Feb. 20, 2017 – Although the FDA announced last August that it would issue four advertising-related guidance documents by the end of 2016, the Office of Prescription Drug Promotion (OPDP) fell short of that goal and apparently will set a very low bar for 2017: It plans to issue only one guidance document in 2017.
According to the Center for Drug Evaluation and Research (CDER) Guidance Agenda for 2017 issued Feb. 17, CDER has committed to issuing a guidance document entitled “Drug and Device Manufacturer Communications with Payors, Formulary Committees and Similar Entities.” The agency announced a draft guidance on this topic on Jan. 19, so it appears OPDP would plan to issue a final guidance on this matter at some point after the comment period on the draft document ends April 19.
This recent announcement leaves in limbo the much-awaited guidance document on off-label/unapproved uses, which industry has been promised for years. The agency held a two-day forum on this issue last November and recently extended the comment period on the topic until April 10; however, without that topic appearing on the guidance agenda for 2017, it remains to be seen whether the agency will act on this topic any time soon.
The Trump administration’s call for regulatory agencies to delete two regulations for every new regulation (which may include guidance documents) could be affecting the agency’s projected plans for 2017 guidance documents. That said, efforts to answer industry’s requests for more guidance on off-label use surely have stalled beyond reasonable expectations.
However, Coalition for Healthcare Communication Executive Director John Kamp noted that “It’s important to not take this report too seriously. New leadership is coming to FDA. The Trump crew will have its own agenda that will likely take hold quickly.”
Feb. 13, 2017 – A memo sent to Department of Health and Human Services (HHS) division heads last week from HHS Acting Deputy Secretary Colleen Barros attempts to better define exemptions from the federal hiring freeze imposed by President Donald Trump on Jan. 23, and may provide some relief to the FDA, which has hundreds of job vacancies.
According to the memo, “a number of position types have been identified as meeting … exemptions from the hiring freeze.” Those specified in the memo include positions that “are deemed necessary to meet national security or public safety responsibilities.”
Under the “Patient Care and Health-related Research” category, the memo specifies that critical positions include “scientific, research, and program-related position that oversee clinical and/or public health programs”; under the “Public Health Safety and Emergencies” category, the memo states that positions that involve preparing for and responding to public health emergencies, such as pandemic influenza, Ebola and the Zika outbreak, are exempt, as are positions that ensure “public health safety through programs such as food, drug and medical device safety” and that respond to national public health emergencies, such as the opioid epidemic.
FDA advisory board members appear to fall under an additional, limited exemption, which states that during the 90-day period that the initial executive order is in place, “appointments will only be considered for those committees that are legally mandated, but not for those that are discretionary.”
The Barros memo follows a Jan. 31 memo from the Office of Management and Budget (OMB) and the Office of Personnel Management which states that exemptions from the hiring freeze are permitted for “filling of positions under programs where limiting the hiring of personnel would conflict with applicable law.” Many have argued that FDA new drug review activities would be included under that exemption.
Indeed, Regulatory Focus reports that Reps. Fred Upton (R-Mich.) and Diana DeGette (D-Colo.) sent a letter to OMB last week asking that it clarify how the freeze specifically impacts the FDA and its ability to implement the 21st Century Cures Act.
“FDA’s ability to carry out numerous new responsibilities under Cures – such as antibiotic approvals, validation of drug development tools, patient focused drug development, and issuance of new guidance – will depend on the agency’s ability to staff up,” the Upton/DeGette letter stated. The lawmakers also asserted in the letter that FDA user fee funds should be made available for hiring.
Coalition Commentary by Executive Director John Kamp
Feb. 6, 2017 — Fasten your seatbelts and put your tray tables in their upright and locked position as you watch the Trump administration land on our industry.
At a recent White House meeting with PhRMA and industry CEOs, Trump made sure the cameras were rolling as he repeated his screed against drug prices and demanded that more drugs be produced in the United States. But, he later followed up by seemingly rescinding calls to negotiate Medicare drug prices and reimportation of drugs from abroad, and promising lower taxes and a “streamlined” FDA. The result is a mixed bag of good and bad for our industry.
Two recent executive orders and leaks about who might be appointed as head of the FDA have increased the anxiety of industry watchers on the future of drug approvals and the new rules needed to advance the goals of the recently passed 21st Century Cures Act.
The two orders that have rattled the industry are: (1) the freeze on federal hiring and (2) the requirement that two rules be rescinded for every new one created.
The FDA policy and approval processes are implemented by its staff, and because the FDA has hundreds of vacancies in the Center for Drug Evaluation and Research (CDER), the hiring freeze is especially troublesome. Indeed, it is not even clear if the freeze applies to new hires paid for by industry fees. A hiring freeze will chill approvals and the development of new policies intended to simplify and speed drug approvals.
Meanwhile, the two-for-one rule is particularly complicated at the FDA, where hundreds of policy decisions are announced through informal guidances that, according to White House representatives, are within the scope of the order.
Most unnerving to FDA insiders and industry policy veterans are the names of some of the possible nominees to be Commissioner of the FDA.
Four names have been mentioned for FDA Commissioner. All have been involved in healthcare startups, investments, and private-sector innovation, which may be a good sign, but several have ideas viewed as extreme by industry.
Two of the possible candidates are friends of Peter Thiel, Silicon Valley billionaire and Trump supporter, but lack the usual medical credentials. The first is Jim O’Neill, managing director of Mithril Capital Management, former deputy at HHS who has openly favored a multiple-step approval system under which drugs would first be approved for safety only. The second friend of Thiel is Balaji Srinivasan, partner at Andreessen Horowitz and CEO of 21.co, who is a fierce opponent of the current device approval process.
The other two potential choices are doctors. Joseph Gulfo, former CEO of device company Mela Sciences, is an outspoken opponent of the breakthrough approval process and favors a new evidence standard for approval. Scott Gottlieb, former FDA deputy commissioner, is a high-profile advocate for improvements at FDA and is the inside-the-Beltway favorite because of his experience at FDA and in lower-volatility positions.
In the face of all this, CDER head Janet Woodcock recently produced a staff video suggesting employees keep their heads down and focus on the work of the agency rather than on the uncertainty of the transition.
Brace yourself and stay tuned. The Trump team comes with high winds and crosscurrents. It looks like it’s coming in hot.
Jan. 27, 2017 – The FDA issued draft guidance last week that is designed to help medical product manufacturers understand how the agency evaluates product communications, including promotional materials, that present information not contained in the FDA-required labeling but that may be “consistent with” that labeling.
“We are aware that firms have questions about how FDA determines when such communications are consistent with the FDA-required labeling, and how they are viewed by FDA,” the agency states in the Jan. 19 Federal Register notice announcing the document’s availability.
The notice also states that although a firm’s communications that are consistent with the required labeling will not “alone be considered evidence of a new intended use,” “representations or suggestions made about the product would misbrand the product and could subject forms to enforcement action if [these statements] are false or misleading.”
The question-and-answer format of the draft guidance spells out the following:
- How the FDA determines whether the communication is consistent with FDA-required product labeling and how the FDA views this communication
- What types of information are considered consistent with the FDA-required labeling
- What types of information are not considered consistent with FDA-required labeling
- What evidentiary support firms should have to support its communications
- What other considerations apply to communications that are consistent with FDA-required labeling
- What the FDA recommends firms consider when developing these types of communications so their materials are not considered false or misleading
- Examples of communications that would be considered inconsistent with FDA-required labeling
- What the agency’s policies are for communications that are not consistent with FDA-required labeling
The draft guidance also would impose a reporting burden on the industry as part of the “third-party disclosure” recommendations, which call on firms to disclose various aspects of study design and methodology for studies relied upon in order to provide material contextual information. Material limitations related to the study design, methodology design and results “also must be disclosed in a clear and prominent manner to help ensure that the communications are false and not misleading,” and should include disclosure of “unfavorable or inconsistent findings,” the agency states in the notice.
The draft guidance also stipulates that disclosure of material limitations of the study relied upon for communication claims “does not correct the misleading message conveyed by the communication.” The reporting burden for this recommendation is estimated at four hours per disclosure.
“This new disclosure requirement is unnecessary,” according to Coalition for Healthcare Communication Executive Director John Kamp. “I don’t think it will survive in the new administration.”
The FDA is accepting comments on this draft guidance by April 19. To view the document, go to: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM537130.pdf
Jan. 27, 2017 – The FDA recently announced the availability of draft guidance for industry covering manufacturer communications with payors and formulary committees, which “provides answers to common questions regarding the communication of health care economic information (HCEI) about approved prescription drugs” by manufacturers. The document also addresses manufacturer communications regarding investigational products.
“FDA is aware that payors seek a range of information on effectiveness, safety and cost-effectiveness of approved drugs, including information from firms, to help support their drug selection, formulary management, and/or coverage and reimbursement decisions on a population basis,” the agency stated in a Jan. 19 Federal Register notice. “This information may differ from and may be in addition to the information FDA reviews in order to make drug approval decisions.”
“We’ve been waiting for 20 years for this guidance to implement the FDAMA 114 section of the FDA statute. It’s useful as far as it goes because it will facilitate communication by drug sponsors with the payor communities. But, it takes baby steps and includes additional reporting to the FDA,” said Coalition for Healthcare Communication Executive Director John Kamp.
The notice makes clear that the FDA expects that any HCEI provided by firms to payors is truthful and non-misleading and that communications will not be considered false or misleading if they relate to the FDA-approved indication for a drug, based on “competent and reliable scientific evidence” and if they disclose prominently and conspicuously any material differences between the HCEI and the FDA-approved labeling for the product. The agency also clarified that the FDA “does not intend to use HCEI about approved drugs disseminated consistent with this draft guidance … as providing evidence of a new intended use.”
In the draft guidance, question A.9 asks if HCEI for prescription drugs disseminated in accordance with section 502(a) is considered to be promotion and whether FDA’s requirements for promotional materials apply to HCEI. The answer: “HCEI disseminated in accordance with section 502(a) is promotion, and therefore, is subject to FDA’s requirements for submission of promotional materials.” As such, firms are required to submit HCEI materials to the FDA’s Office of Prescription Drug Promotion using Form FDA-2253.
FDA estimates it will take firms approximately 20 hours to compile and draft the information the draft guidance would require if they choose to disseminate HCEI materials to payors. The agency is accepting comments on this draft guidance by April 19.
“It reasonable to expect that the new administration will use this draft guidance as a starting point for additional guidance that will increase the ability of drug sponsors to share truthful information with the payor communities,” said Kamp.
Jan. 20, 2017 – The FDA effectively delayed any prompt action on new guidance covering the promotion of unapproved or off-label uses yesterday by extending the comment period related to the November 2016 hearing on this topic from Jan. 9 to April 19, and by issuing a 60-plus page memorandum that outlines the agency’s position on First Amendment considerations for regulating off-label promotion.
“The FDA is now placing the Memorandum in the docket for the public hearing to provide additional background on the issues it is considering as part of its review of its rules and policies relating to firm communications regarding unapproved uses,” the FDA stated in a Jan. 19 Federal Register notice.
The January 2017 memorandum “lays out the best case possible defending the current FDA policies on off-label,” which “appears to be a statement that current policy is constitutional and FDA is prepared to continue to defend it in court,” according to Coalition for Healthcare Communication Executive Director John Kamp. “So far, that hasn’t worked.”
Indeed, the FDA spends a fair amount of space in the memorandum discussing the potential harms of FDA-approved products being prescribed for off-label uses. “The use of approved/cleared medical products for unapproved uses has been associated with harm to patients, fraud, and waste of health care resources,” the document states, adding that recent studies have found “that the majority of unapproved uses for which drugs are prescribed lack adequate evidence of effectiveness, and that the risk of adverse events is higher for unapproved versus approved uses, and even higher when the unapproved use is not supported by reliable scientific data.”
After describing the traditional route for getting additional uses approved, the agency states that “if firms promote their approved or cleared medical products for unapproved uses, these incentives and programs could be weakened.”
In addressing specific First Amendment concerns, the FDA appears to be doubling down on its current position and continues to defend the status quo, although it does acknowledge “a tension” between public health and other interests.
The timing of this memorandum and the extension of the public hearing comment period indicate that the agency would like to tee up the off-label promotion for the new administration. However, courts have not been supportive of the FDA’s position when such promotion is truthful and non-misleading.
“The FDA Memo does a straightforward job defending the existing off-label policy under the First Amendment, but the arguments haven’t worked in courts before and are unlikely to prevail any time soon,” Kamp said. “Instead, the legal and medical talent would have been better spent developing policies consistent with both the Constitution and the public health. Now as new leadership arrives at FDA I am hopeful the process will pick up speed,” he noted.
Jan. 13, 2017 – An amendment introduced by Sen. Al Franken (D-Minn.) to eliminate the tax deduction for drug marketing costs was not included in this week’s Senate voting on the repeal of the Affordable Care Act, thanks to immediate action by The Advertising Coalition (TAC), which focused on messages to all Senate offices that the provision violated good public policy and the First Amendment.
As a result of TAC’s efforts, “the provision was stricken from the agenda even before the full Senate vote,” according to Coalition for Healthcare Communication Executive Director John Kamp.
Franken’s provision had the purpose of establishing “a deficit-neutral reserve fund relating to unfair tax breaks to drug companies” and called for “disallowing the deduction for direct-to-consumer advertising of prescription drugs” and promotional expenses for prescription drugs.
TAC talking points on the Franken amendment asserted the following:
- The First Amendment protects the right of pharmaceutical companies to advertise to consumers; Congress and the FDA have established procedures to assure this speech is truthful and balanced.
- The purpose of DTC advertising is to provide patients with information regarding potential medical conditions or beneficial therapies.
- The Franken proposal potentially infringes on a company’s right to advertise under the First Amendment.
- Advertising has been recognized as essential to business and treated as an ordinary and necessary business expense since the Tac Code was adopted.
- Advertising created millions of jobs and adds trillion of dollars to U.S. economic activity and benefits all levels of our economy. In 2014, advertising supported 20 million U.S. jobs and $5.8 trillion in U.S. sales.
On Jan. 12, Jim Davidson, head of TAC, thanked media and advertising members, saying that the organization is pleased that the amendment was not included in the Senate vote. “We are grateful to our friends who worked to keep it from being added to the list,” Davidson said.
Jan. 4, 2017 – The FDA will examine whether consumers and health care professionals (HCPs) can identify deceptive claims in prescription drug promotion, according to a notice published in today’s Federal Register. Results of the study could lead to an expansion of the FDA’s Bad Ad program to include consumer reporters.
Although empirical research has been conducted on “the occurrence and influence” of deceptive promotion, studies have not been done to determine how well consumers and HCPs can identify false or misleading drug promotion claims, according to the FDA; this ability has “important public health implications.”
The FDA’s concern is that if consumers are unable to identify deceptive promotion, they “may ask their HCPs to prescribe specific drugs that they would not otherwise request. Likewise, HCPs unable to identify deceptive promotion may prescribe specific drugs that they would not otherwise prescribe.”
Alternatively, if the study shows that consumers and HCPs are able to identify deceptive promotion, “then they may instead be equipped to incorporate such information into their medication decisions, and perhaps even report deceptive promotion” to the FDA through its Bad Ad program, the notice states. Bad Ad program reports “are useful to FDA because they allow investigators to focus their efforts in an era where the amount of promotion far exceeds the resources available to monitor everything.”
Although the FDA’s Bad Ad program currently requests that HCPs report deceptive promotion, the agency could, as a result of the study findings, expand that program to consumer reporting as well.
The proposed research calls for two studies, conducted concurrently, that would focus on different health conditions – chronic pain and obesity – and be administered to the two different populations (consumers and HCPs) using mock Websites tailored to those audiences. Pretesting will allow the agency to fine-tune the study’s procedures and measures.
Study 1 (chronic pain) will allow the agency to assess consumer and HCP response to promotional Websites with varying degrees of false or misleading presentations. This study will answer some of the following questions:
- What proportion of consumers and HCPs correctly identify a deceptive promotional piece?
- Does the number of deceptive claims affect that proportion?
- Does the degree of deception affect attitudes and behavioral intentions toward the promoted drug, including intended reporting to the FDA?
- Do these audiences adjust their attitudes and intentions if they recognize the deceptive promotion?
Study 2 (obesity) will focus on the type of deception – implicit versus explicit – and will compare consumer and HCP perceptions and beliefs about a drug following exposure to varying types of deceptive claims and answer similar questions as those addressed in Study 1, but with different context. .
The FDA will be accepting comments on the following topics:
- Is the proposed study necessary for the proper performance of FDA’s functions?
- Is the FDA estimate of the study’s information collection burden accurate and are the methodology and the assumptions used valid?
- Are there ways to enhance the quality, utility and clarity of the study?
- Are there ways to minimize the burden of the collection of information?
Comments can be submitted to the agency until March 6.
Jan. 3, 2017 – In its last blast of 2016, the FDA’s Office of Prescription Drug Promotion (OPDP) sent Untitled Letters to two companies on Dec. 21, both citing videos available on YouTube that allegedly promote investigational new drugs (INDs) as safe and effective for the purposes for which they are being investigated. These Untitled Letters bring the 2016 tally up to eight; with the three Warning Letters issued for promotional infractions, the total number of enforcement actions in 2016 was 11.
The Untitled Letter sent to Chiasma Inc. cites a video that promotes octreotide capsules (also referred to by the proprietary name, MYCAPSSA™), an IND for which there is no marketing authorization in the United States. Indeed, the FDA had previously told Chiasma that it did not believe the company’s application had provided substantial evidence or efficacy to warrant approval, and “advises Chiasma that it would need to conduct another clinical trial in order to overcome this deficiency.”
The video at issue “presents claims that promote ocreotide capsules as safe and effective for the purpose for which it is being investigated” – to treat acromegaly.
“These claims make numerous positive and conclusory statements about the safety and effectiveness of ocreotide capsules, such as suggesting that ‘the drug is safe’ and ‘the effectiveness of the drug was proven in clinical trials.’” Although OPDP acknowledges that the statement “Product is an investigational new drug and not available for commercial distribution” is included as a SUPER on the screen for eight seconds at the end of the video, it states that “there is no disclaimer that would sufficiently mitigate the extensive claims and presentations throughout the majority of this video.”
The Untitled Letter sent to Zydus Discovery DMCC cites a video that suggests saroglitazar tablets (also referred to by the proprietary name LIPAGLYN™), an IND, are safe and effective to treat patients with diabetic dyslipidemia and hypertriglyceridemia with Type 2 diabetes specifically, although “there is no marketing authorization within the United States” for the drug.
According to OPDP, the video includes claims and presentations that promote the IND for purposes for which it has not been approved by the FDA, even though the product is approved in another country. “The claims and presentations, including the broad statements regarding the drug’s approval as the ‘world’s first’ furthermore are misleading,” the OPDP letter states, and suggests “that the drug is approved throughout the world, including the United States, when that is not the case.”
In both cases, the OPDP requests that the companies cease violating the FD&C Act and submit written responses to the OPDP by Jan. 6, 2017.
Dec. 21, 2016 – The late year spate of enforcement letters from the FDA’s Office of Prescription Drug Promotion (OPDP) continued on Dec. 13 with two new Warning Letters sent directly to company heads, bringing the number of Warning Letters to three this year, plus six of the lesser Untitled Letters.
How clearly product risks are communicated is a common thread in the two new Warning Letters issued by OPDP that cited United-Guardian Inc. for false or misleading risk and benefit presentations in a professional e-mail, and Spriaso LLC for false or misleading risk presentation, inadequate communication of indication, and failure to submit Form FDA-2253 for a Web page.
In its Dec. 13 letter to United-Guardian, the OPDP stated that a professional e-mail for RENACIDIN® Irrigation Solution, indicated for dissolution of bladder calculi of the struvite or apatite variety by local intermittent irrigation through a urethral catheter or cystostomy tube in lieu of surgical procedures, contains “multiple claims and/or representations about Renacidin; however, it fails to communicate any risk information.”
OPDP points out that promotional material can be misleading not only by the representations they make, but also by “failure to reveal facts material in light of the representations made or with respect to consequences that may result from the use of the drug as recommended or suggested in the materials.” The “click here” link to complete prescribing information “does not mitigate the omission of the risk information from the e-mail,” OPDP states.
Further, benefit claims about the product made in the e-mail are not supported and omit specific information from the approved physician labeling.
The OPDP’s Dec. 13 letter to Spriaso states that its Website includes a page that “is concerning from a public health perspective because it creates a misleading impression about the safety and approved indication for TUXARIN ER™,” which is indicated for the relief of cough and respiratory symptoms associated with upper respiratory allergies or the common cold for adults 18 years of age and older.
OPDP takes issue with unsupported claims made on the Webpage about Tuxarin ER that omit any risk information about the product. According to OPDP, specific claims about the product are misleading “because they suggest that Tuxarin ER is safer than its competitors based on differences in dosing formulations and the safety profiles of individual ingredients.” The product contains codeine phosphate (an opiate agonist antitussive), and is associated with serious risks, OPDP states, such as respiratory depression and drug dependence.
The Web page also is problematic because it makes claims that “fail to adequately communicate the full approved indication for Tuxarin ER,” and because the company failed to submit the promotional material to the FDA accompanied by the Form FDA-2253, according to OPDP.
The OPDP asks both companies to cease misbranding their products, submit a written letter of response to the agency by Dec. 28, 2016, and include “a comprehensive plan of action to disseminate truthful, non-misleading and complete corrective message about the issues discussed in this letter” to the audiences that received the initial messages.