Impact of COVID-19 on Regulatory Enforcement and Approvals – Part 2

Empty FDA Advisory Committee Meeting Room

Earlier this month I published a blog posting that raised questions related to the potential for disruption of approvals in the wake of FDA actions to limit inspections due to the COVID-19 pandemic. Subsequently I had the opportunity to pose questions to FDA regarding the impact of the current circumstances on future approvals and the ability to meet PDUFA dates in a timely manner. The Center for Drug Evaluation and Research (CDER) responded as specifically as they apparently could under the circumstances. Bottom line – it would appear that while disruptions to the approval process are possible, the agency is operating and attempting to put into place measures to mitigate disruption. And while virtual AdComms are not a certainty, it would also appear to be something that is possible – at least they are thinking about it.

Here is what they said verbatim:

  1. What is the expected impact on approvals of the recent decision to postpone inspections? On 3/18/2020, for the health and well-being of our staff and those who conduct inspections for the agency under contract at the state level, and because of industry concerns about visitors, we announced that we have temporarily postponed all domestic routine surveillance facility inspections. These are facility inspections the FDA traditionally conducts every few years based on a risk analysis. Importantly, all domestic for-cause inspection assignments will be evaluated and will proceed if mission-critical. We will continue to respond to natural disasters, outbreaks, and other public health emergencies involving FDA-regulated products. Importantly, during this interim period we’re evaluating additional ways to conduct our inspectional work that would not jeopardize public safety and protecting both the firms and the FDA staff. This can include, among other things, evaluating records in lieu of conducting certain onsite inspection on an interim basis when travel is not permissible, when appropriate.
  2. Does FDA plan on attempting virtual advisory committee meetings? As this remains a dynamic situation, we will continue to assess and calibrate our approach. Where possible the agency will leverage technology to host meetings allowing for remote participation. We thank you for your patience. In considering necessary steps for protecting public health, including our sponsors, our committee members and our workforce, we are cancelling or postponing all non-essential meetings through the month of April. We will reassess on an on-going basis for future months. Where possible the agency will leverage technology to host meetings allowing for remote participation.
  3. Is there an expectation that PDUFA dates will be missed, or will they be extended due to the crisis? CDER is fortunate to have existing policies on the use of flexible workplaces, as well as the IT infrastructure to support a large number of staff simultaneously working offsite This gives us the ability to ensure the safety of our workforce and the continuity of our important public health mission during government disruptions. CDER remains fully capable to continue daily activities, while responding to the public needs of the current COVID-19 outbreak. As this remains an evolving and very dynamic situation, the FDA will continue to be flexible and transparent as possible.
  4. Will new drug applications be considered during this time when presumably the FDA workforce is working remotely? CDER continues to perform our drug review activities as well as contribute to other vital functions of the Agency. As you may know, we are working around the clock to monitor and mitigate emerging coronavirus-related issues with our federal partners, international regulators and medical product developers and manufacturers to advance response efforts to combat the coronavirus disease (COVID-19) outbreak. Our application review teams remain focused on their work, and we are doing everything possible to maintain continuity of operations in a very dynamic situation.

What do we know from this? The situation we are presented with means that certainties in any conversation are off the table given the situation we are facing. But what this tells us is that the FDA workforce is equipped to work remotely. It does say the agency is striving to find alternative means to do what it cannot do in person and to meet the necessities of the review process. It does foreclose the possibility of delays, but affirms that efforts are going into getting work done as usual. That means that we will not really know for certain until upcoming PDUFA dates come and go. To that end, I track all the dates of which I am aware and record decision dates and will let you know that tells us as we tread further along in this environment.

Be well. Be safe. Be kind.

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Posted in Advisory Committee Prepapartion, Approval Announcements, Current Affairs, FDA Policy | Tagged , | 5 Comments

Principles for COVID-19 Healthcare Communications – 1 Keep it Simple, Keep it Organized

On February 21 I published a piece on LinkedIn – Communications Considerations for Medical Manufacturers as the COVID-19 Epidemic Emerges – that provided an overview of some of the communications considerations for pharma, biotech and device manufacturers related to the COVID-19 pandemic. It seems a good idea to look at some of those things I discussed in the piece a little more close up – and so I am thinking a series of postings here on the topic.

A frequent communications pattern with emerging pathogens is going from too little information to a deluge of information, sprinkled in with a dose of misinformation. We have all been receiving in our in-boxes emails with updates from everyone in business – banks, airlines, car rental companies, even my hardware store. It is a lot to digest and it is coming at us during a time of stress. Moreover for those in healthcare there are special considerations to communications given the range and impact of topics that must be covered – from supply chain to workforce to business continuity and even eventually, recovery.

Let’s begin generally, however. I reviewed a missive today sent by a healthcare manufacturer that was long and thick with narrative. The range of topics was pretty vast, covering everything from managing business continuity to financial impact on current sales to products in the pipeline and the status of clinical trials. It was all important information. But it was long and thick narrative.

In crafting communications about the very important range of things about which medical manufacturers must communicate, it may be good to borrow some common tips from media training about organizing messages for the spoken word and apply them to the written word. A long press release or statement with paragraph after paragraph is a lot to ask of people – especially now. Another thing I stress in media training is that you have a person’s full attention for the first few minutes you speak – and then minds naturally begin to wander.

Therefore in creating either general statements, or ones that are geared to very specific audiences, here are some guidelines:

  • Plan your messages – It is always important to define what the goal of the communication you are writing actually is – what do you want audiences to walk away with? If you don’t craft the communication with those goals in mind – and shape it so that the audience walks away with the three most critical things you want them to remember – then it is not likely the audience will get their on their own.
  • Lead with the important messages – Given that people may not read the whole communication – lead with your most important messages – and may it be suggested that in this time, at least a part of that be centered on the impact of what you are doing on people
  • List topics – If you are covering a range of things, organize your messages and sort it out for the audience. Guide their eye to the material which interests them. Not every audience needs to read every single thing in the release and the presence of a long narrative may discourage a thorough reading rather than promote it. Parsing your messaging into categories allows the audience to sort out what is important to them – and it doesn’t overwhelm them.
  • Flag the really important message – If there is something you really want to have stand out, flag it for the audience. This can be done visually with bold-face and italics and underscoring (or any combination thereof) or by including it upfront in a quote from a CEO or agency lead with very pointed language – “The most important thing we want people to know….”

These are straightforward tips and communications at its most basic – no rocket science here. But in a time of crisis it is sometimes easy to overlook some basic principles because there is so much to say and that must be said urgently. But when that is the case, what often happens is that in our zeal and need to push messages out, we do so in a way that undermines the ability of our audiences to absorb them. And so we begin with this simple reminder.

Photo by Markus Spiske on Unsplash

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FDA Guidance on Clinical Trials During COVID-19 Pandemic

Much attention has been paid to the impact of the COVID-19 pandemic on the supply chain for medicines we rely on, but there has been less focus on the impact of medicines yet to come. The advancements in cancer care alone during the past few years have been breathtaking. The medicines pipeline is the focus of many who need and hope for a new treatment for a life-threatening condition.

This week FDA issued a new guidance document entitled “FDA Guidance on Conduct of Clinical Trials of Medical Products during COVID-19 Pandemic“. This would seem to set a record for the development of any guidance document from FDA, some of which take years to cultivate through the draft stage. In it, FDA concisely enumerates some of the many obstacles to conducting a clinical trial in our current circumstances – quarantines, travel restrictions, sites that are under lockdown, supply chain of the investigational compound to name a few.

There has already been a lot written about it providing explanation already and there is no point in recreating the wheel and here is among the best courtesy of the Regulatory Affairs Professional Society. But briefly, FDA encourages sponsors to consult with Institutional Review Boards (IRBs) very closely and sanctions also the deviation from protocols of the trial may be initiated unilaterally in order to protect health and well-being of study subjects. It is a worthy goal, to be sure, but where there are such adjustments made by study sponsors, one can imagine that it will later ultimately complicate the assessment of the trial when it comes to the approval process.

FDA also stated that sponsors should be prepared to assess patients for safety from a distance given the potential of travel restrictions. This most certainly means the use of the telephone, but makes the case – as the pandemic does across many areas – for creativity when it comes to exploring virtual means for exchanging information. That goes from telemedicine, to the release of data at virtual medical meetings.

Much of the document is geared to considering the impact of the pandemic on the role of study participants. But there are also likely to be issues where those who are involved in conducting the trial itself – the investigators – are also negatively affected, impacting the collection of data.

In short, FDA has injected more fluidity to respond to circumstances into the process. While important, it is not likely enough to overcome absolutely all the obstacles to conducting clinical trials in this environment. And once this is over, there will be more complications as these trials are assessed for approval and as the gold standard for consideration of new medicines is preserved during this difficult time.

Photo by Louis Reed on Unsplash

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Impact of COVID-19 on Regulatory Enforcement and Approvals

Atrium at FDA

The impacts of the COVID-19 pandemic bring change shifts the status quo on a daily basis with both breadth and depth. Everything we as individuals and as a society would normally do is undergoing change. FDA regulatory oversight is one of them. And some of them are likely to impact timelines for the approval of new products.

Last week, FDA took the profound step of announcing that the agency would be “postponing” foreign inspections of facilities given the realities of the pandemic stating that this would be in effect until the end of April. Acknowledging that the decision would impact product application reviews, the release stated that “most” foreign inspections would be postponed and that those deemed mission-critical would be considered on a case-by-case basis. The agency cited as a factor in its decision the confidence had in the use of alternative methods and tools of enforcement. The term “mission-critical” was not defined. As the virus spreads domestically, it also calls into question how the agency will be forced to further pull back its activities.

For example, regarding advisory committee meetings and other public meetings, the alternative methods and tools do not appear to be available. One wondered if the agency was equipped and ready to conduct these meetings virtually. After all, if university courses can be taught virtually is there ability to conduct an interactive session among the advisory committee members with input from the public. The answer at this time would appear to be not. The word “postpone” is the watchword of the day. And in fact, the FDA calendar there have begun to appear notices that meetings are being postponed.

A meeting of the Non-Prescription Drugs Advisory Committee that was to have been held March 11 was postponed. On the meeting notice page, there was a message inserted that said that the meeting would be postponed until further notice due to extenuating circumstances. A second advisory committee meeting – the Blood Products Advisory Committee – to be held April 3 is also postponed, but a meeting set for April 16 has not yet been postponed nor have any meetings scheduled after that date. Meanwhile there are workshops that are scheduled for as soon as March 23, and one presumes that they, too, will be postponed, but there is nothing up on the site as of yet.

The impact of the inspections issue and the postponed advisory committee meetings are both likely to impact the ability of the agency to meet approval commitments. But an unknown factor is the capability of the agency to support its large workforce to work remotely, which would obviously affect the consideration of new drug applications where there are not advisory committee meetings being held, among other things. Domestic enforcement efforts also becomes a question. This year had seemed poised to bring out a robust number of new medicines, but that is now in some reasonable question.

FDA has a lot on its hands right now and emphasis is obviously on facilitating the production and use of test kits for COVID-19 and doing everything to speed and encourage treatments and vaccine development. That said, the communications around the regulatory process and approvals here in the U.S. needs clarification, and should be consistent and credible. Specifically does

  • How much impact will the inspection issue have on approvals?
  • Does FDA plan on attempting to conduct advisory committee meetings virtually at some point in the future?
  • Will PDUFA dates be missed, or will they be extended due to the crisis?
  • Is the FDA workforce working remotely and if so, how well-equipped is the agency to accommodate that? Hopefully in the coming days, the answers will be available.
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OPDP Issues First Letter of the Year

Hey! 2009 called. They want their Warning Letter back!

Last week FDA’s Office of Prescription Drug Promotion (OPDP) posted the first letter issued for 2020 that was sent in February for the most common violation of all – related to the minimization or omission of risk information. This evoked shades of April 2009 when the agency issued letters covering 45 brands to 14 companies for banner ads on the Internet. Only a month before OPDP had said that the guiding rule of thumb in regulatory enforcement in digital media was that they were concerned with the “message not the medium”. Then they issued a slew of notice of violation (NOV) letters aimed at a medium.

But the reason for those letters, and this one, was one that was indeed about the message. It lacked risk information on its face and presumably it was offered at the landing site to which the sponsored link took one who clicked on it.

Even though the letter involves and age-old regulatory issue – the inclusion of risk information – and a set of facts we have seen before, there are some things to take away from this particular letter. Not only did the agency take regulatory action on this promotion, but it issued a Warning Letter (WL) rather than a Notice of Violation (NOV) a/k/a Untitled Letter. What are the insights from this action? I have no line into OPDP, but here are a few independent observations:

  • First of all, in this instance, the promotional communication was in connection with a product that also has a boxed warning on the label. The presence of a boxed warning indicates a special concern regarding the use of the product that is being emphasized. It is also a surrogate marker for those responsible for promotional communications to take extra special care. In this case, there were safety issues related not only to a potential for abuse (an area of specific concern overall) to the potential for cardiovascular adverse events if misused or used by patients with specific conditions.
  • Another factor is that the product is a treatment for ADHD – a treatment category which has had (by my count from my database) 13 letters issued since 2005, 9 of which involved the exclusion or minimization of risk information and 4 of which involved the use of a WL over NOV. If you are responsible for communications for a product, it is not a bad idea to get an idea of the causes of regulatory actions by OPDP in the past – what were the tripwires and lessons to be learned?
  • And there is the fact that the advertisement was directed to the use of the product with children. When dealing with a vulnerable population it is important to take extra care in communications to ensure that the potential for a violation is utterly minimized.
  • Finally, the letter refers to complaints from theBad Ad” program, indicating that this effort of OPDP to deputize health care professionals to be alert and inform FDA of potential violations is still active.

Enforcement has been at a very low rate for a long time, but low enforcement does not mean no enforcement and the agency has said that it is turning its focus to communications which pose a higher level of concern such as risk information lacking for products with a higher level of risk profile and for pre-approval promotion. Every promotional communication requires scrutiny, but when a product has some specific traits – a category that is scrutinized, a vulnerable population and/or a boxed warning – these are characteristics that merit heightened regard.

Photo by Goh Rhy Yan on Unsplash

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