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Industry Groups Have Concerns With Off-Label Drug, Device Info Draft Guidance

Thursday, April 5, 2012
By Bronwyn Mixter

In comments to the Food and Drug Administration, drug and device industry groups said that although they generally support the objectives of the draft guidance on responding to unsolicited requests for off-label information about prescription products, they have some concerns with certain aspects of the draft.

FDA in a Dec. 30, 2011, Federal Register notice (76 Fed. Reg. 82303) solicited comments on the draft guidance, Responding to Unsolicited Requests for Off-Label Information About Prescription Drugs and Medical Devices. Comments were due March 29 (6 MELR 8, 1/11/12).

The promotion of off-label or unapproved uses of drugs and devices is illegal. However, as FDA noted in its draft guidance, once a drug or medical device has been approved or cleared by the agency, health care professionals can lawfully use or prescribe that product for uses or treatment indications that are not included in the product's approved labeling (i.e., off-label uses).

PhRMA Has Concerns
In its comments, the Pharmaceutical Research and Manufacturers of America (PhRMA) said it “strongly supports the direction of the policy goals and objectives of FDA's draft guidance to ensure that biopharmaceutical companies may provide complete and useful information to health care professionals, health care organizations, formulary committees, caregivers, and patients.”

However, PhRMA said, it is concerned with certain aspects of the draft guidance that “appear to be arbitrary, unduly burdensome, and impractical, and will inhibit an open and productive dialogue between scientific and medical professionals by chilling scientific speech.” Specifically, the group said it is concerned that the draft guidance distinguishes between public and private responses to unsolicited requests for information.

In the draft guidance, FDA recommends that public questions regarding off-label topics be answered only through nonpublic responses. PhRMA said this proposed policy should not be implemented because:


  •  this aspect of the draft guidance is a significant new policy that has never been set forth in any regulatory document previously;

  •  this policy will result in less medical and scientific information being conveyed to physicians and could inhibit the ability of biopharmaceutical companies to correct misleading information or convey key safety data in public fora such as major medical meetings; and

  •  any FDA policy that would ban speech in public settings would be inconsistent with the protections afforded by the First Amendment.


PhRMA also said FDA should clarify its policy on oral responses to unsolicited questions because the draft guidance focuses on written responses.

Additionally, PhRMA said the agency should provide more comprehensive guidance on the use of social media. The draft guidance includes examples and issues related to the use of social media, but PhRMA would like a guidance document specially addressing social media.

'Overly Restrictive,' BIO Says
The Biotechnology Industry Organization (BIO) said in its comments that it has “several significant concerns that certain aspects of the draft guidance are overly restrictive and would not serve the best interests of the public health or further the important goals of scientific exchange.”

Specifically, BIO said it has concerns regarding FDA's proposal to treat a question during a live presentation similarly to a public written request for information.

The draft guidance describes nonpublic solicited requests as those that are “directed privately to a firm using a one-on-one communication approach.” It also states that the company should provide information responding to such requests only to the individual making the request as a private, one-on-one communication.

“A number of common interactions involving requests for off-label information occur in settings that would not typically be considered 'public,' but may not be 'one-on-one' or meet FDA's proposed definition of 'non-public,'” BIO said. “In many of these situations, a manufacturer response based upon FDA's proposed expectations for the handling of a public request would be impractical, infeasible, and contrary to the common goals of providing important public health information to requesters.”

BIO requested that FDA clarify that nonpublic communications may occur in more than one-on-one settings--for example, if a manufacturer addresses physicians in a group practice.

Additionally, BIO said it has concerns that the draft guidance states that requests that are prompted “in any way” by a manufacturer are not unsolicited requests. BIO said it believes that the phrase “in any way” is “overly broad and would inadvertently capture actions of a manufacturer that are not intended to be subject to the draft guidance, but rather constitute legitimate scientific exchange.”

As an example, BIO said manufacturers provide information as part of legitimate scientific exchange by sponsoring publications that contain information about the unapproved uses of their products, and a published scientific article could inspire requests for additional information about unapproved uses.

BIO asked FDA to delete the phrase “in any way” or to provide further clarification on the agency's intent of the phrase “in any way,” so “legitimate communications are not considered versions of prompting.”

BIO also requested clarification on business reply cards and internet sites that are made available to health care providers to request information from manufacturers.

The draft guidance states that manufacturers should maintain records of the nature of each request, the identity of the requestor, and the response given. “While this information can be readily collected for electronic, written or phone inquiries to the firm, in a setting such as a public meeting, it is often not practical to collect information that may be provided verbally to a requestor,” BIO said.

BIO asked FDA to clarify that when information is provided in an informal setting, information identifying the requestor and response need not be collected by the firm.

Devices Industry Cites Confusion
The Advanced Medical Technology Association (AdvaMed), a devices industry group, said the draft guidance “raises confusion through impractical or at times limited examples or line drawings that do not reflect the appropriate recognition and bounds of legitimate scientific exchange.”

AdvaMed said that “as written, the applicability of the guidance is too broad, in that it fails to distinguish the venue in which the off-label request is made, and other circumstances regarding the request.” The group said that the circumstances of each unsolicited request will be different.

“We assume that this guidance is focused on a commercial or a non-scientific situation and not during scientific exchange of information, but this should be clearly articulated for cases of scientific exchange,” AdvaMed said.

The requirement in the draft that people submitting requests be “completely independent” could “exclude anyone who has ever had a financial relationship with the manufacturer from making an unsolicited request,” AdvaMed said. “FDA's underlying objective, that the request originate independent of the manufacturer, can be met by excluding the actual firm and its employees from raising such requests, and reiterating that the request may not be promoted by the firm.”

Additionally, AdvaMed said, FDA should “better define” what constitutes a live presentation public forum. “A firm's medical staff should be able to respond to questions posed by other healthcare providers as part of scientific exchange,” the group said. In such a case, “it would be entirely appropriate for a Medical Affairs person to respond in the public forum. Furthermore, if the off-label inquiry posed a patient safety situation, the way the guidance is currently written, the firm or their representative could not clarify the misinformation to the audience that heard the inquiry.”

The group also said the language in the draft “should make more clear that the use of business reply cards is permissible, so long as they do not themselves hint or flag off-label uses.”

AdvaMed asked FDA to revise the requirement that manufacturers always provide complete copies of the materials they reference in response to an unsolicited request because this requirement is “impractical.”

“Permitting manufacturers to summarize the information available, along with [the] opportunity for the requestor to obtain a full copy of the material described, allows for a more efficient, and meaningful communication,” AdvaMed said.

FDA also should provide more specific guidance on social media, AdvaMed said. “FDA should consider an approach that allows for companies who choose to respond in social media to provide timely truthful non-misleading non-promotional information rather than be forced not to respond online to the propagation of uninformed, inaccurate information,” the group said.

Separate Docket.
FDA also opened another docket seeking comments and information on communicating off-label uses of marketed products and the use of products that are not yet legally marketed for any use, according to a notice published Dec. 28, 2011, in the Federal Register (76 Fed. Reg. 81508). Comments on the agency's docket, identified by Docket No. FDA-2011-N-0912, were due by March 27 (see related story).

In the Dec. 28 notice, the agency said that in a July 2011 citizen petition, Allergan, Eli Lilly, Johnson & Johnson, Novartis, Novo Nordisk, Pfizer, and Sanofi asked FDA to clarify its regulations and policies on when manufacturers may legally disseminate information on unapproved uses for drugs and devices (5 MELR 455, 7/13/11). FDA said the seven companies' petition requested clarification on areas including manufacturers' responses to unsolicited requests, scientific exchange, interactions with formulary committees and payers, and dissemination of third-party clinical practice guidelines. The law firms Ropes & Gray and Sidley Austin LLP submitted the petition on behalf of the companies.

FDA said it is evaluating its policies on sponsor or investigator communications and activities related to off-label uses of marketed products and the use of products not yet legally marketed. The agency said it would like to obtain comments and information related to the scientific exchange of information to assist with its evaluation.

By Bronwyn Mixter


The draft guidance is at http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM285145.pdf. Comments on the draft guidance are at http://www.regulations.gov/. Enter FDA-2011-D-0868 for the comments docket.

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