interviewed Chad Landmon, JD, chair of intellectual property and FDA practice groups at Axinn, Veltrop & Harkrider, on the FDA’s emergency use authorization (EUA) process for COVID-19 vaccines, such as the expedited process for the recently authorized Johnson & Johnson COVID-19 vaccine.

So, Chad, how does the EUA process expedite the FDA’s normal approval procedures?

 Sure, thanks for having me today. So, the EUA process at a basic level is expedited, and basically the way this works is it starts with an emergency declaration by the HHS secretary.

The EUA process was put in place actually by various legislation over the years. A lot of it was actually focused early on terrorism aspects and worries of some sort of biological or radiation weapon being used. So over time, the various legislation has addressed how the EUA process works, but at its core it starts with an emergency declaration from the secretary of HHS finding that there's an emergency—some sort of public health emergency, some sort of threat or actual terrorist attack—and then that pretty much puts FDA into motion on how they handle these.

Very generally, it's an expedited process where the agency works very closely with the applicant—often actually the request is made from somebody within the government, so from NIH, from CDC, from FDA to the applicant—and then they work pretty much to expedite all stages of the development.

So, a lot of times, instead of doing things in steps where you complete phase 1, and then you do phase 2, then you do phase 3, a lot of things are kind of done all at the same time to get the review done quicker. There's a lot more interaction between the agency and the companies in terms of what needs to be done, what studies need to be done, how the review process works, and it's really put not only at the top of the queue, but all of FDA's resources are kind of thrown at it in order to get the review done quickly.

Right. How does the speed of the EUA process for COVID-19 vaccines and tests over the past year compare to the normal expected timeline for an EUA or an approval by the FDA?

 Yeah. So as far as EUAs, it's kind of hard to do a comparison. I mean, they all move very quickly, so there's been EUAs in the past for the Zika virus, kind of one of the more recent times where we've had a series of EUAs. But for testing and other things within FDA, they all move very quickly.

I think during COVID-19, we saw some incredibly quick movements on EUAs, particularly as has had to do with PPE and other testing items early on, and then with the vaccines as well. It's hard to say whether it's quicker or slower.

As compared to the normal approval process, I mean it really shaves years off of the approval process and development process. Normally vaccines probably would have gone through a 3 to 5 year development cycle in review by FDA, and as we saw less than a year, if not significantly less than a year, for the review by FDA.

Right. What is the process the agency goes through as it considers whether or not to grant EUAs?

 Yeah. So, it starts by the agency determining first that there's some sort of serious condition or disease that's being treated. It has to also look to see that there are no alternatives out there on the market that can be used that are already approved, and then the standard is very different.

So, a normal approval standard is the agency determining that a vaccine, a treatment, whatever is both safe and effective. The EUA threshold determination is just that the vaccine, the therapy, or whatever it is may be effective, and that's a significant difference. 

Basically, FDA looks at whatever information it has, whatever information through abbreviated clinical studies, or whatever has been done, and it makes a determination that the vaccines, as we've been talking about, that they may be effective in doing what they need to do. So, obviously it's a shorter analysis, it's looking at less information than would go into a full approval or a full review, and FDA then finally kind of does a risk benefit analysis. So, it looks at okay now that we know that it may be effective, then how risky is it. 

So, through the safety studies that have been done, through whatever other information is out there how risky is it, and how beneficial will it be. I mean, obviously with COVID-19 worldwide pandemic, I mean we don't need to get into the extent of the death and loss and everything that's going on, but the risks were obviously very big, so if you look at something that may be effective, you need to do that balancing act, and FDA came out in favor, at least with these vaccines, that the risk benefit analysis was in favor of authorizing these vaccines.

Videos

Pharmacy Times® interviewed Chad Landmon, JD, chair of intellectual property and FDA practice groups at Axinn, Veltrop & Harkrider, on the FDA’s EUA process for COVID-19 vaccines.

How the FDA’s Expedited EUA Process for COVID-19 Vaccines Works 

interviewed Sarah Browne, MD, senior director of vaccine development at Altimmune, on the commencement of enrollment for a phase 1 clinical trial of 

AdCOVID, a single-dose, intranasal, adenovirus vector COVID-19 vaccine

.

During the discussion, Browne explained that so far, all of the authorized vaccines are injected by a needle into the muscle, making the immune response a systemic immune response. For this reason, the AdCOVID vaccine is unique in that it’s administered as a spray into the nose, allowing the vaccine to be introduced to the nasal mucosa, creating a mucosal immune response in the body.

“The reason that this is important is because if you think about respiratory viral infections, like SARS-CoV-2 or influenza for example, they infect through the nose and get into the respiratory tract. So, there's really a special kind of immunity called mucosal immunity, which is generated at that site of infection,” Browne said. “So, by introducing the vaccine to the nasal mucosa via the intranasal root, you generate that special immunity to block the infection where it enters and potentially to also prevent it from exiting so that you avoid transmission.”

Since clinical trials are in the first human study, Browne explained that the majority of the data will be available in the spring, driving subsequent studies into the safety and immunogenicity.

“Moving into the summer and the fall, we'll be getting into advanced development. We're optimistic we could apply for an emergency use authorization or potentially an approval in early 2022,” Browne said.

Browne also noted that there are specific advantages to this vaccine being needle-free that will impact distribution and administration prospects.

“I think the needle-free aspect minimizes the need for health care providers to administer the vaccine, so you could really imagine just broad scale up in vaccination programs in community-based outreach that doesn't require that cold chain,” Browne said. “So, you could go to regions that don't have the same sort of take technological capability and give the vaccine broadly.”

Pharmacy Times® interviewed Sarah Browne, MD, senior director of vaccine development at Altimmune, on the commencement of a phase 1 clinical trial of a single-dose, intranasal COVID-19 vaccine.

New Single-Dose, Intranasal COVID-19 Vaccine May Prevent Transmission, Disease

interviewed Farah Towfic, PharmD, MBA, director and CEO of operations at US Pharmacopeia (USP), on the announcement from Pfizer and BioNTech regarding the update on cold storage requirements for their COVID-19 vaccine. Approved on February 25 by the FDA, these changes will offer greater flexibility to administrators to bring more vaccine to more people around the world.

Towfic explained that this updated cold storage requirement for the Pfizer and BioNTech vaccine will allow more pharmacies access to the vaccine than was previously possible.

“The undiluted frozen vials can be transported and stored at the conventional pharmaceutical freezers for a period of up to 2 weeks, and that's of course in addition to the 120 hours that's allowed in the refrigerated state,” Towfic said. “So that's exciting—it gives many more pharmacies access to the vaccine.”

With more pharmacies getting access to the vaccine, more people will also be able to sign up to become vaccine providers as well, according to Towfic.

“It actually enables more health care providers to be able to help get more vaccines in arms for more people because it essentially gives us 19 days total, that 2-week period in a traditional freezer, plus that 5-day period in the refrigerator,” Towfic said. “It helps us to be able to get the 600 million doses in arms much, much more quickly.”

In order to ensure as many doses of the vaccine get used per vial, Towfic explained that there are 

specific methods outlined on the USP website

 that vaccine providers can use to make sure they are always able to draw the sixth dose of the Pfizer and BioNTech vaccine.

“One of the key questions that we wanted to address 

was that sixth dose, knowing the supply of the vaccines is limited. We're trying to ensure no vaccine amount goes to waste it,” Towfic said. “In the toolkit, we actually highlight a process to optimize that vial pressure so that you can ensure that you'll safely get that sixth dose out of every single vial. It's a way for you to be able to administer more doses to more people so that we can quickly get to the other side of this pandemic.”

Pharmacy Times® interviewed Farah Towfic, PharmD, MBA, the director and CEO of operations at US Pharmacopeia, on the FDA’s approval of the Pfizer and BioNTech COVID-19 vaccine’s updated cold storage requirements.

Pfizer COVID-19 Vaccine’s Updated Cold Storage Requirements Will Get More Doses in More Arms

interviewed Amesh Adalja, MD, FIDSA, FACP, FACEP, a senior scholar at the Johns Hopkins Center for Health Security, on how the issuance of the proposed emergency use authorization (EUA) for Johnson & Johnson’s single-dose vaccine may impact the current COVID-19 vaccine distribution and administration process in the country.

 Hi, I'm Alana Hippensteele from Pharmacy Times. Today, I’m speaking with Dr. Amesh Adalja, a senior scholar at the Johns Hopkins Center for Health Security, on the implications of the recently released results of a new analysis by the FDA that show that the COVID-19 single-shot vaccine candidate by Johnson & Johnson provides strong protection against severe disease and may reduce the spread of the virus. With these results, the FDA could issue the EUA for this third COVID-19 vaccine candidate quite soon.

Following the announcement from Pfizer and BioNTech updating the cold storage requirements for their COVID-19 vaccine to the more standard temperatures of -13 degrees to 5 degrees Fahrenheit and the standard refrigeration temperatures of this Johnson & Johnson vaccine, how might this affect distribution prospects for these vaccines?

 It makes it much easier if you don't have a very onerous cold chain. If you can get this vaccine closer to the people that need it, that you don't have to have deep freeze storage places, that you don't have to worry about the cold chain being broken and vaccine vials becoming non-viable.

So, I do think it greatly expands the reach of the Pfizer vaccine, and I think it will make it easier to conduct vaccination programs without having to worry about whether or not the temperature wasn't maintained in the adequate range. So, this is also good news for the Pfizer vaccine.

 Right. The Johnson & Johnson vaccine can be stored at standard refrigeration temperatures for up to 3 months, which is much longer than the current 2 weeks at the recently updated temperatures required for the Pfizer vaccine. What might this mean in terms of where each vaccine may be sent to be administered, such as rural areas versus urban areas?

 The easier it is to store a vaccine, the more versatile it can be. So, with the Johnson & Johnson vaccine having an even less stringent cold chain, you can really get that into pharmacies, you can even do door-to-door vaccination with something like this with mobile vaccination units. You could do a lot more with a vaccine where you don't have to worry about storage.

So I do think that you may see the vaccines kind of targeted towards places where there is cold storage availability, where there isn't cold storage ability, and I think the Johnson & Johnson vaccine may be a vaccine that many Americans have access to very easily, very close to their home without having to go to a mass vaccination site, without having to go to a hospital, and I think that's good because we want this vaccination to be as seamless and easy as possible, just like getting a flu vaccine, and I think the Johnson & Johnson vaccine takes us significantly down that road.

 Yeah, absolutely. Thank you so much for taking the time to speak with me today, Dr. Adalja.

Amesh Adalja, MD, FIDSA, FACP, FACEP, discussed the distribution prospects for the Johnson & Johnson COVID-19 vaccine in light of it being possible to store it at standard refrigeration temperatures for up to 3 months.

Expert: Johnson & Johnson Vaccine ‘May Be a Vaccine That Many Americans Have Access to Very Easily, Very Close to Their Home’

interviewed Amesh Adalja, MD, FIDSA, FACP, FACEP, a senior scholar at the Johns Hopkins Center for Health Security, on how the issuance of the proposed emergency use authorization (EUA) for Johnson & Johnson’s single-dose vaccine may impact the current COVID-19 vaccine distribution and administration process.

The vaccine was found to have 85% efficacy in the prevention of severe disease and 100% efficacy in the prevention of hospitalization and deaths. Why is this differentiation important to understand, and what does this mean in relation to the overall efficacy of the vaccine?

 It's important to remember that COVID-19 really garnered headlines because of its ability to kill, because of its ability to cause severe illness, and because of its capacity to compromise hospital capacity with a high rate of hospitalizations in certain individuals. That's what these vaccines are designed to combat, that's what this public health emergency is about, that's what flattening the curve was about—it was trying to keep the curve below hospital capacity.

So, when I look at a vaccine, the 3 things that matter are serious illness, hospitalization, and death—that's what I look at the most. I think that when you look at the Johnson & Johnson vaccine, it is very robust when it comes to those 3 variables and, as I said earlier, when you remove the ability of this virus to cause serious illness, to cause hospitalization, and to cause death, it's a much easier prospect to deal with.

We deal with many different respiratory viruses that spread every year, but they don't have the ability to cause disease at that level that requires hospitals to change their capacity management. I think that's the goal that I think of with these vaccines—it's not trying to get to COVID-19 zero. We're not going to get to COVID-19 zero. This virus has established itself in the human population, it's going to be with us. Our goal is to tame it, to defang it with these vaccines, so those are the numbers I look at: serious disease, hospitalization, and death. All of our vaccines, including the Johnson & Johnson vaccine, are very good at that. I think they are the path to normalcy, the path to reclaiming our lives.

 Right. The FDA’s review found that the vaccine efficacy against severe COVID-19 was similarly high across the United States, South Africa, and Brazil, noting specifically a 64% efficacy rate against the South African variant. What does this mean in relation to this new vaccine’s ability to remain effective against COVID-19 variants that have emerged?

 It's great news because again what matters with the vaccine is its ability to stop serious disease, hospitalization, and death. The Johnson & Johnson vaccine, in the face of the South African variants, still was able to accomplish that, so I think that's great news.

Unfortunately, some of the headlines in the popular press had it the wrong way. I would have written the headline the way I just said, that the South African variant was no match when it came to severe disease, hospitalization, and death [in terms of] this Johnson & Johnson vaccine, and it did well in the face of [the variant]. I think that's what we have to keep focusing on is what we want these vaccines to do, and that's to reduce the harm that the virus is causing and never allow this virus to be able to compromise hospital capacity. The Johnson & Johnson vaccine doesn't even with the South African variant, where it may be a little bit more tricky when it comes to how well it blocks against symptomatic disease, but severe disease is where I draw the line, where it matters.

Amesh Adalja, MD, FIDSA, FACP, FACEP, a senior scholar at the Johns Hopkins Center for Health Security, discusses how Johnson & Johnson’s COVID-19 vaccine provides effective support in prevention of severe disease and hospitalization.

Expert: Johnson & Johnson COVID-19 Vaccine Has Joined Group of Vaccines That Are 'The Path to Reclaiming Our Lives’

So, Dr. Adalja, how might the issuance of the proposed EUA for this single-dose vaccine from Johnson & Johnson impact the current COVID-19 vaccine distribution and administration process in the US?

 In the short term, we won't probably see a major impact because there's not a lot of doses on hand. But as we get further along, closer to spring, I do think there's a significant benefit of having a third vaccine on the market, especially a vaccine that is only a single dose that doesn't require onerous cold chain requirements. So, it will be just another item on the menu that is going to get us closer to herd immunity, closer to protecting all our vulnerable populations, and closer to putting the pandemic behind us.

 Will administration of this new vaccine still need to follow state guidelines regarding priority groups for vaccinations, and how might this affect the opportunity to ramp up the current rate of vaccinations in the country?

 This vaccine is going to kind of fit back into those guidelines for priority groups that each state has developed because, right now, this vaccination program is really a government effort, so it's going to be just another candidate that they use.

I do think in general what we're finding is that some of the priority groupings have served as sort of a constraint to getting vaccines into people's arms. There needs to be a good faith effort to kind of stick to the priority groups because we're trying to reduce the damage the virus causes by protecting those who are most likely to have serious disease, need hospitalization, or die because that's really why this virus even came to light is because it was causing serious illness. So, that's really important.

But I do think we have to have flexibility at the vaccine clinic level, so that we can just get as many people vaccinated as quickly as possible and worry less about the process and more about actually the action of getting vaccine into people, even if they may fall off a priority group if, for example, there are leftover doses available or whatever it might be—I think that's going to be a key moving forward is having that flexibility.

 Johnson & Johnson announced that once the EUA is issued, 2 million doses will be available to ship to the US immediately, with supply set to increase to approximately 20 million doses by the end of March. How might this quantity of additional vaccine affect the current speed of immunization in the country and prospects regarding future reopenings?

 I do think that any amount of vaccine we get to combat this virus, even if it's just 2 million up front, is going to get us closer to where we want to go. Like I said, this is something that's going to have more of an impact as we get farther along, as more doses are delivered, but the more people that are vaccinated, especially those vulnerable populations, the ones that are most likely to be hospitalized, that makes it much easier for public health authorities to relax guidance when they know that there's no way that the virus can compromise hospital capacity again.

We're already starting to see that when you look at the nursing home data, for example, nursing home cases are down significantly, nursing home deaths are down significantly, and hospital capacity is becoming less of a concern because nursing home patients were one group of individuals that really could threaten the hospital's capacity, and that’s when you remove them from the equation. We're dealing with sort of a different type of an infectious disease, and more of that will be coming as we get more of our community-dwelling high-risk individuals vaccinated as well.

 Right. Currently, the proposed EUA for the vaccine is for adults 18 years of age and older. Might this proposed population expand in the future, and what does this mean for vaccination prospects for children?

 I do think that the vaccination population is going to expand in the future, but it's going to be data-driven because, remember, every vaccine is a risk-benefit calculation, and it's very different if you're deciding to vaccinate a 14-year-old versus vaccinating a 71-year-old because the risk of severe disease is usually in children very, very low, and they've not been shown to be major magnifiers of spread.

So, there's a lot of different calculations you have to make when you're vaccinating a child to make sure that it's actually worth it for them, and it may not be these first-generation vaccines that ultimately is what we use as a pediatric formulation. It might be some second-generation vaccine that we don't know about because there are some considerable side effects, and if children aren't likely to get severe disease and there aren't major spreaders, it may not be one of these original vaccines that we use in children.

I think, again, this has to be data-driven. There are studies going on with some of the other vaccines in pediatric populations, so I think we'll come to an answer for this soon, and I do suspect down the road children will be vaccinated against COVID-19. I just don't know which vaccine formulation will be the most optimal one for them.

Pharmacy Times® interviewed Amesh Adalja, MD, FIDSA, FACP, FACEP, a senior scholar at the Johns Hopkins Center for Health Security, on how the proposed EUA for Johnson & Johnson’s single-dose vaccine may impact the COVID-19 vaccine distribution and administration process.

How an EUA for the Johnson & Johnson’s Single-Dose COVID-19 Vaccine May Impact Vaccine Distribution, Administration

interviewed Kenneth Thorpe, PhD, the Robert W. Woodruff professor and chair of the Department of Health Policy and Management at Emory University, who is also the former deputy assistant secretary at the HHS from 1993 to 1995, on how pandemic preparedness lessons from COVID-19 may be beneficial to apply to tackling the antimicrobial resistance (AMR) health crisis that faces health care systems.

 So, Dr. Thorpe, the Biden administration recently released the National Strategy for the COVID-19 Response and Pandemic Preparedness report on how to defeat COVID-19. How does the report address the threat of antimicrobial resistance, and why is it important to prepare for?

 Well, I think having this 200-page game plan on how to address COVID-19 is very important because there's a unified message in it in terms of the extent of the problem. There are solutions in it that are very clear in terms of vaccine manufacturing, supply, and distribution, enabling the Defense Production Act to bring that element into it, FEMA into it. So I think it's really jump started our response to COVID-19, which I think is very positive.

We need to have something similar for antimicrobial resistance. This is a problem that's been around for years and years and years, yet we really haven't had sort of a unified focus on solving the problem. We have not to date had any type of congressional solutions.

The good news is that there are 2 important proposals sitting in Congress right now that would address the problems underlying antimicrobial resistance vaccines. The challenge with this market is that the return on investment for pharmaceutical companies is low; the payments and the prices are low. Obviously, it's a limited patient population. So, to deal with this, we need a 2-part strategy.

One is to provide financial incentives for manufacturers to develop innovative vaccines. So, there's a proposal in Congress called the PASTEUR Act, which would provide funding up to 3 billion dollars in financing to help get these vaccines online. So, we need to provide the financial incentives to get the vaccines made.

We also need the reimbursement incentives that once they're on the market, that hospitals and health care providers can afford to provide them. So, a 2-part strategy of our group, the partnership to fight infectious diseases is working on both fronts to try to get those legislative strategies put into place.

 Great. What are some of the potential consequences if we do not prepare for health problems related to antimicrobial resistance?

 Well, the research I've done on this has shown that over the last decade the number of antimicrobial resistant infections is doubled. So, we're up to just under 3 million a year. It's a cost accounting for just under 40,000 dollars, so unless we put into place some initiatives to stem this, the cost to the health care system will continue to increase, the amount of mortality linked to it will increase, and it's really one of the underlying huge health care problems that is going to have broad implications on getting access to health care.

Certainly, if you go in for a surgical procedure, you want to know that you have an antibiotic in place that is going to prevent infection, and if we don't have those antibiotics, it could have a very deleterious effect on surgical procedures overall.

So, we need to find a focus on getting these innovative vaccines into place and make sure that they are affordable. So, if we don't do it, I think the health care outcomes really are going to be very deleterious in terms of patient mortality and costs to the health care system.

 What has the United States done so far to prepare for this health crisis, and what more should it be doing?

 Well, we need to be doing several things. One is that I think we need to have a public education campaign so the public even understands the extent to which this is a major problem, which it is. I don't think most people really understand the extent to which these superbugs are increasing, these gram-negative bacteria are growing. So, there's got to be first of all an awareness of the problem, and that's something that Department of Health and Human Services and others can really help in really providing public education on the extent of the problem.

Second is that we need these legislative solutions. So, we've got to have these post-market incentives built in so that pharmaceutical companies will get back into the vaccine discovery marketplace and the vaccine distribution. So, as I mentioned before, the PASTEUR Act is in a very important piece of bipartisan legislation that would do that. So, I think we're hoping that this year, if we can get these legislative action items into place, it'll go a long way towards providing the right financial incentives for pharmaceutical manufacturers to get back into the market.

 Can health systems use some of the existing infrastructure created during the COVID-19 pandemic or before in order to begin to address these concerns?

 Yeah, I think so. The response to any type of pandemic has got to be clear messaging understanding infrastructure, and I think that what's being built up now with the COVID-19 that the Biden administration is doing is clearly very important because it's focusing attention on the importance of discovery, vaccine manufacturing, and vaccine distribution. Those are going to be 3 key elements for antimicrobial resistance as well.

So, having that type of focus and infrastructure in place, we're hoping that the microbial resistance infections can piggyback off the work that COVID-19 from the Biden administration is putting into place.

 Right. What are some of the lessons learned from the COVID-19 pandemic that may apply to concerns related to antimicrobial resistance?

 Well, I've mentioned this before: One of the key things to me is messaging; that having a clear understanding that COVID-19 is a real problem, that there are ways to try to mitigate it through public health measures and through other measures, such as providing air filtering systems into businesses that kill the virus—that technology exists, and we should be using that right now.

On the AMR side, getting the same type of messaging out that this is a growing problem. We need the pharmaceutical manufacturers in the game to put into place vaccines that are going to be effective against these growing threats.

 But to do that, we need to have some public policy and legislative initiatives put into place, just like COVID-19. Obviously, there's a big package in Congress right now—the 1.9 trillion dollars worth of funding to deal with the problem, in terms of distribution in particular, and buying vaccines&mdash;we need to have a similar legislative package. Not that scale, but we need to have a similar legislative package for AMR.

 Do you think COVID-19 burnout may cause delays around preparing for future health crises due to the impact of the pandemic on health systems right now? If so, what could be done to address this?

 Well, I think this has been lingering. I think that the COVID-19 response has been very important because it's drawn attention to the need for vaccines and the need for effective distribution of vaccines. So, as I've said, this is not a new problem with AMR, it's been sitting there for years, but we just haven't had the public policy response needed to deal with the underlying problem.

So COVID-19 provides a pathway of identity and information and attention to the need for vaccines and the need for an infrastructure and distribution system, and I'm just hoping that we can legislatively piggyback off of these COVID-19 legislative efforts.

 Right. What do you think is the value of the pharmacist in addressing the antimicrobial resistance health crisis?

 Well, I think they're going to be critically important because we want to make sure first of all that our pharmacists and scientists understand which vaccines are effective in dealing with different types of underlying bacterial infections, where there's a urinary tract infection and so on.

So, having the pharmacists as part of the solution will be critical because we rely on them to make sure that we are prescribing the most effective antibiotics to deal with different types of underlying bacterial infections. So, they're going to be sort of the center stage, so to speak, of our response to dealing with AMR. 

 Right. Do you have any closing thoughts?

 No, which is first of all thanks for having me on—this is a problem that's in the COVID-19 world, which understandably is taking 99% of the health policy and public health attention, as well it should. But this antimicrobial resistance issue is a long-standing problem that we need to find a solution for today.

So, I'm hoping that by having the focus on the need for vaccines, the need for infrastructure and distribution, that we can finally address this underlying issue of antimicrobial resistance and get the legislative solutions that we've talked about passed this year. I think that that will go a long way towards providing a solution for us to try to slow the growth in this continued increase in antimicrobial resistant infections.

 Thank you so much for taking the time to speak with me today, Dr. Thorpe. Now let’s hear from some of our other MJH Life Sciences brands on their latest headlines.

Pharmacy Times® interviewed Kenneth Thorpe, PhD, the former deputy assistant secretary at the HHS during the Clinton administration, on how pandemic preparedness lessons from COVID-19 may help to tackle the antimicrobial resistance health crisis.

The Pandemic May Provide the Infrastructure Necessary to Address the Antimicrobial Resistance Health Crisis

interviewed David Silverstein, JD, MS, a partner in Axinn’s Intellectual Property and FDA practice groups, on what may be coming to market in the rapidly growing cell therapy space, and the role pharmacists may play in this emerging landscape.

 Hi, I'm Alana Hippensteele from Pharmacy Times. Today, I’m speaking with David Silverstein, a partner in Axinn’s Intellectual Property and FDA practice groups, on the FDA’s recent approval of Breyanzi, which is Bristol Myers Squibb (BMS)’s first cancer cell therapy, for the treatment of late-stage lymphoma. This approval marks the company’s entry into the rapidly growing cell therapy space.

So, David, why is this approval significant, and what does it mean for the current cell therapy landscape?

 Sure, well first, thank you for having me on your program. This is a very exciting time for cell therapies and immunotherapies. Breyanzi, as you said, is a treatment for late-stage lymphoma and is BMS's first approved cell therapy, so clearly it's significant for BMS, but this approval is significant in an even larger sense because it evidences a continuing growth of this class of therapeutics.

It's the fourth FDA-approved [chimeric antigen receptor T cells (CAR T)] therapy for non-Hodgkin lymphoma, and it joins treatments sold by Novartis and Gilead, so these are major players in the field. It's exciting to see yet another one added with BMS. What it shows really is the industry and FDA are working together at a quickening pace to figure out how to develop, review, and commercialize these kinds of complex therapies.

 Right. Why do you think the cell therapy space has been rapidly developing more recently?

 Well, there are several reasons. I mean, for starters, there's tremendous market potential for these therapies. Over 7000 genetic diseases are estimated to be treatable using gene therapies. Currently, there are over 900 [Investigational New Drug (IND)] applications for ongoing clinical trials using these therapies, and I think as the benefits of these therapies have become more apparent to stakeholders, to biopharma, we've seen a dramatic increase in the level of investment, both from outside sources and by the developers themselves. This takes the form not only of physical capital, but also human capital in the area.

So, these therapies require quite a degree of specialization and training, and we're seeing these large pharmaceutical companies, and small ones as well, step up to the plate and get involved. With that being said, FDA's list of approved cellular and gene therapy products still fits on just a double-sided sheet of paper, so there's a long way to go still.

Another reason I think we've seen recent activity in this space in the near term, there's going to be expiration of some of the foundational platform patents in the CAR-T space, and I think with those patents soon to expire, we're going to see more and more development work underway in order to get to the market as soon as they can after this patents expire without having to take licenses or incur extra risk.

But most importantly, I think what's responsible for this increased pace and in developing these therapies is that FDA has stepped up to the plate. FDA has begun issuing guidances that provide much greater certainty to developers. If you look at FDA's list of cellular and gene therapy guidances, for example, the first going back to 1998, there was one, and then there was a large gap in time until 2007 when another one came out. Then it was about 1 or 2 a year until about 2015. We saw 3 in 2017, another 3 in 2019, culminating in 2020 when there were 7 guidances. Here we are in the second month of 2021, and there have been 2 already. So, I think it's showing that FDA is recognizing the importance of providing a clear path and for regulatory approval and the clearer that path the less risky it'll be for developers to embark on the [research and development (R&D)] processes to bring these already complex products to market.

 What is the regulatory landscape for other innovative cell and gene therapies, and how does this landscape impact the ability for new therapies to come to market?

 Well, FDA has made clear that supporting the development of and approval of gene therapies is a quite significant priority for them, and they do that a number of ways. In addition to the guidance as we just mentioned, FDA encourages developers to take advantage of FDA's expedited programs. For example, seeking breakthrough therapy designation, regenerative medicine advanced therapy designation, fast track designation, and just generally priority review and accelerated approval. So, FDA is willing to work with the developers. I think that's important that FDA's willingness to engage especially in the IND stage.

It's almost more important than any other type of product where the development path, the regulatory path has already been established and well-trodden. It's important that FDA is setting out its expectations, the stakeholders are able to set out sort of their constraints, what they're able to demonstrate, what they're not able to demonstrate, and work together in concert.

One of the things that FDA is also doing is, with these therapies in general, is placing a tremendous focus on preventing off-target effects. This is something that's fairly unique to these types of therapies—cell and gene therapies&mdash;as opposed to biologics or small molecules. But FDA frankly is learning along with the industry. This is a rapidly developing field, so a lot more work has to be done on FDA's part to provide the industry the support it needs.

 What are some of the challenges developers and the FDA are facing when seeking regulatory approval and reviewing applications for these new therapies?

 Well, there's numerous challenges on both industry and FDA. With these therapies, we're dealing with living drugs. There are highly complex processes involved to create them, and the generated products, the therapies themselves, are highly complex. So, with those come fairly unique set of challenges. Given the complexity of making these, it's essential to establish consistent and scalable platforms that can achieve high manufacturing yields. This isn't as simple as synthesizing a small molecule from scratch or having a cell line E. coli, for example, pump out protein of interest. These involve often viral vectors. The infection rate is very low, in short, the yield you get is very low. So that that creates a whole host of challenges. And historically there's been a lack of established and qualified processes, consistent analytics, and, as I mentioned, clear regulatory guidelines.

Another thing that's fairly unique to these types of therapies is, for safety reasons, it's essential to observe how these genetically modified cells behave over time. That by default expands the development timeline for these therapies to years or decades even. That's not really found in developing other products. On the manufacturing side, simply put, I think there's a general consensus we just don't have enough manufacturing capacity to produce these therapies for many of the diseases that could benefit from having them developed.

There's—with the viral vectors, for example&mdash;tremendous challenges in bringing these therapies to market is the scale up for clinical trial use, not to mention commercial scale. To address this, limitation gene therapy makers are exclusively partnering with or even buying outright [Contract manufacturing organizations (CMOs)], and what we'll see is there's only limited capacity available to begin with, and it's being scooped up by the forerunners in this space. We're going to see a little bit of a lull as the industry struggles to sort of fill in for that need of CMOs. It's akin to a layperson. They wonder, “Well how is it we have so many pharmaceutical companies, but we only have a handful that have come out with COVID-19 vaccines.” The reality is these aren't the run-of-the-mill products that the host of pharmaceutical companies can just turn on a switch and start making. It takes specialized equipment, takes specialized know-how.

Then once the company gets into the business of making these, quality control is a challenge. The requirements are incredibly high, as they should be. FDA is vigilant and will not hesitate to put clinical holds in place. This happened, for example, back in 2018 with Sarepta’s phase 1 and phase 2 trial for micro dystrophin gene therapy. There were trace amounts of DNA that were found in in the plasmids, and FDA put a hold on. So those are challenges that exist that, especially when the development isn't completely vertically integrated, when you're working with partners, CMOs, or development partners, it poses its own challenges of ensuring quality control, ensuring everybody's on the same page with regard to what impurities are tolerated, what deviations are tolerated.

Another factor, I would say, is limited talent pool. These are specialized equipment, requires specialized training to use. There's definitely a relatively small talent pool for skilled workers who can oversee the manufacturing operations for these therapies. Not only does this impact industry, but it also has an impact on FDA. FDA needs the same skill set to review applications, to inspect sites, and so that's something I think we'll see that will be met. It's great job opportunities for pharmacists in training or at any stage in their career. I think this is an exciting area that's up and coming, and there's only going to be greater, greater demand on it.

In a nutshell, I guess FDA is in the industry getting up to speed on these new technologies. As we said, with the rolling out of more and more guidances, that'll provide clarity to the industry with increasing the talent pool, increasing manufacturing capacity. That'll create opportunities for industry to meet the needs that the market is showing is there.

 What are you keeping your eye on in the cell therapy field in 2021?

 I think the first thing comes to mind—the natural extension of these 4 CAR T therapies that have been approved for treating lymphoma would be extending those to treat solid tumors. I think that would be tremendously beneficial to patients. Solid tumors are a tough nut to crack when it comes to existing therapies, and so extending CAR Ts to that would be very exciting. I think that's kind of a natural next step for the companies that are there already with CAR T.

But I think, outside of CAR T, I think we're going to see a number of [clustered regularly interspaced short palindromic repeats (CRISPR)]-based technologies and therapies come into clinical trials and eventually be submitted as BLAs. That's a very hot field. A lot of R&D money is being spent on it, and it's getting a lot of attention. Speaking of talent pool, it's attracting a lot of talent. So, I think that's going to be one to watch as well. I don't think we'll see anything necessarily is in the pipeline to come to market in 2021, but I think we'll see R&D programs embarked upon, we'll see even clinical trials start. I think it's an exciting field.

 Yeah, and is there anything important for pharmacists to understand about the cell therapy field today?

 I think, as I'm saying with the skills required, it is a specialized field, but it’s coming. This will become more and more mainstream as time goes on, and there's a tremendous role for pharmacists to play.

Some of the roles that pharmacists can play, for example, with CAR T, their cell therapy are involved in policy development, electronic medical record billing, patient and staff education, patient selection, procurement, and storage and handling. I failed to mention it earlier, but one of the challenges in cell therapies in particular is they have to be made near where they're used. So there's tremendous regulatory hurdles, import restrictions, if they're made abroad and imported because these are living cells, viruses are involved, and so it's much simpler to have these made locally, so to speak, within the United States for the US market. So, pharmacists will have an involvement in procurement, storage, and handling these products. They have to maintain, just like the COVID-19 vaccines, low temperatures, handled the appropriate way so they're not adulterated, or even inactivated before use.

Other areas where pharmacists will have involvement are medication administration, supportive care, management of adverse reactions, naturally, and quality tracking. So there's a lot to be done. I think, while these may seem sort of niche specialist, specialty products right now, I think given their potency and the potential to be really tremendously effective against these horrible diseases, I think we're going to see more and more of these in the coming years. So there's a lot for pharmacists to get involved with.

 Fantastic, thank you so much for taking the time to speak with me today, David.

Pharmacy Times® interviewed David Silverstein, JD, MS, a partner in Axinn’s Intellectual Property and FDA practice groups, on what may be coming to market in the rapidly growing cell therapy space, and the role pharmacists may play in this emerging landscape.

A Look at What’s Ahead in the Rapidly Growing Cell Therapy Landscape

interviewed J. David Robertson, PhD, the director of University of Missouri Research Reactor (MURR), on a new collaboration between MURR and Advanced Accelerator Applications International (AAA) to work on the development of a targeted therapy for certain types of cancerous tumors.

During the discussion, Robertson explained how MURR and AAA are working together on this new cancer fighting collaboration, how MURR is able to support this cancer research, whether the use of reactors is a common practice in the field, what the goals of the collaboration with AAA are in terms of outcomes, whether there is a timeline on this project in terms of the collaboration, and how this potential new cancer therapy might impact the field of cancer research.

Robertson noted that in order to understand the impact this potential new therapy could have, a little history on research developments in the field is necessary for context.

“Over the last several years we've seen some great progress in the use of targeted radium therapeutics for treating metastatic cancer. For example, Bayer has a product called [radium Ra 223 dichloride (Xofigo)] which is effective in the treatment of metastatic bone cancer associated with prostate cancer in men. That's really changed the market space,” Robertson said.

He explained that in AAA and MURR’s previous collaboration, they were able to develop a prior targeted radium therapeutic that presented with positive patient outcomes, which led to this next collaboration between the organizations on another therapeutic.

“Then of course AAA’s success with their drug [lutetium Lu 177 dotatat (Lutathera)], which uses again lutetium-177 made here at the research reactor to treat neuroendocrine tumors of the mid-gut,” Robertson said. “Again, a very successful treatment with good outcomes in patients. So, the pharmaceutical industry is really, I would say, investing in the development of new targeted radium therapeutics based upon the success that we've seen over the last few years.”

Robertson also discussed what medical research MURR has been involved in previously, what kinds of projects MURR has worked on in areas such as neurology and archaeology, how research at MURR helped to develop certain medical diagnostic tools, and how coronavirus disease 2019 has impacted MURR’s operations over the past year.

Pharmacy Times® interviewed J. David Robertson, PhD, director of University of Missouri Research Reactor, on a new collaboration with Advanced Accelerator Applications International to develop a targeted therapy for certain types of cancerous tumors.

New Cancer Research Collaboration Seeks to Develop Targeted Radium Therapeutic

Crystal Lewis, third-year pharmacy student at Washington State University, said her top 3 study snacks are coffee, salty snacks such as Chex Mix or cheetos, and popcorn.

Crystal Lewis, a third-year pharmacy student at Washington State University, about her top 3 study snacks for pharmacy students. 

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