FDA Notifies Pharmaceutical Companies of Possible Problems in Analytic Studies Used for Some Approved Drug Products
In what could be a nightmare for some pharmaceutical companies, the FDA has notified some pharmaceutical companies that analytical data (primarily bioequivalence) provided in support of some NDAs and ANDA’s may need to be re-evaluated and repeated. Seems during inspections of a Canadian facility of MDS Pharma Services question were raised about the validity of their results.
FDA Notifies Pharmaceutical Companies to Confirm or Repeat Analytic Studies Used in the Approval of a Number of Drug Products (from FDA website)
Here are the primary areas of concern from the FDA letter.
- Failure to conduct a systematic and thorough evaluation to identify and correct sources of contamination.
- Failure to investigate anomalous results.
- Lack of assay reproducibility between original and repeat results.
- Assay accuracy not assured under the conditions of sample processing.
- Biased manipulation of study data resulting in the acceptance of failed runs (emphasis mine).
- Failure to demonstrate the accuracy of analytical methods with appropriate validation experiments and documentation.
That these were allowed to go on shows a noticeable disregard for cGMP. Most of these are fundamental issues and not even in areas where there is typically disagreement. It is hard for me to fathom how this could go on! Especially troubleing is the bias manipulation item!!
What is even more interesting is it occurred over the course of four years from 2000-2004 but it is only now that the FDA is sending notices to those potentially impacted. What is also interesting to me is that there is no press release about this on MDS’ own news page. The time period covered is four years from 200-2004! While the FDA website has the warning letters they are poor photocopies and in pdf format and hard to read. Here is another source of the FDA letters in a more easily read format.
FDA Warning Letter, MDS Pharma Services (Facility Inspection)
FDA Warning Letter, MDS Pharma Services (BMIS Inspection)
Here is the actual letters the FDA sent to the affected companies:
Letter to sponsor of Pending Abbreviated New Drug Application(s) (ANDAs)
Letter to Sponsor of Approved New Drug Application(s) (NDAs)
On a personal level, one of the drugs mentioned is loratidine the generic name for Claritin. I personally use this and wonder which generic companies are affected. This is the only specfic compound mentioned that I saw but there is likely others.
This should be a warning to many companies when they rely on others for results. I think it will be a blow to MDS Pharma services and find it very confounding that they have yet to get on top of this issue and put out any sort of statement. In light of all this, I certainly would steer any of my clients away from using MDS Pharma Services.
This is also what many refer to as the cockroach syndrome. If you see one, you know there are more in hiding. My question is if this sort of disregard for basic science principals occurs in this instance, there are almost surely other incidents that have not yet been uncovered.
Technorati Tags: FDA, FDA enforcement, FDA inspection, MDS Pharma Services
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January 25th, 2007 at 2:22 pm
I am a former employee of MDS P.S. I left the company at the beginning of 2004 just as this whole
Situation came to light. I am now working for a major pharmaceutical company who has insourced much of
of thier Bioanalytical work. (They used to use MDS intensively). I will say this. MDS was run like
a clock. The volume of work they conducted was immense and it was conducted extremely well. This
one study was an unfortunate one…due to poor management and judgement.
When I compare MDS’s proceedures and methods to ones currently in place in the “Big Pharma” there is
no comparison. I was shocked when I first left MDS at the crudeness and sloppiness of the B/A
Studies conducted at my new “Big Pharma” employee….it was like night and day. If my current dept.
was a CRO it would have been shut down years ago. CRO’s (like it or not) HAVE to be run well because
they are watched intensely by the clients and the FDA. How many occurances of “Bad Data” have
occured in “Big Pharma”….I guarantee a lot more….but they can get away with it.
There were a lot of great people at MDS and a lot of great scientists….and it is unfortuneate that b
because of one or two people and their poor decisions everyone suffers. I hope they get back on
their feet and that Big Pharma starts using CRO’s more for Bio studies….because a CRO does one
heck of alot better job on the studies. (The only ones that do go to the CRO are the ones that we
can’t get to work…or if it involves a chemical/compound that is dangerous….ahh….CRO’s are
treated sooo well)
January 25th, 2007 at 7:40 pm
You are right that CRO’s in general are pretty good because they get auditted all the time from both sponsors and the FDA. I just found the wording from the FDA on “bias manipulation of trial data” to be one of the harsher wordings I’ve seen.
June 17th, 2007 at 6:52 am
MDS flags a fundamental weakness in the systems at FDA that limit their (and industries) ability to identify “bad actors” and either avoid working with them or scrutinize the heck out of them. FDA’s structure was built with an assumption that the only thing to track was a physical plant or address. I have spent half of my life managing up the org chart for quality and integrity. You spoke about the “cockroach concept”. Well how about the “litter box mentality”. A cat leaves a mess, spreads a little sand over the problem and walks away as if it never happened. People and Corporations do the same. However, their culture and personal ethics (or lack)go with them leaving no physical address that can be entered into the FDA database. Problems like this almost always track back to a management failure and the people and decisions they made. Things hit the fan at a MDS and they move on. Do they infect another site or are they born again? Who knows but they carry their personal “culture and ethics” with them making them a higher risk..
Taking technical shortcuts, playing the odds that it won’t ever be noticed, failing to address or ignoring systemic failure are people issues. Unfortunately, the bad actors (be they scientists, managers or executives) who may be the root cause are not tracked. Wouldn’t it be nice if there was a way to search and backtrack the pedigree of those individuals we entrust our data and careers to to. FDA has FEI numbers firm identifiers in the database and addresses they can search on. How about a “point of control identifier number built into the clinical, pre-clinical and GMP arenas to identify high risk people. When a 911 call comes in the computers immediately let the dispatcher know if the prior history of the location. Domestic violence is flagged and appropriate resources (police/fire/EMS) are dispatched.
If someone’s is on the receiving end of a 483, Warning Letter their history should be captured as well. As is, the letter stays with the site and the manager/PI (cat) moves on to someone else as if nothing ever happened. The best predictor of future behavior is past behavior. Would privacy and due process be a challenge? Yes but it might be worth it. Debarment and disqualification takes years and rarely happens. Linking 483’s and warning letters to the people who made the bad decisions would be a useful tool in decision making. After all we are the ones that have to clean out the litter box. The career you save may be your own.