Good Reprint Practices

The introductory text of FDA’s Final Guidance Document (see image) states that the Guidance represents FDA’s current thinking on how drug and device manufacturers may disseminate reprints related to “off-label” or investigational uses of regulated products.  Importantly, (and we’ll get into this more in subsequent posts) it does not allow for companies to promote unapproved or off-label uses, but rather, it only permits reprints of a certain quality to be disseminated by companies.  Further this dissemination can only occur under very limited conditions.  The distinction between “promotion” or “marketing” and simple “dissemination” may seem arbitrary or fuzzy, but it is important to understand that the information being disseminated under this guidance document is already in the public domain.  Companies already publish their research (whether it is on- or off-label).  In fact, today there are many legal requirements for companies to publish their research in the spirit of transparency and the free exchange of scientific information.

In addition, FDA has traditionally drawn a line between information that is disseminated by companies proactively and without request from the recipient, and, information that is disseminated only in response to requests that were not prompted or requested by the customer or healthcare provider. Information that is disseminated by companies in a proactive manner is generally considered “promotional” and subject to very restrictive regulations.  Importantly, it is illegal to promote a product for an unapproved new use. FDA’s final guidance document allows companies to engage (conditionally) in proactive dissemination of off-label information in a way that FDA will not consider this communication to be promotional, and consequently FDA will not enforce the regulations that it applies to advertising, labeling, and promotion of prescription drugs and devices.

Alternative approaches?  Not so much…

It is also theoretically legal to disseminate off-label information proactively or without a prior request from a healthcare provider, however, as a practical matter, its hard to tell under what conditions the government (in this case, the FDA) would find this to be acceptable.  FDA’s guidance document attempts to articulate the way (or at least one way) in which a company can proactively disseminate off-label information and not violate the law (The Food, Drug, and Cosmetic Act and its implementing regulations).  Another important point about the introductory text of the Guidance document relates to the boilerplate language explaining that alternative approaches may also be legal.  It reads:

“You may use an alternative approach if the approach satisfies the requirements of the applicable statutes and regulations. If you want to discuss an alternative approach, please contact the appropriate FDA staff.”

If you’ve read enough FDA guidance documents, you know that this is pretty standard boilerplate.  Guidance documents themselves do not represent the law, but rather, FDA’s interpretation of the law.  FDA cannot really cite a company for violating a guidance document, but can cite a company for violating the underlying laws or regulations for which the document is providing guidance.  As a practical matter, guidance documents, including this one, represent how FDA interprets the relevant laws or regulations.   While FDA cannot technically enforce the guidance itself (to the exclusion of other approaches) FDA uses its substantial discretionary authority to force (or encourage with overwhelming force) companies to follow the guidance.  

Its easy to dismiss this language here as boilerplate since anyone who has any experience interpreting FDA guidance documents knows that the idea of acceptable “alternative approaches” is largely a fiction.  However, with respect to reprint dissemination, the idea of alternative approaches takes on a bit more significance.  The Washington Legal Foundation case of the late 90s resulted in courts explaining an alternative approach to FDAMA 401 (21 CFR Sec. 99.1) and to FDA’s 1996 (superseded) reprint guidance.  At one point, the FDA was enjoined from enforcing FDA’s 1996 Guidance and FDAMA 401 (21CFR Sec. 99.1), but upon FDA appeal, the Court of Appeals vacated the decision and injunction.  The result (based on a very clever FDA argument) was that FDA could enforce its reprint dissemination requirements in FDAMA 401 (and 21CFR Sec. 99.1), but only if a company chose to avail themselves of an FDA safe harbor by complying with the statute.  FDA could not hold companies in violation of the law prohibiting off label promotion if they did not follow all of the requirements of the statute.  FDA could, however, use its substantial statutory authority to establish new “intended uses” by gathering other evidence.  Other posts will go in to this in more detail.

It is also important to understand that even in the WLF case, the court articulated that FDA could require the following of an reprint reprint dissemination, including that which did not comply with FDAMA 401:

1) that the articles were not false or misleading (which is a matter of extraordinary judgement);

2) that the articles contain conspicuous notification that the uses discussed were not FDA approved;

3) that the articles were from a peer-reviewed publication; and

4) that financial interests of the company in the products or research discussed was dislcosed.  

If one were reading the Washington Legal Foundation case carefully, one would conclude that FDA is still limited in its ability (even under the new Guidance) of enforcing against “alternative” approaches.  However, it is also important to understand that FDA still (at a minimum) can enforce the four conditions listed above.  

…but every silver lining has a cloud

Reprint dissemination is not some toy chemistry set, where you can mix a few harmless powders together and make stuff smoke, bubble or change colors to impress your third grade friends without blowing them to bits.  Alternative approaches are possible, but you’re on your own when it comes to implementing any alternative approach (of course you can always purchase the company of sympathetic law firms or consultants).  Compliance with FDA’s requirements will be difficult enough (of course you can always purchase the help of law firms and consultants).  Having any affirmation from FDA of your compliance is also a shot in the dark.  This guidance does not include any provision for FDA pre-review and if you attempt to get a voluntary advisory opinion from DDMAC, APLB, or CDRH, you’re likely to grow old waiting for a response.  FDA has no time requirements for any such reviews (as it did under FDAMA 401).  If it does entertain advisory reviews (which it may not) they will likely have a low (if not the lowest) priority in the queue.  

Further, and most importantly, reprint dissemination under this guidance is not a golden ticket to market or promote drugs or devices for new unapproved uses.  The Guidance states:

“FDA’s legal authority to determine whether distribution of medical or scientific information constitutes promotion of an unapproved “new use,” or whether such activities cause a product to violate the FD&C Act has not changed. In recognition of the public health value to healthcare professionals of receiving truthful and non-misleading scientific and medical information, FDA is providing recommendations concerning “Good Reprint Practices” for the dissemination of medical journal articles and medical or scientific reference publications on unapproved uses of drugs and medical devices.”

The Guidance language implies, along with FDA’s record on the subject and the DOJ’s contemporary prosecution history, that any protection or safe harbor that this guidance provides, is strictly limited to the reprints disseminated that comply with the guidance.  It likely wouldn’t apply, for example, to marketing plans or tactics (official or unofficial) whose purpose is to increase sales for off-label uses.  Regulatory, legal, and compliance departments will need to pay careful attention, in particular, to sales and marketing objectives that are not aligned with or are not achievable with the limited provisions of reprint dissemination.  The evaluation of your reprint dissemination should consider the entire product strategy to determine if a new intended use is established through separate, but related, strategies or tactics (resulting potentially in misbranding).  Of course, none of these thoughts have been tested…yet.

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