Avid Bioservices Inc (CDMO)

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A night of sub conscience activity!

Writing yesterday’s post related to PPHM’s 2nd ln NSCLC clinical trial sabotage made me read this post again.

This morning during breakfast my mind was continuously attracted to the mislabelling of the Bavituximab and Placebo vials. So I read the post and Jeff Masten’s court testimony again. Then it occurred to me that there are a few questions, if not problems, with all this.

It is this passage that kept my attention:

Later, when Gerald Finken took over Bleecker's role, Buchanan admitted no one went back to check the Perceptive Project Requirements Specification document to make sure it was being followed by CSM.

However, there was serious evidence of vial mislabelling between the placebo and 1 mg/kg groups. In light of the labelling process that CSM should have employed in accordance with cGMP regulations and CSM SOPs, it is inconceivable that the original labels could have been misapplied. And so the inference is that some labels were swapped. (Masten Decl. 16.)

Additionally, the type of labels used by CSM allowed them to be removed and swapped without leaving a trace of residue to evidence such tampering; whereas proper labeling under cGMP regulations would not have permitted this. (Masten Decl. Tf 6.) The industry standard, within the applicable FDA regulations (including those noted above, such as 211.125 and 211.130), is to use labels that cannot be removed thereby preventing the issues which CSM caused.

Besides the fact that I already commented that I found it strange that Finken(the CEO of CSM) took over when J. Bleecker left and not another employee reporting to Angela Buchanan, there is something I overlooked in previous post on the matter.

From the above Jeff Master concludes:

And so the inference is that some labels were swapped.

He comes however to that conclusion based on:

In light of the labelling process that CSM should have employed in accordance with cGMP regulations and CSM SOPs, it is inconceivable that the original labels could have been misapplied.

Masten here ASSUMES that from the beginning the mentioned regulations have been followed AND since the mislabeling was PROVEN in his mind this could only have been because labels were applied correctly and then swapped.
But from yesterdays post the following phrases, in relation to PPHM accusing CSM of “constructive fraud”, were also on my mind:

- the gaining of an advantage by the party to be charged at the expense of the complaining party.

This legal requirement of "constructed fraud" qualification made me write this:

...what would CSM/JB have GAINED at the EXPENSE of PPHM?

Actually, I cannot answer that question. If JB was under orders or operating for a 3rd party, which is still what I think, then she did not gain anything on the expense of PPHM in the sense of THAT requirement of constructive fraud. Nothing of what PPHM lost went to here! Another party will have provided her incentive, let’s assume cash, and possibly that other party may have gained something, but JB? No, JB certainly not directly as required. So that leaves CSM to stand alone in this! We’ll come back on this below.

So could it be that the labels were mis-applied at purpose from the beginning and that CSM simply didn't follow the regulations AT ALL. But then there is that picture from where we know that CSM applies labels manually (one person applies them (the other Angela), one visually checks that (J. Bleecher) and quality control leans against the wall but very probably if not asleep will not be there all the time).

Form another CSM picture we know they also apply labels by machine, BUT that would be for LARGE batches with the same labels and operated/supervised as we could see by a single person. For a clinical trial every label is different because it is coded per patients.

That means that in the MANUAL process JB had to intervene TWICE and not ONCE! Why? Because otherwise standard and regulation compliant labels would have been applied to the vials that could NOT be removed without any trace (as per Jeff’s testimony). But JB only supervises that process, it is the other Angela (or possibly another CSM employee because the picture doesn't show Bavituximab activity and we only know for sure that J. Bleecker worked on our clinical trial) that applied the “removable labels”.

Those labels would have had to be of the SAME size, feel and looks as the other labels because we know NOT ALL vial labels where swapped. So is there PROVE (because PPHM called back plenty of vials during there investigation) that there are vials with removable labels in the lot (maybe because JB was to late to swap them?). Because IF NOT then the TWO TYPES of labels have been applied originally. Non-removable ones and removable ones for the vials of which JB would want to swap the labels later.

And then WERE did she get the removable labels. Did CSM just have boxes of the same looking labels with soft glue lying there available to JB without any internal procedure? People even have to use a card to make a photo-copy these days.

How did she get them in the printing process, because those labels are not hand written but printed by label printers, and how did she get a second, wrong, set printed. That requires more sophisticated software/database tempering. Could she do all that alone?

The below is what she needed AT MINIMUM if the labels where SWAPPED and not applied wrongly at the origin:

- A set of non-removable labels for the vials she will not touch (3mg/kg and some placebo/1mg/kg) with the CORRECT patients coding

- A set of removable labels looking exactly the same (and feeling the same to the person that applies them and Quality control if they check them) with the CORRECT patient coding

- A second set of non-removable labels with the INCORRECT patient coding per EACH REMOVABLE label.

Then she needed to mix the first two sets together, pass quality control and hope the person that applies them doesn't notice the difference between the hard glue and soft glue ones.

Next she needs an opportunity to remove the removable labels and apply the wrong ones. She needs to do this alone (unless she has an accomplish) for at least 25% of 80 vials and this multiple times per patient because there were multiple treatment CYCLE per patient.

Add to that that those vials go to different clinical trial centres and are probably packet specially for shipment. So the time window in which she can do the swapping is limited unless she also is going to open the shipping package and fix it back before the packages are collected.

Furthermore those vials are not there al nicely to be shipped in bulk the SAME day because patients are enrolled over longer periods of time and start treatment at different dates and places.

JB left on a leave in Feb 2011 and left CSM in Aug 2011 (say after 6 or 7 months leave). How many patients did finished treatment at that moment? Since we got interim data some time later we may assume probably most were treated.

So her frequency of tempering must have been VERY high to achieve the 25% with these vials only dripping out as patients were enrolled and not all in bulk. And she needed to do the complete tempering activity as described above EACH TIME, maybe even for a single label at times.

Could it be that because of this high frequency and being force in small windows of opportunity to do the swaping she was caught? Who took over between JB Feb 2011 and Finken in Aug 2011? She must have given a reason for such long leave and not to come back and not renew her Pharmacy Technicians license, showing she knew she wasn't going to work as Tech. Pharma any more.

Could it be that PPHM added constructed fraud against CSM, and not because of JB, because CSM KNEW and didn't say anything and tried to get away with it in order NOT to have PPHM and the FDA on their backs and for sure have to financially compensate? Is that why CSM filed for damage limitation upfront?

That would fit “constructive fraud” because CSM would win something on the expense of PPHM and it would therefor answer the question:

...what would CSM/JB have GAINED at the EXPENSE of PPHM.

Well at least for CSM it would become clear what they would have to gain. And furthermore PPHM could not add this accusation towards J. Bleecker. Technically PPHM has no beef with her, no contract. She worked for CSM and CSM can turn against her. If PPHM wants action in that area they need to file (and maybe they did) a complaint against the PRIVATE person JB and request a gov investigation (e.g. FDA or FBI). It would further not be in PPHM’s hands. For Bleecher the 5 legal requirements for "constructive fraud" qualification are not satisfied.

So I am going to simplify the sabotage case and say:

- Either there was no swapping at all and the labels where applied wrongly with non-removable labels from the beginning and JB just tempered with the rules and the IT-software’s/databases and no way the people at the floor could verify that, even if they had a listing to compare because that one would have rolled out equally wrong. And in this scenario JB could have an accomplice or have been under orders by someone inside CSM and maybe that could even explain her leave.

- Or, JB did swap the labels, as demonstrated above, at high frequencies in short windows of opportunity forcing here to take risk and she was caught and CSM knew on and about Feb 2011, then send her on leave (conceded by Angela Buchanan and apparently worth mentioning in her discussion with Masten for one reasons or another EMPHASIZING in the process that when Finken did take over nobody looked back which is on itself not a regular hand-over of a project but certainly a convenient one in this case). And in this later case the “constructed fraud” thesis satisfies ALL 5 required conditions allowing PPHM to add it to its list of accusations.

AIMO
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