Too Much of a Good Thing?

Regulatory s Role in Reviewing External Corporate Communications Too Much of a Good Thing? By John Driscoll Every regulatory professional is a reviewer. One could even say that the majority of our work is reviewing the writing of others. Since our reviews are not based upon a specific legal requirement, and since they necessarily add significant time (and complication) to a document s approval process, how do companies in this heavily regulated industry decide which documents regulatory affairs (RA) should review? The most obvious criterion is whether or not the document will be part of a future regulatory submission. Only a few documents that are ordinarily part of regulatory submissions are not normally reviewed by RA prior to finalization (e.g., case report forms (CRFs)). The business rationale for tying RA review closely to submissions is that regulatory professionals, through their expertise, are presumed to have the best understanding of the regulatory authority s perspective. RA should, 20 March 2009

therefore, be able to provide valuable input that will lead to the desired outcome of the FDA review. Most companies would not want to put something in front of an FDA reviewer without prior review by a regulatory professional. In the case of submission documents, the perceived benefits of RA review are high. However, for documents that are not intended to be part of a formal regulatory submission, RA review is much less common. For example, many internal company documents that provide critical support for heavily regulated activities (e.g., pharmacovigilance or Quality Assurance) are not ordinarily reviewed by RA, even though they are subject to FDA review upon inspection. In these cases, the potential benefits of RA review are outweighed by the relatively low risk of FDA scrutiny. A more controversial area is RA review of external corporate communications. As most of Regulatory Focus 21

More people will see a television commercial for a drug than will ever likely read its product label. these communications are not subject to FDA review ahead of release, and because enforcement is relatively rare, FDA authority over them is viewed as much less well-defined. As a result, RA s involvement in these documents can vary significantly between companies. This article focuses on the major areas of external corporate communications within our industry and discusses some of the benefits of having RA review these materials. Drug Labeling & Promotional Materials Approved product labeling plays an essential role in the communication of a drug s efficacy and safety information to physicians and patients. Given its potential to impact the public health negatively, a drug label is also the most heavily regulated document within our industry. Since nearly all changes to a drug label require FDA approval (or in a few cases, just notification) prior to implementation, RA is at the center of all labeling development, review and approval in most organizations, including responsibility for writing a drug product labeling standard operating procedure (SOP) to formalize the process. Yet while drug product labeling is the most regulated document in our industry, it is the drug s associated promotional materials that are the most prominent. More people will see a television commercial for a drug than will ever likely read its product label. Moreover, the increasing attention paid by the public to the promotional activities of our industry only intensifies the regulatory exposure. Although corporate marketing departments are responsible for creating draft promotional materials, in most companies RA will be very closely involved in their review and approval (including the internal materials used to train sales representatives). In many mediumsized and large companies, regulatory professionals are employed full-time to focus on promotionrelated concerns. Unlike drug product labeling, promotional materials for drugs do not need to be approved by FDA prior to dissemination in most cases. However, they do need to be submitted to FDA at the time of first use. This submission requirement means that most companies give RA general oversight of the internal review and approval process of promotional materials (i.e., to ensure these pieces are not used prior to FDA submission). In most companies, compliance is achieved through a formal SOP written by RA. If FDA enforcement occurs in the form of a Notice of Violation (NOV) letter (inspections for promotional materials are rare), RA will almost certainly take the lead in responding to FDA and oversee any internal corrective action to ensure that all agency concerns have been adequately addressed. Press Releases Press releases are developed by a corporate communications department (usually investor relations or public relations) to announce company news to the public. FDA has historically interpreted corporate press releases as promotional communications and has objected when it believes a press release is false or misleading per the promotion regulations. Even a press release on a product in development can be subject to FDA enforcement if it is believed to constitute promotion of an unapproved drug. Because press releases are intermittent, most companies have a review and approval process that is much less formal than those for product labeling or promotional materials. Some within our industry have argued that for a publicly traded company, the public disclosure requirements of the Securities and Exchange Commission (SEC) trump FDA regulations, especially considering the typical audience for press releases is the media and investors, not the physicians, patients or managed care organizations that comprise the typical audience for drug promotion. Nonetheless, in practice, RA is usually part of the review of any press release that includes product-specific information. Certainly, some kinds of press releases (such as quarterly earnings statements) do not need RA review, but at a minimum, given the potential for FDA action, any press release that mentions an investigational or approved drug product should undergo RA review. In reviewing something like a press release, however, an important distinction between promotion and other external corporate communications needs to be maintained. Information that would be off limits if it occurred in a clearly promotional context is not necessarily forbidden to be mentioned in a press release. For example, while any mention of the positive results of a clinical trial in an off-label indication would, if uttered by a sales representative to a doctor, likely be considered violative promotion by FDA, a press release disclosing the results of a recently completed study may not be, provided the press release made no conclusions or claims about the safety or efficacy of a drug in the unapproved indication. The transformation of clinical data into product claims will always make the issuance of a press release a promotional activity in the view of FDA. 22 March 2009

Scientific Publications & Medical Science liaisons (MSls) As active members of the scientific community, most pharmaceutical companies will maintain internal publications and medical science liaisons (MSL) groups within medical affairs to communicate new scientific information about their products. These communications range from materials presented at scientific meetings (e.g., research posters) to major articles published in peer-reviewed scientific journals. Although the goal of these groups is the peer-to-peer dissemination of scientific information, FDA has previously targeted certain oral statements at scientific meetings and the use of article reprints as violative of the promotion regulations. Given the history of these actions by FDA, it might appear to be common sense for RA to be involved in the review of any product-related external communications issued or used by these groups. However, this is not always the case. Many within the industry (including many regulatory professionals) believe that including RA as a reviewer of scientific communications disrupts the freedom of a purely peer-to-peer interaction and inappropriately presumes the communication is subject to the regulatory requirements of drug promotion. While this is a valid concern, it is also important for a company to consider the extent to which the marketing department is involved in developing the content of these scientific communications. If there is significant marketing influence (i.e., review), a company should consider including RA review as a counterbalance. Medical Information ( Responses to unsolicited Requests for Information ) Most companies maintain a Medical Information group within medical affairs to disseminate information to physicians if requested. The dissemination of off-label information is allowed by FDA through this channel as long as the information is provided in response to an unsolicited request. In December 2008, FDA s Division of Drug Marketing, Advertising and Communications (DDMAC) sent an untitled NOV letter to AstraZeneca regarding oral statements about an off-label use made by a sales representative to a physician. The FDA letter notes that in the 26 March 2009

course of the conversation, the physician challenged the sales representative s off-label claims and requested additional information to support them. Shortly afterward, AstraZeneca sent the physician a Medical Information letter detailing the available clinical study data on the off-label use. Since the letter was not a response to an unsolicited request for off-label information, DDMAC considered the company s dissemination of the letter to be a violative promotional activity. DDMAC even went so far as to include a copy of the Medical Information letter as an attachment in its letter to AstraZeneca. Of note is that FDA would have had no objection to AstraZeneca s Medical Information letter if it had been in response to a genuinely unsolicited request, but also that FDA will consider these sorts of communications to be promotion if they are not distributed appropriately. In many companies, RA does not review Medical Information letters. Again, there is a valid concern that including RA in the review of such materials fosters an appearance of promotional activity. While it is unlikely (though not unheard of) for marketing to be involved in the development or dissemination of Medical Information letters, at a minimum it is critical for RA to ensure appropriate processes exist for the dissemination of these materials. Conclusion In reviewing external corporate communications, RA needs to be sensitive to the different requirements of each area. The strict promotion regulations do not apply in all cases. A key consideration in whether or not regulatory should be reviewing an external corporate communication is whether marketing is part of the development, review or approval. Any external communication influenced by marketing may be considered promotional by FDA and should have appropriate regulatory review to balance any product-related messages. F Author John Driscoll is a Regulatory Affairs professional in the New Jersey area. He can be reached at jrdrisc@post.harvard.edu.