Vanda Pharmaceuticals Letter

Corporate websites are always a concern for Regulatory ad/promo professionals.   This is especially true for small companies that don't have their first approved product yet or for companies with approved product(s) that don't currently have product websites.

So, where do companies put things about their products in development or their product portfolio if they don't have or don't want to spend the money on product-specific websites?  It's a good question.

In my opinion, corporate websites are designed for people interested in the company.   Those would include investors and maybe, depending on how you look at it, payors,  caregivers, HCPs or patients interested in researching a little more about a company in their research on treatments.   So you have to put enough information on your website to peek the interest of investors and to give the rest of world a glimpse into what your company stands for. The conundrum, of course, is where does general information about a company and its products cross the line into specific information about products and, then, to product promotion?

The recent Vanda Pharmaceuticals letter sent out by OPDP is a case in point.    In looking at the webpage cited it does have indication-like information about two products but not real claims.   Just information about what the products do and pointing to the product website if the reader wants safety information.

To me certain things stand out about this letter:

• It appears that the violation was based on information that appeared on Vanda’s corporate website. 
• As there is no mention of this website being submitted to OPDP under 2253, it is very possible that the company considered this was a corporate website and, therefore, non-promotional and so they didn't have to submit the content to OPDP.  
• The violations cited were totally based on the company giving a pretty straightforward statement of what the product is used for.  No real claims except the indication statement.
• Finally, it appears once again that OPDP is connecting a boxed warning product with the distinction of whether they send out an untitled or a warning letter.

The bottom line here is that OPDP does consider corporate websites as potentially promotional and does review these ad hoc, looking for drug promotion.  

In my opinion this letter was sort of old school in that I think it was sent out, in part, to remind companies to keep their corporate websites totally non-promotional.  Consider yourselves reminded!   

So how should companies avoid these types of situations?  

1.  Take a look at your corporate website content and consider whether someone could reasonably consider that it is promotional.  Not whether YOU think it is promotional but whether some reasonable person might consider it promotional.

2. If you have product listings on your website or in a printed catalog be sure to group them in such a way that it doesn't appear that the grouping creates a claim.   Ditto for any descriptions that go with those products.  I am not saying to go crazy with this but consider if the grouping creates an indication for that drug.

3. Be sure that there isn't information on your corporate website about your drug or medical device that could be considered promotional.   These could include language that has inferred promotion.  Examples would be detailed mechanism of action discussions, summaries of what a drug is approved or being investigated for, detailed disease state discussions (especially if they go into the impact of or complications that could result from leaving a disease untreated or information about how current treatments are not completely effective) or anything else that could easily set the stage for drug promotion.

Look, any company that promotes their drug by doing more than handing out PIs is taking some risk that they may be violating ad/promo regulations.   Three keys to help avoid getting an OPDP letter or have an DOJ investigation is to do things the right way, not make careless mistakes and, finally, consider that any violation is too small for OPDP to cite you for.  Good luck!

FDA Guidance on Medical Product Communications

In June, 2018, FDA distributed a guidance document in the form of a Q&A describing under what cases material consistent with the PI but not in the PI could be disseminated.  
This guidance clearly defines that information inconsistent with the approved PI cannot be disseminated in promotional material.   These include:

1. Unapproved indications – including use as a monotherapy (if approved in combination), use to treat a different stage or therapy of disease, use to treat patients not included in patient population studied for drug approval)
2. Expanded patient populations if PI has limitations to the patient population
3. Conditions of use/handling/storage that are outside of what is in the PI
4. Dosing (e.g., amount, route of administration, strength) different from what is in the PI

FDA also indicated additionally, if the information communicated increases the chance that someone will be harmed by use of the product or if the instructions for how to use the product in the PI were insufficient to use the product in the way described by the communication, then, in both cases, the communication could not be used.

At the heart of this guidance is the idea that promotion has to be truthful and not misleading, some of the parameters of which are described within this guidance.   The importance of this guidance is that it allows the pharmaceutical industry to speak to things that they have not allowed previously, most or all of which have been the subject of OPDP action letters in the past.

What the guidance seems to say is that a number of areas that previously were either “gray”, undefined or clearly forbidden are now possible IF all the considerations above for the communication are met.  These areas that now appeared to be allowable are:

• Comparative studies – Routinely OPDP has said previously that companies should not talk about these kinds of studies unless FDA has seen the data first.   In other words, you had to have that information in the clinical section of your PI. 
• Providing context around (and softening of) statements regarding adverse events.  In the past if you had nausea as your adverse event and in subsequent studies not in the NDA you found that prophalaxis with nausea-reducing drugs eliminated most of this nausea, you really couldn’t say that as, once again, FDA hadn’t reviewed the data in those studies.  This was already mentioned in a 2014 guidance.
• Onset of action – Previously, if your PI was silent to onset of action you couldn’t mention it in your promotional material unless it was a fact but was just not mentioned in your PI
• Long-term safety and efficacy – Previously, you couldn’t talk about long-term efficacy if that data wasn’t in your label and FDA had not seen that data in their review.   Now, if data exists, you may be able to market to it without that data being included in a supplement to your PI.
• Sub-group analysis – As part of what was referred to, in a negative way, as ‘data mining’ it used to be prohibited to promote to sub-groups if those sub-groups were not specifically tested for in the endpoints of clinical studies.  Now it appears that if the data is present you can promote to these sub-groups.
• Composite endpoints – Previously you couldn’t say anything about the individual endpoints that make up a composite endpoint.   Now you can, with proper qualification, give some information about the results of the individual endpoints within a composite endpoint.
• Product convenience and mechanism of action – If new information not in the PI is available then it can be promoted to.   Interestingly, for product convenience this extends to comparative studies with competitive products, as well.
• Tolerability with concommittant drugs – Again, this normally had to be spelled out in the PI as did all information about drug-drug interactions.  Now it appears that information generated after the drug was approved can be marketed to, even if it is never added to the PI.
Of course, in all these cases the statements have to be truthful and not misleading and, as such would have to be scientifically sound.  Depending on the type of claim, the guidance also says that the evidence necessary might be substantial evidence and might only have to be adequate evidence.  Thus, you probably couldn’t do a sub-group analysis on blacks if only two blacks were enrolled in your piviotal study.  However, if you did an entirely separate study on blacks and it represented substantial evidence, the way I read this guidance is that you could promote to that study.
As is always the case, any information used in promotional material has to be truthful and not misleading.   This is always a high bar to hurdle and companies should make sure they are on strong statistical and scientific ground before they make claims that are based on data not addressed in their approved PI.

Arog Pharmaceuticals Untitled Letter

In a letter dated 6/29, OPDP told Arog Pharmaceuticals that they had been promoting their unapproved drug Crenolanib.

The crux of this letter was that it was OPDP's opinion that Arog was making conclusionary statements about Crenolanib although it had not yet been approved.

This type of letter has been sent out many times over the years by OPDP to companies for pre-approval promotion of drugs.   Looking back over past letters the theme is generally the same:

• Companies fail to make it clear that the drug is investigational and not approved
• Companies make conclusionary statements about aspects of the drug where no conclusion can yet be reached because the drug is not approved
• Companies give or imply an indication for a drug that has not yet been approved.  Obviously this is problematic to OPDP as in many cases there are limitations to an indication once approved.
• Use of words like novel or unique or other words that imply superiority
• In a couple of old examples, indicating lack of adverse reactions with the drug

In the current letter OPDP also cited Arog for indicating that their drug was useable with some forms of full dose chemotherapy.

In many of the letters and supposed promo materials sent out to OPDP, the supposed violations come down simply to choice of phrase.  It is impossible to know from the letters whether the company cited has chosen their words purposely, have just quoted words directly from discussion sections of scientific publications or, more simply, just believed so much in their product and were so unaware of the ad/promo regulations and previous OPDP letters on the subject that they didn't realize that what they were saying or doing was pre-approval promotion.

As I said, it is usually all in the language used.  In many cases just the addition, removal or substitution of a few words changes a claim to a statement of current belief (based on scientific data) about an unapproved drug.  Let's look at the language that was cited and see what could have been said (additions in bold, removed text in cross out):

Booth Graphics

o Combination Therapy—Future of A New Hope for AML Treatment 

     o CRENOLANIB - currently in clinical trials  

            o Also being investigated to see if it is combinable with chemotherapy at full doses

o The Goal: Eradicating Activating Mutations  

     o The Hope: CRENOLANIB  

          o Pre-clinical study results suggest that it could be a potent inhibitor of  

                o FLT3   

                o PDGFRα   

                o PDGFRβ 

Webpage

o  Crenolanib - A next-gen  new type of tyrosine kinase inhibitor for use being investigated for use in the treatment of FLT3-mutated AML. 

o Pre-clinical data suggests that Crenolanib, a type I TKI, is could be a potent inhibitor for FLT3-ITD and secondary KD mutants

THERE ARE SEVERAL ATTRIBUTES THAT HAVE BEEN DESIGNED IN TO THIS MOLECULE TO HELP SET CRENOLANIB APART FROM OTHER THERAPEUTIC OPTIONS 

1. In clinical studies Crenolanib, whether delivered by itself or as part of a drug combination, has shown showed benefit in FLT3 mutant AML. 

2. There is some evidence that patients who progress after treatment with prior TKIs may still remain sensitive to crenolanib. 

3. Evidence suggests that Crenolanib has favorable pharmacokinetics and does not appear to accumulate with repeated dosing. 

4. Crenolanib is was designed to be a selective type I TKI that does not inhibit wild-type cKIT.

Now, I am not saying that this language would be acceptable to OPDP as the language I suggest is not exactly scientific exchange and I haven't even read the science to see how definitive the results are, let alone know if FDA would think those results were definitive.  However, the changes I suggest would at least address most of the concerns OPDP presented in this most recent letter.  If we are to take the language in this letter as a signal from OPDP as to what would be acceptable to say about a drug that has not yet been approved but for which substantial data was available, then the message appears clear to me: Make clear the drug isn't approved and don't represent statements about the drug as fact when the validity of those statements will be dependent on the outcome of the review of the drug application by FDA and the resultant language in the approved full prescribing information.

Pfizer Untitled Letter Regarding Estring

I realize I am a little late to the party on this one as the last few weeks have been busy.  But let's dive in:

Pfizer apparently put a testimonial video together that featured a physician and a patient, both of whom were paid spokespeople for the company.   Although I have not seen the video, the OPDP letter was pretty clear.   The physician and patient spoke on THEIR experience with Estring, basically saying that they saw instant relief with no side effects.  However, as OPDP points out, this does not constitute a fairly balanced presentation of the benefits of the drug AND that these statements by the doctor and patient are, indeed, product claims and so must be presented along with fair balance regarding the risks of using Estring.   The video apparently did not have any risk information and referred the viewer to go to a product promotional website or talk to their doctor to get more information about Estring.

So this is a relatively cut-and-dry violation which once again shows that patient or doctor testimonials are promotional labeling/advertising and need to only be used in the following situation:

(a) when they represent on-label, average performance of the drug
(b) when they are presented with fair balance and access to the PI

For videos on the internet these could be handled by having important risk information and URL of the PI embedded within the video or, on a youtube channel, in the space that surrounds the screen on the youtube channel page.  In addition, you want to have careful training of the spokespeople as to what they are NOT allowed to say.  This does not mean you would tell them what TO say.   However, being upfront with people before a video is shot is much easier than having to try to edit a video after the fact to remove questionable statements.

It seems to me that every once in a while OPDP picks a topic they want to reinforce with the pharmaceutical industry and selects a company with a violative approach to use as an example.  While that may not be true the effect is still present.   This letter reinforces what I always tell clients regarding testimonials and what I tell my clients about testimonials is based on the experience I have gained by looking at past OPDP letters and attending national meetings where these topics are discussed.

Collegium Pharmacauticals Letter

OPDP issued its first (untitled) letter of 2018, 3 months ahead of the pace in 2017 when the first letter came out in May.  The letter was sent to Collegium about their promotion of the extended release opioid product, Xtampza ER.

To summarize, the letter claimed that Collegium did not provide Important Safety Information WITH the claims in a booth panel or in a similar prominence, failed to provide appropriate materials facts (regarding abuse deterrence) and put some material facts in a position on the booth panel that were close to floor level and obscured by a table and chairs.  The backdrop of this letter is that Xtampza ER is an opioid product and in light of the opioid epidemic in the country, serious risks of opioids need to be appropriately pointed out when opioid products are promoted.

There is some sentiment in the industry that a promotional booth at a conference is one large promotional piece and that each booth panel does not have to have fair balance if the booth, as a whole, is balanced.  This letter seems to indicate that OPDP doesn't see it that way and that Collegium exacerbated the situation by having the fair balance in different prominence than the claims.   OPDP also took particular exception to placing material facts near the floor of the exhibit panel, obscured by a table and chairs.  Both the disconnect of the Important Safety Information from the claims and the obscuring of the material facts were probably considered by OPDP to be basic mistakes in promotion of a pharmaceutical.  Reading between the lines of the letter it appears that OPDP is saying that these types of basic mistakes are even more objectionable when a company is promoting an opioid.

At this point I will interject my own opinion.  Every company has key points they want to make in their promotional materials.  These are points that in many cases differentiate their product from the competition.  Some of those points may be in the gray area of what is allowed based on their product package insert.   I think this letter points out that if you want to make those claims you should make sure that the rest of the promotional material is pristine in terms of things that could be construed as violations of the promotional regulations.  This letter seems to say to me that OPDP thought Collegium was trying to get every little edge in their promotional claims, in some cases going so far as to do things that appeared to be silly, like putting material facts so low on the booth graphic they almost became footnotes.  I think OPDP looks at promotional pieces as a whole. If that is true, trying to gain every little possible edge can create a straw-that-broke-the-camel's back situation compared to just making one or two appropriately balanced claims that fall in that gray area with the rest of the piece being on point relative to the regulations. I could easily be wrong but this is how I feel I have been successful in my career at helping companies create compliant promotional materials that are, at the same time, effective.

In addition to the above, the origin of the letter and the context of OPDP citing previous communications with Collegium are interesting.  

1. The letter indicated that the violations were observed by an OPDP representative at a meeting in June, 2017.  This shows that even in the new political administration where OPDP regulation may not be as important, OPDP is still going to meetings and looking for promotional violations. Additionally, the lag between when the violation occurred and when the letter issued fits with what I have seen for previous OPDP letters over the years, on average.

2. The letter referenced advisory comments that OPDP had provided to Collegium regarding other promotional materials for Xtampza ER.  In those advisory comments OPDP asked Collegium
to modify those materials to correct many of the same issues that OPDP found with the booth panels. This is not the first time OPDP has referenced previous communications in an action letter but it again points out that refusing to heed OPDP advice can increase the risk of an OPDP letter regarding future promotional materials that have the same issues.  Bottom line: if you choose to or are compelled to seek advisory comments from OPDP, it is wise to heed those recommendations.   Failure to do so can just add more straws to that already weakened camel's back.

None of what I have said above is intended to condemn Collegium's internal review process, what they intended to do or what is done at OPDP.  It is just my opinion on how this letter can be an example that can help companies do a better job of creating compliant and effective promotional materials.

UCLA OPDP Letter

In its latest action letter, which came in under the wire for 2017 as it was issued on Dec. 28th, OPDP cited the University of California at Los Angeles (UCLA) for its promotional claims about an unapproved drug, a radioactive imaging agent, Ga68-PMSA, used in positron emission tomography (PET).   Promotion of unapproved drugs as a specific cause for an OPDP action are relatively rare and a quick search by me could come up with less than 30 letters since 2000, with the vast majority of those to pharmaceutical companies.   In fact, this letter represents only the 2nd letter I could find in that period sent directly to a university for promoting an unapproved drug.  The other letter went to UCLA, as well, a couple of years ago (2015).

OPDP cited UCLA in its 2017 letter for a number of promotional claims about Ga68-PMSA, saying that those claims fall outside of what is allowed for discussing unapproved drugs, i.e., dissemination of scientific information.   Looking at the claims and materials OPDP cited, it appears that OPDP is correct.

As background, there are many recent literature reports about the promise of Ga-68 radiopharmaceuticals for medical imaging.   The results of scientific studies for Ga-68 PMSA are very promising.  However, it is the use and, more accurately, the summation of the results of that scientific data to promote a patient to ask to have this scan or HCP to suggest this scan that is no doubt concerning to OPDP, considering that there is no FDA approved version of this drug.

I think the fact that this came from a university-related medical center is interesting and the fact that it follows on the 2015 letter to UCLA for promoting [F-18] FDDNP, another unapproved PET imaging agent is also of note.

So, what is to be learned from this letter?

What I am about to say is my opinion and, in no way, is meant to say that UCLA did anything malicious.   However, in my experience, scientists not trained in the rules of promoting pharmaceuticals usually don't understand the difference between just giving information to people and active promotion of an unapproved drug.  As I was a drug discovery scientist at a pharmaceutical company before moving to Regulatory Affairs, I get it.  What scientists may consider a fact based on available data is, to OPDP, an unsubstantiated claim if the drug under discussion is not FDA approved.  Scientists don't normally understand that even though a drug may look good in a limited study, it could have risk-benefit limitations that might make it not approvable by FDA or that there may need to be some significant restrictions in use if the drug is approved.   They don't understand that those determinations can only be made after looking at larger studies and all the associated data (e.g., manufacturing) that goes into making sure a drug is safe and effective for human use.  This is not meant as a slam against scientists, it's just my experience as a former scientist and a regulatory person who deals with these scientists in a promotional setting.

This letter and the previous letter to UCLA point out the need for good Regulatory advertising and promotion training for universities and medical centers that are using unapproved drugs.  It also would be helpful if the content of outwardly-facing materials (e.g., websites and brochures) underwent review by someone experienced in OPDP regulations.    Finally, it should refresh for pharmaceutical companies the necessity to have good oversight with the universities that are conducting their clinical trials and the materials those institutions are using to recruit patients.  

Package Inserts in Promotional Materials

Over the years I have seen and heard of a lot of different options for use of package inserts (PI)  also called full prescribing information, in conjunction with promotional materials.

When the regulations call for promotional materials to be accompanied by adequate directions for use, for pharmaceuticals we are talking about the PI.

The question is, what do companies think "accompanied by" means?  There are really two general categories: electronic pieces and hard copy pieces.   Here are some thoughts about each:

ELECTRONIC PROMOTIONAL PIECES - Non-narrative

There are many kinds of electronic promotion: e-mails, websites, electronic ads, social media, internet videos and TV/radio ads.   In all but the last category, the PI is normally 'provided' by including a link to the PI.  That link normally goes to a pdf version of the PI on a product promotional website. If this method is used the link should probably go DIRECTLY to the pdf of the PI and not to the homepage of the website.   Other methods exist like creating a hidden website that only has the pdf of the PI and then linking to that single webpage website.  By standard practice, for TV/radio ads the viewer/listener is directed to a printed ad (or a website URL) that contains the PI.   OPDP has said that internet videos are more like websites than TV ads and, in fact, if a TV ad is placed on the internet (e.g., on YouTube) a company should provide a link to the PI page ON the internet page with the video instead of within the video telling people just to go to a magazine to find the PI as they do with TV ads.  In other words, OPDP feels that once a TV ad is on the internet where space or time is not limited, normal internet rules regarding the inclusion of the PI apply.

ELECTRONIC PROMOTION - Narrative

 During a product promotional presentation like a sales presentation on a tablet/laptop or a product promotional slide show, a hard copy of the PI should be handed out at the beginning of the presentation.   In these cases it would likely not be sufficient to simply show the PI on the presentation screen as that would likely not represent ADEQUATE directions for use.

NOTE: If you are presenting a webinar there are four options I have seen used:

• E-mail the PI to each webinar registrant with the e-mail confirming their registration 
• Shortly before the webinar is supposed to start e-mail the PI to all participants 
• In the confirmatory e-mail provide a link to the PI 
• For hard copy confirmations, include a link to the PI on a postcard with appropriate text letting the reader know what the link is to or for a letter confirmation, include a copy of the PI

Companies should decide which they feel is best for them logistically and for regulatory compliance.

PRINTED PROMOTIONAL PIECES

For printed materials, there are a number of different ways that companies provide PIs with their promotional materials:

1. They print the PI on the promotional material
2. They glue the PI to the promotional material using a sticky, glue-like substance that allows easy removal of the PI
3. They include the PI in a sleeve between two pages
4. They include the PI loose inside a multipage piece
5. They provide the PI separately (but at the same time) as they distribute each promotional piece

There are reasons that companies have for using each of the above.   Based on my experience here are those reasons as I understand them as well as the pros and cons of each one.

1. Some companies feel that it is better if the PI is part of the piece so they know the viewer will receive the PI IF they receive the promotional piece.  Also, for a magazine ad, the inclusion of the PI is a requirement (along with the major statement important information (including safety information) about the product.  In this case a company would have little choice but to buy a couple of extra magazine pages to print the PI.   As indicated above, this does help the company if they are running TV ads about the product as it gives them a place to point viewers to see a copy of the PI.

pros -You will never have a promotional piece given out without the PI; pieces tend to stack better than if you use the glue idea.

cons - If your PI undergoes a substantial safety labeling change that the FDA deems important enough to require the company to implement immediately, you could end up trashing a whole bunch of your promotional pieces (or, in the case of a TV ad, having to reshoot the ad).   Reprinting (or reshooting) these could eat up a good amount of a marketing budget, especially if it is a popular piece.

2. This seems to be very popular and provides a great way to get the PI (usually folded up to a small size) attached to the piece but easily removed from the piece if someone wants to read it.

pros - The PI is affixed pretty tightly to the piece so it is unlikely to be accidentally dislodged.  As above, this eliminates a lot of the human error in proactively giving out the PI.   In some cases, it also makes it possible to replace the PI with a newer version if necessary, although this is not always possible.

cons - Promotional pieces end up with a lump in them, making them harder to store and bulky to pass out.  It may not be easy to remove the glue and replace with another PI if a PI change is mandated so you could end up trashing your promotional material.

3. This requires a piece to have two pages permanently glued together at the sides and bottom creating the pocket.

pros - The best option if you want the PI to be non-obtrusively included AND easily swapped out if a PI has to be replaced.

cons - Probably the most expensive way to include a PI as, for a single page sell sheet, you now have to create a pocket which might more than double the cost of printing.

4. The lowest tech option which can involve the PI (flattened out to make it fit better between pages) being added after printing or can involve the person distributing the promotional piece to a customer or patient actually slipping the PI into the piece before they distribute it.

pros - least costly of the ones so far and represents the easiest option in terms of replacing the PI if replacement is necessary; some companies even provide a set of PIs in a stack like a notepad where a PI is just peeled off every time it is needed (thus, if the PI is changed, the pad of old PIs is just destroyed and replaced with a pad of the new PIs)

cons - this represents one of the greatest risks for the PI not being given out with the promotional piece so when this method is used, the PI is almost always provided with piece as it comes from the printer; most companies still don't feel comfortable with the possibility that some employee may forget to include the PI when they distribute a piece.

5. This separates the act of giving out the promotional piece from the regulatory requirement of providing the PI.   In additional some companies feel that all they have to do is OFFER the PI, whereas other companies feel they have to provide the PI.   For the former group, having PIs available but not included cuts down printing costs of having to include the PI, even loosely, with the promotional material.

pros - If a company feels that their employees are well trained enough, this option represents the most cost effective and versatile (in case of a PI change) way to satisfy the regulations

cons - This option provides the greatest opportunity for someone to forget to provide the PI with the promotional piece and probably requires the most oversight of these 5 methods to make sure a company is being compliant in providing the PI to the person getting the promotional piece.

FINAL THOUGHTS

As product promotion changes some of the above methods of promotion may become obsolete.  They key for me is to make sure that the person receiving the information has access to the PI that is commensurate with the nature of the presentation of the promotional materials allowing, of course, SOMEWHAT for limitations in the nature of the promotional materials.  Notice that I said 'somewhat' as OPDP has said repeatedly that limitations created by use of certain methods of promotion does not eliminate the requirements for fair balance and providing adequate directions for use.   As companies move into new types of promotion they should concurrently develop internal standards for providing the PI (and, of course, fair balance).  In many cases those standards evolve over time for a particular medium but it is way better to have developed your company policy than to do nothing and wait to see what other companies are doing.   Or, you could just ask OPDP what they think!

Disease State Websites and Ads

NOTE: The opinions in this article are mine and are presented solely to cause thought on this subject and do not represent legal or regulatory advice.  Companies or individuals should seek appropriate legal or regulatory help to address these types of issues.

Information about a disease that is provided to consumers and/or healthcare providers has had many names over the years:  help-seeking ads, disease state ads, disease awareness ads, among others, have been used.  No matter what you call them, for a long time FDA has seen the advantages in drug companies providing useful, unbiased, non-promotional information to help educate patients and healthcare providers about diseases.   Likewise, pharmaceutical companies have long used these to raise awareness about a disease both with consumers and prescribers.   In most cases, and logically so, these companies have put their money into developing materials for diseases they have a treatment for. This has created the possibility for these disease awareness materials to be used as 'veiled' drug promotion. 

OPDP put out general  guidance in 2004 on this topic which was withdrawn by FDA in 2015.  To the best of my knowledge there has been no follow-up since that time.   Since the currently available, non-withdrawn documents from 1985 and 1988 are actually precursors to the 2004 guidance, there doesn't appear to be a lot of current, updated information.

From my experience and using the 2004 guidance as a source, I have constructed a series of dos and don'ts to keep your disease state materials pure and not product promotional.

DO

• Provide relevant, specific and useful information about the disease in question.  
• If directed at consumers, advise the consumer to go see an appropriate health care professional

DON'T

• Combine disease awarenss communications with mention or inference of a drug unless you also including fair balance and access to a product package insert (i.e., you are using disease awareness material within a product promotional setting)
• Make the design, images, color schemes, etc. between your disease awareness materials and product promotional materials be the same or similar
• Put disease awareness materials or ads near (or for multimedia, close in time) to product promotional materials
• Present information in such a way that it unduly scares consumers into going to their doctor or convincing them they have a disease because they have a particular symptom
• Present disease state information in an unbalanced way to imply that treatments can do more than they are approved to do (e.g., saying that treatment for diabetes will reduce the risk of heart attacks or strokes if the sponsoring company's diabetes treatment has not been shown to do that)
• Suggest self-diagnosis or suggest the use of unapproved testing as a definitive diagnostic test for the disease.
• In a situation where there are classes of drugs that treat the same disease, highlight the advantages or disadvantages of those classes, especially a class that a company's drug may fall under.
• If there is only one drug that treats a particular condition, discuss pharmaceutical treatment. (NOTE: A company MIGHT be able to include limited statements (e.g., 'this disease can be treated with exercise, pharmaceutical therapy or a combination of exercise and pharmaceutical therapy') about treatment of the disease.  It should be noted that this approach may entail some small risk based on the 2004 guidance and other things I have heard over the years.  Companies need to choose whether they are willing to accept this risk and, if they do, they must be careful on the wording they use when they mention that there is a treatment.  Any mention of treatment should also be in line with the approved indication.   For example, if a drug is approved to treat symptoms the language chosen should reflect that limitation).
• Provide disease state information on a disease that you do not have an approved indication for, especially if your drug is known to be used off-label to treat that condition and you do not have a drug approved to treat that disease.

Some things that I have learned over the years that might be helpful to people are as follows:

• OPDP Submission of Disease State Materials - Look, by definition you don't have to submit your disease state materials to OPDP.  However, I would consider submitting to OPDP your 'portable' (e.g., hard copy or flash drives) disease state materials.  In some cases these materials might up being used with promotional materials.  If submitted to OPDP with that intended use ('may be used in the future with promotional materials') it can help a company if the disease state materials are inadvertently used in the future along with promotional materials.  It also helps set up that these materials will be regulated internally.  
• Create an intended use for disease awareness materials - One thing that I have seen done over the years is that promotional materials can (and probably SHOULD) be approved with an intended use.  If they are used for something else this should involve a separate approval for the new use.   This same thought could be used for disease awareness materials.   If they are internally approved to be used alone, any use of them with promotional materials would have to be separately approved.  This would help to avoid situations where use of these materials could become problematic to the company. 
• Be careful about accidental connection between the drug name and the disease awareness materials - There has been some thought given to whether sales reps should be distributing solely disease state materials as the HCP likely knows that they promote a particular drug.   I have even heard of situations where a sales rep is wearing a nametag with the drug's name on it while presenting disease state materials or, in a laptop/tablet presentation, has the drug logo as their screensaver.  Also, if your website or printed materials cites references, make sure the titles of those citations do not mention or imply a particular drug or make claims about a drug class
• Links to product promotional websites from disease awareness websites - This is an interesting area.   Some companies believe that you should keep your disease awareness totally separate and don't allow links, even indirect ones, to promotional websites from disease awareness websites.   Some companies allow these links but the link (which may read something like "Click here to find out about a new treatment for disease XYZ") must pass through an intermediate webpage with a warning message (e.g., "You will now be redirected to a product promotional website.  Click here to go back to previous webpage").  OPDP has mentioned in at least one untitled letter that direct links between disease awareness websites and product promotional websites (no intermediate webpage) are not appropriate.  However, a few companies apparently still allow that.
• Disease awareness websites that have opt-ins to receive additional information - It is not clear how many companies have this.   However, my experience is that companies that do this do not allow product promotional information to be included in materials sent to people who opt in to receive disease awareness materials as that could be construed as veiled product promotion under the guise of providing disease awareness. 
• Other types of veiled promotion - Veiled promotion could include creating a search engine result that indicates directly or implies that the reader is going to be directed to a disease state website  when, in fact, they are directed to a product promotional website.   For example, such a search engine result could say something like "Click here to learn more about disease XYZ" and then direct someone to a product promotional website homepage. 

There are probably many more examples of gray areas that have come up over the years at drug companies about what are proper and improper disease awareness materials and the practices that surround use of these materials.  I just hope that the information above stimulates you to think about what is and isn't proper use of disease awareness materials.