The U.S. Food and Drug Administration (FDA) is responsible for “the safety and efficacy” of biologic products and medical devices, along with other veterinary, food supply, and cosmetic products that are marketed or sold in the U.S. It carries out this authority by reviewing manufacturers’ applications to sell these items in the United States.

During this session, panelists provided an overview of the role of the FDA particularly focusing on the approval process required to bring new medical products to market. The session reviewed the traditional stages the FDA takes to approve various types of new drugs, the various pathways for drugs to be rapidly approved, as well as how the FDA monitors safety in the post-market “fifth phase”. Panelists also shared insights about the FDA’s role in new drug approval within the context of other federal agencies.


  • Clay Alspach, J.D., Principal, Leavitt Partners
  • Kelly George, Ph.D., RAC, Principal, Regulatory Strategy and FDA Policy, Avalere Health
  • Reshma Ramachandran, M.D., MPP, Physician-Fellow, Yale School of Medicine
  • Ameet Sarpatwari, Ph.D., J.D., Assistant Professor of Medicine, Harvard Medical School
  • Marta Wosińska, Ph.D., Visiting Fellow, USC-Brookings Schaeffer Initiative for Health Policy (moderator)

This event was made possible with support from Arnold Ventures.

Presentation: FDA Drug Approval Pathways 101

Event Resources

Key Resources

(listed chronologically, beginning with the most )

“FDA 101: An Overview of FDA’s Regulatory Review and Research Activities.” U.S. Food and Drug Administration. December 17, 2021. Available here.

“Health Policy Handbook, Chapter 4: U.S. Food and Drug Administration.” Rawal, P., Whitlock, R. Alliance for Health Policy. July 20, 2021. Available here.

“COVID-19 lesson: New FDA chief, when chosen, must crack down on clinical trial transparency.” Rabinovitsj, J., Rohr, C., Ramachandran, R. The Baltimore Sun. May 13, 2021. Available here.

“Drug Approval Pathways.” American Academy of Neurology. December 2020. Available here.

“Fast Track, Breakthrough Therapy, Accelerated Approval, Priority Review.” U.S. Food and Drug Administration. February 23, 2018. Available here.

Additional Resources

(listed chronologically, beginning with the most recent)

“Senate HELP Committee Advances User Fee Reauthorization.” Mahr, K., Owermohle, S. Politico. June 15, 2022. Available here.

“About the Food and Drug Administration (FDA) Sentinel Initiative.” U.S. Food and Drug Administration. 2022. Available here.

“The Basics and the Process of Drug Approval.” DiProspero, D., CRB Group. 2022. Available here.

“Lessons From COVID-19: How Policymakers Should Reform the Regulation of Clinical Testing.” Sluzala, Z., Haislmaier, E. The Heritage Foundation. March 28, 2022. Available here.

“Understanding the History and Use of the Accelerated Approval Pathway.” Stengel, K., Zaleski, Z., West (Olsen), M., et al. Avalere. January 4, 2022. Available here.

“FDA’s Policy Changes for COVID-19 At-Home Diagnostics—Implications for Addressing Other Infectious Diseases and Future Pandemics.” Gottlieb, S. JAMA Health Forum. December 23, 2021. Available here.

“Enhancing Clinical Trial Diversity.” Younossi, A., Sanhai, W., Shah, S., et al. Deloitte. November 11, 2021. Available here.

“Accelerated Approval: Bringing Patients Access to Needed Medicines.” PhRMA. October 6, 2021. Available

“Reducing Medicaid Prescription Drug Costs While Maintaining Beneficiary Access: MACPAC Recommendations for Accelerated-Approval Drugs.” Martin, K. The Commonwealth Fund. August 18, 2021. Available here.

“Accelerated Approval—An Unexpected Pathway To Value-Based Pricing?” Lederer, N., Dusetzina, S. Health Affairs. August 18, 2021. Available here.

“ICER Publishes White Paper Evaluating Policy Options to Strengthen FDA’s Accelerated Approval Pathway for Prescription Drugs.” Kaltenboeck, A., Mehlman, A., Pearson, S. Institute for Clinical and Economic Review. April 26, 2021. Available here.

“Reducing Spending on Prescription Drugs with Limited Clinical Evidence.” Park, E. The Commonwealth Fund. April 8, 2021. Available here.

“Racial Diversity within COVID-19 Vaccine Clinical Trials: Key Questions and Answers.” Artiga, S., Kates, J., Michaud, J., et al. Kaiser Family Foundation. January 26, 2021. Available here.

“KHN launches “Pre$cription for Power,” a groundbreaking database to expose Big Pharma’s ties to patient groups.” Kopp, E., Lupkin, S., Lucas, E. Kaiser Health News. April 6, 2018. Available here.



Clay Alspach, J.D.
Leavitt Partners, Principal

Kelly George, Ph.D.
Avalere, Principal

Reshma Ramachandran, M.D. MPP
Yale School of Medicine, Physician- Fellow

Ameet Sarpatwari, Ph.D., J.D.
Assistant Professor of Medicine, Harvard Medical School
Associate Epidemiologist, Brigham and Women’s Hospital
Assistant Director, Program on Regulation, Therapeutics, And Law

Marta Wosińska, Ph.D.
Visiting Fellow, Brookings

Experts and Analysts

Kirsten Axelsen, M.S.
American Enterprise Institute, Nonresident Fellow

Craig Burns, Ph.D.
America’s Health Insurance Plan, Vice President of Research

Sean Dickson, J.D., MPH
West Health Policy Center, Director Health Policy

Stacie B. Dusetzina, Ph.D.
Vanderbilt University, Associate Professor Health Policy

Andrea Noda, MPP
Arnold Ventures, VP of Health Care- Drug Pricing

Rachel L. Sher, J.D. MPH
Manatt, Partner

Kirk Williamson, M.A.
Arnold Ventures, Health Care Manager


Sally Choe, Ph.D.
FDA Center for Drug Evaluation and Research (CDER), Director of Generic Drugs

Nathan S. Ivey, Ph.D.
FDA, Regulatory Programs Staff

Erica Blake Payne, J.D.
FDA, Regulatory Council Office of Generic Drug Policy


Craig Burns, Ph.D.
Jasper Therapeutics, Vice President of Program Management

Heather Foster, MPH
Association for Community Affiliated Plans, Vice President of Marketplace Policy

Allison Herrity, MPH
National Organization for Rare Disorders, Policy Analyst

Mark Howell, J.D.
American Hospital Association, Director of Policy and Patient Safety

Christine Aguiar Lynch, MPH
Association for Community Affiliated Plans, Vice President of Medicare and MLTSS Policy

Monet Stanford, Pharm.D.
Association for Accessible Medicines, Director of Policy


This is an unedited transcript.

Good afternoon, everyone, and thank you for joining today’s briefing, FDA Approval Pathways, one-on-one.

I’m Devon Lara, Program and Research Associate at the Alliance for Health Policy.

For those who are not familiar with the Alliance Walker, or a non partisan resource for the policy community, dedicated to advancing knowledge and understanding of health policy issues.

You can join today’s conversation on Twitter, using the hashtag all health ly, and join our community at all Health Policy, as well as on Facebook and LinkedIn.

Today’s panel has a Q and A section at the end of the event. We want you all to be active participants. So, please have your questions ready.

You should see a dashboard on the right side of your screen that has a speech bubble icon with a question mark.

You can use the icon to submit questions you have for the panelists at any time.

We will collect these and address them during the broadcast.

Throughout the webinar, you can also chat about any technical issues you may be experiencing and someone will attempt to help.

This event is made possible with support from Arnold Ventures and we are grateful to have Andrea Nota, Vice President of Healthcare and Drug Pricing at Arnold Ventures here to give us opening remarks.

Thank you. Thank you all for joining us this afternoon. Let me start by telling you a little bit about our new ventures and our work in healthcare.

Are not ventures as a philanthropy dedicated to tackling some of the most pressing problems in the United States.

Our health care team is driven by the belief that health care must be affordable and accessible for families, employers, and taxpayers. Our work specifically on prescription drugs focuses on the drivers of high drug and biologic prices which included patent abuses and anti competitive behaviors, market distortions, and high lunch prices and prices that are increasing over time.

We’re also focused on ways that the FDA approval process can incentivize clinically meaningful innovation by using evidence based on patient outcomes and that clinical trial data be more transparent, complete, and comparable across products.

As Congress works towards its reauthorization at the FDA User Fee programs, there has been a lot of discussion about provisions in both the House and the Senate that would modify the accelerated approval pathway, which expedites the FDA’s approval of certain drugs and biologics.

FDA is controversial accelerated approval of the Alzheimer’s Strike at home and CMS as decision to restrict its coverage to patients in an approved clinical trials, generated a lot of recent attention, which put a spotlight on FDA’s drug approval process.

We hope today’s event helps you put this important policy issue into the broader context of the drug development process: FDA’s mission, and its process for approving different types of drugs and biologics.

Thank you to the Alliance Team for your partnership on this event, and really excited for the opportunity to learn from all of the incredible experts on the panel today. And with that, I’ll pass it back to you.

Thank you, Andrea!

Now, I’m excited to introduce doctor Marta pushing, Scott.

My day is a visiting fellow at USC, Broking Shafer Initiative for Health Policy and will be leading our conversation today.

Marta brings experience and expertise in prescription drugs.

Her government experience includes serving as Director of the Bureau of Economics at the Federal Trade Commission.

Chief Health Care economist at the office of the inspector general at HHS, and director of economic staff at the FDA’s Center for Drug Evaluation and Research.

She also served as an economic advisor to the US. Senate finance Committee.

Doctor …, we’re so excited to have you here with us, and I turn the stage over to you.

Thank you so much for your introduction, and thank you to thanks to all of you for joining us, for this important discussion around FDA approval pathways.

Now, I would like to introduce our audience to today’s exciting lineup of content panelists.

Their full bios are included in the webinar materials, but I would like to provide brief introductions here.

First, we have doctor Rajkumar … Chandra on a board Certified Family Physician and second year fellow within the Yale National Clinical Scholars Program, where her research focuses on the re-alignment of incentives for healthcare stakeholders, including pharmaceutical companies, hospitals, and universities towards prioritizing equitable. Equitable patient access to safe, effective health technologies. Previously rush my worked as faculty. As part of the Innovation and Design Enabling Access Initiatives idea at the Johns Hopkins Bloomberg School of Public Health. Next, we have doctor Kelly George, who is a principal of regulatory strategy for FDA policy at the …

health, where she supports clients in navigating the FDA policy environment for drugs, biologics, and medical devices.

Prior to joining …, Kelly focused on pipeline technologies in pre FDA approval phases of development at the innovation institute.

She also focused on business strategy development and in-depth market analysis, in addition to the work with the center Center.

All right, sorry.

We also have, I apologize. We also have doctor …, who is an Assistant Professor of Medicine at Harvard Medical School and the Assistant Director of Programs out of the Program on Regulation, Therapeutics and Law, now called portal within the division of Pharmacopeia, me Allergy and Pharmacogenomics at Brigham and Women’s Hospital.

His research focuses on his interdisciplinary training as an epidemiologist and lawyer, and focuses on the effects of laws and regulations on therapeutic development, approval, use, and related public health outcomes. Finally, we have Clay Spock, who is principal at Leavitt Partners. Clay specializes in federal health policy and advocacy related to the FDA, Medicare, Medicaid, Private Health Insurance, and Digital Health.

Prior to joining Levitt Partners, Clay served seven years on the US. House of Representatives Energy and Commerce Committee.

Now we’re going to let our panelists introduce the topic to us before we get into the question and answer question section of this today’s event. …, let’s start with you.

Hi, everyone, Very much looking forward to giving kind of a broad overview, and really, from a clinical standpoint, I’m a practicing physician who sees patients, and the rule FDA, is critically important for the work I do, not just on the research side, but really for my day-to-day clinical practice in taking care of patients.

Next slide.

So I’ll be speaking a little bit more about FDA’s role in terms of protecting patients, providers, and the public.

Next slide.

So, just some disclosures. Don’t have any relevant financial relationships with any sort of commercial entities that produce any regulated healthcare products.

And I also serve as a co-director for the collaboration on … for Research Integrity and Transparency, or credit, which is supported by Arnold Ventures.

Would you also some advocacy work on the FTAA space, through Doctors for America, which are the FDA taskforce?

Next slide.

So, I’m just going to start off with kind of a level setting, in terms of the FDA and what it does as a regulator.

This is the FDA’s mission statement, and I’ve highlighted some key areas that I thought it’d be good to kind of walk through.

So you can see here, the FDA in its mission statement clearly states that it ensures the safety, efficacy, and security of human and veterinary drugs, biologic products, and medical devices.

And that it helps, it helps dispute innovations that make medical products more effective, safer and more affordable.

And just within these lines, you can see kind of this tension and the balance that FDA needs to strike as a regulator in terms of ensuring timely access to promising medical treatments across drugs, devices and other areas. And also ensuring that they are also truly safe and effective before they reach patients.

The other part just to highlight is that you know FDA does play a role in terms of affordability.

You know, I think that’s something that’s a bit understated in a lot of our discussions around drug pricing. But really, FDA’s role in terms of setting regulatory standards for safety and efficacy drives innovation in so many ways. And they also help to work incentives that also play a role in terms and play a role in terms of affordability of various products. I think some of our speakers are going to be speaking to that later on today.

Next slide.

So just to give a kind of a bird’s eye view of FTA’s footprint, you know, the role of FDA. It’s just incredible just with our day-to-day spending or human lives irregularity of 25% of every dollar that’s spent here in the United States.

And really, from a clinical standpoint and from my work, in seeing patients, the FDA’s role really can’t be understated.

Nearly 70% of outpatient visits actually involve medication therapy, which means that FDA rule, in terms of ensuring safety efficacy of these treatments is critically important.

When I make prescription decisions with my patients, 80% of even hospital ER visits also involve medication therapies.

Then on top of that, the percentage of people who actually use prescription drugs is quite astronomical.

And these are, numbers are that are from the CDC.

I just wanna point out, even worth thinking about, you know, patients are using, or more drugs, five or more drugs is still pretty significant proportion of our population, that are within this group.

The other part of this is kind of FDA’s disproportionate impact, I would say, on our older patients and also can use of color.

So, both of these groups, we know from national epidemiological data or groups that are oftentimes prescribed more drugs and have to take greater numbers of drugs for their day-to-day lives and for chronic conditions.

If, for older adults, this increases over time and we have issues related to polypharmacy that FDA also plays a huge role in and also for communities of color, because of structural racism and other structural determinants of health. They didn’t tend to have, you know, higher burden of disease and be more drugs.

So FDA really has a really disproportionate impact in terms of its regulatory standards in affecting these patient populations. Making it critically important from an equity perspective that these regulatory standards are being upheld as high as high, as high as possible.

Next slide.

So FTA’s focus has actually changed over time. And I just wanted to wanted to paint this picture for folks to kind of understand how the landscape has really changed in thinking about FDA regulatory policy.

Initially, when FDA was constructed, it had a focus on safety, but in the 19 fifties and 19 sixties, when there were, you know, many case reports and indications that for the drug, the …, which was being administered to pregnant persons. You know, for treatment of morning sickness, that there was causing birth defects. There was kind of a shift in terms of thinking about FDA as not an agency that regulates the safety of products that are being given to patients, but also looking at efficacy, and also mandating that sponsors actually demonstrate efficacy of products before approval.

and before, you know, they reach patients on top of that, in 19 62, with a third amendment. This idea of informed consent came into play, so participants that were in clinical trials actually have to be informed of the risks and benefits of treatments that they would be receiving for clinical trial testing. And so this kind of work in a new age with the FDA in terms of, in terms of mandating adequate and well controlled clinical trials to demonstrate efficacy of treatments that were coming to market.

Afterwards, you know, we saw kind of a series of legislation, really focused on speed, or more time, we access to various products, and, you know, this ranged across therapeutic areas, or areas where there, were patients with unmet needs or with limited options really on the market for treatment. And you can see examples of this here, various bills that have been passed over the years and even, you know, regulatory policy that actually made these expedited review pathways that will be discussed later on. Also, come also come to light as well.

And now we have, you know, user fee re authorizations, that happen every five years. They’ve also introduce greater speed in terms of bringing new drugs to market, but really, shifting the landscape in many ways. In terms of how we actually test a new efficacy, I’ll talk about this a little bit later on. Then, of course, we have large packages like 21st Century Cures, again, to this space as well.

Next slide.

So, basically, you know, what does the FDA do? Pro approved drugs, devices, and other medical products. Saving, and effective for conditions of use prescribers adjusted within the drug label, and I just want to kind of hit home that, know the indication that’s approved is really for a specific disease or a disease class by the FDA That’s on the drug label. There’s usually a specific population, so, you know, adult of a certain age or children or a subset of patients within this group, and then also the dose and duration of drug studies.

Also, just to clarify this, I think this is oftentimes loss, the burden is really on sponsors to demonstrate that the drug is safe and effective for proposed use within the application that’s submitted to the FDA. It’s not FDA’s job to actually demonstrate safety and efficacy from the data that’s submitted, it’s really the sponsor’s rule to actually demonstrate.

If you can click the next slide, I just wanted to highlight this. You know, FDA issues will be called guidances, and this is what we call the regulatory policy that comes from FDA, or sponsor, that outlines the parameters, really, for safety and efficacy, to determine what the standards are for regulatory review. And the reason why I highlighted this is because, you know, this isn’t like, you know, the rule of law, and not necessarily, like, finding in many ways, but this is FDA’s regulatory flexibility when sponsors submit applications around, around parameters for safety and efficacy. And so there can be some fluidity to this.

And we’ve seen some recent examples of this, you know, in years past, and there’s been some extrapolation that comes from clinical trials onto the drug label that FDA uses sometimes appropriately and sometimes inappropriately in making regulatory review decisions.

Next slide.

Then, the last thing I just wanted to kind of point out with a star is that, no, FDA doesn’t regulate clinical practice. So, once the product is approved and made available to patients on the market, the clinicians are able to prescribe it for other, aqui will cost off label uses.

And the reason why I bring that up is because, you know, we oftentimes drugs and individual medical products are actually approved for multiple indications. So, when an indication, a single indication, for a particular disease is withdrawn from the market, that drug is still made available for patients for other indications. And clinicians can still prescribers. No for an off label use, and so there comes kind of this sometimes confusion from a critical perspective when indications are actually withdraw the market. But the drug still available for patients, what withdrawal actually means and what, you know, who actually bears the cost of some of these withdrawals? And we can talk about a little bit more about this in the discussion section, as well, especially related to accelerated approval.

Next slide.

So, just to give an overview of FDA’s approval process: this is the traditional approval process and I think the next secret to me, going through the expedited review processes.

You know, drugs are usually developed, oftentimes the laboratories universities, and in public research settings, then, they’re tested in animals to be able to look to see whether or not there are significant toxic effects. If there’s not significant toxicity that’s viewed in animals, then the sponsor is able to submit what’s called an IND application, or investigational new drug application to the FDA, which outlines a protocol for testing in humans, or clinical trial testing.

If FDA review of the IOT application, things that it’s safe to go forward with clinical trial testing, in humans, then the sponsor starts with phase one studies, which is usually done in just a few tens of patients, just to look at safety.

Then, phase two studies, which is then done not in healthy Volunteers as it was in Phase one studies, but, actually, in patients with specific diseases or conditions of interests, again, on very small patient population, to look at safety and efficacy.

Then, from there, if there’s some signal that there might be some efficacy of the drug for a particular disease or condition, The FDA, the sponsor, meet to discuss this and actually plan what a larger Phase three study that’s actually going to be conducted in hundreds. Or if not thousands of patients would look like.

That phase three study looks at efficacy more so, it looks at specific dose doses and durations for the drug, and also looks at other safety issues related to the drug as well.

Next slide.

From there, after the phase three studies are completed, FDA, the sponsor will then convenes actually discuss ahead of a new drug applications being filed, what the results actually showed. Sometimes FDA can say, even before the Phase three study has been completed, that there might need to be changes that actually need to occur. So this can be kind of fluid in terms of how FDA engages with the sponsor, depending on the drug or the therapeutic area that’s being examined.

If FDA things that there’s enough to go ahead with a new drug application, then the sponsor than files. And then within 60 days, FDA’s required to make a decision required regarding filing the drug for review to starting the review process for that new drug application. And then, subsequently FDA under traditional approval within 10 month period of time, has to make an approval decision. And along the way, they actually work with the sponsor around what the drug label will actually include. And what information will be provided for healthcare professionals in prescribing the drug. And then, also, the facility inspections to actually make sure that good manufacturing process brought practices regarding the drug are being employed in producing the drug.

Then, finally, FDA then will approve the drug and send what they call a response letter to the sponsor outlining specific indications for approval. Then, more importantly, and more so, Now, also, if there are any requirements or commitments, they want regarding post approval studies. And this is what we call Phase four studies, that oftentimes looks at safety, but increasingly so, especially with the expedited review pathways, also looks at efficacy of various products that go through this pathway as well.

And with Postmarketing requirements or …, these are required studies that sponsors have to deal with a period of time. But there’s also postmarketing commitments, which are more voluntary and requests from the FDA that they might ask them the sponsor.

Next slide.

So, I just wanted to point out here, you know, any other kind of issues that has come up, especially with the user fee we authorizations, besides, like, how FDA approves these drugs, is how I feel is actually funded.

And increasingly so, what we’ve seen since user fees actually came into being, is that FDA is more and more reliant on these user fees which are submitted by industry sponsors, along with their applications to actually fund FDA’s regulatory review activities.

The balance actually has recently shifted particularly for prescription drugs in the FDA actually more relies. The majority of its budget actually comes or from user fees from prescription drugs specifically for regulation of that space compared to what’s actually being congressionally appropriated.

And because these funds are coming from industry sponsors and negotiated with industry sponsors in terms of how they’re being used, a lot of questions have been raised in terms of whether or not the independence of FDA’s regulator is being maintained. Given that there is, you know, a pretty extensive negotiation period between industry that’s providing these user fees at FDA relies on and the agency itself in making these commitments to industry, in terms of using these fees. So, I just want to put that out there, and hoping that during our discussion, we can talk about this a little bit more.

Then, next slide.

The last point I just want to kind of take away with is, you know, I mentioned that there’s been a shift towards looking at Phase four studies are these post approval studies, especially when we think about expert review pathways that will be discussed next.

And this is our work from our group at Yale quit, in looking at trends over time, in terms of FDA’s use of expedited review pathways, but also the standards for regulatory approval.

What we’re seeing now is that the rigor for a lot of these studies has decreased over time. Oftentimes, just a single trial that’s supporting approval, smaller patient populations, trials that are conducted more quickly.

And oftentimes using proxy measures, or we call surrogate endpoints instead of clinical endpoints to actually justify our approval.

And I’ll say, just from a physician perspective, this increases a lot of uncertainty at the time of approval, or an FDA approved treatment. Whether or not it’s actually clinically effective for my patients. And so, this is kind of the the, I think that a lot of the discussion that’s happening now, with the FDA. How do we rebalance this shift in scales from kind of political certainty? You know, making sure that the mandate of the FDA, of ensuring safety and efficacy of products ahead of approval is also being balanced with time we access. And at the same time, providing insurance is both for patients, but also clinicians, and also payers, in terms of the safety and efficacy of the drugs that come to market.

And whether or not FDA has the authority to actually ensure that continue monitoring. Even after approval, if drugs are being approved much more and more and more quickly.

So I just wanted to kinda leave folks without those thoughts, before we talk about expedited review pathways with our next speaker.

And the next slide.

Thanks so much for your time.

Thank you so much, fresh map for setting this up. So we aren’t going to change gears now and and look at expedited pathways. And Kelly George is going to give us a lot more detail about how that differs from the pathways that … has just described for us.

Thanks, Mocha. Next slide.

Next slide.

Perfect. So for this session, we are going to zoom in. And we’re going to focus on those expo designations and pathways, as well as consider a little bit of what does it mean to balance competition innovation.

As you can see here, F E. Overseas, in the light blue, it starts all the way to give me a clinical development, as doctor Shannon is telling us, all the way through life cycle management of a product, including post market studies, label extension, new indications around ministration. Sophie is looking at these products the entire time from when they start manufacturing, and they start up and all the way through. Once it’s on the market, This is a good number of products, so it’s over 20,000 products. In the prescription drug product market, that’s I consider the over the counter or other hits effects are looking at, is over 13,000 facilities. They’re keeping an eye on how the inspections are going, ensuring the products themselves are manufactured with high quality, and the free product that comes through development to classification is about 100,008. So, it’s just a tremendous amount of work on FDA’s shoulders that they’re trying to keep on top of.

And the question is, how did they take all of that work and really focus their resources and most important decisions? Next slide.

This is by no means a new question, right? Um, FDA has been considering how do they see the, the development in market access for high value products for many years. First question is how you define a high value product.

Question is, what does it mean to prioritize workflow and agency energy? What does it mean to support a product that’s going to have a high value for patients? And, how do you create efficiencies in that in that process? Now, of course, there had been a system back in the seventies, eighties. They had a system of therapeutic potential rating. Is a very generic, not too transparent approach.

The ABC rating, really simple, that A, rating, most attention see, rating got the least, attention.

But, as more and more products came under their, under their oversight, as doctor Ravitch hundred mentioned in 62, is what FDA is also charged with ensuring the market more effective, more and more products will take longer to get the market. So, there are a lot of conversations about how do we create a system that works for, for industry, and for patients, give the agency.

Um, then, we had the aids epidemic, which even pushed everything to the forefront and push that conversation, even even further forward.

Congress took, on this term, drug lab, time it takes for it to be developed, Application Smith, FDA, and FDA review them. Let’s just getting far too long, right, until we see those two first user fee amendments being implemented right after the aids epidemic in 18 92, and you will see each of these State programs in increments of five, because that’s the opportunity for industry and FDA. And really say, what is the most efficient way to deal with. And you will see over the last 30 years you’ve seen, we’ve created new programs to address the needs as, as the pipeline as false.

Next slide.

So, on the four most commonly used programs, accelerated approval, priority review, Fast track, and make them.

First thing I’ll point out here, is that each of these programs, they, function, will provide support at different points in development. So, we have phase one, to phase three.

Then, FDA review, you’ll see accelerated approval in, light blue is really supporting product products. It later in development.

Um, it is a, an approval pathway, so that when we talk about the type of evidence needed for the standard traditional pathway gaming product to market, accelerated approval is a separate set of evidence. Instead of substantial evidence, it’s likely to benefit. And so, it allows for different type of product into the market, and different type of product, to address a separate type of disease, after the aids epidemic. That was really forefront conversation, of how you get those types of products to patients.

In green, you’ll see the priority review, and that’s another XK designation. that is just addressing how long FDA has to review a product. So when this came in, Congress gave FDA deadlines produced.

The FDA looked at, looked at applications and really take as long as they want to come up with their assessment. Really created a deadline is how long it FTA because look in the application: prior to the review was an opportunity in short.

If you had a product that was fully developed and was extremely promising, FTA could really focus your attention. Instead of taking 10, let’s review pages.

To fast track. And they prefer to see they’re both immediately, because these, these are programs that allow for additional agents, engage, right? So, more conversations with FDA, more data being gone back and forth, we’re really, really chat with FDA. And so this is our plan, beats the challenges we have with you guys and have those conversations earlier on. So that the development programs are headed in the right track all the way through, and not necessarily go off the track or do something. They assume it’s going to instead of going the right direction, But have days, and on board, Right? So, that way they can stay in alignment with FDA.


Thinking more about the criteria, Right? So, how do each of these programs identify which products, in which local high value products are appropriate for each of these? So, accelerated approval that is focused on the types of diseases that have long term endpoints. So, it’s a perfect example, but also kids, when you’re thinking about clinical trials for cancer, if you had to wait for every clinical trial, to determine overall’s Bible, there’s two very walls in a house. In the meantime, you have patients are unable to get access to accelerated approval, is passes through which companies can measure shorter endpoints to ensure when they’re likely create benefit. Patients can access to that without having to wait years and years and years for overall survival or another quote from employee to finally pull data.

Priority review, now that is looking at data that’s developed later in development that shows that it’s a significant improvement there. Seek to your efforts.

Fast track, in 19 97, 5 years after the other team came on board, the realization that there was also a need for a product, or additional attention earlier development, so fast track is like you have a, have a product that is: is life saving and there are patients who need currently don’t have a treatment available.

Fast track is an option for those types of patients don’t have that option, whereas breakthrough five years later is substantial permit over available therapy, so that that’s the type of disease where there is a product on the market. But, the product in development that we get breakthrough is even better than the product as already on the market.

Next slide.

So transitioning here from prioritizing and FDA’s energy on high value products. To how do we ensure these high value products are continually develop and incentivize, right, what kind of programs we have. Pleased that balances, competition, innovation, and there are several organizations agencies that come into this space. We have FTC, The fair trade mission is really focused on fair trade. Their folks indicates that the behavior, oftentimes it’s promotional approach for different contracts that companies are working together on that that create monopoly markets are just unfair practices. Thus the US Patent trade office so their entire goal is to give out patents for intellectual property.

These patents do expire after 20 years after the patent is received and then you have market exclusivity, oftentimes market exclusivity and exclusivity can be confused, specifying that patent, exclusivity, US.

Patent office, There’s markets because he is from the FDA and begins at time of approval and will vary in duration depending on what type of exclusivity FDA’s connecting them.

Next slide.

Diving in deeper to these FDA exclusivity is a specific time, each of them are able to have exclusivity on that product. What? That means it can mean that exclusively for a product to not have a competitor following product approved or that a follow-up can’t submit a file.

So if you take new biologic, and she has example, the first five years, for the new village and entity that gets approval, those five years as a sponsor isn’t able to submit a file.

And then for 12 years, nobody will be approved, right? And you can see that all the way through. And then there’s, there’s exclusively such pediatric studies, which is six months, and I’ll be added onto other candidates.

These these are really incentive to create this temporary protection from competition to ensure companies have innovative products are able to recoup their losses in developing an incentive to continue it.

Next slide.

So where are we now? 

programs we have 74% of novel products being approved from Cedar 2021 that was received an expedited designation or pathway, 68% of them had priority review and about a third had abstract salary approval right there. I put this up there to really think through what I might, I might add that if 74% of products are expedited pushed down the line, are they really at the phone line?

A lot of things are changing, and I’m wondering to what extent have we want to continually form this program’s goals? Or to make sure we’re focusing on those types of truly bring high therapeutic value to patients?

And the thinking that competition innovation, this is a chart looking at generic entry claiming. So we have 55% of small molecules that have junior competition, that is, enters the market at the time you would expect, and then 29%, that’s silly.

On an average of 12.5 years, a small molecule drugs, and working for competition, whereas they only got five years exclusivity. So, I think that you guys, to think through what is the appropriate time for innovative product to have exclusive access to the market?

But, but simply put that it’s certainly something that needs to be continually to address, to identify, how do you balance that competition versus innovation.

Next slide.

So, thinking on, for whom all over are these the bread X-ray programs to have an existence protocols work Well? This innovation, imbalance, function we want to take on board, we are having a changing environment. There are a number of trends that are going to require more and more efficiency and how FDA and how industry options to bring products to market. one is simply that we are having far more products that are targeted and very small populations, orphan product. The farmer has come into clinical trials and being run where data is being collected. And the products that are being a running clinical trials and Canadian pipeline or just far more complex, telling a little dot there, You have small molecule. Then the larger one that’s a biologic. You can see the difference in complexity between these two compounds.

And then I add anything about the size of the cell therapy, that’s probably the size of the room or city, right, So, the idea of bringing these more complex parts to the market and helping them treat patients needs, it’s really a different pair.


Thank you, guys. I do want to show you the Appendix I put together next.

Next, if you guys are interested in knowing the details in these next day programs, you’re able to download the slides next.

This is all the details of the market exclusivity.

Thank you so much, Kelly, just as actually a very nice table that I recommend people download. So with that, I would like to turn the floor to Amit who will talk some actually about a lot of the work that Portal has done to identify some of the trends that both Reshma and Kelly spoke to. and then also talk about what this these trends mean for payers.

Amit just sounds great, Can you guys hear me OK?

Wanted to meet. We can hear you. OK. I just wanted to make sure so pleasure to be here. And next slide please.

So I’m going to talk a little bit going off of doctor … and doctor George’s comments. What happens once a drug is FDA approved now that comes with certain commitments? And unlike other countries, we don’t have a national health technology assessment, So there are other countries, like Germany that will take a look at the comparative effectiveness of a new drug, or countries, like England, Then we’ll take a look at comparative cost effectiveness of a new drug, But we don’t do that. And so there are various groups that might try to determine what the value of a new drug is. But there’s no national scheme for that, and that presents an interesting question. one.

We talk about what is happening as FDA puts more oversight in the post approval space rather than the pre-approval space, and in terms of what we see with payers, it’s important to recognize that once a drug is FDA approved, Medicaid must generally cover all FDA approved drugs. There have been some states that have attempted to request waivers to Institute closed formularies for Medicaid but those have not come to pass thus far. So really whether it is a transformative drug or a clinically marginal drug, Medicaid is obligated to cover it. Now it can impose certain procedural hurdles to getting the drug. But in general, it’s going to have to pay for it.

Medicare must cover all drugs and six classes. and those include anti convulsants, anti-depressants, plastics, cancer drugs, anti-psychotics, anti retrovirals, and immuno suppressants. Now it’s standard for whether or not it needs to cover the drug. Otherwise that don’t fall into those classes, that those strikes must be reasonable and necessary. Those closely aligns with FDA’s approval standards, but they aren’t the same.

And so, importantly, also, when we got to Part D for outpatient, patient administered drugs, the Medicare Modernization Act of 2003 prohibited CMS from negotiating on behalf of Part D plans. So, in a sense, it’s important to recognize that. We have an environment in which we sort of tie in some major payers hands in important ways and determining whether or not to cover certain products that should be coupled with the fact that there is very aggressive marketing of pharmaceuticals and much of that money isn’t spend on the most transformative drugs. Those drugs don’t really need an excessive amount of marketing dollars. $30 billion, Justin.

2016, spent on marketing of Drugs, Disease Awareness Lab tests, and health services. And a paradigm that the Federal Trade Commission Node and a well back in the seventies is important. There is an interesting dynamic that is, Market doesn’t function. Like other markets, because the payer pays doesn’t choose, and that results in perhaps some inappropriate prescribing. And it’s important that we have mechanisms that can address that. What we’ve seen right now is, we have soaring nets, And what I mean by that is after rebates and other concessions are taken into account soaring net launch prices and price increases. Next slide.

So, doctor Ramachandran talked about this a little bit, this shift from pre to post market assessment. So, it’s important to recognize the FDA’s fast. The overall median time to total approval in 2019 was about nine months for a new trend in 20 20. Doctor George updated, Some even newer statistic, 68% of new drugs qualified for an expedited development review Again. Going back to some evidence that doctor …

site at each important to recognize that in terms of the evidence that is being used to support new drug approvals, there is less evidence and less rigorous evidence. Now, that is really a political choice, but it’s important to see the facts here. So when considering the aggregate pivotal trial, supporting each indication approval, the proportion of indication supported by at least two pivotal trials decreased from 80% to 60% to 52%. The proportion of indications supported by only single group controlled trials, increased from 4% to 12%, to 17% over the span of a two periods. Over over three currents are over between decades. And so what is the implication of this?

Well, from a political standpoint, it may result in the earlier access to some safe and effective therapy. So that’s an important choice. It’s a policy decision, but it can also result in more drugs, entering the market better later found to be unsafe or ineffective. Next slide.

So what are we seeing now while we’re seeing more drugs, but how good are they and for what conditions? So there have been an increasing number of drug approvals over time. If you take a look at the mean annual number of drug approvals from 19 90 to 19 99, you have 25 for few chuckle at 2010 to 20 19. You have 40, and here’s where I’d stop, and just say that when we talk about innovation, I think that’s so important, that innovation doesn’t just mean new drugs, That means the quality of those trucks. And so, particularly when we’re talking about incentives for innovation, sometimes there are incentives that will yield more drugs, but not necessarily new drugs that are clinically transformative, and that’s an important distinction when we talk about what might be helpful in terms of producing a more suitable market.

So, somewhat new drugs that have come to market there is no doubt, have been clinically transformational, so velocity, or cure for Hepatitis C Kim Mariah, Gene therapy, is coming to market, but of all new drugs approved by FDA in 2017. About two thirds were rated by expert organizations in Germany, France, and Canada, to offer no minor additional benefits over existing treatments. So, this goes back to the lack of a sort of health technology assessment body in the US to sort of say, well, how did he strikes compare to what’s already on the market?

Pumps are Cool.

Companies Act, rational. And they will act to maximize profits, and that is normal, and that’s to be expected. But because of that, and because of the way that FDA has interpreted its standards for drug approval, it is easier for companies to get oncology and orphan products to market.

There is vastly disproportionate focus on indirect companies and getting these products to market and away from risky, and non profitable markets centrist, central nervous systems, drugs, and tropical diseases. So you can just see this two headlines here. one Statistic, one headline, Amgen exits neuroscience, so your company’s exiting the neuroscience space, because it is very difficult, very risky. And then you see here, in terms of Neglected Tropical Diseases, how much do they constitute compared to the overall number of new products that are entering a market? Next slide.

So, specifically, when we focus on accelerated approval, as of May 2022, there have been 270 after onset of an approved entity, accelerated approval pathway, the most common indications or oncology and rare diseases.

Now, this is a very important pathway. As doctor said, it presents the opportunity to get promising new drugs to market.

Now, I’m going to just highlight some of the challenges of the pathway at the time of approval.

Use drugs have more uncertain benefits than do drugs that go through the normal approval pathway, and that’s an attentional, an extra weight, a pathway is intended to setup.

But there’s no checks on the price of those drugs, and so if you took a look at just in Medicaid and medicaid’s Fair. 9.1% of its spending on Accelerated Approval Drugs, which constituted only 0.4% of prescription use. So we, it is important to get post market evidence of the effectiveness of these drugs and their safety. And one example that we can talk about more in Q&A, but I’m sure everyone on the call has heard about, is that Academy otherwise? Known as …, and so the list price of the restaurant was approved under, an accelerated approval pathway is $56,000 ice.

Or a private company that will take over a non-profit that will take a look at the comparative cost effectiveness of the drugs, estimated that for a cost effective price would be $11,000 per year of this drug. Because of the coverage of this drug, before, CMS later made it coverage with evidence determination, by CMS, announced the largest increase in premiums in 15 years, because of how many people they thought might be getting a stroke. Now, the evidence in support of discharge was very, very minimal, and we can talk about that, also.

So the problem is there are minimal incentives to complete required post approval trials, and there’s limited enforcement. So if you take a look at just a period from 19 92 to 20 16, 13% of accelerated approvals in which 13% were on the market median of 9.5 years without confirmatory evidence that it’s an incredibly long time. If you take the … example, FDA gives Biogen up to nine years to complete this Phase four studies so we’re really operating in a period where you take a look at what doctor … was saying from a clinical standpoint. We’re not getting that evidence in quick enough time. There’s also a lengthy process for withdrawing and education.

Not the drug McCain is a classic example and the result is that there’s a greater a gate keeping role that is meeting to be played by payers and here you have Medicare basically saying that we don’t think the evidence for some drug like … Canada. Is that great?

And we’re going to insist on certain conditions, if we’re going to cover it. And I think that’s a way of the future that you’re increasingly going to see. Next slide.

Yep. Thank you.

Thank you so much meat.

And so, with that setup, I wanted to pass it onto Clay who can talk about the political environment within which some of these reforms are being discussed right now.

Well, thanks so much for the opportunity. Great to be on the panel. And it’s Margaret indicated, Gonna kinda walk through the current political environment on the next slide, Just a little bit of an outline of what you can expect.

Don’t worry, I’m not going to talk that long as much as I have them into as many them, a sections.

But what we’ll walk through what we’ll do is just go through the overall political environment that kind of of what we’re under, as we look at the approval pathway, and then go into a deep dive on the FTO user fees and the reauthorization effort.

The reason for that is the timeliness I think we all know that congress is hopefully on the verge of reauthorizing enacting legislation to reauthorize it user fees. And so, it is, it is the focus right now.

We will go through examples of past congressional efforts just to show where these reauthorization, pasteurii authorizations have fit.

Especially in the expanded programs that were talked about earlier.

And then talk about the current Congressional effort.

And I think goer real high level overview of that and knowing that in the discussion section, we’ll talk a little more.

So with that, we can go to the next slide, and the next slide for that.

So, basically, the current political environment is made up of not just what FDA does.

Obviously, it’s also made up of other other factors as well.

Really, those factors are the three branches of the Federal government, as well as current events from the FDA standpoint. What feeds into this environment could be formal rulemaking, example as the accelerated approval pathway that came forward.

That was discussed earlier, guidance documents. Just recently on Friday, there was a breakthrough therapy designation guidance document. It came forward. Those play a really large role, especially in FDA, just given the significance of guidance and guidance documents that are put forward. The oversight activity of FTA is a very important element, as well. That will go a long way toward feeding into what Congress may do, as well as the regulated industry as to how they’ll react. And finally, individual reviews, those play a really large role in looking at it.

As we talk about Agile home, obviously, that was just one aspect of the utilization. It’s already approval pathway, and here we are. We’ll talk about that. It’s where it fits as part of this current reauthorization effort.

On the congressional side, we see oversight. We also see legislation.

While the legislation will be the focus today, what I discussed, the oversight really is significant, and needs to be a big piece of this part of the discussion, where Congress spends its time, and how it does it, and whether it does it.

I would argue, in a productive way or unproductive way, play a pretty, really large role in how, and including is how the approval process looks.

Unfortunately, we’ve seen examples of Congress and how that can be non productive, especially just given the what FDA does in their important role in, in this whole effort.

Finally, current and current events, that is another really big piece, as we look at these, as we look at this approval pathway, we have the, also have emergency use authorization that we’ve heard and learned so much more about because it could’ve been 19.

That is, really, as we look at how drugs get to market, that’s an important factor as well.

Suffolk Gummed, I guess, news and activity around, outside of just drugs. So other medical products are regulated by FDA.

Play a really large role, and really and how FTAs, viewed, especially that Congress and stakeholders, to infant formula shortage, is a really big example. Right now, it’s playing a really large role as much as, it’s not, There’s no user fee, there, it’s playing a large role as part of the user fee effort.

And then, finally, the courts, I think the courts, you’ll see different cases that come forward, which opine on FDA authority in different areas will likely see a significant role in the courts around after the decision on Friday related to data in Dobbs the FDA and its role in its authority vis-a-vis the sea states. It’s going to be something that will be litigated likely. And so, the courts are loom large in this as well.

But as I mentioned before, given the timeliness, we’re going to spend our time on the FTA user fee reauthorization process and so we can keep forward to that slide please.

So next one.

So what are these user fees? I’ve used the term a bunch of times already and so let’s kind of do an overview as to what they actually are.

So these are user fees and these user fees have come forward. They were started in 19 92 as part of Paducah Prescription Drug User Fee Act.

And they were done to provide additional resources for FDA to help basically review applications and around the review process.

This has since proliferated, where since 19 92 we’ve had other user fees that have come forward that are part of this process. one is the medical device user fee is also generic drug user fee, and by similar user fee, those two came in in … in 20 12.

These are very important, because it’s, as others have mentioned, they form a significant amount And part of the budget for FDA. I think FDA needs more resources. And appropriators are going through that process now to try to provide that. But these user fees provide a significant amount, and are really necessary to ensure that there is timely, timely review of these products. We saw before 19 92 of the acute nature.

And what that did to, to patients, and the wait times that were there, how it had a negative impact on innovation. And since 199992, this Purdue Purdue, and these other user fees, have added significantly to ensure that patients have timely access. Now, one thing to note is that these do expire.

So whereas we, if you look at the federal government, you look at agencies, others, there are a number of authorizations that have expired. The Congress has no intention and has not looked at.

These user fees are different in that they do expire at the end of September.

What that means is, if they do not, if Congress does not act, basically, those funds are no longer available.

And FDA employees that have been on the front lines of helping, whether on the vaccine side, to therapeutics, to diagnostics across the board, to providing what is necessary for our world to deal with coded. They could lose their jobs. And so, that is something nobody wants. And the hope is that Congress could step forward and, and get this done as soon as soon as possible get this law enacted as soon as possible.

I think the hope would be at the end of July, because there’s this pink slip issue, where, under, under Federal law, there’s 60 days is required. Notice for federal government employees, if there’s an expectation, they could lose their jobs.

But the, but, so that’s called, like, pink slip, issue, speak slip, issue, Unfortunately, kind of where we are. We’re not sure that that deadline will be met by Congress, but it is important that hopefully they get done as expeditiously as possible definitely by the end of September.

So, with that, on the next slide, these user, she programs, after a negotiation, with industry, on the next slide, go to next slide, day.

These user fees provide a significant amount of reform, in and of themselves, the commitment letters, if you review them, You’ll see a significant amount of, basically, policy that comes forward. Whether it’s additional money for liquidity, for context, for cell and gene therapy, for CBRE, to provide those resources necessary so that they have the scientific.

The scientists necessary to look at this very challenging issue to more patient engagement, something That’s been a huge part of priority for Congress stakeholders and FDA for a number of years. Definitely since 20 12.

Um, so those, just, in and of themselves, they provide significant amount, An important policy change, and resources that are necessary to do that.

But they also, what they do, is they provide a vehicle for Congress to conduct additional oversight of FTA.

So you’ll see in hearings as part of the process, there’ll be asked, Congress will be asking questions on, are we reaching the right balance on, on promoting innovation to providing safety, to ensuring access big questions to specific questions. On.

Just, very, topics to, some may consider minor, but are really important for Congress to make sure that to work to FDA, work with stakeholders, to ensure that the policy, the law there is as up to date as possible.

Some of those policies that come forward are those Policy Reform, those riders, those add ons, are different words forum, but that that gets added onto the legislative vehicle, because this is a must pass. I mentioned that these user fees do expire, and so it isn’t must pass. It’s a vehicle for change for reform. And so you’ll see Congress stakeholders, even FDA, will ask for additional authority, so that they can update the statute and update their ability to address just the public health public health concerns or challenges, or that are out there.

On the next slide, we can go through just how they’ve done that in the past.

Next slide, please.

And then next slide. So here’s just some examples of what we’ve seen in the past for dama, the Food and Drug Administration Modernization Act in 97.

That was the basically where could do originally got re-authorized. You’ll see as part of that legislation, that’s where Fast Track team came to be. So Congress moving and looking at the approval pathway and working with FTA to provide that necessary legislative change.

On the next slide, I’ve talked a lot about innovation, but safety, obviously, is a really important factor as well, for FDA.

And in 2007, there were concerns related to the authority of FTA due to some challenges, some issues that had arisen in the pharmaceutical market.

So with that team, REMS, the Risk Evaluation and Mitigation Strategies, the rams that are attached to individual drugs as they get approved. So the FDA ways that benefit risk, they have that ability to add these ramps to ensure that that balance is reached and they believe it’s safe and effective It can reach to reach the market. So that’s just an example of where those authorities have not only been on innovation, but also on safety as well … On the next slide. That was 2012.

Where you saw the introduction of the breakthrough therapy designation that we’ve heard about during this webinar as well. I’m sure we’ll have additional discussion on too.

And then there are also some changes that were made related to the Accelerated Approval Pathway and others as well. So that was happening in 20 12 and then finally in 20 17 as part of the reauthorization, Fedora is as it’s known.

On the next slide, that is where patient engagement I mentioned in patient engagement has been a big priority issue for a number of different, you know, stakeholders including FDA in Congress.

There were additional, there were additional policy that came forward around patient experience data, and I think we’ll see, we see that as part of this re authorization to continued.

You’re building on that patient experience and trying to find ways to better incorporate it as part of the approval process. And I think we’ll continue to see that in the coming years as more. As we better understand how to systematize that and as different diseases and conditions and those living with those diseases conditions can can better get incorporated. one can incorporate in that process. So I’m the next slide. I’ll skip ahead to slides. We’ll kind of talk about the current and where we are right now.

So, where we are right now is FDA transmitted. The commitment letters that basically embody and have all the information on that agreement between industry, as well as FDA on what the user fees and how those we utilize the next five years. Those came in January, and since that time, the legislative process has been Underway, Energy and Commerce Committee, and Senate Help Committee related to that. So we’ve seen legislative hearings, and we’ve seen different discussions on a number of topics.

And now they gave, basically moved from move from discussion now to moving the field through the legislative process right now where they are in the formal negotiations. This is not a formal conference as you’re seeing with you cica, which is a bill that’s being considered right now, this is informal, so Health and Energy and Commerce Committee staff are working together to try to come forward with an agreement.

That we basically reauthorize these user fees take additional riders as well, and get back to President Biden’s desk as soon as possible.

It’s the expectation that they will try to do this as quickly as possible, but as we’ll discuss further, these are just these bills are are heavy with additional policy, not just in drugs, in the drug world, but also dietary supplement cosmetics. There’s also a paradigm shift in diagnostics. It’s incorporated called valid and so, with that, these negotiations are very, substantive and could take a long time.

And so, I think, as much as stakeholders and FDA and Congress want to get this done as soon as possible, there’s a sense that it may take longer than expected to get that done.

Now, let’s go to the next slide on, on, in the House bill, which has passed the House on it.

Big bipartisan vote, which is very encouraging.

It does include a number of key provisions, including on accelerated approval, so accelerated approval, because of aging home. And other other things has been a really big focus for Congress.

And so, we’re seeing elements in the House Bill, as well as the Senate bill, on Accelerated approval, as well as with real-world evidence. That some want to incorporate further incorporate as part of that accelerated approval pathway, as well. So, I’ll let you can circulate these slides later. These are just some of the provisions that are included, as around accelerated approval. On the next side, is the Senate. What the Senate includes, and they’ve moved through their help, they Help Committee that had not gone to the floor. It also includes a number of pieces related to accelerated approval. Basically, according to the sponsors, to help make it clarify, if somebody approval authority, as well as to provide additional pieces where you can see here there’s an iteration, inter-agency co-ordinating council to help FDA as it looks at it.

I’ll conclude now, just going to concluding thoughts, where if you skip a few slides, is, next slide, please, what we see here is that the current political environment, and we’re all living through this, it is incredibly, right.

I mean, every day, it’s not just in healthcare, but there’s a different event that happens. We’re, unfortunately, sometimes tragedies that come forward to make this political environment incredibly fluid, especially with FDA.

And right now, the reason why we’re spending time on this user fee reauthorization process is it will be the center focus on FTA issues the next few months.

And no issues could arise. You know. But we’ll see that this is going to be where we, hopefully the Senate, the House President Biden, to get an agreement and move forward. Move it forward, expeditiously.

This drug approval process though, as much as there will be changes, include including possibly on accelerated approval as part of this, it’s going to continue to evolve post this real authorization process. So, as much as we focused and I focused on that today, please know that there will be, because of how important this is, there will be. It will, it will continue to change.

That’s going to be because advances in science, I would argue that we’ve heard earlier about, you know, the lack of evidence and the lack of the clinical trials are robust.

I would argue that, maybe, that’s because the science has, has advanced so much, and we know so much more about those drugs in the underlying biology, such that those clinical trials, as much as they are an integral part, they don’t.

They don’t have the evidence is there to approve such that we need to get back to patients in an expeditious way as well as we don’t need to subject patients to those clinical trials.

If we know it works, that focused on access is going to be a really big part of this, right? Not only we saw the right to try, to continue to see, right? To try, we saw that a lot during the Trump administration, Whether it pre, pre market or post market, Post Market Access is going to be really important here That if they can actually get to patients, And so I know that he’s going to be a really big discussion.

As we see these seven gene therapies come forward, and we’ve been trying to better understand that.

That is something that, out of the FDA contacts, but trying to figure out like where value fence, where some of these risks, these, these arrangements can be forward. These value based arrangements can come forward to help in that regard.

And then, Finally, on to demand for patient engagement.

That’s going to continue to be the very important part of this, and continuing to figure out, like as much as we talk about FDA’s role to patients’ role, is even larger, right? Where they are The ones who are going to be taking these therapies, or end date their, their views on what matters, has to be front and center.

We seem really great evolution and advancements in that. I think we’ll continue to see that.

And then, finally, we’ll close with the congressional side of this, where a lot of my time has been focused.

It can be very productive and very helpful.

But we also have to understand that it needs to be met with a very substantive and thorough end adult conversation.

Because as much as everybody points fingers around an Agile, how were others, Congress and stakeholders I think, need to take and understand the FDA is under tremendous pressure as they look at these reviews.

And we need to make sure that we’re not just knee jerk reaction, whether it’s a change to the accelerated approval pathway or winning blame at somebody when it may be that the actual challenges that need to be addressed, Or we need to better prepare them and help them as on these on these issues. For example, in the neuroscience space, providing the resources necessary for FDA. So it has the latest science. And so that, as these challenges, or look, at these challenges day, to get to where cancer, and oncology is that, they understand the mechanisms of action. They understand the underlying science that has made, the ability to utilize accelerated approval, that much more beneficial because they know when a tumor shrinks it of drug is working, and it should get to a patient.

So with that, I’ll close and turn it back to you, Marta, thank you very much.

Thank you so much, Gli, so, actually, if I could now invite all of the panelists to come on video.

And also, for those of you in the audience, I know some of you have been submitting questions, I invite you to submit your questions. I am not going to be able to get to all of them.

We only have 15 minutes of discussion left, and so I wanted to encourage you to just send in questions that directly relate to the issues of accelerated approval. I might not be able to get to some of the, sort of other drug related questions that are really important, but probably outside the scope of this presentation discussion.

So let me actually just to take, take Congress, aside for a moment, I wanted to ask about FDA’s ability, willingness, and and interest in in addressing some of the issues that need to raise in terms of evidence generation.

I wanted to ask sort of your your take on that don’t: do we need Congress to be involved in, in, in the solution or not? You know, 1 1 example that comes to mind is the breakthrough designation pathway FDA just issued a guidance. So I wanted to ask your thoughts around FDA’s role in being able to address this sort of balancing and potentially rebalancing of the, you know, creating a lot of access but how do we generate the data?

Actual rationale?

Maybe I’ll start with you, and then let me know who else to jump in.

Yeah, sure, I can definitely speak to this.

Mean, there’s a number of a clear: there’s a wide authority, are pretty broad authority that FDA does have to actually take carry out these actions, even in terms of like Accelerated approval. The way the current statute is actually written is that FDA actually has pretty broad authority to employ standards for oversight of accelerated approval drugs, but more importantly, also withdrawal.

And so, there’s kind of this little bit of attention that occurs in terms of FDA. Wanted to exercise the authority, or kind of receiving validation through a congressional vote, through a user fee, No writer, that actually has accelerated approval report, that comes into play, as well.

But one of the things that we have been like noting and looking at a number the policies that FDA has expressed supportive, so each year FDA actually submits a budget to Congress, and as a part of that, they actually include legislative reforms that they’re supportive of. Those give a great story, and the sheet tells you where it’s very telling to actually what FDA’s willing to actually do in terms of, you know, performs or policies that they are willing to move forward on. And in there, you’ll see that they’ve actually highlighted a couple of things that are already in the user pre-packaged, most notably the accelerated approval reforms that Congress is considering and even going beyond what’s actually in front of House and Senate actually currently. But these sorts of reforms are things that that the agency could actually do outside of statute, through guidance throughout regulatory policy, the rulemaking as well. There’s some concern that Congress will codify. You’re going to tie FDA’s hands. So, let’s say, for instance, Congress’ specific stipulations on around withdrawal of drugs.

Or even with breakthrough designation, for instance, that’s the guidance at FDA comes up, came out with. Let’s say Congress says, we know we’re gonna actually put specific rules about how FDA is going to withdraw these drugs, hobbies, and withdraw breakthrough designation that actually ties FDA’s hands, know, regardless of administration. You know, who comes in as FDA Commissioner who is in that seat as an appointment as an appointee in terms of what they were able to do. And so there’s a little bit of a tension between that in terms of what Congress actually propose and then also what FDA supportive of what Congress does, You know, obviously meet with FDA. They routinely to actually get their insight in terms of what’s capable and what’s not. And the other part of this, that comes into play, the administrative burden. And that relates also what sorts of resource capacity that they have. No user fees be negotiate with industry, does not allow for those user fees to be used for FDA activities, that FDA is heavily reliant on Congress for appropriations. And in the medical device space, that’s particularly important.

Because we’re seeing right now you with me, do for being discussed, Things like post market surveillance or post approval studies are not really being a part of the medusa discussions. Whereas FDA needs resources and staffing to be able to actually do that and that’s where Congressional appropriation comes into play. So even though they want to do these things and carry out these activities, they might not be able to do so just because of budget constraints and resource capacity as well.

Any other also type in there to think about here is, is the trends we’re seeing in type one versus type two error? Concerns for FDA if FDA were to approve a drug that should be approved versus FDA not approving a drug, that should be.

Right. And I think I can help really leaned into this conversation as you have more folks. Having a conversation of what FDA is and is not proving and what the evidence looks like, it’s going to shift FDA’s approach to that type one versus type two error.

I’ll jump in to just to say agree with the thought that there’s not a number of there’s a lot of authority for FTA under its 505 Food, Drug Cosmetic Act, and I think looking at some of these activities as more of a validation exercise rather than authority exercise. I mean if you look at breakthrough designation from 20 12 FTA could have done that without that statute, but that helped FTA leadership move that forward. And bring work.

That important authority and showed Impatiently for Congress to the support of Congress, Pat on the back, to push, to, to, to stress that at FDA.

And so that, as we look at that tension, it’s really important, and that FDA, who’s implementing, you know, FDA’s implementing this, their implementation.

A lot of times, when I was on the Hill, we would talk to folks about some of the challenges, and we’re hearing you out, and they said It’s not a problem with the statute. It’s on the implementation.

And so, we don’t actually need you to do anything. It’s just a matter of getting FTAs. Yes, just asking you to do that. So, it’s an important consideration at the statutes are moving forward as to actually why if they’re necessary and why they’re necessary.

So, a related question is around, you know, going back to evidence generation, right? How do we solve the evidence generation problem? one of the approaches that has been proposed and discussed is what’s called real-world evidence, and it was, I think, mentioned very briefly in one of your presentations, Kelly, I was, I was hoping you could maybe help define what that is, and sort of where we stand on it currently, And then, I’ll open it up for discussion about, you know, To what extent this helps move the needle in the right direction.

So, Kelly, absolutely. So, real-world data and real-world evidence, this is the type of data that’s collected outside of traditional, right? And this is by no means, a type of data set.

Originally, it was defined in legislation, play first Century Cures.

six gave FDA the mandate to actually use real-world evidence, not just safety studies as the past, but also for new indications of new products coming into the market.

What we saw during a pandemic, however, was that role and evidence really gave the agencies had more experience for all that evidence. It hits so many headlines, that it supercharge the attention. Right? You saw all over the place. And I think both the agency’s gaining experience and having to do with evidence in real time, to understand what’s going on with …, as well as the attention it caught. All types of folks who in the past, we’re not necessarily interested, or part of the conversation of this generation, are now coming in asking, what is the evidence? How can I leverage, right, And how can you use nitrile, what happens with clinical trials to really show valuable product and better check how that? Because that’s, I think that’s where we’re headed. But I would caution that it’s gonna take time to get there, right? RCTs took so many years to mold into what we see today or whatever system on that same path in the train was heading in a direction.

Public health emergency really supercharge it, but there’s a long ways to go into we can get to mold into what we really need.

Kelly, before I turn it over to other speakers RCTs, can you please clarify what that means? Randomized controlled trials of the bread and butter of how normally these kinds of traditional controlled clinical trials, the way we typically run. As a clinician, I wanted to ask you sort of your thoughts about real-world evidence, and how this fits in this picture.

There’s been a lot of discussion about real-world evidence, especially even within the user fee agreements, particularly around accelerated approval, and to support regulatory decision making FDA.

I mean, there’s some promise, for sure, especially in terms of identifying safety signals, or novel drugs that we’ve seen. The FDA uses this extensively with the central initiative in particular.

And, you know, the idea of being able to use electronic health record data, patient registries of non traditional data that’s outside of the typical clinical trial space, to be able to rapidly generate evidence around safety in particular, has been very promising on the efficacy. So, it’s been a mixed picture, to be honest, and there’s, you know, some promise. But, again, as Kelly mentioned, we’re just not quite there yet.

And so, some of the caution that we have, especially around legislation, codifying the use of real-world evidence to support, or even potentially replace clinical trial evidence comes from some of the research that we’ve done. That shows. that we have some limitations in terms of these sorts of data Being able to do so. So, particularly for accelerated approval, there’s been proposals to use real-world evidence to replace clinical trials for post approval studies, to actually confirm clinical benefit. And our research has shown in looking at the past decades, approval, accelerated approval drugs, we actually try to replicate those clinical trials using real-world evidence.

We’re not actually able to do so, and, in fact, for a majority of clinical trials, or approved FDA treatments, we also find the same thing in our research, as well.

So there is definitely promise, only this past year, Did FDA actually have a supplemental indications, using real-world evidence for program?

Which is a drug used to treat for kidney transplant patients in particular, And they, actually, And we found that, that real-world evidence data could be used as a complement or supplement to clinical clinical trial data. Not just by itself.

So FDA is working very painstakingly put out like 4 or 5 guidances this past year alone around real-world evidence, to be able to get a better picture about how this can be shaped. But there’s still some kind of bread and butter, like barriers. Like the fact that electronic health records don’t speak to each other across different health systems.

Agency providers in different places, and oftentimes, you know, patient registries don’t include a control arm to be able to assess whether or not a drug that’s being looked at is being compared to a placebo or comparator.

And so I think there’s, you know, certain limitations to this. And so are worry with some of the congressional proposals that the horses out of the barn a little bit too fast, and that we need to have additional safeguards and studies that the FDA is already doing right now, to be able to know for sure that real-world evidence can be used effectively.

An enemy. I also know that this is a topic of great interest to you. So I wanted to know if you had any additional comments?

Sure, I think doctor Ahmed Chandra and covered a lot of my thoughts, but I think it’s important to know the ongoing efforts that FDA is taking, and So one I just want to highlight is one. That involves my division, as it’s called, the duplicate, really. Trying to figure out where there is the capacity for water evidence to fulfill some of the objectives. We’re seeing, what the challenges are that are remaining before moving too quickly on, relying on, from a regulatory standpoint, on evidence, that we still don’t know some of the weaknesses.

So, let me take a question from, from the audience. and add a little bit to. The question is, At what point well personalized drug prescribing by NDA testing be incorporated an FDA interaction? We’re sort of a broader question around, you know, personalized medicine, medicine for one. How do you see, well, I guess one question is when is this coming, and how does this fit in? All of what we have discussed in terms of, again, creating access, and also trying to generate evidence and for, for physicians and for payers.

Who would like to try that on?

Happy to jump in. I think it’s hard to say, for sure, when personalized medicine, now, we don’t really have a crystal ball to actually, you know, for certain, when, personally, medicine would come into play. There’s obviously a lot of ongoing efforts to actually make this happen, and even clinics being piloted around the country to actually look at what we call personalized medicine, but also precision medicine as well. And some of this also relates to looking at, you know, the fact that clinical trials oftentimes include specific subpopulations of patients.

They oftentimes include, like, younger, healthier patients usually tend to be more white patients, and the fact that we just need more representation in clinical trials. And so, a reaction to that has also been personalized medicine. The idea that we’re going to be able to prescribe medicines to patients, but also having an understanding that the patient that the medicines actually work, for, the patients, that they are indicated for.

And so, I think there’s a little bit of attention around that. In terms of investments, in terms of personalized medicine, but also efforts to do more whole scale representation, diversity efforts in clinical trials. And that’s some of the things are being invested in the user fee legislation.

You know, FDA has been trying to do this for a long time, A lot of encouragement of sponsors to actually increase representation of clinical trials in this space. But I think the big part that’s missing in this is enforcement. In the lack of enforcement that’s led to kind of continued issues around making sure that the drugs that are being approved, and whether indicated for actually reflect the clinical trial populations that are being tested in, there’s oftentimes a disk.

And so, you know, obviously, that kinda brings in the role of personalized medicine, but whether or not that’s gonna be operationalized. And then thinking about reimbursement and how payers play that role, that’s going to be very, very interesting to see in years to come. And I’m sure some of our other folks on this panel might have some comments on that piece as well.

I can just add this area that’s fine for global harmonization. Right, though, the way you develop a personalized medicine is challenging the manufacturers challenge to pull together with our current clinical trial system. But, if we’re looking at very specific subpopulations and having globally harmonized harmonized regulations, allow those products to actually be developed with the same expectations, from US. To Canada, to the UK, to Europe, and across the globe. And so, I think we see a lot of regulators having those conversations. And, using this as the next step, beyond …, of how do these conversations happen, how do you harmonize the regulations for personalized medicine?

Yeah, no, I’m realizing that the time is, basically, up for us. We could have a discussion. We’re probably at another hour. There are a lot of questions that we didn’t have a chance to get to, but what I wanted to do in the last couple of minutes, is to ask each one of you to give us closing remarks, what are the things that are sort of your takeaways for it? For the audience, What is it you want to leave them with and really like in NaN each. So, maybe I will start and let’s go in. The order in, which we actually that the presentation.

So, reshma, for sure. I think the main thing I want to just take away for the audience to take away is that there’s a balance that needs to be struck here, right, between timely access, you know, potentially promising treatments. And this is something I face as a clinician every day in. Seeing patients in. Which sometimes there’s, you know, limited access or are limited access, and are no options at all.

In terms of not having like FDA approved therapies and Alzheimer’s disease is kind of a quintessential example of this or I see a number of older adults that have Alzheimer’s disease, we don’t have it in place.

But the FDA approved drug those you know potentially promising and a number of us were waiting with baited breath to see if this might be something that we could use for our patients. And we were unfortunately like really disappointed that regulatory standards and approval centers were compromised with educators with agile home, ultimately in terms of compromising patient safety but also efficacy as well. I think the big thing, I want to just make sure that, you know, what the user fee agreement, that’s the tension that we’re seeing here, The need for balancing time we access, and not just E, but also making sure that safety and efficacy. or, again, quality of these products are being approved by the FDA. And ensure the FDA rules of regulator is being stated. and not necessarily catering to the industry sponsors that are providing the user fees in the first place.

So one of the things I’m thinking about as, as we consider reforms to FDA as a whole to the next phase programs, as the loop is coming up, keep in mind that many of the frameworks that sessions we have in place were created in a world of small molecules. If in a world of much more localized production and distribution of products, we now have far more complex products, more specific subpopulations trying to target trying to get more diversity in clinical trials. There’s just a very different types of products that are coming through the market, and different types of questions we’re trying to answer. So I’d say now’s a good time to consider reforms, but it’s worth harnessing, understanding what is the fit for purpose? Not just a fit for purpose. That existed decades ago. But the fit for today’s purpose? And how do we appropriately create that balance to incentivize the right products to market but to have a sustainable market place going forward?


Sure. I think I would just like to leave the audience with the notion that we are heading into an increasing situation in which there is going to be a little bit less stock placed, and FDA approval. And a little bit more of a gate keeping role being played by payers. And I think this is going to come as a jolt to the system. I think a lot of people are not necessarily going to be happy about this, but we need to make sure that there are rules in place that ensure that we’re not rationing. On the basis of cost alone. That we are really having the ability to promote access to quality products, and that’s going to take all stakeholders to come to the table.


First, and thanks so much for the opportunity. This has been a great discussion.

And have just say, just get a lot of credit for lines for health policy. These are discussions that need to be had, these, these, as we look at the approval process, it’s got to evolve, right?

We’re going to have these the better science we’re going to have, just different factors coming in. And so having these discussions around where to go, especially agree with the panelists around selling gene therapy, somebody’s challenges are going to be even more acute.

And so, we just need to make sure that we are having these discussions so that, yeah, access can be, you know, we can make sure patients get access to these because they are all of these SBA programs, they deal with serious and life-threatening diseases, and we need to make sure they can get access. So thanks for the opportunity. It’s been a great discussion. Thank you, Thank you, Clay. And thanks. Thanks to all of our great panelists for their insights on this until in this important topic. This is all the time we have for today. For the audience, please take time to complete the brief evaluation survey that you will receive immediately after the broadcast ends. And, please keep an eye on the Alliance website for details about future upcoming events. And, a recording of this webinar and additional materials will be available on the Alliance website. This concludes today’s webinar on FDA approval process: Andrea, …, Kelly, Amit, and Play, thank you so much for joining us today.