We are on the record at 9.12 a.m. August 28, 2015 in the matter of Commonwealth of Kentucky Pike Circuit Court Division 2, Civil Action Number 07-CI-01303, Commonwealth of Kentucky versus Purdue Pharma. This is the deposition of Dr. Richard S. Sackler, if I could have the attorney state the name into the records. Do you want to just go ahead and read the list of names?  Let's just say our name. We'll pick it up. Jason Sayers on behalf of Abbott. Dan Danford on behalf of the Purdue Defendants. Donald Straber on behalf of the various Purdue Defendants. Oh, sorry. Richard Silver in-house at Purdue. Jay Henneberry on behalf of the Purdue Defendants. Tyler Thompson on behalf of the State of Kentucky. Anthony Ross on behalf of the State of Kentucky. Ed Mitchell Denham from the Attorney General's Office, behalf of Kentucky. Did you state your name please? Richard Sackler. And you are here today to give testimony in a case pending against Purdue various entities by the State of Kentucky. You're aware of that? That's my understanding. Mr. Thompson, before you get started, I'd just like to note that I expect we will be designating portions of this transcript as confidential pursuant to the order. Is that correct, Mitchell? Yeah, it is. Sure. Okay. We want to disseminate it until you all designate and we respond. There's a certain period in the rule when you get shot. Right. And just so you know, I know you're not from Kentucky. Is that correct? That's correct. All objections other than to the form of the question are preserved in Kentucky. I'm going to start with a quick question from the bottom of the video. What is your current role at Purdue? Excuse me, there are a number of defendants with some portion of Purdue name and the distinction can be significant. So I'd ask when you phrase your questions, specify which Purdue entity you are talking about. Well, let's talk about the number of Purdue entities there are. How many Purdue entities are there? I don't know. There are upwards of 69 different corporations perhaps that the Sakura family owns. Is that correct? If you've counted them, I can't differ with you. I don't know the answer. There are a number of Purdue entities. The Purdue Frederick Company Inc. Does it still exist? I don't know. Tell me what companies that you currently have a role with that involve Purdue? Purdue Pharma. Do you sit on the board of any other Purdue companies? Not to my knowledge. What about Mundy Pharma? I sit on the board of a consulting firm which consults to Mundy Pharma. Does the Sakura family own Mundy Pharma? Yes. What about what is Mundy Pharma? Mundy Pharma is a name that is attached to many different companies such as just similar to Purdue. Is that company over in Germany? There is a Mundy Pharma company in Germany. What about Roxanne? Does Purdue own Roxanne? No. Did they own Roxanne in the past? Never. Do you know how many current companies are owned by the Sakura family? No. In discussing Oxycontin, how many companies were involved in the production, manufacturing or distribution of Oxycontin? Could you specify the geography? In the world. Many. I've never counted them. Does Purdue do licensing agreements with other companies to sell Oxycontin? It does. Do they own parts of those companies? No. How many companies does Purdue own that distributes or dispenses Oxycontin? Many. Can you tell me the names of them? A few of them, but not all of them. Are you still the director of Purdue Pharma, Inc.? I'm not sure. Are you still a general partner of Purdue Pharma LP? I am not. It is owned by two trusts. In July 30th of 2014, were you a director of Purdue Pharma, Inc.? Not that I'm aware. This is a affidavit filed in the southern district of West Virginia. And does that appear to be your name? That does. Once dated July 30th, 2014, it says declaration of Dr. Richard S. Sackler. I am a director of Purdue Pharma, Inc., the general partner of Purdue Pharma LP. I've held this position since 1990. That's what it says? And that's what it says? How involved were you in the production and marketing and promotion and the training and management of Purdue sales representatives for Oxycontin? I object to the form of the question. Should I answer? Go ahead. You can answer. It depends on the time. And when you say it depends on the time, why do you say that? Because I was involved in the areas at a supervisory level, not as an active level, for a period of time that began with the launching of Oxycontin and ended in early 2003. When you were involved on the supervisory level, but not the active level, how much of your day-to-day activity was devoted to Oxycontin? It varied enormously. In this declaration, it says, during the time period set forth in the amended complaint, 1996 to 2009, I was not directly involved with the day-to-day marketing or promotion of Oxycontin, the training or management of Purdue sales representative, scientific research into the conversion ratio from MS-contin to Oxycontin. Those responsibilities principally fell to Purdue senior management in research and development, regulatory affairs, sales training and marketing, among others. Is that accurate? Yes. I want to show you an email Dr. Sackler dated Monday, May 31st, 1999. Do you know who Dr. Cornelia Hinch is? I do. And who is that? She was general manager of Munda Farma, Australia. Okay. And to give us a little bit of context, you all had a drug called MS-contin, a morphine sulfate that was an immediate release narcotic opioid or narcotic. Is that correct? It was controlled release. Controlled release, I'm sorry. And that was used primarily for cancer patients or malignant end patients. Is that correct? Majority of use, yes, but not... I don't think primarily conveys an accurate picture. Majority of use was for... Over 50%. It was sort of felt by Purdue Farma that morphine had a stigma attached to it that kept doctors from prescribing it across the board. Is that accurate? Yes. And you all had a... May I amend that? Yes. It didn't prevent doctors from prescribing it across the board. It was an inhibition to the use of the product in every application. Okay. Have you ever gone back and studied the history of addiction and how it has played out in the 19th and 20th century? I'm not a student of that literature. All right. What was your understanding of why doctors did not want to prescribe morphine for anything or had a stigma about prescribing it for anything other than cancer and malignant pain? As I said before, the stigma prevented many physicians from prescribing it for any pain. Why do you think that stigma existed? I'm not a student of the issue, but I believe the stigma existed because of a popular understanding shared by both professionals and by laymen that morphine was an end-of-life drug if it was to be used at all. Okay. Were there concerns about addiction and dependence with respect to morphine? Some people had those concerns. Going back to building our context here, you all had a drug called MS-Contin that you had the exclusive right to sell. Is that correct? That's correct. Do you know when that exclusivity was set to expire? I'm not certain that I know the date. Do you recall that one of the concerns that Purdue's senior management had, I'm using Purdue in relation to Purdue companies that are involved with OxyContin, and rather than just sit here and name them all out, can we agree that when I say Purdue, I'm referring to Purdue companies involved with OxyContin? That's correct, because I said at the outset there are different Purdue entities that are defendants in the case, and the distinction between them may at times be significant. And so if you lump them all together under Purdue, we're going to get a record that will not be easily decipherable at the end. Let's talk about it then. Which Purdue companies were involved in the cell and distribution of OxyContin? Both Purdue Frederick and Purdue Pharma were involved in the early years of selling the product. Were there any other Purdue companies involved in the selling of the product? Not in the U.S. Who had the exclusive right to sell MS-Contin? At first, it was Purdue Frederick. I don't know at what point Purdue Pharma acquired rights to sell it, or if it did at all. What is the distinction between Purdue Frederick and Purdue Pharma? Purdue Frederick was the original company that my father and uncle acquired in 1952. It was a shell company, and it was the first pharmaceutical company that they owned. Purdue Pharma was established in the early 1990s to take on new products and to also take on the risk of new products and also a few established products. But not all. Were there any actions taken with respect to Purdue or with respect to OxyContin that would not fall under the Purdue Pharma umbrella? I'm sorry, could you repeat the question? Are you maintaining that there are any actions done with respect to OxyContin? It's creation, production, marketing, sales that do not fall under the Purdue Pharma umbrella. Its creation was done in Purdue Frederick until the early 90s when that responsibility was transferred to Purdue Pharma. And then Purdue Frederick continued to exist though, correct? It did. And was Purdue Frederick also a company involved with marketing, promoting, sales and production of OxyContin? I'm trying to give you an accurate answer because this is confusing and complex. There was a period of time in which once Purdue Pharma became involved, that Purdue Frederick was involved. But Purdue Frederick was never involved nor Purdue Pharma in manufacturing the drug, which was, when it was developed, was manufactured by a company named PF Laboratories. Okay. Other than the manufacture, did Purdue Frederick and Purdue Pharma both play a role in the... I can't recall in detail whether they both played a role or whether when Purdue Pharma took on the project it carried most of the weight. Is there any difference between the employees of Purdue Frederick and Purdue Pharma? There were differences. Any difference in the board of directors? That would test my memory and I'm not sure. All right. Well, let me go back to... Let's talk about OxyContin. And I'm going to use the term Purdue for both Purdue Frederick and Purdue Pharma. If at some point you feel like there's a distinction to be made, you let me know, okay? But at a time when... Mr. Thompson, I object to your combining the two under the name Purdue. If you're going to do it, then I'd like to have a standing objection to that combination. What is your reason for the objection? My reason is, as Dr. Sackler has explained briefly, there were two entities that did different things at different times. And if you lump the two together, inevitably there's going to be confusion in terms of the witness's answer. Okay. Let's do this. I'm going to refer to Purdue as Purdue Pharma LP and also Purdue Frederick LP. If at some point you feel like it's only Purdue Frederick or only Purdue Pharma, you let me know, okay? It's kind of a burden, but with the help of my attorney. Sure. Because there may be issues. It's going to be, it tests my memory to separate the two. So I'm sorry for the confusion, but it is important. For instance, let me ask you this, sales reps. Were sales reps employed by Purdue Frederick or Purdue Pharma? For a period of time they were, each sales rep was employed by one, but not necessarily the other. Do you know which sales reps were employed by Purdue Frederick or Purdue Pharma? I don't know. Do you know if they received different training? I believe the training was the same.  Okay. All right, so back in the 1990s, when you were developing MS-Contin, this exclusive license that you had to sell MS-Contin was going to expire, and there was going to be competition from generic companies, correct? Well, the product MS-Contin was developed in the late 70s and early 80s. And so are you discussing development or are you discussing a later time? The later time when its license is about to expire. Eventually, we knew that there would be competition for MS-Contin. And one of the things that, in developing Oxycodone controlled release, one of the concerns was how to position it for market and whether you were going to position it and obsolete MS-Contin or try to position it alongside MS-Contin. Do you recall that issue? I object to the form of the question. Could you repeat it? I'm not sure I understood. Yes. One of the concerns when you were developing Oxycodone or, I'm sorry, Oxycontin controlled release was how you were going to position it for market share and whether you were going to position it and make MS-Contin obsolete and take that market share that MS-Contin had or whether you were going to position it alongside MS-Contin and sell them both together. Do you recall that concern? I recall discussions, but that wasn't the principal driver. The principal goal was to produce the best product we could, and we believed when we started it and subsequently, should I stop? No. We believed it was and is a better product than MS-Contin. Thank you. Here's a memo dated to Richard S. Sackler from Robert Kaiko. Do you know Dr. Kaiko? I do. He's a PhD. He is. What was his role? He was the person who undertook or ran the project and was involved in the project of developing Oxycontin and was, as a clinical pharmacologist, was deeply involved in selecting formulations that would be most likely to achieve the desired effect. And under here it says rationale for another controlled release opioid analgesic. This is Bates number. It's actually got two Bates stamps, so it's PDD<PHONE_NUMBER>. But it says rationale for another controlled release opioid analgesic. MS-Contin may eventually face such serious generic competition that other controlled release opioids must be considered. Other pharmaceutical firms are thought to also be developing other controlled release opioid analgesics. Mr. Thompson, if you're reading from a document, could you show it to the witness? Sure. That's why I was holding it over here in the front. It's hard to read from that distance. One extra copy? Yeah. Great. Great. Just always handy. Do you have a copy for me? We'll see. Thank you. So do you see down there the second highlighted portion that says rationale? Mine is not highlighted. So. Yeah. I'll tell you where I go. Okay. Okay. So the second highlighted portion, rationale for another controlled release opioid analgesic. And do you see the first sentence below that? I see. That's a cross title. Yes. I was looking at the text. And the text below that says MS. Cotton may eventually face such serious generic competition that other controlled release opioids must be considered. Other pharmaceutical firms are thought to be, to also be developing other controlled release opioid analgesics. Did I read that correctly? You did. And was that a concern at that time? It was a secondary or tertiary driver. And then if you'll turn to the next page and look at the second paragraph and I'll read that, it says, while we have reason to believe that other pharmaceutical firms are formulating controlled release morphine and controlled release hydromorphone, there is no evidence to date that this is being done with oxycodone. A controlled release oxycodone is thus less likely to initially have generic competition. And was that a consideration when deciding to come out with oxycodone or oxycontin? Not for me. All right. Now, we read your paragraph 11 where you discussed that you had limited role in the tone. Do you have a copy of that? Yes, paragraph 11. Let's make this exhibit one to the deposition. Need to see that backwards. Is this the same as this? Thank you for underlying. Yeah. And this declaration said that you were not directly involved with the day-to-day marketing or promotion of oxycontin, the training or management of the produced sales representatives, or the scientific research into the conversion ratio of MS-contin to oxycontin. Is that correct? That is correct. I want to show you an email. Let's mark this exhibit two to the deposition. Which one is it? Allow me to just clarify. I'm emphasizing directly involved. I didn't do any of the work. I didn't do any of the training. I was not a salesperson. But as a senior executive, I certainly was aware of what was going on. And I consulted with other senior executives about what was going on and what should be going on and so on. And then this email that was just handed to you a few moments ago says, again, it's Cornelia Hinch. It's dated May 29, 1999. It says, if you'll read the highlighted portion, it says, this is an email from you to her, correct? Yes. It says, you won't believe how committed I am to make oxycontin a huge success. It is almost that I dedicated my life to it. After the initial launch phase, I will have to catch up with my private life again. Did I read that correctly? You did. When you say you dedicated your life to it and that you have no time for your private life, what were your day-to-day activities with respect to oxycontin? May I read the whole document? I haven't seen this for 16 years. Have you read your deposition in the endo litigation? In preparation for this? Yes. No. The context of this was to encourage Dr. Hinch, who was the head of the Australian business and was meeting with great success with MS Com to pay perhaps more attention than I thought she was paying to the prospects of potential for oxycontin. And so this was in the spirit of motivating her. It was true that I was very gladdened to see that oxycontin was meeting with such a strong, positive reception by both physicians and patients. And I was working hard at the business, but you would misinterpret this if you thought that I was working only on oxycontin. That was not the case. Thank you. When you say you were encouraged by the number of physicians that were selling it? Prescribing it. Prescribing it. You were not aware at this time were you, or were you aware that your company was committing a felony in how they were marketing and branding the drug? I objected to the form of the question. I was not aware at all of what you're saying. And when I say I was heartened by physicians' reception, when I did speak to physicians at meetings, I didn't go on sales calls, but at some meetings and conferences, they were extremely enthusiastic about the effectiveness and the safety and the reception their patients had, response they had to the product. That was what I was referring to. Because, as I had told you before, our goal was to make a better product than MS-contin. And I believe this was one of the ratifications of that. Let's mark this exhibit. Three. You already had it. No, the witness has it.  Can you tell me? I don't see it. You're holding it. One and two. That email that you have your hand on. There's three. I've marked it twice. That may be the problem. Yeah, it just got marked twice. If you've marked it twice, it's a three and two of the same. Okay, then I have it because I have two. And we'll get into this a little more later on, but you're aware that Purdue pled guilty to a felony charge of misbranding a drug, which was Oxycontin, with the intent to defraud or mislead. You are aware of that, correct? That is Purdue. That is Purdue to your earlier statement. That is Purdue Frederick, is that right? Okay, so when you said Purdue, you meant Purdue Frederick. Purdue Frederick Company each. Yes, I am aware. Is it your understanding that the fraud only occurred with respect to the Purdue Frederick Company and not with respect to Purdue Pharma LLP? That's my understanding. But I'm not an attorney in them. That's a very deep legal question. Did you do any investigation to find out whether sales reps employed by Purdue Pharma were exceeding what they were allowed to do when they were marketing, that they were making claims that were untrue? You have objection to form, you can answer. When you say you, are you referring to me personally or are you referring to the company? I'm referring to you personally. I did not conduct or manage any investigation, but from the time we learned at top management levels that there was an abuse and diversion problem, which was years before the settlement with the government, we launched multiple investigations, both with inside resources and people and with external attorneys and others to identify, and this was before any charges were made, to identify if we had, in any sense, misled or caused this to happen. More important, we spent enormous resources to try to mitigate the problem, whatever the cause was. And that effort, which was launched sometime in 2000 or 2001, continued right through the period that you're referring to of the plea with the U.S. government. And did you all launch this investigation as soon as you learned there was a problem? Yes, within months or weeks, I can't recall. 16, 15, 16 years ago. Who's Michael Friedman? Michael Friedman was at that time the head of sales and marketing. Have you seen his presentation at Purdue that he... You know what at Purdue is? The Bureau's internal newsletter that goes out to all the employees. I don't believe I saw a presentation at Purdue from him. We'll get to that later. This is a memorandum dated July 15, 1992, meeting with Shia Nugi held Wednesday, July 24, 1992 from Dr. J. W. Watkins. And there's a distribution list. And I assume you are Dr. R. S. Sackler. Is that correct? That would be me. And if you would turn to page six of this document, that is PDD<PHONE_NUMBER>. And to give it a little context, Shia Nugi, is that a Japanese company? It is. At one time were you all talking about doing some sort of business with them involving potentially OxyContin controlled releases? Yes. And did you do business with them involving OxyContin controlled release? Yes. Let's look at page six if you would. The... Looks like maybe the third paragraph down that begins with Dr. Kaiko. Yes. You see that? Dr. Kaiko presented two options identified for positioning of OxyCodone acrocontin. Now, is that the controlled release? That was our working title of the controlled release system. Versus MST-contin tablets in the U.S. The first was relevant if PF, who's PF? Purdue, Frederick. Did not suffer substantial erosion of its MS-contin market by generic competition. This envisioned using OxyCodone acrocontin tablets over the entire spectrum of pain in patients whose treatment had been initiated with this product whilst MS-contin tablets would be used as therapy for chronic, severe pain in patients who were changed from other medication including OxyCodone acrocontin tablets. An alternative scenario would apply if MS-contin tablets were subject to erosion by generic competitors. In this case, OxyCodone acrocontin tablets would be promoted for the use across the entire pain spectrum including those patients who might otherwise receive controlled release morphine. Did I read that correctly? You did.  Where you're referring to Japan, which is where Shianogi either had or was negotiating a license for OxyContin. Was it also your intent in the U.S. to promote it across the entire pain spectrum? It was our hope that it would be well received from pain moderate to severe pain requiring opioids. Let's mark this as exhibit. And here is PDD<PHONE_NUMBER>. OxyContin launch team memo dated 33195. And OxyContin was actually launched in January of 1996. Is that correct? That sounds correct. And what this says, if you will turn to page three. First of all, let me ask you this. Do you recall having any significant problem with MS-contin with respect to addiction, abuse, diversion or any of the problems that you experienced with OxyContin CR? I recall never hearing about that. So let's look at page two, the last paragraph. It says, our meeting ended with a question and comment period. Michael Friedman emphasized the threat that AB rated generics posed to MS-contin. We're not sure when AB rated generics will be launched, but we don't think it will be until 1996. Inevitably, AB rated generics will arrive and this is why it is of extreme, timely importance that we must establish OxyContin. OxyContin can cure the vulnerability of the AB rated generic threat and that is why it is so crucial that we devote our fullest efforts now to a successful launch of OxyContin. Did I read that correctly? You did. And who is Lydia Johnson? I don't know. This department, it looks like it's the marketing department. Is that right? I just see a distribution list. I don't see a source. I don't know. It says that the department is marketing, but I don't know Lydia Johnson. Was it your belief that it was of extreme, timely importance that OxyContin be established because AB generics were going to arrive and compete with MS-contin? No. Let's mark this as exhibit four. No, we already have four. I'm sorry. Then this would be five. Is this what he's reading? That would be a question for these gentlemen. I think you already marked this, Tom, as four. Pat, don't worry about marking it. We'll make sure it gets marked. It has been ordered. Yeah, okay. Okay, I'm sorry. Where are we on the numbers? I don't think this has been marked as an exhibit. I thought the launch team memo was included. No, four is something at a research center. The Japanese government. No, this has not been marked as an exhibit. So that's five, right? It'll be five? I'll keep track. Yeah, this should be five. Okay. Dr. Sackler, do you know how much money to date has been generated by the sale of OxyContin? I don't understand the question, money generated. How much money has Purdue Frederick or Purdue Pharma made off the sale of OxyContin? I don't know. Okay. There was an article last month in Forbes. The OxyContin Clan, the 14 billion newcomer to Ford's 2015 list of the richest U.S. families. Have you seen that? I have seen it once.  Presently? Yes. Approximately two-thirds. I've looked at the... That's Purdue Pharma's sales. Purdue Frederick does not sell anymore, correct? You've got another number of other entities that generate income from the sale of OxyContin, correct? Overseas. Yes. And approximately 90% of the profits of the company come from OxyContin. Question. The company you're referring to now, Purdue Pharma? Purdue Pharma. I don't believe it would be 90%, but it is certainly a majority. Do you currently make over a billion dollars a year selling OxyContin? Objection is the form I do. By you now you're talking about Dr. Sackler. Yes. No, I don't. All right. Does Purdue Pharma make over a billion dollars a year? I'm not sure. I don't think it would be that much. Let's talk about gross sales. Are gross sales over three billion dollars a year? No, they're not. What are the gross sales? Well, I think what you're looking for is net sales because in the industry, a lot of money is inherently rebated back to purchasers, insurance companies, hospitals, et cetera, through wholesalers in rebate agreements which are negotiated. And so I believe the net sales are in the range of this year a billion dollars. Your question was directed to Purdue Pharma. Right. Purdue Pharma. Right. Are there any other Purdue entities that make money that would not be included in that $1 billion sales? Not in the... The connection to the form of the question. You can answer it. Not in the United States. Do you know how much the Sackler family has made off the sale of OxyContin? I don't know. But fair to say it's over a billion dollars. It would be fair to say that, yes. Do you know if it's over $10 billion? I don't think so. You know if it's over $5 billion? I don't know. All right. This appears to me... It's been marked as exhibit five. It's PKY6. exhibit six. PKY173810206. Appears to be a profit calculation for a Purdue entity. Can you tell me which entity that is? If it's not on the document, I couldn't possibly tell you. Did Purdue Frederick still exist in 2006? I'm not clear. I think it did. This appears to be a profit calculation for OxyContin tablets only. Do you see that? I do. And it appears that at least by 2006 profit contribution was $4,718,767,000. Correct. You've read the number correctly, but profit contribution is not profit. And what would you subtract from that? All of the money that was invested in the business to develop new products would be a major deduction from that. Let's mark this... Well, let's... You're right. I think it is. Look up at the top where it says gross profit. $7,502,367,000. That's a second. Small type. That's a second. Gross profit. See, gross sales. I say rebates and net sales. Okay. I'm with you on gross profit. Thank you. So deducted from that is shipping warehousing. You have $536,000,000 paid to Abbott for co-promotion commission. That's correct. You have an S&P expense. What's that? Sales and promotion. All right. That was $141,000,000 on sales and promotion. Is that correct? That's correct. R&D expense, $308,000,000. Right. And I'm looking for the number. I'm sorry. Sales force? Yes. I see that. But can I explain? That's the R&D associated with the product. Right. Not the R&D for other products. Right. And then sales force is 960 or 87,222,000 that they've been paid. That's what it says. And then it's got a G&A expense. What is that? General and administrative. All right. $492,000,000. Yes. Over how many years? 96 to 2005. So it's nine years. Am I counting correctly? You are. Then there is product liability and patent litigation expense. You had oxycontin litigation expenses. Then you have profit after all those are subtracted on oxycontin of $4,718,000,000. Is that correct? That's what it says. I can't testify that it's correct, but that's what it says. Let's mark this as plan 6. It is marked. Do you want the original? I'm trying to go a little bit longer. If you all need a break, we can take a break.  Do I have to wait? We are off the record at 10.06 a.m. We are back on the record at 10.18 a.m. All right. That's about this. Do you have a copy of that? Somebody already didn't have an exhibit list here. Dr. Sackler, I want to ask you about one more thing in exhibit 4. If you look at the second paragraph, there's a comment that says, when discussing oxycodone acrocontin, which is controlled release oxycodone. I'm sorry. Just taught me on a little bit. Page what? The first page. Page second paragraph. Okay. It says, the molecule lacks the stigma of morphine and may be a particular advantage in the 5% approximately of patients who cannot be adequately treated with morphine. Was it your understanding that approximately 95% of the patients out there could be treated with MS-contin? No. Do you disagree with that statement? I do. I disagree. What percentage do you think of patients could be adequately treated with MS-contin? Between 50 and 75%. And what studies are you basing that on? I'm basing it on general experience of being involved with MS-contin and oxycontin since 1980. Did you ever do any studies to determine what percentage of patients could be adequately treated with MS-contin? I don't remember any. Did you ever do any studies on abuse liability for oxycontin before you all put it on the market? I'm not aware of any. Let me show you what's been identified by Bates Stamp PDD<PHONE_NUMBER>. I'll ask you if you can identify this. May I have a copy? Thank you. Does this appear to be a memo to you from Paul Goldenheim? It is. Who is Paul Goldenheim? At the time he was head of research and development. And just to kind of walk through this memo from the bottom down there, it looks like you had sent a memo on March 14th of 97 to a number of individuals at... I'm looking for that. I'm looking for my... Oh, from me. Okay, I see that. Okay. I'm sorry, I see now it's two emails. Okay, thank you. And the paragraph at the bottom says the B-F-A-R-M. What is that? That was the German regulatory agency at that time. It says we're asked whether oxycontin could be classified as a controlled drug or whether it would be possible to obtain a relaxed status because of the difficulty in extracting oxycodone from the matrix. And the fact it was less liable to abuse because it was unknown. So just dialing down on that first sentence, you were wondering whether oxycodone could be less regulated in Germany. Is that correct? I believe that I was reporting something to Paul that I must have heard, but I was not involved in making any discussions or meetings with B-Fram. Okay. May I just read the rest of it if we're going to continue on this? Sure. I'll tell you, I'll read it to you. It's okay. The next sentence says the B-F-R-M, which understands the German regulatory authority. That's correct. Answered that unfortunately oxycontin would definitely be classified as a controlled drug for all strengths as is morphine. There could be no exception because of the controlled release protection because there had been a few reports of abuse and there were limited data on long-term use. Did I read that correctly? You did. Okay. And then you have here in CAPS, we have a lot of use data in the U.S. with very, very, very few ADEs. What are ADEs? Those are reports to the agency, to the FDA, and ADE stands for Adverse Drug Experience. All adverse drug experiences are reportable to the agency. Anything we are aware of, we must report periodically. Anybody else, however, can also report ADEs to the agency. And so the agency maintains a catalog for every drug of ADEs. Okay. And then you have in CAPS continuing, we can run another long-term trial to get more data. And if the abuse potential is equal or lower than with other non-scheduled drugs, would B-fram unschedule it? That's your question, correct? That was a question. And then Dr. Goldenham writes back on the subject of, is this an opening to descheduling the agent? And descheduling means make it less restrictive, correct? That's how I would understand it. And if it's less restricted, would you think that you could sell it to more people? It would be easier for physicians to prescribe it. It's going to increase sales. That is reasonable because they could prescribe it. If it were schedule three instead of schedule two, as are some drugs, physicians could prescribe by telephone. And his response is, we do not have any abuse liability studies. And this is as of 1997, correct? That's correct. To date, have you done abuse liability studies? Yes, many. When were they done? I don't know when the first ones were done, but they were done repeatedly for many formulations, subsequently, of both oxycodone and of other abusable opioids, both in controlled release form and in immediate release form. Have you done abuse liability studies for oxycodone and controlled release? Yes, the new formulations definitely. And when were those done? I don't know exactly, but before the products were submitted to the agency. You're saying the new formulations? The new formulations. When were the new formulations submitted? I'm doing this from memory now, about 2008, but I could be in error by a year or two. So by 1997, two years after this product was on the market, he says, we do not have any abuse liability studies. I think this is a dead end. Adding naloxone, I think, is the only possibility, but this is a difficult project from the clinical perspective. We are investigating for hydrocodone. Was that his response? That is what he wrote? He's basically saying they're not going to schedule this. Unless perhaps they might if it incorporated naloxone. And naloxone is an additive? It is a reversal agent. It blocks the effect of opioids. And you all did not incorporate naloxone, correct? We subsequently did in some markets, in Europe in particular, and to some extent elsewhere. Did they require you to do that? No, we did it for another reason. What was the reason? We discovered that it did not block the effect of the opioid, apparently at all, but it did reduce the gastrointestinal side effects dramatically, including constipation, which is the most common side effect for any opioid. I could add that by the time we had a full press to develop abuse-resistant form of Oxycontin, we did do extensive work with another antagonist called naltrexone. And naltrexone did, when it got released, block the effect of the opioid. But unfortunately, after a huge investment, we could never be certain that it wouldn't be released when it was taken orally. It was almost perfect, but it had to be perfect because the agency said that if it released and blocked the effect of the opioid in patients, they would not approve it. And we could not reach perfection. Let me show you an email chain that's been produced. Mark this. And it's PDD 29520806-439. And if you start at the back, I believe, this email chain begins at the back. And this is an email from you dated, the last email is the first email, and it's dated 3297. Wait, I'm seeing 31197. Oh, 3297. It's sort of a little out of order, isn't it? I'm sorry, yeah, there is my tour off. Okay. Oh, no, 31297. 22797 is the first. Okay. Pardon?  Not the last. Okay. Yep. Yeah, I'm not sure the pages have been assembled properly. Yeah. These are the, this is the way this document was produced to us. And the reason that there's a skip in the Bates range from the last two pages is because Purdue produced a totally random document in between it. But if you look at the Bates numbers of the original Bates stamp on this document, they're consecutive among those pages in a consecutive email chain. So I have taken the liberty of removing the completely erroneous page that has nothing to do with this email chain and produced it to us. I have a question about that. The question is, he has a different formulation that he's talking about. No, he's got the same document. Exactly. We're just trying to make sure that we're all working from the same document here. So if you'll go to the 22797 email. That's it. Yeah. No, I had to look for it. I expected it at the end, but it wasn't. Okay. Yes. It says, this is from Walter Wimmer at Mundy Pharma, Germany. And that's a company that's owned by the Sackler family, correct? It is. And who's Walter Wimmer? He was the general manager at that time. And he says, dear Bob, first paragraph, in the course of this conversation, he explained to you that due to his discussions with BFARM, he does see a 50% chance to get OxyContin off the narcotic drug status provided you could give some information on the very low abuse potential of our CR formulation. Did I read that correctly? You did. And then in response to that, if you go up to the top, Dr. Robert Keiko has an email dated 22797. He does. And he says, while my thinking is still developing, frankly, I'm very concerned. And I would have to recommend against the uncontrolled but monitored proposal at this time, parentheses, perhaps, if only to make sure the risks are appreciated and accepted before we proceed as proposed. Do you know what risk he was discussing? I have no idea. Did you ever discuss with him why he was recommending against going uncontrolled but monitored with respect to OxyContin? I don't even know what it means. Sorry. If I read the rest of it, do you think it would give me a clue? Or I infer that because you didn't highlight it, you don't think it would shed any light on what was meant above? Well, let's read the rest of it. It might help. He says under paragraph B, I don't believe we have a sufficiently strong case to argue that OxyContin has minimal or no abuse liability. And this is dated 1997, correct? Yes. He says in the U.S., OxyCodone containing products were once less controlled than now. Abuse resulted in greater controls. Is that accurate? I believe it is. And what he's saying there is these weren't as controlled at one time and they got abused and that's why we have controls now, correct? I believe that is the case. He says OxyCodone containing products are still among the most abused opioids in the U.S. This information is available to BFARM, the German regulators. That's certainly true that the information would be available to them. And he says the local tissue necrosis that can result from injection of OxyContin fixed in quotations for such abuse is not likely to be a deterrent to abuse. Let us not forget that in New Zealand, MST is the most common sources of parentarily abused morphine slash heroin. And were you aware at that time that OxyContin, there was a concern that OxyCodone opioids could be injected or abused? I don't remember this memo and I don't remember whether I had read the whole chain carefully or not. And then he says our dossier acknowledges, by dossier I assume he means the documents Purdue has, our dossier acknowledges a small handful of patients in our research program. And that means studies you all were doing, is that correct? That's what I would understand. Who were suspect in terms of their drug accountability. Do you know if that was reported to anyone that if you're all dossier had a handful of patients who were suspect in terms of their drug accountability. I don't know if it was reported but I'm confident it was. If it was an FDA submitted trial, it would have been in either the safety summary or the efficacy summary. Do you remember the issues with the Roth reprint where there were patients who they determined had withdrawal symptoms and that was not reported? No, I'm sorry. Are you familiar with the Roth reprint? No. You know whether that was part of the plea agreement that Purdue Frederick had when they played guilty to a felony? I don't recall. And it says under paragraph C, we do not have a post-marketing abuse monitoring system and database from which we could conclude that diversion abuse is not occurring. Were you aware that you all put this on the market in OxyContin CR and did not have a post-marketing abuse monitoring system or database from which you could tell whether abuse or diversion was occurring? I was not aware of that. I don't believe it was a requirement. At the time, I'm sure we would have fulfilled all the FDA requirements that they asked us. Do you think it would have been a good idea before putting OxyContin controlled release on the market to have an abuse monitoring system and database from which to tell if it was being diverted or abused? Absolutely, yes. And then under paragraph C, it says if OxyContin is uncontrolled in Germany, it is highly likely that it will eventually be abused there and then controlled. This may be more damaging to OxyContin internationally than any temporarily higher sales that could be cleaned from an uncontrolled status. Let us not forget the experience with buprenorphine, which was initially uncontrolled, reports of abuse in Germany in part eventually led to lots of bad press and controlled status. Worldwide sales suffered even where buprenorphine had already been controlled. So given the above, what do others have to offer that should prompt us to pursue the proposal for uncontrolled status for OxyContin anywhere? Question mark. And was that the response of Robert Keiko? It appears to be so. And who was Robert Keiko? He was in charge of the development program of OxyContin. Was he the chief medical officer? But he was respected, his opinions were respected and were heeded. And then the next email which comes from you is Dr. Richard Sackler at Norwalk. Give me just a little time to find it since they're not in order. But okay, Norwalk, could you read the date please? It looks like it's 3-2-1997. 3-12. 3-12-1997? I'm looking at 3-2. It says 020397, but I think the way it's computed is really March 3rd. Okay. I see something from 3-12. I see something from 11-3-97. It's page 5. Oh, I don't think I have page 5. Okay, thank you. This is your response to Robert Keiko saying this is a bad idea for all these reasons. And you say, this is the first time I've heard of this idea. What makes us believe that we can accomplish it? Walter, how substantially would it improve your sales? What you're talking about there is if we can get it uncontrolled in Germany, how substantially will it improve sales, correct? Yes, it would appear that that's what my question was. Please give a five-year projection with control and without. Does each member of the EU, is that the European Union? Yes. Decide this for themselves or would one lead? If one would lead, then is Denmark or Germany more likely to agree? And then Harry Klutsko of Mundy Pharma writes you back on March 7th and says, Dear Dr. Richards. Just a second. So we're now on page one or two. That's the same page, the one right above. Okay, I'm sorry. Please find, stated below, our five-year projection of OxyContin without and with controls as requested. And it was projected that with first-year non-narcotic drug with control would be 3.0000 TDM. Do you know what that is? I assume total or something, Deutschmarks, something, Deutschmarks. And that would be 3 million? That would be my understanding. And then turn over non-narcotic drug without control is 10 million? The first year. Yes. And on the fifth year, it was projected to be 18 million with control but 30 million without control. That's what it says. And then you wrote back on 3897 right above that one and it says, BK advised that the regulatory authorities did say- Okay, BK, sorry. I heard DK. And advised the regulatory authorities said that Oxy would be scheduled and so would be under narcotic control. Does this correspond to your info? If so, is this matter now closed or is there some appeal or other procedure you would want to consider? So, you still saw the advantage of getting Oxy-contin-CER uncontrolled and were wondering if there was some way you might appeal the German decision. Objection of the form, that's not what the statement says that you just read. Well, correct me if I'm wrong there. Why did you say is there some appeal or other procedure you want to consider? Okay. This whole experience is actually like reliving a third of my life and I had completely forgotten until I saw this document that Walter had been very hesitant to pursue the development or the marketing of Oxy-contin because he didn't believe it would sell very well. He turned out to be completely wrong and when it was introduced it did extremely well. We were of the contrary opinion but he said he came back and he did quite a bit of work without any reference to anybody else on determining or trying to get the B-farm to consider and not scheduling it. And this whole stream was occasioned by that. Many of us in the U.S. were not enthusiastic about not scheduling it. In Germany there is no equivalent at least at that time that I recall of anything like Schedule III. You are either an abusable drug and thus you had all the abusable drug controls or you were not. And we were not in favor of this but we were trying to be polite and solicitous rather than saying this is a terrible idea forget it, don't do it because we still felt that with the controls which we thought would be appropriate and were appropriate obviously it would still be very welcome, very useful to patients in the German market. So this whole stream this whole trail really was occasioned by that but I don't remember anymore so if we go on and we are going to relive another few days of my life. Sure, let me ask you if you thought controls were appropriate why were you asking here raising the issue if there was some appeal that could be taken just to be polite not to just shut him down. Okay, well let me ask you this let's go to the next one which is page 4 he writes back yes Richard this does correspond to the information given by Mr. Gerich our registration office we also attended the meeting with the BGA this matter is now closed there is no way of appeal is that what he told you? It seems to be what he told me and then you wrote back and said when we are next together we should talk about how this idea was raised and why it failed to be realized I thought that it was a good idea if it could be done was that your response to? That's what it said but I didn't mean it I just wanted to be encouraging I was very glad it was closed up at the top there's a note there's another response from Walter Wimmer who says to get the product off narcotic drug status it would be possible to combine oxycodone with naloxone provided the development cost weren't too high that was sent on 312 and then the top one is cut off but it says Paul Michael would this be a feasible approach here in the US? I don't know of any C2 narcotic that is descheduled when naloxone is added to you is that a question you were raising? It looks like I raised it just as a matter of information as I said they eventually did develop that product and it was extremely successful but at the time they researched it they quickly discovered that naloxone didn't achieve the desired blocking effect but they made another discovery that was even more valuable you got this one? would I be correct that Purdue Pharma never conducted or retained anyone to conduct studies regarding addiction and physical dependency rates of oxycodone products at least as of March 4, 2002 I don't know the answer are you aware that counsel for Purdue Pharma's answered interrogatories that requested the names of all individuals retained by Purdue Pharma to do studies regarding addiction and physical dependency rates of oxycodone products and copies of all studies and he answered we never conducted or retained anyone to conduct studies regarding addiction and physical dependency rates of oxycodone products Mr. Thompson if you're reading from a document could you show it to the witness? I'm just asking if he's aware of it because I'm trying to move the deposition along so are you aware of that? no I'm not aware of his statement are you aware of any studies conducted or retained or anyone being retained to conduct studies regarding addiction and physical dependency rates of oxycodone products probably 2002 I'm not aware of any or I don't remember any you got these in 2002 I was the president of Purdue Pharma and this would not have necessarily this wouldn't have required my approval or knowledge unless it was it led to something that was surprising important and unexpected I still want to ask about this Mr. Thompson did you put in a different number to the last document that we were discussing which was a series of emails? it was eight it's the oxycodone product team alright I'm going to switch and ask you a little bit about the oxycodone project team and this is a memo dated December 14, 1993 PDD 9520 509 356 and a few paragraphs I want to try to cover here if you will look at the bulletin points on the front page the second one from the bottom says marketing oxycontin tablets will be marketed against Percocet and Duragesic the oxycontin line may replace our MS-contin line if MSC generics are competing that's correct and that's not the is that the malignant cancer group of patients or is that a non malignant cancer group of patients? I don't understand the question you may answer MS-contin as I said before was used in treating both cancer patients and non cancer patients and there was no focus I don't believe or consideration in this statement whether it would be both I think do you have a knowledge of what Percocet and Duragesic was used mostly to treat? Percocet was an extremely widely used product used to treat both short and long-term pain conditions both non malignant and malignant and then if you'll turn over to paragraph 2.3 and this is 1993 it says abuse toxicity bench top study the results of a spoon okay I see 2.3 you said yes thank you the results of a spoon and shoot study have been sent to the FDA what was the spoon and shoot study? I don't know I could guess but I don't know was that a study done to determine if the drug could be abused by extracting oxycodone from the tablet? it's a reasonable guess but I don't know the details of what that study was under 3.2 the last sentence says a crushed tablet study may be conducted if we decide such a study is needed you know if you ever decided such a study was needed well what's the number on that I'd just like to read it 3.2 last time I'm sorry thank you 3.2 yes okay I read that I don't know if such a study was done okay and then on 5.4 the last sentence says Mike in Orato was he a guy in charge of marketing? no he worked in the marketing department but at this time he was not in charge he was a middle manager in marketing Mike in Orato asked if we had any quality of life questions in our ongoing studies Robert Reader stated that we did not but that we could include quality of life questions in future studies do you know if quality of life questions were included? I believe there were studies later that included quality of life measures but I am not certain of that I'm certain it would have been favorable but I'm not certain just what studies were or were not done let's mark that as exhibit market exhibit 9 oops yep with respect to oxycodone and morphine do you know whether oxycontin is more powerful or less powerful a drug than morphine? it depends what you mean by powerful I think Dr. Goldenheim was he an employee of I think he testified that oxycontin was twice as strong as morphine is that your understanding? if the question if powerful means potency absolutely it is twice as potent as morphine and we were very proud that we discovered this first in animal studies and then in human studies and we made it widely known perhaps even before the drug was introduced but certainly in the package insert in all the promotional material do you know how many doctors or what percentage of doctors thought that it was equal to or less strong than morphine? I would assume very few if they were promoted to I can't believe that they wouldn't have understood that that formed the basis of our recommendations of dosing of the strength of the tablets that were developed and in fact it was consistent with physician's own experience with Percocet where they would administer a 5 milligram dose and if they used morphine they knew that 5 milligrams of morphine would achieve very little pain relief if given orally perhaps somewhat more if given by injection let's mark this as plaintiffs exhibit 10 this is the a memo dated 1992 august 10th oxycodone project team meeting minutes I'm sorry, August 10th and it is PDD<PHONE_NUMBER> 39 I had 30 the first page is 39 correct and if you'll look at this it says a literature search the second paragraph a literature search on oxycodone and oxymorphone is being conducted I'm sorry this is just not very clear give me a second the issue a literature search are we looking at the same page? you're on page 2, I'm on page 1 I thought you said August 10th okay this one is August 4th second paragraph a literature search on oxycodone and oxymorphone is being conducted by one of the summer employees do you know who was doing the literature search? no a son or daughter of one of the people who work for Purdue Frederick or Purdue Pharma fifth paragraph down second sentence says the current consideration is to develop 20, 40, 80 and 160 milligram tablet in addition to the 10 milligram tablet now in the clinic and whose idea was it to develop 20, 40, 80 and 160 milligram tablets which page are you reading from? first page just what I called out fourth paragraph, second sentence okay thank you this was a team decision it was discussed extensively if you'll go to the second page um first paragraph it says with regard to the package insert and the first year advertising claims it was discussed that Mr. Segar should meet with others and rework the quote draft package insert the purpose would be to idealize the insert and coordinate the contents with the advertising claims and clinical trials program the package insert should include comparative claims it must be kept in mind this is a working document why did you want to coordinate the package insert with your advertising claims? the package insert is the bible for the product it is the core document from which all promotion or communication with physicians is to be based it is typical in the industry that a lot of work is expended to make the package insert as comprehensive and complete as possible and this is a you talked about physicians being aware of oxy cotton being twice as strong as morphine a second ago let me hand you let's mark this as exhibit 11 this is an email it says the author is may I have a comment oh I'm sorry it says the author is Dr. Richard Sackler at Norwalk dated 528-97 are you familiar with this email to Michael Friedman? yes who's Michael Friedman? he was head of marketing and sales ok and let's drop down and see what Michael Friedman has written first paragraph he says my purpose in writing this memorandum is to clarify our position on the very complex issues raised by Mike Cullen during the phase 4 team meeting in which were the subject of Dr. Richard's inquiry when they say Dr. Richard's who's that? that was me first paragraph we are well aware of the view held by many physicians that oxycodone is weaker than morphine we all know that this is the result of their association of oxycodone with less serious pain syndromes this association arises from their extensive experience with and use of oxycodone combinations to treat pain arising from a diverse set of causes some serious but most less serious this quote personality of oxycodone is an integral part of the quote personality this personality of oxycodone is an integral part of the personality of oxycodone when we launched oxycodone we initially intentionally avoided a promotional theme that would link oxycodone to cancer pain we specifically linked oxycodone to the oxycodone combinations with our old way, new way campaign we made sure our initial detail piece provided reps with the opportunity to sell the product for a number of different pain states with all of this we were still concerned that the drug would be slotted for cancer pain and we would encounter resistance in the nonmalignant pain market and says our pricing of the product was geared toward the nonmalignant market we knew if we priced low per milligram for the higher dose cancer patient we would be priced way too low per milligram for the standard nonmalignant pain patient where we really wanted to make a market we feared that the quote cancer pain experts in quote would object to the 2 to 1 ratio and that 2 to 1 ratio is the ratio of oxycodone, oxycontin to morphine is that correct actually if you want to strictly understand the ratio the 2 to 1 would refer to the ratio of morphine to oxycodone okay that's not the other way around I know that's what you meant to say yes and resulting cost of therapy for high dose patients however we had no choice given our position for oxycontin in any case we're developing hydromorphone code I've lost you here okay in any case we're developing hydromorphone code for the high dose patient right okay I'm at the end of paragraph 4 and then it says despite our initial uncertainty we've been successful beyond our expectations in the non malignant pain market yes and non malignant pain market is sort of the chronic arthritis back pain those types of patients well those are most typically moderate pain patients some of them may be severe but there are many less common conditions that produce severe crippling life destroying pain and we had an indication and still have for all pain states that are appropriately treatable with opioids for an extended period of time we want it so non malignant really is a distinction all pain other than the pain directly caused by the encroachment and destruction of tumors tissue in the patient and then he says here doctors use the drug in non malignant pain because it is effective and the personality of oxycontin is less threatening to them and their patients than that of the morphine alternatives I apologize for this unspecific term but I feel it captures the notion that there are image related attributes that influence drug acceptance while we might wish to see more of this product sold for cancer pain it would be extremely dangerous at this early stage in the life of the product to tamper with this quote personality to make physicians think the drug is stronger or equal to morphine we are better off expanding use of oxycontin in the non malignant pain states and waiting for hydromorphone in 1999 to relaunch cancer pain why was it felt that there would be a danger it would be extremely dangerous at the early stage in the life of this product to tamper with this quote personality to make physicians think the drug is stronger or equal to morphine the context of this was as you know a threat of emails that actually he alludes to I started the whole context and the whole discussion of Mr. Friedman here and in other I'll pause here because I think it's really important for you to understand this the whole context was not to the context was not stigmatize oxycodone in a way that morphine was stigmatized morphine was seen as an end of life extreme duress patient extreme duress often dying of cancer but not only cancer it was reserved by most physicians if it was used at all even when patients were in serious severe even crippling pain because telling a patient I'm going to put you on morphine I'm going to prescribe morphine for you now we got to use morphine however the physician told the patient was associated with a death sentence oh thinks the patient he's telling me I'm going to die even worse my doctor is putting me on morphine he's giving up on me we didn't want oxycodone to change the personality of oxycodone but you could say all the associated feelings of oxycodone which were generally appropriate to a narcotic we didn't want that to be polluted by all of the bad associations that patients and healthcare givers had with morphine did you think that if physicians thought it was stronger or equal to morphine much less twice as strong as morphine that they would be less likely to write prescriptions and sales of oxycodone would go down no if it's personality was changed if it was stigmatized as an end of life drug it could limit its usefulness the term stronger here meant threatening nor frightening there is no way that this intended or had the effect of causing physicians to overlook the fact that it was twice as potent it was called out in virtually every promotional piece of literature it was reflected in a conversion chart which we had developed for a few patients who were being treated with morphine where we made it very clear if they're on any daily dose of morphine you cut that dose in half for oxycodone every action we took before the product was launched with the FDA in the package insert in promotion all detailing emphasized that it was twice as strong some physicians had formed their own impression that it wasn't twice as strong it was less strong and we insisted that they observe we said with this drug doctor it is twice as strong even when they said no I think it's one and a half times as strong and some physicians even said I think it's about the same potency as morphine we would insist no please use it the way we have researched it and the way the FDA has approved it now and I think we were effective in getting that message across in time to most and eventually almost all physicians this is 1997 two years after the launch of oxycodone control release correct so it's been on the market now over well January 96 we're now in May of 97 and it says we are well aware of the view held by many physicians that oxycodone is weaker than morphine and the conclusion of this was I do not plan to do anything about that and you wrote back and said I agree with you general agreement or are there some holdouts is that what you wrote up at the top of the I did and I agreed with them then and I agreed with them now because I knew what he meant and so did everybody else know you what he meant and more important our actions in promoting that twice as potent as morphine never wavered we never disguised it or hid it we emphasized it so you weren't doing this because the pain market for non-malignant pain was a much greater market share is that your testimony no no that isn't we wanted to address both markets the email which perhaps you want to explore or not that started this was as he says in the first paragraph something that I had inquired about and what I had inquired about was an error on my part when we before we launched oxycontin we thought that our sales would be about equally divided between cancer pain and non-malignant pain we knew that the market for non-malignant pain was much larger of course fortunately for all of us cancer is not as much less common than other pain states but we had expected it would be about 50-50 I had seen some reporter attended a meeting where I learned it was about 20% of our sales and thus I wrote to Michael and said why what's going on here why aren't we getting more cancer sales let's look at the email you wrote to Michael Cullen at Norwalk let's mark this as plaintiffs exhibit 12 and Michael Cullen writes on June 2 of 97 and that was after the email we were just looking at and says in recent team meetings we've discussed the issue that oxycontin is perceived by some physicians particularly oncologists as not being as strong as MS cotton now oncologists are cancer doctors correct so even the cancer doctors don't think that oxycontin is as strong as MS cotton according to this that's not what this is let me rephrase it you were aware or at least Michael Cullen was advising you that oxycontin is perceived by some physicians particularly oncologists as not being as strong as MS cotton is that correct that's what the words say this perception has had some effect with physicians switching to MS cotton with more severe cancer pain patient it has actually had a positive effect with physicians use in non-cancer pain and there he's saying non-cancer physicians that don't think it's as strong as MS cotton we're having a positive effect from that and I'm assuming he's talking about cells wouldn't you yes he says since oxycodone is perceived as weaker opioid than morphine it has resulted in oxycontin being used much earlier for non-cancer pain physicians are positioning this product where Percocet hydrocodone and Tylenol with coding have been traditionally used so he's saying here physicians are using it because they think it's weaker than morphine correct he's using the word weaker but not meaning less potent than morphine within at this time it appears the people had fallen into a habit of signifying less frightening less threatening more patient acceptable as under the rubric of weaker or more frightening more less acceptable and less desirable under the rubric or word stronger but we knew that that the word weaker did not mean less potent we knew that the word stronger did not mean more potent and we knew that because by this time surely anybody who was using this product recognized it was more potent they knew it was more potent so it's very unfortunate for your understanding as well as anybody else's understanding that all those issues of the stigma of morphine of the frightening nature of morphine of morphine being a cancer drug end-of-life drug it's a very unfortunate for your understanding and for most people's understanding that the word weaker and stronger was used we understood what it meant but let me ask you this you were advised by your senior employees that physicians perceived oxy cotton controlled release as less strong than morphine many physicians perceived it that way correct? Words used but didn't mean that they believed it was less potent because I knew they believed it was more potent their own practice proved they recognized it was more potent as I said before Percocet was 5 milligrams. Did you do any studies yourself or conduct any investigation to determine what percentage of physicians believed that oxy cotton controlled release was less powerful than morphine and we're not aware it was twice as strong as morphine but less potent. Yes I don't know of such studies but in common parlance and discussions with physicians if really a substantial if any substantial number of them believed believed in the believed had an erroneous belief excuse me if any held an erroneous belief and said to a representative oh this is this stuff is less potent than morphine the salesman had ample materials to demonstrate to the physician that he was in error and was instructed to use those and did use it and I wish we had a survey had done a survey to demonstrate it in retrospect but it was so generally accepted that it was at least one and a half times more potent by even the skeptics most skeptics and there weren't many but generally recognized to be twice as potent as morphine it just never occurred to us. Sure and it's your belief that your sales force was telling these physicians that it's actually twice as strong as morphine and correcting that misperception that they had. Absolutely it was in the package insert the promotion in the conversion tables and in the recommended dosing which so promotional pieces your symposiums your review articles your studies would all point that out. I can't say that everyone would point it out in every page but it should have been an important part of most promotional materials. Well let's read the rest of Michael Collins email dated 297 well after the launch of Oxycontin paragraph 3 says since the non-cancer pain market is much greater than the cancer pain market it is important that we allow this product to be positioned where it currently is in the physician's mind if we stress the quote power of Oxycontin in quote versus morphine it may help us in the smaller cancer pain market but hurt us in the larger larger potential non-cancer pain market some physicians may start positioning this product where morphine is used and wait until the pain is severe before using it marketing has decided that by that they're talking about the marketing group correct marketing department marketing department so it says marketing has decided that the effects of the phase 14 should be predominantly focused on expanding Oxycontin use for non-cancer pain and then if you look at the last paragraph it says it is important that we be careful not to change the perception of physicians toward Oxycodone when developing promotional pieces symposia review articles studies etc and what they're talking about there is let's not clear up this misconception that physicians have that Oxycontin is um not as strong as in S-contin correct I object to the point of the question Mr. Thompson you in reading this skipped over two sentences I'll ask that you go back and read this with the two sentences that you omitted the one beginning with the sales force can teach the oncologist oh sure our approach to cancer pain will be to get physicians to use it earlier instead of products such as Percuset, Vicodin or Tylenol-3 the sales force can teach the oncologist the proper dose and titrate Oxycontin to ensure that they stay with it as the pain increases now oncologist are the cancer pain doctors yes correct that doesn't say anything about all the non-malignant for doctors all the doctors that treat non-malignant pain correct but they would be taught the same thing how to titrate because that was the fundamental doctrine of treating pain with opioids start low and titrate and adjust the dose in other words upward well the whole purpose of this email is that you not teach the non-malignant pain physicians that Oxycontin is twice as strong as morphine and let them continue with their perception not correct no not correct let's continue reading the rest of it then last paragraph it is important that we be careful not to change the perception of physicians toward Oxycodone when developing promotional pieces symposia review articles studies etc am I correct that what he is saying in here is let's not clear up the misperception in any of our promotional pieces symposia review articles or studies don't change the personality don't change this to an end of life cancer drug to a drug that shouldn't be used except at the end of life when everything else has been exhausted that was the thrust I may just add something here there's a conflation within this which you wouldn't understand and that was when in the first paragraph which you read where he said that oncologists think it isn't as strong as MS. cotton here the meaning that we understood certainly I understood and anybody who was involved was the cancer doctors who were using the drug were stopping at they had established a notional idea based on their past habit of using Percocet that they shouldn't go above 40 to 60 milligrams a day of oxycodone and the reason they developed that habit that practice limit was not because of the oxycodone it was because of the Tylenol which was the more toxic agent in that combination you're probably aware that recently the FDA has recommended lowering the maximum daily Tylenol dose from 4 grams a day to 3 but even then 4 grams a day was recognized as being the then practical limit so oncologists who were using oxycodone as Percocet were just in the habit well you're getting 40 milligrams a day of oxycodone your pain is coming back rather than titrate those patients to a higher oxycontin level they said well we gotta switch to something else and that was really what was going on and in part why oncologists use of the product had not developed as well as we had wished that it would develop and that was understood and contained within this dialogue not all that documented here let's go back and talk about it a little bit more so in the first paragraph he says we've discussed the issue that oxycontin is perceived by some physicians particularly oncologists as not being as strong as MS-contin although this perception has had some effect on cancer pain it has actually had a positive effect with physicians use in non-cancer pain so what he's saying there if I'm reading this correctly is that because they think it is not as strong as MS-contin when they need a strong drug for cancer pain patients some of the physicians aren't switching to it because they don't think it's as strong and that may hurt sales a little bit there but with the non-cancer pain where you don't want as strong a drug as an end-of-life malignant cancer pain patient might need it's actually helping ourselves that they have this misperception because they are going ahead and prescribing it because they don't think it's as strong as MS-contin is that what that first paragraph is saying? that's what the words say but the meaning of strong here would be effective it is not as effective and the reason they thought it was not as effective is they had a mental notion of a limit and they didn't follow the doctrine of titrating increasing the dose when the pain is getting worse and all of this was really known I mean by 1997 of the people who disagreed and thought that oxy-contin was not 2 to 1 they thought it was 1.5 to 1 that was by far the most common objection still stronger than morphine but not quite as much stronger as we said it was they had been persuaded if they used the drug oh yes particularly those oncologists who switched from MS-contin so then he says since oxycodone is perceived as being weaker opioid than morphine it has resulted in oxy-contin being used much earlier for non-cancer pain so he's saying more people are using it earlier for non-cancer pain because they think it's weaker not less potent more acceptable to the patient not frightening not stigmatized as morphine unfairly was by history that was the meaning and I've lost my thought here could you just repeat your question so I can finish my answer and what he's saying here is the non-cancer pain doctors which is the much bigger market share when you're trying to sell oxy-contin is the non-malignant pain market it's actually helping cells there again as I've testified before the term stronger and weaker was it a very unfortunate term you want to use effective? in the case of here effective yes in the case of cancer because they were using it let me explain one other thing at the time that this product was introduced the World Health Organization had promulgated a step-ladder approach to cancer pain and when oxy-contin was introduced we properly with the agreement of the FDA said that oxy-contin was appropriate for the second step and the third step that's where the start with and stay with theme came from um so I I know that this could cause real confusion reading these documents if you're not involved day to day but there is no way that any of the people on these documents understood stronger to mean more potent, weaker than oxy-contin we had never departed from a strong promotional theme that it was twice as strong as morphine and then down at the bottom he says let's take the middle paragraph since the non-cancer pain market is much greater than the cancer pain market is it important we allow this product to be positioned where it currently is in the physician's mind let him believe that um oxy-contin control release is not as effective as morphine no I said the effectiveness really applied to the oncologists who were saying ah this isn't as effective you know I have to when the pain gets really bad I switch them to something else and that was the one place in which we would have understood it as effective and I've explained that we believe that that was a consequence of them just having a mental limit he says if we stress the quote power of oxy-contin versus morphine and that is it may help us in the smaller cancer pain market let him know that it is more powerful than morphine that will help in the smaller cancer pain market correct that's what he says but hurt us in the larger potential non-cancer pain market some physicians may start positioning this product where morphine is used and wait until pain is severe before using it nothing is coming back probably to the cancer market I'm not sure we always said it was a powerful drug we implied that we wouldn't use the words because words can elicit a whole variety of responses and then the marketing department has decided that the efforts of the phase 4 team should be predominantly focused on expanding oxy-contin use for non-cancer pain that's the group that if you clear up the misperception may be less likely to prescribe according to what he's written here if you change the character of the drug in their mind if you tell them it's a cancer drug it's for end of life care yes, you might change their perception we didn't believe that that was appropriate nor did the FDA nor did the opinion leaders believe it was appropriate it truly was a drug that in appropriate doses could manage moderate and severe and extremely severe pain where patients needed an opioid to manage their pain it's important also that you understand that for 100 years and even today there is no drug that is more effective or safer than opioids for treating pain over the long term and it was a shame that for decades no opioid was used in many most perhaps overwhelming majority of patients who had severe pain do you think it might compromise patient care if Purdue Pharma allowed patients physicians to believe that the drug they are prescribing them is weaker than morphine could you just repeat the question I just want to get the do you think it might compromise patient care if Purdue Pharma was aware that many physicians felt like Oxycontin was weaker than morphine to clear up that misconception no, if they believed it was less potent than morphine we clearly cleared up that misconception we told them it was twice as potent we told them to use doses that were considerably lower than the morphine doses that they might have been accustomed to what we didn't want to do is to turn this into a cancer drug and this is 1997 well after the launch well after your package insert has been put out and all that correct and Michael Cullen says it is important that we be careful not to change the perception of physicians toward Oxycodone when developing promotional pieces symposia review articles studies etc correct is that what he wrote looks like that's what he wrote and did not say no we need to clear up this misconception immediately what you said is I think that you have this issue well in hand if there are developments please let me know that's what I said but the misconception that you're referring to didn't exist the misconception that this was a benign harmless weak drug for treating pain was not the perception that existed so that was not the error that he was I don't know quite what he let me just read what he said here where were you reading from please we've gone through this a number of times so where were you reading from here we were reading from you just read me something from from your top where you said I think that you have this issue well in hand but where you said I was responding where was that where he says it is important that we be careful not to change the perception of physicians toward oxycodone when developing promotional pieces symposia review articles or studies that's correct not change the character of the drug not change not change it into a frightening scary end of life drug all right let me hand you let's mark this as Planes Exhibit 13 this is an interoffice memo dated 1994 and this is from Michael Friedman what was his role in 1994 he was head of marketing and sales and it's to to the three people he reported to and that's Mortimer Sackler Raymond Sackler and Dr. Richard Sackler that's correct and under discussion if you go to page four it says we believe that the FDA will restrict our initial launch of oxycontin to the cancer pain market did you believe that at the time he may have believed it I didn't believe it however we also believe that physicians will perceive oxycontin as controlled release percocet without a set of minifin and expand its use now is oxycontin controlled release percocet without a acetaminophen that would be one way of describing it because there are only two active ingredients acetaminophen and oxycodone is a a sedaminophen it's a sedaminophen it's a sedaminophen oxycodone is oxycontin controlled release more powerful than percocet depends on the dose the initial dose at 10 milligrams twice a day would be equivalent to the standard introductory dose of percocet four tablets one tablet four times a day in other words four so it would be the same dose when you all did studies did you find out that 10 milligrams of oxycontin had the same effect as a placebo and it was really only the 20 milligram that was effective I don't recall that but it's possible we do not want to position oxycontin in a way that will discourage physicians from using oxycontin for the chronic non-malignant pain where are you reading from again next paragraph the next sentence especially when we have studies available that demonstrate efficacy and safety for this indication do you know what your studies showed about non-malignant chronic pain patients developing tolerance or dependency or withdrawal from oxycontin I don't have them immediately in my mind that's been marked correct what do you guys think what are you guys thinking time-wise for lunch do I take it what's going on we are on the record at 11.45 a.m we are back on the record at 11.57 a.m hand you a document it is dated April 23 1997 and on the bottom of paper And on the bottom of page one is an email you sent regarding San Antonio and it says 42297. This is PDD<PHONE_NUMBER>. And it's to, looks like Michael Friedman. Michael, I am somewhat surprised that 18 months into marketing significant groups of experts, oncologists for example, believe that Oxycontin has a sealing effect. What did you mean by sealing effect? It has a dose above which it would not be effective. That was what I meant, not be effective. What materials could we pull together that would smash this critical misconception? Can we put together some approaches and test whether they would be potent weapons in this effort? And he writes back and says to you, there will always be misconceptions about drug substances for controlled release drugs. Many of these misconceptions are the result of residual attitudes associated with the immediate release forms. I'll just read the whole thing. For example, morphine has a personality, quote, that was shaped when it was an IV drug. Oxycodone has a personality, quote, that was influenced by many years of Oxycodone use in Percocet. We built a large part of our platform on this personality and it is to differentiate Oxycontin from NS Conson and Dura Jesus. This differentiation has led to much non-malignant business. Marketing is next paragraph. Marketing is not only about what you are, it's about what you are not. We have had success beyond our expectations, that is in part due to the unique personality of Oxycontin. Even as we seek to increase the use of the drug in higher doses, we should be very careful. As you know, the strength of the drug is principally a barrier in malignant pain. If we do not want to change the image in a way that will discourage non-malignant use, a barrage would be ill-advised. You wrote back excellent points. What about rifle shots? Is that correct? That's correct. That's what I wrote. Over here, before that, there's a letter to you from James Lane. He's pointing out that he sat in some oncology focus groups. What page is that? It's page two. The second page of what you handed me. Oh, Jen, yes. Okay. It says, issues affecting the oncologist utilization of Oxycontin are, MDs feel the product dosing has a ceiling, don't feel it is as strong as MS-contin, like and are very comfortable with MS-contin and don't see a need for another product except where MS-contin fails. Interestingly, when asked to describe what they like about Oxycontin, they are, for the most part, decided all the key points our reps are or should be stating in their sales presentation. The anesthesiology focus group was of less, Saturday evening, was of less value. However, their primary concerns were that Medtronic pump being used by the orthopods and the need for Purdue to educate surgeons on proper post-surgery pain management in fears with opioid prescribing. Is that the email that prompted you to write the letter? It might be, I don't recall. I'm sorry, I prompted you to write your email. It could be. Why don't we mark that as exhibit 14? But I'm not sure. There could be another email in which I pointed out the lack of sales development with oncologists as compared to our plan. So I'm not sure that this is, but it would have been around the same time, perhaps. Maybe I looked at the results with oncologists after I read this. I'm nice about this. So this is the 1993. That's already in evidence. It's the May 1993 memorandum. Are we finished with this? Yes, sir. I want to go back to the May 1993 memorandum. And this is the July 92. What exhibit number are we talking about? Wait a minute. Can I see what you have here? Sure. Let me just clear this up. Yeah. It's not enough yet. Okay. Okay. April 2nd, 1993. Yeah. Let's, I'm sorry. Let's jump to the April 2nd, 1993 memorandum. Let's mark this as Sackler 15. What is PFRC at the top of this? Purdue Frederick Research Center. And it's the R&D meeting. R&D meeting. And it is dated April 2nd, 1993, correct? That's what it says. And part I wanted to ask you about, if you go back to page 10, and you were in attendance at this meeting, correct? I don't, let me check that. I certainly don't recollect by date. Are Sackler attending? Yes, that was me. All right. So on page 10, it looks like you're discussing an osteoarthritis study that was being done. Okay. Where on page 10? I am on the third paragraph. Okay. I'm sorry. Fourth paragraph. It says page 10, but it doesn't look like what you have here. Yes, it. Is it? Yeah. Okay. So read along with me. The section over here, RR. Do you know who RR is? Robert Reeder. Okay. What was his job at that time? He was a senior medical researcher. And he says here in this paragraph, the protocol for the placebo-controlled study of these two dose levels in patients with osteoarthritis was discussed with C right. Now, would that be Curtis right? That's what I would understand. And at that time, he was the person who was reviewing Ural's OxyContin submission to the FDA. He was the medical reviewer, that's correct. And he's the guy that actually approved it to be sold or allow you all to sell it from the FDA. That's my recollection. You all ultimately hired him a few years later, didn't you? We did hire him, but not after his tenure at the FDA. He spoke to somebody of Purdue when he was planning on leaving the FDA. And Paul and I discussed it and agreed that we should not hire somebody who had reviewed our product and left. And so he went to another company regrettably for us because he was very, very knowledgeable and very smart. He went there for a short period of time and then came to work for you? I don't remember. It was certainly... My recollection is a couple of years, two or three years, but I don't recall exactly. The record, I'm certain, could be produced. All right, well, let's take a look at page 10. The protocol for the placebo-controlled study versus two-dose levels in patients with osteoarthritis was discussed with C-right. He stated there were very strong opinions of members at the FDA that opiates should not be used for nonmalignant pain. And this study... Let me just follow you if I may. I'm a slow reader. I'm sorry. But I just do want to follow you. Great. Well, I'll read it again. He stated there were very strong opinions of members at the FDA that opiates should not be used for nonmalignant pain. And this study would not be greatly accepted by the FDA as it is written now for that reason. C-right has suggested rewriting the protocol in order to make it clear osteoarthritis is being used as a convenient pain model. He would also like to... the open-label extension to be eliminated from the protocol. What do you refer to as the open-label extension? In many trials of chronic use drugs, after the trial period, which might have been 12 weeks, was completed, the subjects in the trial were given an option to continue being treated and monitored by their physician. It's completely at their election or choice. Some decide that they want to. Some decide that they don't. And we continue them on medication for an extended period of time. This is extremely common in all kinds of trials. P. Goldenheim stated the open-label extension could be done as a post-marketing study. B. Keiko and our reader will meet with P. Lakatur to communicate what is necessary to revise the protocol. The protocol must be clear that we are not going for a general indication for the treatment of osteoarthritis with oxycodone. And then down below that, it says, Dr. Richard Sackler asked if there was consensus within the pain group about the appropriate use of opiates for certain patient groups. B. Keiko stated this is a very controversial area. And most people in the pain group say that well-controlled studies are necessary to investigate the questions. Dr. Sackler, next paragraph, says, Dr. Sackler has suggested a smaller group meet in-house to clarify the political issues. What were the political issues? The political issues would have referred to the preferences and the sometimes prejudices of physicians and other experts. Over whether you should prescribe opioids for nonmalignant pain. And for what conditions in nonmalignant pain? I don't think there were very many people, or any people really, of any reputation who would have proscribed that has prohibited the use of opioids for nonmalignant pain. But there were a lot of opinions when it came to listing one condition or another, or another, or another. Pain is the most common symptom that patients have and present to doctors. And so every doctor has his own opinion as to what is best and what is appropriate for treating pain. Or in some cases, what pains are not appropriate to be treated at all. And this is a highly personal and contentious issue in the medical world and has been so for a hundred years. And that's the reason that morphine was stigmatized and not prescribed generally for nonmalignant pain. It was more reserved by physicians for end-of-life hospice care and cancer pain in the medical community. I don't understand the connection you're drawing. I think the situation with morphine is unique. And it doesn't relate to what we're talking about here. What about heroin? Was it prescribed for pain? It is prescribed for pain in many countries and is part of the pharmacopeia. For example, it is very popular in the UK. Is it controlled? It is, just like morphine. For end-of-life pain, mostly? I can't tell you that because I don't know. But it is, I don't believe that it established itself as an analgesic in the United States at any time even when it was an analgesic and was available.  Are we finished with this? Yes, we are. Project team meeting minutes of Tuesday, August 17, 1993. It says here under marketing, there's some initial interest in having a 5 milligram and 10 milligram immediate release oxycodone capsule produced. Do you know why marketing wanted those produced? I could guess, but I don't know specifically why they wanted it. Well, if you don't mind, turn back to page four. On page four, what I really want to ask you about is potential studies. And Mike Enorato is the guy we mentioned earlier who was in the marketing department. And he's the guy in charge of perhaps the sales force that goes out and tries to sell. No, he would be in charge of the marketing execution of the strategy. So he would be intimately involved with the promotional materials, secondarily involved with training, and would be the person who would set the direction and themes that would be used. But he wouldn't be a person who would be responsible for sales, although he might go out in the field and he should determine what is happening. Let me rephrase it then. As part of marketing, he's the guy who is supposed to get the word out and hopefully increase sales by advertising the product and convincing people to write prescriptions. Not directly. The salespeople were the principal agents of getting the word out to use your expression of putting the materials in the hands of doctors, etc. I don't recollect that advertising ever played much of a role in the promotion of OxyContin. Let's talk about, if you look at 4.3 potential studies, Mike, I'm going to read that paragraph. Mike Inarato said that an OxyContin vs. Percocet comparative study... Must be. Oh, you weren't reading OK. From potential studies. Sorry, this is so small. It's not so easy. Mike Inarato, and unfortunately that's the way Perdue gave it to us, so we're stuck with it too. Potential studies. Mike Inarato said that an OxyContin vs. Percocet comparative study would be useful for marketing purposes. Now, in trying to decide whether the drug is safe, is it normal to have the marketing people decide what studies will be done? They might be involved in commenting on it or suggesting things, but normally it's the medical department that has the primary responsibility both for the medical research strategy and certainly the implementation. Through such a study, I'm going to read the next sentence. Through such a study, OC881105, has previously been conducted and published in abstract form. It was a single dose study using non-GMP released material. Mike Inarato stated that a multiple dose study would be best to support claims relating to relief of post-surgical pain, low back pain, and herpetic neuralgia pain. For my review of that, it looks like he's got claims he wants to make and is trying to design studies to support him. Is that what that appears to you? No. Half yes, half no. What I think he is doing here in the general is he is in a group meeting presenting ideas for consideration by the group. Certainly, this was not directive and he was not in a position to direct any studies be done or not done. In the next sentence, says Mike Inarato stated marketing would like to position differently than MS-Cotton. Robert Reeder, who is Robert Reeder. He was the senior medical officer in this minute of the meeting. Let me just read, catch up to you. Well, he does tell you this to support claims. Robert Reeder stated that the FDA has suggested that we do not issue claims supporting the general use of a schedule to opioid in patients with non-malignant pain. Robert Reeder indicated that decisions to make additional claims could be developed after the product is marketed. Jim Conover agreed with Robert Reeder, but added that any study conducted in patient with non-malignant pain could be included in the clinical studies section of the package insert. Robert Reeder added that any proposed marketing claims and their supported studies should be first reviewed with our legal and regulatory departments. Perhaps the marketing concepts could be reviewed now. Robert Reeder stated that the marketing could start thinking of a five-year plan on potential marketing studies and strategies. Did I read that correctly? You did. And you have another? This one here. I'm going to hand you this. Are we finished with this? Yes, sir. Exhibit 17. I'm going to move it all these in evidence as exhibits one through 16 and 17. And this appears to be a speech you gave. Is that what this is, or a publication you made? This looks like it was a news paper or magazine-like internal document for the field force principally. I think it was basically the field force. And in-house marketing is salespeople who would like to see their picture there or be quoted or whatever. And it's the winner of 1996. Is that right? That's correct. And if you'll turn to page eight for me, please. I'm sorry. I missed both. I'll turn to page two, please. Oh. Over on the third column. Yes. Halfway down it says the development and launching of OxyContin tablets is the first time that we have chosen to obsolete our own product and we have done it before the competition has slowed our growth of sales. And you were referring to MS-Contin that you obsolete it? Is that correct? That's correct. And then at the bottom it says we have the most powerful selling package insert in the category and in the industry. And is that accurate? I'm trying to see where it is. We have which paragraph in that column? The very last paragraph. We have the most powerful selling package. Yes. Okay. That is correct. And if you'll turn to page eight, it says a speech at the top continued from page two. So I'm assuming this is a speech you gave? It may be, but I don't know. We'll see. OxyContin was brought to NDA. What's NDA? To NDA filing. That's the filing of the new drug application. Right. From early phase one work on time and in an incredibly compressed period of two years time. That's because an NDA usually takes longer, correct? Well... And let me just preface it with the reason it takes longer is because there's a number of studies that have to be done, both animal and human, to determine if a drug is safe and efficacious, correct? Right. In general, that's correct. But in this case, you all got it done in an incredibly compressed period of time of two years. Robert Reeder set the goal in November of 93 to file by December 31st, 95. And we submitted on December 28th, 95, three days ahead of schedule. This didn't, quote, just happen. It was a deftly coordinated, planned event that took dozens of worker years of effort to succeed. True. The most demanding NDA package for any analgesic product ever submitted didn't languish at the agency. Unlike the years that other filings linger at FDA, this product was approved in 11 months, 14 days. Our previous best approval time for other products was measured in years, not months. Much can be attributed to the unparalleled teamwork of the product team and the FDA's approval team, which came into being as responsive our joint desires to operate within the context of a new time frame. Both we and the pilot Doug Division at FDA were motivated by the same goal to set the highest standard NDA with the broadest app indications approved in the shortest possible time frame. Did I read that correctly? You did. Okay. Did you have any questions about that? Nope. I just wanted to know if that was the statement you got and is it accurate? This was a... I believe it is accurate. I'm certain that the facts in there were accurate. The tone was very upbeat. Almost a team enthusiasm building expression. I believe the facts are correct. And I perhaps... I don't regret trying to energize our sales force. I think that was my mission. But this isn't what I would have written if a board had been... or said if the board had been there. I wouldn't have been... The tone would have been more restrained. I'm not embarrassed by the tone. In the context, I think it was very reasonable. Do you have any questions about the reason it was so quick or anything else? No. We got a lot of documents to get through so I'm trying to hit the off points and ask you about... One of the things that they wrote you... Do you have the other pages of this? When you got your approval, if you look at the last page on overall conclusion, and this is a document from the medical officer review, Curtis Wright. This is part of the approval... part of the FDA approval process. He's the guy that now works for Purdue Pharma, correct? No. He hasn't worked for Purdue Pharma for a long time. Okay. Regrettably, but... Hired by Purdue Pharma subsequently, correct? He was hired by Purdue Pharma. And his last... Maybe three years after this. I don't recall exactly. And... Why don't we go ahead and mark this as exhibit 18? His overall conclusion on the last page is CR oxycodone, that's controlled release, correct? Yes. It appears to be a BID alternative to conventional QID oxycodone. And approval is recommended. Care should be taken to limit competitive promotion. What is competitive promotion? I'm not sure what he meant. I could guess that he means promotion comparing this to other agents that are used in various pain conditions. But that's a guess on one part. I think the next sentence explains it. He says, the product has been shown to be as good as current therapy but has not been shown to have a significant advantage beyond reduction in frequency of dosing. So other than you don't have to take it as much, the FDA has concluded that there's no benefit other than it's not been shown to have a significant advantage beyond reduction in frequency of dosing. Not been shown in the NDA, yes. Let's... Probably announcing lunch. Probably so. Let's go off the record. We are off the record at 12.32 p.m. We are back on record at 12.32 p.m. Do you have this one? Mark 22nd. Yes, in case I need another... Okay, if I need another pair of glasses. Yeah, Mark 22nd. Something stronger. I may have stronger ones, you know. Some of these documents are so difficult to read. Yeah, they're difficult. This is the OxyContin Project Team memo. Do you know if you ever reviewed this memo? I wasn't on the project team. I don't know if I reviewed it. I'm curious. I could read through this. Was it sent to me or not? I don't know if it was or not. It looks like I was not on the circulation list. Well, this list down here is... Yeah, there is a circulation list. It appears that it was not. And if you would go over to page 4, the last paragraph down to the bottom, 6.2, Mike Inarato asked if marketing would be able to review the package insert. Do you have any idea of why marketing wanted to review the package insert? Surely. There are many reasons. Robert Reeder stated the package insert will be circulated to marketing and other reviewers at the same time as the protocol review. As I said earlier, the package insert was becoming, originally 20 years prior to this, package inserts were very, very brief and very simple. Over time, the agency wanted them to be more complete documents. And then it had regulatory implications as well. So if you look at the history of use of package inserts, they by this time had become fairly long and extensive documentation for the physician. Their notion of being printed in that tiny format and stuck with every package, in a sense, was inconsistent.  But it was available to physicians in a variety of other forms. The physician's desk reference, I think, you must be familiar with, which was the way most physicians then would read a package insert. It was just a compilation of all the approved products package inserts. What is marketing going to add to that? First of all, I have to understand what the package insert is going to say about the product so that they can think of how they're going to present promotional materials. Secondarily, they might, if the package insert is in draft form and under discussion with the agency, turn to the responsible medical officer, as an example, or the regulatory people and say, you know, this could be misunderstood. This could represent a problem. And so they would contribute to the clarity. But the medical department was, and regulatory department, with the principal owners of the document in the company, and the owner of the document for the government was the Food and Drug Administration. And of course, they had determinative power as to what it ultimately ended up as. He'll turn to page 5, under 7.0, Marketing. Yes. It says, Post-Marketing Studies, QQL, Pharmaco-Economic, Percocet, Dura-Jezek. Robert Reeder discussed some of the planned post-marketing studies. These included an OxyContin vs. MS-Contin comparative study, the Dura-Jezek comparative study, which is currently on hold, and a Relative Potency study comparing OxyContin to MS-Contin. Robert Reeder stated that we would need additional studies to recruit several hundred patients in order to get data to support claims for non-cancer pain. This was on March of 1994. Do you know if those studies were done? I'm sure they were done after approval. But I don't know whether any were done before approval. Do you know if they were done before the drug was put on the mark? I don't know. Who is Robert Reeder? He was the senior medical officer on this project at Purdue Frederick. And then it says Mike Inarato, again he's the marketing guy, correct? Right. Stated that a Percocet comparative study would be a benefit to marketing. Mike Inarato replied to Bob Keiko's question and claims by answering that equal efficacy of OxyContin to Percocet with better quality of life would be a beneficial claim. Mike Inarato stated in the future, Tramadol would pose a threat to the OxyContin market. And then down below that, it says 7.2, marketing claims studies desired. Mike Inarato gave a presentation on the results from the focus groups. A copy of the market research results would be issued to the OxyContin team. The results of the focus groups are attached. The results cover issues such as benefits, positioning, and claims. Do you know whether the studies recommended by Robert Reeder were done before it went to market or the studies requested by the marketing guy were done before it went to market? I don't know. Then there is a, if you go to page, the very last page I guess it is, OxyContin presentation 3294 up at the top. Just a second. OxyContin presentation, I see it. And it says down at the bottom, it's got all the list of, OxyContin will be positioned as the only opioid combining the efficacy and safety of OxyCotone with the convenience of a 12-hour schedule which allows for precise and accurate conversion and titration while allowing the patient to lead a more normal quality of life. OxyContin is the opiate to start with for patients who may be on Percocet, Lord Taber-Weichmann, and the opiate to stay with as the disease progresses. Now, that was a marketing campaign, correct? That was correct. Yes. And start with stay with campaign. Do you know who came up with the start with stay with marketing campaign? I wish I could lay claim to it, but no, I don't know who came up with it. And then it says... That was not the launch campaign, in a sense. It may have been a subtext of the launch campaign, which was the old way and the new way. It says at very at the bottom, less potential abuse than other opioids. Do you know where that claim came from? I don't know. Looking at, is this after the package insert? No, no. It was before the package insert was approved. I don't know. Do you know whether OxyContin had less potential abuse than other opioids? I don't know. What this refers to. Do you have this one? Do we mark that one? We did not. Just mark that as 19 Median and Evidence, and here is this one. This is PDD<PHONE_NUMBER>. This appears to be the... Do you want to mark it? Yes, let's do that. Now it's 20. Are you keeping these? Yes. Okay, it's number 20. OxyContin Tablets Project Team. Okay. And this is June 22, 1994, correct? That's what it says. And on page 2, Marketing, it says... Wait, wait, I see June 8, not June 22. Oh, the date it sent is June 22 over on the right. Oops, okay, my mistake, okay. So it's Project Team Meetings from June 8, you're correct. On page 2, under 1.0, Marketing, under the OxyContin Tablets Project Team Meeting Minutes, Mike Inaratu gave an overview of the oxycodone market referring to sales and growth charts and prescription data. Mr. Inaratu also presented our current strategy for introducing OxyContin Tablets to the market. OxyContin Tablets will be targeted at the cancer pain market. Was a decision subsequently made not to target, specifically at the cancer pain market? I would infer that, but I don't know when. But at least by June 8th of 1994, the plan was still to target the cancer pain market. Yes. It doesn't say that, however, that we... Let me just read this again. It'll be targeted at the cancer pain market. It doesn't say that it will not be promoted to the nonmalignant pain market. OxyContin Tablets will be targeted at the cancer pain market since it is possible that morphine generic products may soon be in competition with MS-contin tablets. We will target patients who are currently receiving MS-contin as well as those patients who are thought to eventually use MS-contin tablets, i.e. on the analgesic ladder, late step one, step two, and step three. The bulk of opioid business comes from 7,500 physicians, 3,000 of whom are oncologists. That's correct. So you all had market share from MS-contin, correct? Yes. And in order to keep from losing that market share to generics you are going to be priced much lower than MS-contin generally, correct? That was the trend at that time, yes. What you did is put out OxyContin an obsolete MS-contin and if you could keep the MS-contin market through the use of OxyContin you wouldn't lose any market share there and if you could expand it to nonmalignant pain you would gain all of that market share, correct? I object to the form of the question. At the minimum it's compound. Sure.  So could you just break it into two questions and I'll answer them both. Can you read the question back? And stop after one. What you did was put OxyContin an obsolete MS-contin and if you could keep the MS-contin market through the use of OxyContin you wouldn't lose any market share there. And that's what this seems to say and certainly that was an element of consideration and part of the strategy. What I think might be missing here is any discussion of the nonmalignant pain market which you asked me a question. Could you read question two? And if you could expand it to the nonmalignant pain you would gain all of that market share, correct? We would not gain all of the nonmalignant pain market share but we could augment or add to the cancer pain market nonmalignant pain. And I'm quite surprised actually that this didn't discuss nonmalignant pain as late as June 8th. So for whatever reason the either Mr. Enorado or the person who was writing the minutes didn't seem to include that because I don't think, not to my recollection, was there ever consideration of restricting this product to malignant pain alone. It was widely used, Percodan, Percocet, widely used in nonmalignant pain. Down below that it says marketing has been interviewing potential advertising groups and is close to selecting one. Do you know which advertising group was ultimately selected? I don't know but I'm sure we could find out if that were important. And then under publications right below that manuscripts for studies C90-0708 and OC93-0101 have been sent to Dr. Stansky and Mandima for review as potential authors. Why was Purdue sending out manuscripts to doctors to be potential authors? I can't say for sure but two possibilities arise in my mind. One possibility is that the manuscript had come to us in draft form and we had helped them fill in details such as the references and so forth. That was one of the ways that companies help authors lighten the burden, so to speak, of writing a paper. The second possibility is the first draft might have been written in-house and sent to them for their review and their correction and additions. Well it says as potential authors. It would appear that they authored the manuscript even though it really came from Purdue, correct? Objection. It's a collaborative effort. We can't, we don't impose on any author what they submit. What they submit for publication is submitted from them, by them and totally in their control. Do you know if Dr. Stansky and Mandima were paid by Purdue? I don't know. Do you know whether these manuscripts ultimately identified Purdue Pharma as being any part of the author? I don't know, but it was not infrequent that employees of Purdue Pharma would be co-authors on manuscripts. I don't know whether in this case they were. And then if you'll turn over to page four of this document. It says clinical. Status of core clinical program. Robert Reader, now he's the... Senior Medical Officer on this product. Robert Reader stated that this OC-92-1102 study, OAPain, has been completed and preliminary data is currently being reviewed. It appears that the 10 milligram tablet is similar to placebo in efficacy, but the 20 milligram tablet was significantly different compared to placebo. Were you aware that the 10 milligram tablet was similar to placebo in efficacy? I don't recall that. That would not be unusual in any analgesic trial, however. You have this one before I'll go now. Then I'm going to ask you about the Meetings of the International R&D Meeting. This is... Did we mark that? We did. This is a PDD... I'm sorry. We can go ahead and mark it if you want. PDD<PHONE_NUMBER> Exhibit 21. Which appears to now we're into November of 94, and present was Dr. R. S. Sackler, correct? If that's what it says, I must have been present for the least part of it. And on page 13... Oh, yes, I was probably present for all of it. Page 13, third paragraph. Dr. Ying asked if there were any... Oh, just a second. I'm sorry. Page 13, this one? You're reading from the top here? Yes, I'm reading from the middle of the paragraph. About the eighth line down. Dr. Ying asked if there were any statistically significant results. It was confirmed that the 20 milligram product was significantly better than the placebo, but the 10 milligram product was not. And was that brought up at the meeting? It must have been... This is minutes of the meeting, so I'm sure this was... These minutes were generally of good quality. If you'll turn over to page 11, and this is shortly before the launch of OxyContin, correct? Renowned in November of 90... No, it was not. This is over before the launch. Yeah, November of 94. It says in the third paragraph, halfway down that paragraph... Yes, Dr. Reader? Dr. Reader. It says advantages for OxyContin are that not all patients can be successfully treated with morphine, and that there is a stigma attached to morphine so far as many patients and physicians are concerned. And that stigma is what? It's an end-of-life, in many hands, principally cancer drug associated with a whole bunch of negative associations. Were one of the negative associations side effects addiction, dependency, tolerance build-up? Yes, but the dependency did not differentiate it from any other opioid. It was not more dependence causing or less. And under this, in summary, the efficacy of the product has been demonstrated in... I'm sorry, go to page 12. Okay, thank you. It's therapeutic... Okay, I'm on page 12. Can you help me with the paragraph? From the top or bottom? Yeah, third paragraph from the top. Actually, four. Of course, it's in summary. Yes, thank you. The efficacy of the product has been demonstrated in six double-blind clinical trials involving 713 patients. Therapeutic conclusions are the equivalence of one milligram of OxyCotone to two milligrams of morphine sulfate. That's correct. All right. Number two says equivalence to IR OxyCotone. Immediate release. Yeah. So they're saying controlled release is equivalent to immediate release OxyCotone? The implication here is in terms of potency, I assume. Number three was the need for dose titration. Yes. And number four says the need for the availability of a rescue formulation. And number five said the need for aggressive management of side effects. Why would you need the availability of a rescue formulation? At this time and still today, the doctrine of using opioids is to titrate to effect. But in some conditions, cancer and others, the dose that has in general a good effect may suddenly be insubstantial due to what's called breakthrough pain. And breakthrough pain could be the occasion by movement or trauma or just occasion by the fluctuation in the pain state. Rather than maintaining a patient on the highest number of milligrams of any opioid around the clock just to prevent breakthrough pain, the normal practice, and I think it's the prudent and safest practice, is to give the patient an immediate release form ideally of the same analgesic agent that they can take when they have breakthrough pain on an as needed basis. Were there studies done at Purdue that showed that blood plasma levels, that the medication, instead of lasting for 12 hours, really lasted between 8 and 12 hours? There were blood level studies that showed the profile of blood level, but there is no prediction of what blood level you will need to control what pain. So when we, what we attended to were the clinical results of treating patients at a 12-hour basis, and that was what we've researched. Now, may I just fill in a little bit? Sure, let me ask you this though. What your research actually showed is that Oxycontin-controlled release provides pain relief somewhere between 8 and 12 hours, correct? I think there were some patients who appeared that way, but principally most were 12 hours. Allow me to just elaborate just a bit. Normally people take a Tylenol tablet every, or two tablets every four hours, but they will get essentially the same effect if they take one tablet every two hours. What we had found was in most patients, this was found as the drug was marketed, who complained that at 8 or 9 hours they were back in pain. Yes, they could be treated every three times a day, but if you took that dosage, the daily dose, and divided it twice a day, Q12 hours, they were just as pleased with the pain relief. It was simply that the physician, perhaps by habit or for other reasons, rather than increasing the twice a day dose, increased the daily dose by telling the patient, well, take it every eight hours, and it would work fine. Do you recall Purdue Pharma running into a real problem with their rescue drug, because they were trying to decide how to market it and whether to say it was for three to four hours or for six hours, and there was a real debate at the company of how we're going to market this because we're going to hurt ourselves one way or the other, depending on whether we say our rescue drug is three to four or six, because it's the same and you're marketing it two different ways. Actually, in the form of the question, it consists of multiple questions and parts. You can answer it if you can. I have a vague recollection of it. If you could show me some documents. If you wanted to pursue this with other questions, please show me some documents. I do have a very hazy recollection of a very minor complication, but perhaps it was a big regulatory complication. I don't remember. I couldn't explain it to you. So we'll go back to that in a second. Okay. Let me continue to read from this document. It says, Dr. Keiko reported that file studies, it's a fourth paragraph, undertaking to show that the 10, 20 and 40 milligram tablets were bioequivalent and dose proportional. In normal subjects, it has been demonstrated that at the same total daily dose, the controlled release product given 12-hourly showed the same two-fold fluctuation as the immediate release product given six-hourly and that this held across the four-fold dosage range. And were you all aware of that in 1994? I'm not certain what this means. I'm sorry, but I don't know, I don't know what two-fold fluctuation means. I'm sorry. Did you ask anybody when you were at the meeting? I'm sure I understood it, but I have my best guess is that whoever was taking the minutes somehow perhaps even didn't understand the discussion or may have understood it, but wrote it up in a way that doesn't make any sense to me now. Going down to the fifth paragraph, a clinical study has been undertaken comparing oxycodone BD versus immediate release oxycodone QID in patients previously stabilized to pain relief. And then if you drop down, the study demonstrated that both products maintain baseline pain control and pain intensity was the same throughout the day. The acceptability score was the same throughout the study and the same for immediate and controlled release products. And then if you drop down to the next paragraph, the conclusion from the study was that the 12-hour product was equivalent in efficacy to immediate release oxycodone. And is that why the FDA said other than how many times you take the product, being the dosing requirements, there's really not any other benefit? I can't tell you whether this was the study that convinced the FDA of that, but the finding is completely consistent with that. There may have been other studies that led them to that conclusion with this being just supportive of that conclusion. In pain studies, I might point out that the biggest advance in measuring pain, which of course is a personal experience, no doctor can look at you and say, oh, you've got a pain level of three and you have a pain level of six. There's no way of doing it. You have to depend on the patient's report. And the huge advance that led to all the research in analgesia and pain relief was called the McGill visual analog scale that was developed in the 50s in McGill University in Montreal. 70 years later, we have no advance on that. And needless to say, I suspect everybody in this room has gone to a doctor where they say, do you have pain? And if you say, or to a nurse, when they take your blood pressure, yes, I have pain. And they ask you to rate it. That is clearly better than just saying, patient has pain plus, yes or no. But it's not a lot better. It's not terribly, it's not reproducible. And it is highly influenced by the environment and other factors that affect the report that the patient gives. So very often, you can compare a highly effective pain reliever to a placebo and you get in the study no difference. And that is widely recognized and that probably related to the study that you talked about earlier. The FDA, however, would have required studies that showed a difference and they did before they would approve the product. In other words, the negative was dismissed as a failed study by the FDA. The positive studies control because... Do you recall the study being dismissed as a failed study? I don't know it was dismissed. It was studied, but they must have concluded that that finding is not consistent with either their expectation or ours or more importantly, other studies and experience. And clearly the product's success in treating patients in pain, which is indisputable, would put a lie to anybody who would say, oh, oxycodone is no better than placebo. I don't think any doctor would assert that for treating pain. Maybe they would say in terms of urinary incontinence, it's not effective, but for treating pain. But whether it's effective or not, it also depends on other factors such as abuse. You can kill somebody and take away their pain, but that certainly wouldn't be effective, would it? I don't think that death would be considered a sign of efficacy. Yes, I mean in the extreme, yes, what you say is correct. So just because it takes away pain doesn't mean it's a good drug, does it? No. All right, let's look at Sackler exhibit 13 again. I did want to ask you one question about this. There's always a balance between effectiveness... I'm sorry. There's always a balance between effectiveness and safety. If you go to page 4, 1.4, it says, if physicians perceive oxycontin as controlled release percocet, it is likely that they will start to use it in place of oxycodone combinations. As physicians become more comfortable with the use of oxycodone combination market, it is possible they will start to use oxycontin in place of class 3 hydrocodone or coding combination drugs. And class 3 are not as regulated as class 2, correct? That is correct. Therefore, it is imperative that we establish a literature to support such use. Who at Purdue Pharma was trying to establish a literature to support a class 3 use for oxycontin? Object to the form of the question. The answer to your question is nobody. We had no plan, program or expectation or intention to change oxycontin from class 2 to class 3. In fact, it is not too long ago the FDA has reclassified hydrocodone as a class 2 drug. So you think that where it says therefore it is imperative we establish a literature to support such use is referring to physicians believing where it says physicians perceive oxycontin as controlled release percocet. It is likely they will start to use it in place of oxycodone combinations. Is that what that development of literature is referring to, in your opinion? Probably. Who was trying to develop that literature? I don't know. That would have been a combination. That would have been the medical department to do studies and then have them published. That would have been a research effort. Do you have that? Is that what this is? Are we finished with this one? Off the record, do you want to break through the launch? Do you want to break through the launch? Do they bring launch yet? Yes. We are off the record. I thought it wasn't. We are back on the record at 2.03 p.m. All right. Dr. Sackler picking back up after our break and we've taken a number of breaks but I'll just remind you at any time you need to stop or need a break just let us know. Thank you. We'll stop again. We were talking earlier about this issue of rescue oxycontin. Let me hand you what we're going to mark as exhibit 22. If you go back to the last page there is a memo dated 9.21.95 from Robert Reeder, R-E-D-E-R. He says currently our draft PI that's package insert, correct? Yes. And therefore our sales material have the same dosing of rescue