has also agreed that it would reinstate its supply of Avastin to compounding pharmacies if the FDA gave the company legal and regulatory authorization to do so.” Has Genentech requested this authorization or does it intend to do so? What would have to be done to obtain such authorization?
Dawn: Well it’s a pretty complicated situation since right now there are no studies ongoing or even planned that are of the rigor that would enable a formal sBLA submission to the FDA. So it’s a pretty unique situation. The specifics of how that will happen and what discussions will happen with the FDA, that’s something that we have yet to work out with both the AAO and ASRS. Basically they asked us, ‘Would you reconsider if the FDA gave you legal and regulatory authorization to continue these contracts?’ and we agreed to that, but the specifics have not yet been worked out. In our minds it would have to be some kind of a written statement from the FDA providing authorization to us to continue to provide Avastin to compounding pharmacies free of FDA action. And it would also have to be with the acknowledgment that we will not change our current manufacturing processes.
David: Are there other issues you would like to address?
Dawn: In the first round, when we first put out our October 11 letter, there was a lot of criticism that we did this for financial motivations. And I think that our current course of action and our willingness to work with the ophthalmology community softens that a little bit and hopefully sends a signal that this was not all about finance for us and not all about profit. We acknowledge that it is a very difficult situation for all parties. It’s been difficult for us and it’s been difficult, obviously, for ophthalmologists. But we are confident that Avastin will continue to be available and that physicians who want to continue to prescribe it will be able to do so.
David: It’s a tricky situation.
Dawn: It’s a unique and difficult situation. And obviously what physicians can do today with Avastin given the rules that govern them on off-label use are very different than what Genentech can do with Avastin. It’s a different set of rules.November 1, 2007