RCA Radio is a podcast bringing you the latest news and insights in regulatory, compliance, and quality assurance. A transcript for “Episode 006: Expedited Approvals and the Regulatory Impacts and FDA’s Long Term Strategy” follows. Listen to the episode here and on your favorite listening apps, including Apple Podcasts and Spotify.
Erika Porcelli: Hello, and welcome to RCA radio, a podcast covering the latest news and challenges in regulatory compliance and quality assurance facing the life science industries. I’m your host, Erica Porcelli today. We will be further discussing the impacts of the COVID-19 pandemic. As companies modify operations to assist with shortages of critical care items in the market. The FDA is also pivoting in order to provide the necessary approvals, to get products into the market. In this episode, we will be discussing expedited approvals and relevant regulatory impacts as well as the FDA’s longterm inspection strategy. Today I’m joined by Sue Schniepp and Lisa Michels. Sue is RCA’s Distinguished Fellow and Lisa is RCA’s general Counsel and Regulatory Affairs Subject Matter Expert. Sue and Lisa welcome. So obviously, you know, I know we’ve had a number of conversations internally, and this is really at the forefront of everybody’s mind and we are truly in an unprecedented time, you know, everything from hand sanitizers to ventilators to vaccines are being fast, tracked through the approval process. And I’d like to begin by asking a very basic question in either of your careers. Have you seen a crisis that has taxed the FDA with such a high demand for expedited approvals?
Sue Schniepp: I have not. This is unprecedented from my perspective.
Lisa Michels: I agree with that as well. This is a very unusual circumstance and never throughout my career. Have I dealt with such an influx of companies that have been trying to get their products approved through some of these expedited pathways and certainly the interactions with the FDA to date for many of our clients has also been unusual in that they are really working around the clock to make sure that some of these programs are successful.
Erika Porcelli: So, you know, I know we kind of throw around the term EUA quite frequently and for many people that aren’t involved in our industry, you know it is defined as an emergency use authorization, Lisa, at a very high level, what would you convey that that truly means for companies that have a product that they do want to get fast tracked for approval to help with these shortages.
Lisa Michels: So the Emergency Use Authorization program is actually governed under certain sections of the food drug and cosmetic act and in particular it’s section 564, 564A and 564B. And essentially what it is. It’s a method where products that are not approved or approved products for an unapproved use can get streamlined and facilitated by the FDA to get a temporary approval status in order to be used as a method to bring new drugs, medical devices, biologics, what the FDA refers to as medical countermeasures to combat various illnesses, diseases, whatever the particular emergency situation may be.
“It’s a method where products that are not approved or approved products for an unapproved use can get streamlined and facilitated by the FDA to get a temporary approval status in order to be used as a method to bring new drugs, medical devices, biologics, what the FDA refers to as medical countermeasures to combat various illnesses, diseases, whatever the particular emergency situation may be.”
Erika Porcelli: So I think we all kind of understand that, there are many companies that are seeking this, um, EUA and, you know, a smaller group being granted that what are the potential longterm regulatory impacts, if any.
Lisa Michels: I would like to mention first is just in terms of, you know, there are a lot of companies that are definitely trying to get their products approved through this program. However, there are some preliminary criteria that has to be met in order for companies to try to take this pathway and the first is that there has to be a declaration of a state of an emergency. And that can be either determined by this secretary of Homeland security for like a domestic type of an emergency or the secretary of defense, if there’s like a military emergency. And what’s more relevant to us of course, is the secretary of health and human services for a public health emergency, which obviously the COVID-19 pandemic meets that qualification. So that’s kind of the very first preliminary stage gate that has to be in place. And then in terms of what companies need to do in order to go through this pathway is that there are basically four statutory requirements that also must be met.
And that is obviously the first is that there’s a serious life threatening disease or condition in this case with what’s going on right now in the world is COVID-19 and the information that is submitted to the FDA under emergency use authorization, there has to be some level of effectiveness. There has to be no alternative available. Um, and what that also may mean in terms of no alternative, that also mean a lack of availability of products. So not just necessarily that there is no alternative type of product out there, but if there are products that are much needed to combat some of these situations, and there’s just not a lot of them available that can also qualify and then there has to be a risk benefit analysis. So the interesting thing about these EUA applications with the FDA is that it’s really kind of a case by case basis.
The restrictions that would normally be in place for any type of 510(k), PMA, Denovo, or any other type of regulatory submission, whether it’s for a medical device or for a drug or a biologic product. Those are very stringent standards and requirements related to safety and effectiveness, good manufacturing practices, CGMP, things of that nature need to be in place under the EUA program. Those restrictions are somewhat lifted, and it’s obviously in an effort to try to fast track and streamline the review process to try to get some of these products out there to combat some of these disease States or illnesses in doing so. In my opinion, is it can lead to some inconsistency because with the sort of the relaxation of some of these requirements, there is really no particular set of standards other than those statutory requirements that are applied.
“it can lead to some inconsistency because with the sort of the relaxation of some of these requirements, there is really no particular set of standards other than those statutory requirements that are applied.”
Every company kind of has different information that may be submitted in terms of what is available from a safety and effectiveness perspective that, you know, I think is leading to some inconsistent products that could be in the marketplace, which ultimately could have a more significant impact then is intended. And the FDA really is tasked with a very challenging balancing act that they must play where, you know they’re looking at the pros and cons of doing either nothing or doing something and weighing the harm of the potential issue the disease, state, the condition against the potential harm of the product itself. And again, there’s no cookie-cutter method for what exactly every potential company is going to submit because they may be at different stages in terms of the approval status of the product, or maybe it’s an approved product, but it’s now going to be used for a different indication, different intended use. So it’s a very interesting and challenging time right now and I think the longterm consequences are potentially going to be some inconsistency in terms of some of these products that have been approved through this EUA process.
Erika Porcelli: Sue, what are you seeing on the pharmaceutical side? I know that you’re heavily involved with PDA and I’m sure that you’ve had many conversations on this topic as well.
Sue Schniepp: Well, yes, there’s, what we’re seeing is a lot of guidances that have come out from the FDA, in respect to pharmaceuticals. I think that’s the whole industry, not just the drug side, but also the device side. And a lot of those guidances have to do with how to operate under challenging conditions. The one that comes to mind is operating or changing your policies and procedures to be in sync with the rate of high absenteeism, meaning if people are out because they’re sick, how do you continue to make product under these conditions? And it also covers very interestingly enough it covers social distancing and some of the things that you can do to your policies to still adhere to your commitments to the FDA, but to work under these extraordinary circumstances. So I think anybody can go to the docket and see the federal register and see where they have released a number of these policies.
What’s also very interesting is some of them are not necessarily new. They’re up for commenting again, but I’m the one that deals with high absenteeism, of course, was issued quite a number of years ago. And I believe it was in response to the SARS epidemic, or it could have been for Ebola, but FDA was ahead of the time at that point in anticipating some of the issues that might come up, if there were a pandemic and they’ve been able to quickly bring these guidances forward so that the industry, and I think it’s the entire pharmaceutical industry biotech, medical device, traditional drugs. So the industry has some guideline and what’s accepted in these extraordinary times.
Erika Porcelli: So I think we’ve all seen that there are many companies that are traditionally not medical manufacturers, whether it’s hand sanitizer, PPE, venolators, things of that nature. So I think there’s two things. What should they be aware of if they have any EUA for their product and then secondarily to that? So when the crisis is over, right, but secondarily to that in your opinions, how is the FDA going to manage and handle some of these EUA’s ways that were issued to companies that did not submit a 510(k) or go through a formal approval process to keep their product on the market?
Lisa Michels: So for purposes of the EUA approval, what companies need to consider is that this is really a temporary authorization and it lasts for the duration of the determination of the emergency. So once that state of emergency is concluded, then companies have to, if they want to keep the product in the marketplace, then they have to go down the normal standardized process, which would be submitting the typical regulatory submission, whether that’s 510(k) PMA, Denovo, if a drug application or a biologics application. They will have to be prepared to go down the route where the stringent controls are back in place. Again, in some cases under this EUA process, the FDA has been, lacks in terms of the requirements to comply with CGMP’s. So companies that are in this sort of gray area, where perhaps they’re not as familiar with what the requirements are from an FDA perspective, depending on what their product is and manufacturing requirements and so forth.
“what companies need to consider is that this is really a temporary authorization and it lasts for the duration of the determination of the emergency. So once that state of emergency is concluded, … they have to go down the normal standardized process.”
They’re going to have to be able to quickly maneuver and obtain more stringent test data, cleanable data in some cases. So it’s going to be a paradigm shift. Again, there’s a lot of companies trying to jump on the bandwagon in an effort to bring products to the market, which could be beneficial. But I think that there’s also still uncertainty out there because none of us really know how long this pandemic will continue to be declared an emergency, but companies really need to start considering the plan B to an approved EUA. And that is in the background. They should be proceeding with gathering the appropriate information, data, clinical support, labeling requirements, things that are going to be necessary. This pandemic emergency is declared over.
Sue Schniepp: And I think it depends a lot upon what they actually are making. So for instance, not all of the companies that are retooled to produce, let’s say gowns or masks are going to not necessarily want to continue in that business once the pandemic is over or in a steady state. So they’re going to retool back to what they were making before right now they’re helping out to supply us with necessary equipment. So not everybody is going to want to continue forward with the new product that they were granted an EUA for, but I do think that there are some that are going to want to continue in the game. And as Lisa suggests, those are the ones, those companies are the ones that are going to have to go back and redo their filings and make them more robust to hit the current standards today.
Erika Porcelli: And I think for some of these products, and please correct me if I’m wrong, but some of these products like actual devices that are out in the market under this EUA, there will need to be some type of plan in place if they are not going to seek a formal clearance such as a 510(k) there’ll need to be a plan in place for them to recall these products, right? And be warehoused in the event of a similar emergency happening. Is that correct?
Sue Schniepp: Yeah.
Erika Porcelli: Okay. Well, it’ll be interesting to see. So I guess my last question on this topic is really aimed at we don’t know how long this pandemic or this emergency will last and what should, what should we, or even those manufacturers that are manufacturing product, at what point will there be a formal notification that we have moved out of that emergency status?
Lisa Michels: That will actually come from the government, the term of the EUA. When an EUA is approved by the FDA they receive a letter, you can go to the FDA website and see the listings of all of the approved EUA’s. The labeling or fact sheets that are required for practitioners, as well as, lay people or, you know, patients that may be using the product and when those, when the EUA expires because the pandemic or the state of emergency is no longer in place, the FDA will notify all of the different companies that have been approved through the EUA process. So they will have to have some, you know, secondary plan in place to either continue pursuing the appropriate regulatory pathway based on the normal protocols that will be in place outside of a pandemic situation outside of an EUA approval process.
“When an EUA is approved by the FDA they receive a letter, you can go to the FDA website and see the listings of all of the approved EUA’s.”
And I think that is going to be a very interesting challenge for a lot of companies. You know, the deputy has issued I believe it’s almost 50 different guidance documents out there on COVID alone, different policies, guidance documents for submissions, handling certain aspects of the medical products or just in general, how companies should conduct them under these circumstances. So, you know, there has to be sort of a planning, proactive planning for companies not only to comply with these policies, procedures that have been issued, you know, these guidance documents that are issued by the FDA, but then what happens afterward and the FDA is going to have to go back and in some cases, some of these guidance documents and policies and procedures will still remain in place, but in some cases they may also need to be altered or changed to go back under sort of a standard state of affairs non-emergency situations. So again, this is a very unprecedented time, and it’s going to be very interesting to see how industry responds as well as how the FDA responds.
Sue Schniepp: Yeah, and I think we also have to understand this is not going be all of a sudden one day the pandemic is over. There’s going to be a fading out as things get under control as the new cases get reported and start to go down and we see that curve go down, we’ll see the demand go down. We’re not at that state yet and then of course it’s when a vaccine comes out, it’s going to be a while before everybody can get that vaccine and treatments will still be explored. But I think we have to recognize that it’s not going to be just a quick it’s over everybody, cease and desist. There’s going to be a period of time where things will start to drop off because the demand lessons, we haven’t hit that yet but we will and I think that’s when you’ll see players start to drop out or retool back to what they were doing before.
“There’s going to be a period of time where things will start to drop off because the demand lessons, we haven’t hit that yet but we will and I think that’s when you’ll see players start to drop out or retool back to what they were doing before.”
Erika Porcelli: Any final thoughts on EUA’s ways. Otherwise, I would like to move on to another topic that is similarly in line with what we’re already discussing.
Sue Schniepp: Nope, no more comments on that. I think that was good.
Erika Porcelli: So I think Sue, what I’d like to do is I’d like to move on and discuss FDA investigations and inspections a little bit. What is the FDA’s current thinking with regard to resuming in-person inspections? I know they’ve been doing a lot of virtual.
Sue Schniepp: I think that, first of all, I think that they’re resuming food inspections and that is to maintain the food supply chain. I don’t know when they’ll resume in-person inspections for the pharmaceutical industry. I suspect that’s going to depend a lot on some of the company policies that are put in place in terms of how many people they allow on the site, the social distancing requirements, it would be very difficult to have the FDA tour your facility and stay six feet apart. And so I think that working through how to do virtual audit is going to become critical both for the manufacturers, the suppliers, and any of the regulatory authorities. We know that, so for instance, if you, a lot of quality staff is working from home during these times and it’s manufacturing and maybe a limited quality people on site the people who host the audits may not be available, right? They could be working remotely. So they would have to have permission to come into the site, be tested, whatever the requirements of the company are to in order to enter that manufacturing facility. So I think it’s going to be difficult and I think everybody has to think of a way to make the virtual audit work. And that requires us to think a little bit more outside the box, then the traditional face to face audit.
“I don’t know when they’ll resume in-person inspections for the pharmaceutical industry. I suspect that’s going to depend a lot on some of the company policies that are put in place in terms of how many people they allow on the site, the social distancing requirements, it would be very difficult to have the FDA tour your facility and stay six feet apart.”
Erika Porcelli: Yeah. I think even when we get to a place where things are more normal and folks start to begin to return to work and they do start to resume in person inspections, you know, how is social distancing going to affect the effectiveness of the inspections performed?
Sue Schniepp: I think it actually will inhibit the effectiveness of an audit. And so, I mean, there’s, everybody’s learning Zoom and, all of these tools to have meetings and I realizes it’s not perfect as being face to face and being able to read people’s body language and look at them. However, I think it’s, for what we’re doing, we have to learn to use these tools to perform effective audits. So somebody could walk the facility with their iPhone or iPad provided, it’s entered into the manufacturing area appropriately. There are a lot of companies that have cameras set up, so that could be live streaming or tapes could be shared, but all of this would have to be. What are there nondisclosure agreements that might have to be put in place in order to do these confidentiality agreements in order to be able to share that kind of information?
I think that’s a question that has, the dialogue that has to take place between the company and their agency and I think each one might be different. So it’s going to be very tricky, but it can be done. I think it can be done and I think it can be effective. I think we just have to think a little bit differently about things and what it requires and there’s going to be more wrap ups or daily wrap ups will have to be over Zoom or WebEx or whatever. And I think that’s going to require some thought to, and people will have to approach this with an open mind and realize that there’s going to be stumbles in trying to do virtual audits, there just will be stumbles, but nothing that can’t be overcome with a little bit of work and working through the issues and the snags as they come up and finding solutions, that’s nothing that can’t be done.
“people will have to approach this with an open mind and realize that there’s going to be stumbles in trying to do virtual audits, there just will be stumbles, but nothing that can’t be overcome with a little bit of work.”
Erika Porcelli: Is there anything that companies should start to think about and be prepared for when the FDA notifies of an intent for an inspection like, let’s say it’s not until a year from now, but we don’t know where things are going to be with regard to virtual versus in person. Are there considerations that should really be thought about now to be prepared?
Sue Schniepp: What I would focus on right now is really doing a much better thorough job of the, my internal audit programs. I would step them up to the next level. Look at more things, follow up, more due diligence, follow up on some of the responses. We aren’t always effective as an industry when we do the internal audit programs and companies need to get out the check, the box mentality, and really get into this is very important because the results of the internal audit, although the FDA doesn’t look at them and, and actually they’re protected, it’s still critical because that’s data and information that shows you’ve taken due diligence and maintaining your GMP status of your facilities. I also think there’s a lot that can be done with investigation procedures, to be able to continue to hit the Mark on those and make them thorough and investigations and root cause.
“We aren’t always effective as an industry when we do the internal audit programs and companies need to get out the check, the box mentality … it’s still critical because that’s data and information that shows you’ve taken due diligence and maintaining your GMP status of your facilities.”
And there are some elements in the quality system that cannot be compromised and investigations into root cause for deviations is one of them, but there’s a way to do it and we have to not be stuck in, “Oh, my SOP says I have to be done with this in 90 days” and gives our, give ourselves a little bit of flexibility on some of those internal procedures that might have timelines because it will take a little bit longer to work through some of these under these extraordinary conditions. I think one area of improvement certainly could be changed control and speeding up the change control requirements from determining who needs to really sign many times change control systems will have signatures of reviewers that really don’t need to see the information that they might be peripheral to the operation, but their signature is required for whatever reason. It’s time to start taking a look at that and make sure that the people who need the information, who are going to be executing the change or implementing the change, implementing the change are really the ones who are assigning it, understanding it and implementing it appropriately to accommodate operations during these extraordinary times. Lisa, from the device side, what would you predict there?
Lisa Michels: I think that it is going to be sort of a paradigm shift in terms of kind of following through with the requirements, making sure that, you know, regardless of the state that we may be in right now under these circumstances, or, you know, the state going forward that the primary concern I think is to be in a state of compliance. And that is a situation that right now is kind of a moving target and things will change as the FDA provides more guidance out there, things in terms of the changing behaviors and requirements that need to be in place for facilities companies to function going forward. So, I think from the device side it’s going to be very similar, just on the, along the same vein as drugs, biologics, or any other type of product it’s a changing environment.
And I think that there has to be some malleability in order to understand and adjust to the changes in these circumstances and be prepared to change on a dime if necessary. Be prepared at all times because we don’t know when these things are going to change, but we need to have sort of a common ground, a common level set of compliance in place. And I think as long as companies continue to understand that ultimately their goal, as well as the FDA’s goal, regardless of what the product is, is to have safe and effective products out there and to manufacture these products in a way that are going to produce safe products whatever procedures, audit prep, things that need to be done in order to be prepared and continue to be in that state of preparedness is going to be critical.
“as long as companies continue to understand that ultimately their goal, as well as the FDA’s goal, regardless of what the product is, is to have safe and effective products out there and to manufacture these products in a way that are going to produce safe products whatever procedures, audit prep, things that need to be done in order to be prepared and continue to be in that state of preparedness is going to be critical.”
Erika Porcelli: So ladies, any final thoughts on either the emergency use authorization or ongoing investigations?
Sue Schniepp: Yeah, I just think this is a time to step up your diligence, your due diligence, not to you step off of it and do everything in a haste, but to actually think about the changes, I mean, I know there’s enormous pressure for people to continue to produce, but we need to approach it as Lisa said, maintaining good GMPs, whether you’re device, whether you’re pharmaceutical, whether you’re a supplier, the burden is now on the company to maintain their GMP and to up that due diligence and make sure they’re doing things right and can instill doing things compliantly.
Lisa Michels: No, I just echo what Sue said. This is an opportunity, I think for companies not only to help the general public, but also to help themselves and become better companies and be more aware of what their requirements are. Not only for some of these limited circumstances and getting products out there under emergency use. And just in terms of, you know, sort of the, the lack of stringent requirements, but to have methodologies, procedures, processes in place that will allow them to adapt, because I’m quite sure that this is not going to be the last type of emergency public health concern that we’re going to see. And I think that this is a really good opportunity for companies to become better and to be more compliant and FDA savvy and make sure that their products are safe and effective and ultimately can help the general public in a crisis like this.
Sue Schniepp: Yeah, and in 2005, Janet Woodcock from the center for drug evaluation and researcher, Cedar had a quote that says her realization was to have a maximally efficient, agile, flexible pharmaceutical manufacturing sector that reliably produces high quality drug products without extensive regulatory oversight. I think this is certainly a time when we can realize that vision of Janet Woodcock and that’s what I think companies need to do is show that they can do it without the extensive regulatory oversight, without the FDA being there at their facility in person and auditing them, but that they can self regulate.
“have a maximally efficient, agile, flexible pharmaceutical manufacturing sector that reliably produces high quality drug products without extensive regulatory oversight.”
Erika Porcelli: Well, ladies, thank you so much for taking the time to provide us with your insight this afternoon. And finally, thank you to our listeners for tuning into this episode of RCA radio. Be sure to subscribe, to be the first, to know when we upload the next episode in our series covering supply chain management. I hope everybody has a great day and thanks again.