Topic: Off Label Promotions

Order Description You are a regulatory affairs professional in a Fortune 100 medical device company. Your company's executives heard that the regulatory landscape is changing when off label claims are made. Based on the attached reading materials, please put together a slide deck of at least 4 slides on the recent events that have occurred since Aug 2015, in chronological order. Please clarify for your company's executives if these recent events are making it easier or more difficult for making off label promotions. This copy is for your personal, non-commercial use. For high-quality copies or electronic reprints for distribution to colleagues or customers, click here or call +1 (908) 748-1221. Printed by Ms. Dawn Bronkema, AtriCure, Inc. FDA Seeks To Resolve First Amendment Suit By Pacira By Brenda Sandburg / Email the Author / View Full Issue Regulatory & Policy News / Word Count: 1204 / Article # 01151102004 / Posted: October 27 2015 12:10 PM Executive Summary Judge extends date for agency response to firm's complaint as parties continue settlement talks; case reveals two chinks in FDA’s off-label regulatory regime armor, former FDA advisor says. FDA is in settlement talks with Pacira Pharmaceuticals Inc. to resolve litigation over FDA’s interpretation of labeling for the post-surgical pain treatment Exparel (bupivacaine liposome injectable suspension). The discussions, along with FDA’s removal of a warning letter from its website, indicate the agency may be trying to limit the issues in the case. Pacira and two doctors filed suit against the agency in September contending FDA was narrowly interpreting the approved use of Exparel and blocking “truthful and non-misleading” communication about its broad application. The complaint also requested a preliminary injunction enjoining FDA from taking any action against the company’s speech about the product during the course of the litigation. (See "First Amendment Suit From Pacira Challenges FDA Labeling Interpretation" — "The Pink Sheet" DAILY, Sep. 9, 2015.) The agency had been scheduled to respond to the complaint by Oct. 26. But on Oct. 22, US District Court for the Southern District of New York Judge Lewis Kaplan issued a revised scheduling order extending the date to Nov. 16 so the parties could try to finalize a settlement or determine if a settlement is possible. Related Articles: 6 Off-Label Pacira Warning Letter Dropped From FDA's Website “The Gray Sheet” Oct. 19, 2015 Device Firms Should Not Ignore Pharma Off-Label Suits, Experts Say “The Gray Sheet” Sep. 16, 2015 First Amendment Suit From Pacira Challenges FDA Labeling Interpretation “The Pink Sheet” DAILY Sep. 9, 2015 FDA May Cut Its Losses In Off- Label Promotion Case “The Pink Sheet” DAILY Aug. 31, 2015 Off-Label Promotion Ruling Increases Pressure For FDA Policy Change “The Gray Sheet” Aug. 17, 2015 Laerdal Heartstart 3000 modifications do not require 510 (k)s, FDA says. “The Gray Sheet” Sep. 11, 1995 Key Documents: 3 Click a document title to review. Pacira v FDA scheduling order 10 22 2015 Pacira v FDA PhRMA amicus brief Pacira v FDA MIWG amicus brief FDA Seeks To Resolve First Amendment Suit By Pacira :: “The Gray Sheet” :: Pharma &... Page 1 of 4 https://www.pharmamedtechbi.com/publications/the-gray-sheet/41/44/fda-seeks-to-resolve... 11/8/2015 The parties “have engaged in and continue to engage in settlement discussions in hopes of resolving this case or, at a minimum, narrowing the dispute,” the order states. “The issues presented are complex, and require the direct participation of numerous agency and Justice Department officials, including high-level officials, such that despite concerted ongoing effort the parties will be unable to resolve their disputes by Oct. 26, 2015,” the order says. Pacira’s time to reply to FDA’s response was extended to Dec. 7. Chinks In FDA’s Off-Label Regulatory Armor In a signal that settlement talks were underway, FDA took the highly unusual step of withdrawing a warning letter the Office of Prescription Drug Promotion issued to Pacira in September 2014 objecting to its Exparel promotional materials. (See "Off- Label Pacira Warning Letter Dropped From FDA's Website" — "The Gray Sheet," Oct. 19, 2015.) Pacira announced in February that it had resolved the issues cited in the letter. But the firm decided to challenge FDA after Amarin Pharmaceuticals Inc. won a ruling that it could engage in off-label communications about its fish oil pill Vascepa (icosapent). (See "Off-Label Promotion Ruling Increases Pressure For FDA Policy Change" — "The Gray Sheet," Aug. 17, 2015.) The Exparel warning letter said promotional materials suggested the drug is safe and effective for use in cholecystectomy and colectomy while the approved labeling recommends dosing only for bunionectomy and hemorrhoidectomy surgical procedures. Pacira argues that FDA is attempting to retroactively revise Exparel’s label to limit the approved indication. Susan Lee, a senior associate at Hogan Lovells, noted another instance in which FDA has removed a warning letter. In that case, Laerdal Medical Co. petitioned FDA to withdraw a 1994 warning letter regarding modifications to its defibrillators. (See "Laerdal Heartstart 3000 modifications do not require 510(k)s, FDA says." — "The Gray Sheet," Sep. 11, 1995.) The agency subsequently withdrew the letter. Lee said the Pacira situation is unusual since the company already conducted corrective advertising. But she said the company may have felt removal of the letter would help with a Department of Justice investigation. The company announced in April that it had received a subpoena from the US Attorney’s Office for the District of New Jersey for documents pertaining to Exparel marketing and promotional practices. Lisa Dwyer, former senior policy advisor and deputy chief of staff to the FDA Commissioner, said that in taking down the letter FDA has stoked speculation that it may be looking to effectively moot some of the issues in Pacira’s complaint. FDA made a similar move in the Amarin litigation when Center for Drug Evaluation and Research Director Janet Woodcock sent the company a letter saying it did not object to some of the company’s proposed communications, thereby effectively narrowing the issues to be litigated, she noted. Dwyer, who is now a partner at King & Spalding, said the Pacira suit reveals “two chinks in FDA’s armor” with regard to its off-label regulatory regime. Topics Covered in this Article Click a keyword for related articles. General Topics litigation Subjects Regulatory Post-Market Regulation Advertising Promotion & Regulation Industries Medical Devices Biopharmaceuticals Companies Pacira Pharmaceuticals Inc. Amarin Pharmaceuticals Inc. Laerdal Medical Co. Jazz Pharmaceuticals PLC FDA Seeks To Resolve First Amendment Suit By Pacira :: “The Gray Sheet” :: Pharma &... Page 2 of 4 https://www.pharmamedtechbi.com/publications/the-gray-sheet/41/44/fda-seeks-to-resolve... 11/8/2015 First, the agency has been vague about how it distinguishes between on-label and off-label indications. In light of recent case law, she said, the complaint arguably raises Fifth Amendment due-process concerns as well as First Amendment concerns. The second vulnerability pertains to Pacira’s allegations that FDA’s regulatory regime precludes the company from making on-label “comparative effectiveness claims” without “substantial evidence.” Dwyer said it is hard for FDA to maintain that all comparison claims must be supported by substantial evidence in light of court decisions in the Amarin and Caronia cases. In the Caronia case the US Court of Appeals for the Second Circuit threw out the conviction of a former sales representative for promoting the off-label use of Jazz Pharmaceuticals PLC’s Xyrem (sodium oxybate). The court concluded that the government cannot prosecute pharmaceutical manufacturers and their representatives under the Food, Drug, and Cosmetic Act “for speech promoting the lawful, off-label use of an FDA-approved drug.” FDA could appeal the Amarin decision to the Second Circuit, but given the court’s Caronia ruling, the agency may wish to avoid getting another opinion on its off-label polices. At the request of both parties, the district court stayed the litigation until Oct. 30, at which time they are to file a joint letter advising the court as to their next steps in the case. (See "FDA May Cut Its Losses In Off-Label Promotion Case" — "The Pink Sheet" DAILY, Aug. 31, 2015.) Device And Drug Firms Watch Case While the Pacira case is challenging FDA’s interpretation of an approved indication rather than promotion of an unapproved use, it focuses on what is permissible commercial speech. The pharmaceutical and medical device industries see the complaint as another chance to press FDA to allow more open communication with doctors about unapproved uses. (See "Device Firms Should Not Ignore Pharma Off-Label Suits, Experts Say" — "The Gray Sheet," Sep. 16, 2015.) The Pharmaceutical Research and Manufacturers of America and the Medical Information Working Group each requested permission to file amicus briefs in support of Pacira. The court has not yet ruled on their requests. Both groups also filed amicus briefs in the Amarin case. PhRMA's brief argues that FDA’s attempt to narrow Exparel’s approval through an informal warning letter exceeds its authority. It says that if the agency wishes to narrow a drug’s labeling after having approved it, the agency must notify the manufacturer and provide an opportunity to comment. PhRMA also objected to FDA’s position in the warning letter that two adequate and well-controlled trials are necessary to show “substantial evidence” of effectiveness. “That there is only one adequate and well-controlled clinical trial supporting” the company’s statement does not mean it is untrue or misleading, PhRMA stated. “It simply means that there is one adequate and well-controlled trial instead of two.” “The substantial evidence standard is not and cannot be the sole measure of what is true and non-misleading,” the association added. FDA Seeks To Resolve First Amendment Suit By Pacira :: “The Gray Sheet” :: Pharma &... Page 3 of 4 https://www.pharmamedtechbi.com/publications/the-gray-sheet/41/44/fda-seeks-to-resolve... 11/8/2015 Copyright © 2015 Informa Business Information, Inc., an Informa Company. All rights reserved. | www.pharmamedtechbi.com Contact us at (888) 670-8900, +1 (908) 748-1221, or [email protected] Advertising | Sponsorship | Reprints & Licenses | Privacy | Terms and Conditions Social: Twitter | Facebook | LinkedIn View: Mobile | Desktop The Medical Information Working Group, a coalition of pharmaceutical and device companies, has filed two citizen petitions asking the agency to clarify its policies on truthful, non-misleading communication about off-label use of products. “Because a company’s truthful, non-misleading speech about off-label uses of its approved product is constitutionally protected, as was the case in Caronia and Amarin,” MIWG’s brief states, “a company’s truthful, non-misleading speech about arguably on-label uses also should be protected.” • This story has also been published in "The Pink Sheet" Daily . "The Gray Sheet" brings selected complementary coverage from our sister publications to our subscribers. This copy is for your personal, non-commercial use. For high-quality copies or electronic reprints for distribution to colleagues or customers, click here or call +1 (908) 748-1221. Printed by Ms. Dawn Bronkema, AtriCure, Inc. FDA Seeks To Resolve First Amendment Suit By Pacira :: “The Gray Sheet” :: Pharma &... Page 4 of 4 https://www.pharmamedtechbi.com/publications/the-gray-sheet/41/44/fda-seeks-to-resolve... 11/8/2015