January 24, 2013 ~ Great thanks extended to Courtroom View Network for access to court proceedings.
Day 10 of the Linda Gross v Ethicon trial in a New Jersey courtroom brought another look at the inner workings of Ethicon, a division of J&J that brought the controversial Prolift pelvic organ prolapse mesh to market.
It was a group effort and Sean O’Bryan, Sr. Project Manager for Regulatory Affairs, was one of the cogs in the corporate wheel with a March 2005 launch date for the Prolift pelvic organ mesh.
He was responsible in the early stages and gave “immediate impressions” what regulatory considerations would lie ahead especially in the area of safety and efficacy.
“I think of myself as an internal FDA person” he said in the deposition.
O’Bryan relied on others to complete the task.
In a videotaped deposition shown to the jury O’Bryan named Medical Affairs, the development group, design control and engineering as team members. All would have to sign off on the project before it would be sold.
According to O’Bryan, no one had the final say over the project.
Medical Affairs, headed by Charlotte Owens, would need to inform him about the potential risks and adverse events. “I expect them to distill that information to see if it’s appropriate to put in the literature” he said on videotape.
Attorney Slater showed O’Bryan the Code of Ethics for Regulatory Professionals. O’Bryan was familiar with it. He would do public speaking on the structuring of an FDA submission or how to hold meetings with the FDA.
Yet when it came to the Prolift, a revolutionary new medical device – a precut mesh in a box complete with trocars for permanent implantation – O’Bryan and the team decided the previous generation Gynemesh, was similar enough to the new Prolift.
O’Bryan: “The reason we didn’t feel the need to submit a new 510(k) was because the changes were not significant enough to warrant a new 510k.”
That’s in sharp contrast to company documents shown Tuesday that showed within Ethicon Prolift represented a “Major Mindshift” on several key aspects of pelvic organ prolapse surgery, “which may require a greater shift of thinking.”
An FDA approval plan could require clinical data but attorney Adam Slater established Ethicon never recognized the need for clinical data and Medical Affairs never determined clinical data was needed. All of the various departments would rely on that type of information for assurances of safety and efficacy, hazards, potential harms and risks.
Slater asked: “If Medical Affairs advocated that clinical data was needed, then you would have been duty bound to make sure the regulatory pathway was to seek a 510k clearance correct?”
A 510(k) application would have allowed Ethicon to notify the FDA it planned to sell the Prolift providing it furnish similar devices or “predicates” already being sold to assure safety and efficacy. Trouble was there was no predicate for the TVM (transvaginal mesh) implant procedure.
Ethicon never sought FDA clearance either through the 510(k) process or through the more rigorous premarket approval. Prolift was sold without being brought to the agency’s attention and it wasn’t until three years later that the FDA learned what had happened.
Instead of sanctions, the FDA approved the Prolift mesh implant.
O’Bryan left Ethicon in March 2005, the same month Prolift was launched.
Patient Label and INSTRUCTIONS FOR USE
O’Bryan was involved with the development of the Instructions for Use (IFU) and patient brochure, the primary document doctors look to for warnings and precautions. His involvement with the IFU development was to evaluate it for general grammar, text and content. Again, it would be the team that set the tone.
“No one individual owns the IFU per se it’s a team effort,” he said.
O’Bryan said he relied on the medical team to tell him what belonged in the product insert warning which would include adverse events and contraindications.
End users of the Prolift, that is physicians, would be assured by the language that appeared with the Gynecare Prolift brochure. It said “Federal USA law restricts this device to sale by or on the order of a physicians.”
Slater asked would that language indicate to a physician that it is legal to market the product under federal law? O’Bryan said they would “know it’s gone through our design control and it’s legally marketed.”
In reality, the FDA didn’t even know Prolift was being sold until three years after it was launched, a violation of FDA rules and requirements.
MIA from IFU
O’Bryan and Slater went down a laundry list of the things not included in the IFU:
*Mesh pore collapse
*That significant complications can affect the woman’s qualify of life
*Scarring resulting in implant contraction could lead to significant consequences to the patient
*Mesh retraction contributed to recurrence, postoperative pain, vaginal rigidity, mesh thickening and dysparunia as identified by Ethicon’s own research team in France
Slater asked if he as Regulatory Affairs manager would want that information included.
Slater: “To the extent that Medical Affairs knew that was a risk that could occur with the Prolift, if Medical Affairs believed that, you would expect they would have brought that to the attention of the team and advocated for that to be included as further explanation of the potential injuries a patient could suffer correct?”
A: “I assume they would make that assessment.”
Q: “And you don’t recall these consequences of implant contraction being aware of those things?”
A- “You are correct I don’t recall.”
O’Bryan was shown the European Journal of Surgery 1999 which showed Medical Affairs would be knowledgeable about mesh retraction linked to tissue inflammation after implantation. He asked if O’Bryan had any recollection of bringing that information to the design team so it could be warned about in the IFU.
A “I don’t have a recollection of that.”
Q: “Do you have any recollection of your design team evaluating what would happen women who need to have mesh removed and the extent of damage that could occur as a result.
A: “I don’t have memory of that.”
Q: “If Medical Affairs understood some women would need extensive surgery that would leave them with extensive morbidity and damage to the vagina and pelvis, if Medical Affairs understood some women would face that, that’s something you agree should be in the IFU correct?
A-“I would assume that they would take that into assessment and reflect it in the IFU.”
Q:”It’s not there right?
A:”It’s not there.
Later Thursday afternoon, the jury was shown the videotaped deposition of Linda Gross’ physician Dr. Feagins, as well as a biostatistician to comment on the data Ethicon collected concerning Prolift.
That story will follow. ###