Declaration of Jeffery Masten attached to Court filing. Same caveats on the OCR scan regarding accuracy and glitches from my original post. Research the original Court filing for complete accuracy.
FROM: DECLARATION OF JEFFREY MASTEN IN OPPOSITION TO DEFENDANT'S MOTION FOR PARTIAL SUMMARY JUDGMENT
I. Jeffrey Masten, declare: 1. I am competent to and would testify to the following if called upon to do so as a witness. 2, My professional career has primarily been devoted to quality assurance in the pharmaceutical industry. My career began in quality assurance with EH Lilly & Company where I worked from April 1980 to November 1997. After that, I worked for Avcntis Behring until March 2002, where I held the title of Director, Quality Assurance upon my departure. I next worked for Genentech from April 2002 until April 2010, where I held the position of Sr. Director, Quality. While working, I studied for and received my M.B.A. from the University of Notre Dame, Mendoza College of Business in 2002. After my departure from Genentech, I joined Peregrine Pharmaceuticals, lac. ("Peregrine"), where I worked from May 2011 through February 2014, holding the title of Vice-President, Quality. 3. When I joined Peregrine, the Phase II bavituximab trial (the "trial") at issue in this case was already underway. I was assigned the quality assurance responsibilities for the trial when I joined Peregrine. The trial is discussed in the accompanying Declaration of Joseph Shan. The Audit 4. Because of concerns about how the trial may have been administered, I and others at my direction, on behalf of Peregrine, audited the performance of all of the contractors in the study. The audit team ultimately concluded that CSM was the sole cause for errors we observed in the trial. Indeed, I was advised by CSM management that there was an intentional action taken by CSM to switch the vial labeling for the "A" and "B" treatment arms. All other parties we spoke with agreed that the Perceptive Clinphone specifications were supposed to be followed by all vendors, yet upon review and discussion with all the other vendors, none were aware that CSM took this action to switch the labeling. CSM informed me that they switched the labeling to protect the blinded nature of the trial design. 5. As part of the audit, I flew to F argo, North Dakota to get to the bottom of the problem and visited CSM on September 19,2012. I initially met with Angela Buchanan, the Director of QA at CSM, on September 20,20i2. Buchanan admitted to me that Project Manager, Jeanette Bleecker ("Bleecker"), had switched the treatment code assignments for the control (placebo) and 1 mg/kg arms in violation of the Project Requirements Specification document and CSM Standard Operating Procedures ("SOP") and apparently did not mfoim any other management employee in the company. Initially, Buchanan said to me that she had no idea why this was done. Buchanan indicated that she was still a friend of Bleecker's and volunteered to me that Bloccker had taken a one week bereavement leave in late February 2011, and then terminated her employment on August 5,2011. She also explained that later, Gerald Finken, CEO, took over Bleecker's role while she took her leave, and apparently continued to approve the same switching of labeling for the two treatment groups without QA knowledge. 6. Under my direction, of the 8,000 vials manufactured for the study, approximately 7500 vials were retrieved from sites around the world, and of those, 99% contained enough volume to determine their contents. Our audit confirmed that all C group patients were correctly treated with 3 mg/kg bavituximab doses. However, we found serious evidence of vial mislabeling between the placebo and 1 mg/kg groups. In light of the labeling process that CSM should have employed in accordance with cGMP regulations and its own SOPs, it is inconceivable that the original labels could have been misapplied. And so the inference is that some labels were swapped. Additionally, some of the type of labels used by CSM allowed them to be removed without leaving a trace of residue to evidence such potential tampering; whereas proper labeling under cGMP regulations would not have permitted this. The industry standard, within the applicable FDA regulations (including those noted in 21 CFR Parts 211.125 and 211.130), is to use labels that' cannot be removed, thereby preventing any possibility of label tampering. The number of mislabeled vials is small but, by extrapolation the mislabeling problem potentially implicated mathematically up to 25% of the total vials labeled for placebo and up to 25% of the total vials labeled for 1 mg/kg treatments. 7. In carrying out its tasks, CSM was obligated and contracted as a Contract Research Organization ("CRO") to comply with industry standard good clinical practices ("cGCP") established by the 'international Conference on Harmonization ("ICH") Guidelines, and to comply with various Food and Drug Administration ("FDA") mandated good manufaeiiiring practices (ncGMP") regulations including, without limitation, those set forth in 21 CFR Parts 210 (Current Good Manufacturing Practice in Manufacturing. Processing, Packaging, or Holding of Drugs, General), and 211 (Current Good Manufacturing Practice for Finished Pharmaceuticals), 8. Under proper cGMP labeling, there should have been no possibility any product mislabeling could occur at the inception of the study, or anytime labeling of investigational product was required. Further, the only judgment Ms. Bleecker had to exercise was to anticipate adequate amounts of doses to be shipped to the treatment sites so that inventory was not wasted and vials were always available to the patients when needed. However, when the approximately 7500 vials were recovered, some appeared to have their label removed and a few had no label at ail. 9, The audit also revealed that Bleecker took other bizarre actions that she did not apparently do for other similar client trials. She did not inform any other vendor and did not disclose that she had made any deviation to the Perceptive Clinphone protocol. Significantly, she didnt advise her Director of QA, Angela Buchanan, that she had taken this step. Had Ms. Bleecker been authorized to make such a change, she was required to notify certain of the vendors; most notably, Perceptive, Upon such a change, Perceptive would have been required to redo its validated Clinphone and the Project Requirements Specification, which would have taken a significant amount of time and money to revise, revalidate and obtain approval prior to the trial commencing. She and CSM did not do that. And so these unilateral steps by CSM are not explainable or defendable from an industry practice and regulatory standpoint. Additionally, she maintained her own tracking of product inventory to and from the clinical trial sites, as some sites returned their unused product vials as well as some used product vials. We were informed by Ms, Buchanan (QA) thai this practice was not according to CSM SOP and not performed for any other client's trial. 10. Based on our audit, CSM violated 21 CFRPart 210 (Current Good Manufacturing Practice in Manufacturing, Processing, Packaging, ocr Holding of Drugs, General) and 21 CFR Part 211 (Current Good Manufacturing Practice for Finished Pharmaceuticals). CSM violated 21 CFR 211.125 (labeling issuance) by using labels that could be removed and reapplied, and by switching the label assignments to the treatment groups. Based on our audit, CSM also violated 21 CFR 211.130 (packaging and labeling operations) by not labeling the vials in a manner that potentially allowed them to be accurately tracked later. CSM also violated 21 CFR 211.142 (warehousing procedures) by not ensuring the vials were stored in a manner ensuring the identity of the contents, strength, quality and purity could be determined later. Based on our audit, CSM also violated 21 CFR 211.150 (distribution procedures) based on the various examples in which supposed placebo patients (according to CSM based on the swap of the "A" and T,B" arms), actually showed indications they did receive some levels of bavituximab. 11, Additionally these violations also transgress corresponding industry standard practices set forth by the ICH.
AI
