Avid Bioservices Inc (CDMO)

[Protector]

The 'Discrepancy' files

A lot of discussions on this board are about the lawsuit filed by Peregrine against CSM. I'll try to write a post with a more complete analysis whether CSM, PPHM/Avid or both CSM and PPHM could be part of the error(s) that lead to the discovery by Peregrine of the discrepancies case.

Which are the parties involved
There are only two parties involved. CSM the CRO that conducts the clinical trial and Peregrine/Avid that ordered the clinical trial. All other parties that may have participated at some extend in this clinical trial can only be sub-contractors of CSM under the end responsibility of CSM.

Who does what
Peregrine orders a double blinded clinical trial with a CRO that is licensed by the FDA to conduct such clinical trial under FDA regulation.
Avid, Peregrine's fully owned subsidiary and therefor considered as one party with Peregrine, provides the drug under investigation, Bavituximab (Bavi) that it manufactures itself in its FDA approved cGMP facilities, to the CRO.
CSM, the CRO, does all the rest.

How and who does Peregrine Audit during Clinical Trial
Peregrine doesn't, AT ALL. It is not only not allowed under FDA regulations but it can also not hire a third party to do so that would report back to Peregrine. Even more CSM is responsible under its FDA License to not divulge any information to other parties that don't have the need to know. The board dealing with censoring patients for instance is a party that may receive limited information on a need to know basis. Double Blinded means only the CRO knows what patients are assigned to what arm of the clinical trial. Peregrine, the treatment centers and the patients must wait until the data is unblinded.

Which parties could have made the errors leading to the discrepancies?
Theoretically CSM, one of its sub-contractors or one of the manufacturers providing Bavi, Placebo or the SOC product. But for our case we can exclude all but CSM. Why! Because CSM is responsible for ALL sub-contractors and deliveries it receives and redistributes, EVEN those coming from Avid. CSM is responsible to test deliveries and make sure they are what the manufactures claim they are. This guarantees that Avid could not deliver some stronger Bavi version (if that would exist) or that the SOC manufacturer doesn't change anything to his product that would invalidate the trial or that the placebo is the placebo decided upon in the trial design.

What does the CRO do then?
The CRO receives products in bulk because it cannot place detailed orders of the dugs and placebo because it cannot give away any data about patients, patients assignment to trial arms, dosage related to body weight, etc. Furthermore the CRO must make sure that at the treatment centers people cannot directly or INDIRECTLY detect what patient is receiving what treatment. That means they label and code these products in a new package after which one doesn't see any difference between placebo and Bavi. Not by the color or smell of the substance, nor by the bottle and not even by the path of delivery or some administration related to it. Only sending it to a lab could distinguish them.

What is the nature of the error leading to the discrepancies
The labeling and coding of dosages for SOME patients (not ALL) did not fit the sample test results. This error results in a discrepancy where what one reads from the labeling and coding when the data has been unblinded does not adhere with what the sample tests show.

Could Avid by involved
Avid, Peregrines fully owned subsidiary, is a manufacturer of Bavi that ships bulk Bavi to CSM because it, as every other manufacturer of placebo and SOC product, may not be given any information about the clinical trial that it would need if it where to ship any other form of deliveries then bulk!
The CRO samples the bulk to make sure that Avid, as being Peregrine, cannot cheat and deliver something else and then get undeserved credits for Bavi if the clinical trial is successful. Avid does no labeling, and certainly no coding, except for the labeling of its bulk shipment. Avid does NOT deliver the placebo, nor the SOC product and cannot mix up products either because the Bavi for the 1mg and 3mg arms are identical. Bottom line, Avid isn't involved in any activities that would qualify with the nature of the error leading to the discrepancies and its own possible errors (other product) must be detected by the CRO. Avid manufacturers on demand so a wrong product shipment to the CRO should result in another party receiving Bavi! That would be a double error of which it is very unlikely it wouldn't have been detected either then!

But still, assume Avid made wrong deliveries and CSM didn't detect it, what then!
Except for the fact that CSM would remain responsible because they needed to discover it during sampling Avid could be held responsible by CSM for its deliveries. This also should have been discovered long BEFORE unbinding and action would have been taken.
We know for sure such action hasn't been taken, it is a material event Peregrine would have had to announce at that time. Furthermore if this was the problem then the nature of the error would not be labeling or coding because it is not because Avid would have delivered another substance that CSM would have made a parallel labeling and coding error for that substance, what a coincidence would that be!

Peregrine Filed Lawsuit against CSM for neglect
A company may have several reasons to file a lawsuit.
To site Bungler

preserve your claim, preserve your jurisdiction, but allow the defendant the opportunity to resolve the issue through cooperation instead of through costly and contentious adversarial proceedings,

In all scenarios if management files without having a case then they know that in the end CSM will not let it rest and they'll have to sit on the broken pottery. So rest assured that they will have hard evidence and depending on the nature of the error will have know immediately whether Avid could be involved or not.
As a consequence of the knowledge they would have first investigated Avid deliveries before filing a lawsuit against CSM.

Is there other, possibly circumstantial, information pointing to CSM.
Yes there is. First the party that made the error had to be in a position where they could make the error in such a way that it would only affect SOME and NOT ALL patients. CSM did all activities for which there was opportunity to make such errors on an ARM based level or a TREATMENT FACILITY based level or on any other grouping qualification level.

Furthermore every person of good will will accept that after Peregrine's announcement of Sept 24th and the filing of the lawsuit that same day, it is impossible that CSM would not be aware of being sued even though they are not served yet.

We know they are not served because there is no return from the server at the court and we know they didn't spontaneously reply to the filing either because there isn't any such activity trace at the court either.

So why would an FDA Licensed company such as CSM of which one of its main businesses is to conduct such expensive and important clinical trials allow its name and reputation to be smeared without even the slightest reaction, as if nothing happened?

It is simple, they wouldn't unless they know Peregrine has a case and that it would be best for them to settle in silence and limit the broken pots. Its faster, cheaper, less embarrassing, better for reputation and their business. In all other cases, if Peregrine didn't have a case, believe me they would have made sure everyone, including their current and potential future customers, would know! In that case we would know it too and we don't!