"This misconduct appears to be significant enough to cast doubt on the data generated…If the foundation of the laboratory is corrupt, then the data generated will be also,” according to the auditor. The FDA adds that Cetero also failed to conduct an adequate internal investigation to determine the extent and impact of the violations, and failed to take sufficient measures to assure data integrity within those five years (you can read the May 2010 and December 2010 inspection reports here and here).
The agency is asking drugmakers to check their databases for trials that were used to support New Drug Applications and Abbreviated New Drug Applications during those years - and to be prepared to repeat or confirm the results. Drugmakers will need to determine whether retesting is required. And those with pending applications will have to repeat bioequivalence testing or retest samples using a different lab (read samples letters here and here). Cetero performed bioequivalence and pharmacokinetic testing.
The FDA has asked Cetero for each study, drug name, study number, and the name of drug sponsors. For the moment, the FDA says it is "unlikely" these "data integrity" failures willl affect the safety and efficacy of drugs on the market and there is no evidence of any problems. But the agency adds that its request that drugmakers review testing is a precautionary measure. This is due to a "pattern of misconduct" over that five-year period.
According to a July 26 letter to Cetero, the FDA is taking this action for three reasons - widespread falsification of dates and times in lab records for subject sample extractions, apparent manipulation of equilibration or ‘prep’ run samples to meet pre-determined acceptance criteria, and a lack of documentation regarding ‘prep’ runs that prevented (Cetero) from conducting an adequate internal investigation to determine the extent and impact of these violations.”
We have asked Cetero to make one of its executives available and will let you know if they agree.
13 Comments
Kind of like the vaccine studies, I would say, that don't look at the difference between immune systems of exclusively breastfed babies and babies given antibiotics or artificial milk and nutrition or the whole picture at all. Where is the ingredient list that you are injecting into a baby's immature immune system before they are three weeks old? Their gut isn't even digesting anything really until they are older. The chorionic villi that line the intestine aren't mature for at least three weeks. That is a proven fact now. Do we really understand the complexities of the immune system and the whole body's interaction? I think not. But why update your science when you have something to sell? Just inject every baby with your fear based remedies and make it mandatory cause you can't sue the government after your child is damaged.
The part of the details that struck me on this was where the 'smoking gun' (so to speak) was found; in the electronic work folders on the analytical systems and in the electronic access card readers. All of this speaks to the integrity of electronic data - which is the real key to the updates in 21 CFR Part 11 that we are waiting for.
This case is not a standard inspection so it won't be part of the 'tag-along program' by CDER and ORA that Ed started covering over a year ag (I couldn't find the more recent link):
http://www.pharmalot.com/2010/05/fda-to-audit-pharmas-electronic-recordkeeping/
... but I would expect that it will be input into what the state of industry compliance is.
Gee,if FDA inspectors found problems that are this serious, maybe they should meet with HHS EMR and/or the health care reform folks who are responsible EMR implementation and oversight.
If they are enforcing this in clinical settings, they best be doing so for finished products in all FDA Regulated industries. Dietary Supplements included. If not, they are biased, incompetent, or severely understaffed.
Oh yeah, but let's cut spending.
Mindless dopes...
JW
Sticking to only one of many questions:
If a manufacturer finds it must adjust a product to keep from losing an AB rating - what kind of notification will be issued about product changes to allow doctors and patients to be aware of potential differences in T 1/2, peaks, troughs, kinetics? There really is nothing worse than taking something that is supposed to be the same from lot to lot - only to find it isn't. Even if it is improved. Monitoring and a dosage or scheduling adjustment may be needed.
Well, the FDA failed to catch this in 2005, and it went on for five years. That is not acceptable. It's common sense. As with all things, I'm sure the FDA will actually utilize their authority to significantly deter unconscionable significant instances of misconduct throughout the industry. There is no good reason that instances such as these are still occurring. Sorry FDA, you failed.
But it's a new day. Learn from this. We'll be watching. Attentively.
FDA should dig deeper into investigating all of Cetero sites. This is just the surface of what lurks underneath - ran by corrupt execs from MDS and their alliances.
Falsus in uno Falsus in omnibus
Cetero, wasn't he the lead singer for Chicago?
The whole issue of clinical trials is a disgrace. The protocols are written by the pharmaceutical industry who manipulate so that results are favourable for themselves.
Investigators are not required to register planned group and sub-group analyses.
If a protocol is discontinued the results don't have to be passed on to the regulatory authorities.
But why are trials stopped? Because "there are difficulties”. One “difficulty” may be because some patients die!
Mindano, FDA regulations require all severe adverse events occurring in clinical trials to be reported within 15 days. Any imbalance in AEs that is observed between treated and control groups must also be reported. If an IND is discontinued for safety reasons, a complete safety report must be filed with NDA.
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm?cfrpart=312
http://www.nejm.org/doi/full/10.1056/NEJMp1103464
Annual reports are also required for all compounds in clinical developmentj, including a full safety update.
Investigators are not required to register planned group or sub-group analyses that they plan to use for internal purposes, but endpoints that will be used for approval purposes must be prespecified. Otherwise the FDA will not consider them for approval purposes.
Sorry, that should have been "FDA" not NDA at the end of the first paragraph.
Mindano, the sponsor owns the data. Thus the investigator has no way to do his/her own subgroup analyses unless the sponsor gives him/her the data. For a multicenter study that means access to the PI's patients only. Since that is usually far less than the total data set, the PI doesn't usually have enough patients to afford the statistcal power to do any kind of cogent analysis.
Concerning: FDA should dig deeper into investigating all of Cetero sites. This is just the surface of what lurks underneath - ran by execs from MDS and their alliances. Falsus in uno Falsus in omnibus
It is amazing other Cetero site inspections have not been scheduled and sponsors continue to place trials with them.