From the Boston Globe article yesterday
"In a telephone interview yesterday, Cordis vice president Brian Firth wouldn't discuss sales figures or market share, but said the company cut production after Taxus came on the market in March. He acknowledged for the first time that Cordis has gotten widespread complaints that it can't meet demand for its stents.
But Firth said Cordis has begun hiring and training personnel to increase its supply, and the extra stents should become available after October."
So, Brian Firth wants us to believe that when Taxus was launched Cordis recognized it's superiority, conceded the market to BSX, and then fired it's trained employees who had been manufacturing for 100% of the market before the Taxus launch.
Powerplay tells us Cordis has a manufacturing problem, they can't get Cypher to stay inspec beyond 5-6 months. Cordis plans to get this production problem solved by this falls launch in Japan.
Who do we believe?
Does Cordis just concede the market where they can't win and then move on to a market where there is no competition for awhile as Firth implied. Or have they been unable to meet the FDA specs from the first warning letter they received? Only powerplay admits there is a product problem.
Inquiring minds want to know.
To your question. Yes, although other phenomena may be occuring to yield the same effect. These problems can be very complex and inconsistant. Sort of like having a car that only fails when your spouse drives it. Hmmmm, better not let my wife see this. Realize that shelf life is established by the supporting stabilty data for the pivot clinical lots and the initial commercial development/process validation lots. It is entirely possible that after producing several commercial lots for initial distribution some percentage of the lots were predicting a possible out of spec result prior to the allowed six month dating. I suspect this is the real reason Cordis has refrained from labeling product with the full 6 months data. Usually when this occures a company will have an established statistically backed strategy to ensure that you have confidently resolved the technical problem. You certainly do not want to issue a recall as we recently observed. All in all, I suspect that Cordis is repeating hard learned lessons that other companies have experinced by not having the appropriate experienced talent in critial decision making positions.
Thanks for the response.
If I understand you correctly, you are saying that it's unlikely there are issues with either the drug degrading, or diminishment of the total drug load on the stent - but rather that prolongued storage could lead to subtle changes in the polymer, or polymer-drug interactions, which alter (increase or decrease) the release rate of the drug. Is this correct?
Powerplay has suggested that Cordis has kept to a 3 month shelf-life ever since approval - even though they appeared to have been granted 6 months by the FDA. Can you speculate as to why they might do this? Could the full 6 months have been contingent on acquiring certain data first.
I am not familiar with either compound. However, drug stability and content can usually be well controlled on storage. Drug degradation tends to be more of a function of proper packaging and storage conditions. Uniformity at lot clearance is an issue of production, assuming the raw drug material was uniform. Drug availability, as you refer to drug binding or other mechanisms, tend to affect the invitro release rate on storage testing leading to either or both changes in average lot data and individual systems (increased variability; both high and low RR). It is the latter that typically is the bane for new drug delivery technologies until they mature. New technologies can also experience unusual RR problems several years after market introduction due to the accumulation of subtle changes in the processes and materials that the original QA/QC development did not anticipate. It is not an easy business. It can be a profitable one.
Powerplay, you seem to be in the know. I have a question about your explanation of the 3 month shelf life, which sounds reasonable. The problems Cordis alledgedly has maintaining the +/- 5% spec. -- is that related to total dose, or to release kinetics? Why do you think age of the stent matters? Is the drug degrading in the packaging or is it migrating from the copolymer to the topcoat? Any thoughts on that?
Thanks for the informative posts.
I've been making what may well be gross oversimplifications of the pharmacokinetics that lead to DES shelf-life limitations.
Do you have a sense of what happens to the drug load on the stent while it sits on the shelf?
Does the drug slowly leave the stent, as I have been assuming? Or does the drug stay put and it's more an issue of degradation / reactions of the drug within the polymer?
Powerplay - With respects to your criticism of the FDA guidance on drug delivery release and content specifications, there are very sound reasons for the apparent "tight" limits. These are 1) lot to lot uniformity on content and drug release to demonstrate in-control processes/materials 2)relatively small changes are allowed during appropriate storage conditions such that the product at the end of its shelf life will perform identically to the product when manufactured. The reason for this is that the product is approved based on the clinical safety and efficacy results achieved from the lots produced and used in the pivotal clinical Phase III trials. The statistical data ranges are critical because they ensure that each lot is statisitcally uniform and that only a very small percentage of product may, in fact, reach the patient that was outside that used in the pivitol clinical trials. The statistical basis is extremely well thought out and proven over the years. It derived from attempts to standardize lot content uniformity for pills, etc. ANY COMPANY or management that initiates pivitol clinical studies without understanding the implications of these specification guidelines does so at their risk to bringing the product to the marketplace in a timely fashion. Sometimes new companies and VPs new to this business do not want to believe this and have to learn the hard way.
Thanks for the info on Cyphers Japanese launch. I believe it was down played to avoid annoying any further the Docs in the 500 labs that weren't important enough to Cordis to have a production line 'dedicated' to them.
I AM a woman, no more s/he stuff, ok? Haven't I been accused of having too much to say? What more proof do you need and the nerve of me, and I'm not even an expert.....
Thanks for all the detail.
If I might trouble you with one last question - as an SRDX long, I am particularly interested in the performance of the Cypher polymer.
Is the SRDX polymer problematic, or would these tolerance issues arise with any polymer designed to (over time) elute the entire drug load? (I am assuming that the Cypher shelf-life problem is that the drug slowly leaves the stent onto packaging etc. - correct?)
If so, one of the grand ironies in all this might be that since Taxus retains 95% of the drug in the polymer they could be virtually guaranteed of staying within spec (w.r.t. prematurely eluted drug) while actually being at risk for a lot more variability in the delivered dose i.e. since only 5% of the drug isn't permanently bound to the polymer, if 1% of the drug load leaves the stent prematurely (while on the shelf), it really amounts to a loss of 20% of what was actually available for delivery to the vessel.
"BSX changes balloon platforms just prior to U.S. launch with no clinical testing resulting in > 5 deaths and > 200 open heart surgeries to remove stuck BSX/Taxus balloons,"
B.S. where do you get these numbers from? Maude or your dreams.
Right! The masters of honest data reporting (people like piled in s--t), saying that JNJ should report all of the data. What a joke. JNJ ALWAYS reports the data. Their investigators get to see the data and make their own slides, not have it shoved down their throats like BSX. BSX is the one that has adjudicated away dozens of events in Taxus 4, hidden the results of the horrible Taxus 5 (overlap DANGEROUS), etc. The other point from you is also piled high with BS. The FDA DID give JNJ a 6 month shelf life. Read the approval specs! JNJ DID self-impose the 3 month shelf-life for patient safety at the expense of profit; something so foreign to jerk-offs like you who work for the scum of BSX that you cannot fathom a company that cares more about paitients than profits. BSX sure doesn't. Their sticky non-deflating high late loss POS stent should be pulled from the market. The sooner the better.