DarshanTalks Podcast

Narrator: This is the DarshanTalks Podcast. Regulatory guy, irregular podcast with host Darshan Kulkarni. You can find the show on Twitter @DarshanTalks or the show's website at darshantalks.com.

Darshan: Hey everyone. Welcome to another episode of DarshanTalks. We have a regular guest with us, Nirpal Virdee, and, Nirpal, as you guys have heard from his accent is from the UK and was going to talk to us a little bit about Brexit. We've had a couple of talks before, but Brexit is ever-changing and constantly evolving. And, Nirpal's going to talk to us a little bit about that and how it's going to impact the life sciences. So welcome, Nirpal. Tell us a little bit about yourself first.

Nirpal: Hey, Darshan. Always good to be back with you and going through some of these key topics. So it's been probably a bit too long, so I'm glad we were able to do this. So, yeah, I'm Nirpal. You've probably come across my podcast with Darshan before. I head up Transparency & Disclosure at Certara, and really specialize in the subject matter on our engagements with the law, guidelines, rules around the world, and sort of how we can align our services to best support sponsors. So I'm often talking about this and trying to make sure that we implement some of this guidance back to our sponsors as effectively as we can.

Darshan: So, Nirpal, you actually spoke at a conference yesterday and I have to imagine people... We're doing virtual conferences, but I imagine you get a lot of questions. What are the big questions around Brexit that you keep hearing?

Nirpal: Yeah, so very timely, actually. It was a very surreal sort of engagement just because I'm so used to having a chat with a larger crowd and really engaging with them. So it was a bit unusual to be trying to do this all virtually sitting at my desk and getting folks to give me some virtual questions. But there was a lot of interests with obviously what's happening with COVID-19 and how that translate to transparency, types of guidelines, and trying to get some of that data out. We're hearing, of course, that agencies feel that they do need to really push for more of this data to come out faster than it has done before.

So there's quite a lot of questions about Europe and it was a European audience. What's the EMA trying to do in terms of COVID-19, knowing that a lot of the transparency type of guidelines that they had in place have been on a hold that we all know due to Brexit, that we're going to be talking about. So, yeah, quite a lot of questions about that, and there was quite a bit of interest around MHRA and what might be happening in the UK. So we definitely covered a couple of pointers, maybe not in a whole lot of detail, but yeah, very interesting mix of questions, for sure.

Darshan: So let's sort of not pay the huge conference fees, and ask the questions anyways. How is the EMA dealing with Brexit and how has MHRA sort of dealt with the EMA? I know that's sort of the big 700-pound gorilla in the room, and that's a lot to chew on, but love to sort of hear your take on it.

Nirpal: Yeah. I mean, it's going to be a completely different type of relationship, right? Where UK has really been at the forefront of EMA, not only physically in terms of where its headquarters were, but obviously, the UK and its reputation and its skillset, were really one of the lead countries when it came to submission approval and evaluation and all those aspects. So it's a very different type of relationship. So MHRA, they've had to really come to terms quickly around how they would manage this process outside of EMA.

So there's been a lot of internal things going on. Some things that have actually been posted by the government, just on how progress has been made.

Narrator: This is the DarshanTalks Podcast. Regulatory guy, irregular Podcast, with host Darshan Kulkarni. You can find the show on Twitter @darshantalks or the show's website at darshantalks.com.

Darshan: Hey everyone. Welcome to another episode of DarshanTalks. We have Tia Lyles-Williams, who is an entrepreneur extraordinaire. And, I'm really excited to have her, because we're going to have some really interesting conversations.

We discussed a few different topics, and we started off with, what should we talk about... The rise of companies in the Philadelphia area, and the change in biotech.

We think that's a really interesting topic to talk about. But then we started talking a little bit about queer communities, and we started talking about the importance of representation. We started talking about diversity.

And Tia and I land up talking a little bit about what all of this means, and how do you get people to have the right conversations and to show what's possible. Tia was great, she was open to having these conversations. So Tia, before we launch in, tell us a little bit about yourself.

Tia: All right. So Tia Lyles-Williams, Founder and CEO of LucasPye BIO, as well as our sister company called HelaPlex. And then, I have an overarching financial holding company called Goffman Bogart. I say that all in one. So when you see that stuff in my LinkedIn profile, you don't think I started a whole bunch of companies. They're all related.

Born in Gary, Indiana raised in Houston, Texas for a majority of my life. By the time I did high school, we had moved to Atlanta, Georgia, specifically the suburb, Marietta. I graduated from Wheeler High School. And then, from there, it didn't take too long, I was on my way to Howard, right after I graduated, that following August. Did my four year degree in Biology at Howard University. At the same time, I had an internship with the Howard University Cancer Center.

I was always doing something. I also did some type of a Spring break. I did something where it was like a med... What do you call it?... doing the rounds with the medical students, so I got to solve surgeries, whole lot of surgeries.

And then also I had an internship at NIH and at Walter Reed Army Institute of Research, out in Silver Spring in the naval base, so I've been around a little bit.And then I took my first corporate job outside of a lab setting of those at Human Genome Sciences in Rockville, Maryland. That is now called GSK. I got sick, took a year off. When I got better...

When I took the year off, I moved to Atlanta to stay with my parents for a year. It was a year on the nose. I had been living out of my parents' house all those years. it was very difficult in my, what was it, at mid twenties, I think at like 24, 25 to be going to live with my parents.

A year on the nose. Once the doctor gave me the green light, I followed my friends to the LA area and I was out there for around seven to eight years. And I ended up working for Amgen, Baxter.

And Avid Bioservices. That was my first CDMO. And then from there, I took a job in New Hampshire for a year. We'll get to that topic, as we talk about diversity and laws of biotech and pharma. And then from there, I took my last job as an employee or contractor with Jazz Pharmaceuticals, prior to starting LucasPye BIO.

That's where we at nearly, I think it's 20 years this year, I've been in this game from benchtop to also recruiting patients for clinical trials, developing drug processes for the big manufacturing facilities and actually performing them and leading the team.

And then also being a gatekeeper on the other side, as a customer with Jazz Pharmaceuticals. To decide which CDMO we wanted to work with and why.

Narrator: This is the DarshanTalks Podcast. Regulatory guy, irregular podcast with host Darshan Kulkarni. You can find the show on Twitter @darshantalks or the show's website at darshantalks.com.

Darshan: Hey everyone. Welcome to another episode of Darshan Talks. We have one of our favorite guests. We have Kenny White, who has a really interesting, there at the back, one that in the right situation will talk back to you because there's a fun story behind it. We are going to be discussing insurance and reimbursement and Verily, and what all this means. So Kenny, you want to introduce yourself?

Ken: Sure. Kenneth White, I go by Kenny. I am the national managed care practice leader for Willis Towers Watson, and the director of the Payor Solutions Center of Excellence at Willis. And I have a long history of being a healthcare lawyer. I practiced law for almost 30 years in healthcare as a trial attorney before taking my job at Willis six years ago.

Darshan: Just want to specify because he's mentioned Willis, nothing we're saying represents what Willis' official position is. This is just Kenny's personal opinion.

Ken: Or Aon for that matter now that we're in the midst of all of that, so.

Darshan: Correct.

Ken: Although I understand that my email address will get shorter.

Darshan: I live for the days when my email address get shorter with my long name, it was always painful to fill out SAP.

Ken: Now. Well, [email protected] is a lot to say, [email protected] is a lot shorter.

Darshan: I'm with you.

Ken: We'll see how that...

Darshan: So Kenny, tell us a little bit about what happened with Verily and what does this mean? And is there any impact on healthcare?

Ken: Okay. So as many of the tech companies, some that are very much into insurance, Riccardo, InsureTech companies, the other ones it's Verily would probably be referred to as an InsureTech company because it's born of a tech company. So with, with Haven, when Chase and Amazon and Berkshire all got together and created Haven, everybody was sitting back going like, what is this going to be? Every time Jeff Bezos walks to a microphone, people listen because he's Jeff Bezos. So he came out with this idea and everybody just went like, Oh, this is going to be a big deal. So far, it hasn't been a big deal. They ran through several CEOs. They'd been through several CFOs, some innovation directors, et cetera, what it looks that's going to be as more of a way to seriously impact, the health and benefits being provided primarily by those three entities, which obviously is a lot of employees.

So anything that many MP employees are going to do as a thing together, will impact the rest of the industry. Verily on the other hand is a company that is being created to provide, what they call, stop loss. It's not really stop loss, it's provider excess loss and stop loss.

Darshan: What is stop loss? And what is provider access?

Ken: Okay. So stop loss, traditionally is an insurance product that allows self-funded health plans, to access a re-insurance market to cover outlier claims. So most claims fall within a range, of a dollar to a couple of 1000 dollars, in terms of what the actual payout is, not the actual bill charges. But you have significant cancers or blood disorders, or unfortunately what people we refer to, as bad babies in the legal world, where you had multiple millions of dollar claims. Those are claim outliers. That depending upon the size of your pool, if you have 500 employees in your plan, that's a huge hit.

If you have, $150,000 in your pool, it's still significant because you're probably going to have more of them or two or three of those.

Darshan Kulkarni: Hey everyone. Welcome to another talk about transparency. My name's Darshan Kulkarni, and I will be talking to you about some of the changes that we have in the context of transparency. If you want to hear more about what I do and what kind of topics that may come up and that I might be able to help you with, just go to darshantalks.com and you can hear more about what I get into.

Darshan Kulkarni: What you want to look at is, when you look at global transparency in the context of clinical trials, you really want to start considering the type of information that is being requested. While there are numerous global authorities really talking about global transparency, you're really seeing the impetus coming from three major authorities of this moment, which is the US, so the USFDA, there's the EMA, and there's Health Canada. Just in January of 2019, there was a headline that, in the US, only 62% of clinical trials are being reported, and that the UK parliament was clamping down at universities because they were not disclosing the clinical trial results. So obviously this was hugely problematic.

Darshan Kulkarni: The US obviously, as many of us know, really use something like clinicaltrials.gov to help look at clinical trial transparency. There are some exclusions. For example, phase one studies do not get included. It must relate to FDA regulated drugs and biologics. So for example, if you're doing a study for China that's never going to enter the US, you don't have to register that in clinicaltrials.gov, and then a controlled clinical investigations may, in certain cases, not be reported. Must be reported. Then there is medical devices and small feasibility studies are excluded. Prototype testing is excluded and FDA required pediatric post-market surveillance, however, is included. So to be included in clinicaltrials.gov, the trial must have one or more sites in the US, the trial's conducted under an FDA investigational new drug application or investigational device exemption, and the trial involves a drug, biological, or other other device product that is manufactured in the US or it's territories and is exported for research.

Darshan Kulkarni: So in general, for a applicable clinical trial to be subject to the results, the requirements must be submitted by the responsible party no later than 12 months after the primary completion date. There are specific rules for studies that were terminated. Then Commissioner Scott Gottlieb, then FDA Commissioner Scott Gottlieb, in January, 2018, basically said that the FDA is taking on transparency measures to look to support the innovation and scientific inquiry related to drugs. Now that has gotten a little sidelined in recent times, not only because of COVID, but because of the FDA's own perspectives on what transparency should look like. In 2018, Commissioner Gottlieb came out and said, "Today, we're launching a new pilot program to evaluate whether disclosing certain information included within CSRs, which is clinical study reports, following approval of an NDA improves public access to drug approval information. In this pilot, we will select up to nine recently approved NDAs, who sponsors volunteered to participate and post portions of clinical trial related summaries from pivotal trials that were submitted to the FDA by the drug sponsor on drugs at FDA."

Darshan Kulkarni: Since then no additional CSRs were posted and professionals, including Peter Doshi, Jennifer Miller, and Matthew Herder, came out on January 23rd, 2019, and said no additional CSRs were posted. So there was this disappointment in the community.

Darshan Kulkarni: Then you also have to look at the Civil Monetary Penalties Act. In October, 2018, the FDA put out a guidance basically saying that i...

Narrator: This is the DarshanTalks Podcast. Regulatory guy, irregular podcast, with host Darshan Kulkarni. You can find the show on Twitter @darshantalks or the show's website at darshantalks.com.

Darshan: So, I recently got my hands on the Oculus Quest. It was really difficult to get your hands on for several months and was really disappointing because as soon as I got it, I found out that they're looking at bringing in Oculus Quest 2 onto the market already. Having said all that. It's interesting to hear people talk and I've experienced virtual reality without wires. I'm really excited about the future. One of the key things ... I happened to be a bit of a traveler and one of the key things that you always notice is that, while photographs are great, they never quite communicate scale and they never quite let you engage with the actual subject of your photograph. One of the key components and key problems associated with that is that you have what's called the windowpane effect, which is you always feel like you're looking at something from inside a windowpane.

Darshan: So, it's always at an arm's length, if not further. VR seems to fix that problem. VR being virtual reality, there's also something called augmented reality, which is AR. And the idea is that if you're using VRAR you might be able to engage ... If it's AR you might be able to engage with some computer aided systems that lets you engage with technology in the real world. So for example, let's say you're a surgeon and you're about to start cutting into someone's blood vessels, the AR system, using something like a artificial intelligence and start naming which vein is which one, helping you decide which vein or artery to cut, so that you can actually get to the organs you need to. In the pharma industry obviously there are medical device advantages, for sure, but there are some also drug advantages. For example, you could use AR/VR for molecule modeling.

Darshan: You could use that for a heightened version of informed consent. And if you are involved in remote working, which is what a lot of companies are doing right now in the context of COVID, one of the big problems with remote working is that you don't get to engage with individuals like you. And therefore there's actually being a ... You're starting to see a taper in the improvements that people saw with remote working. AR and VR gives you some of those advantages back, because you get to engage with people right next to you. So, the question is what are the bioethical challenges associated with ARVR? So, one of the key components is that AR and VR the most common one, the most popular one right now is Oculus Quest. Oculus Quest is owned by Facebook, which has seen it more than its share of privacy issues pop up.

Darshan: So, let's analyze virtual reality and augmented reality using traditional bioethical principles. The first one being respect for persons. And again, in the context of transparency, you've got to make sure that people know that their information is being collected. They have a clear understanding of what data is being collected. Why is it being collected? And what are the implications of that? This is actually similar to what GDPR and CCPA also require. So, that makes it easier. The question is, are companies going to follow suit, or is it just a checkbox system that you sort of just click through because, no one's ever going to read them. There is also the idea of non-maleficence and beneficence, which is in the context of innovation. You're starting to be at the cutting edge and you're starting to develop cutting edge technology. That's going to benefit a lot of people.

Darshan: This provides the opportunity for true patient centricity because you get to engage with patients in a rem...

Narrator: This is the DarshanTalks Podcast, regulatory guy, irregular podcast, with host Darshan Kulkarni. You can find the show on Twitter at Darshan Talks or the show's website at Darshantalks.com.

Darshan: A really important discussion to be had is about the role of cannabis and drug development in the context of cannabis. As we all know, there is already a product that uses naturally occurring cannabis, or at least components of it, which is Epidiolex by GW pharma, by Greenwich pharma. However, the fact is that there are more and more companies that are interested in doing this, and there's always been this overarching problem about the FDA and the federal government not encouraging research in the cannabis area. To change that, companies have always accused the FDA of hiding the ball if you will. The FDA took a long overdue step of putting out a guidance on how to actually do research in the context of cannabis. They put out a guidance called cannabis and cannabis derived compounds, quality considerations for clinical research guidance for industry.

Darshan: The key portion of this is the idea of how they start by defining a drug. According to the FDA, a drug is any product that is intended to diagnose, cure, mitigate, prevent or treat a disease, or any product other than food intended to affect the structure and any function of the body. Now, the key reason this is interesting is because the FDA takes this position and therefore renders a lot of the state approved or state eligible cannabis... So the products that are available because each state says that as long as you meet these criteria, we're going to allow you to make drug-like claims. Suddenly those are rendered drugs under the definition of the federal food, drugs, and cosmetics act. And it's not suddenly, it's always been the case, but the FDA is sort of putting it down again.

Darshan: In 2018, there was the farm bill, which changed how cannabis is treated on the controlled substances act. So essentially what they came up with, and they said, that there's a new definition of hemp, which includes cannabis and derivatives or extracts of cannabis with no more than 0.3% by dry weight of the compound of Delta-9-THC. So the bill removed hemp from the definition of marijuana provided in section 102 of the controlled substances act, which means that hemp is no longer a controlled substance under federal law.

Darshan: So essentially now you've got to think about hemp and you've got to think about marijuana. Marijuana is still technically a regulated under the controlled substances act, but hemp has been pulled out from under it. And you qualify for hemp only if you have no more than 0.3% by dry weight of THC in it. The key component and the key question that companies have asked over and over and over again is, "Where do we get the cannabis?" For the most part sponsors, including sponsored investigators are required to meet all FDA requirements to conduct human clinical trials, regardless of the source of cannabis or any other botanical product under studying the trial.

Darshan: NIDA, which is a National Institute of Drug Abuse, drug supply program provided the only domestic federally legal source of cannabis for clinical research. So cannabis for this drug supply program was grown under contract by the University of Mississippi at the National Center for Natural Products, natural products research. But the 2018 farm bill changes that, essentially saying that under the 2018 farm bill, hemp may be produced as a source of cannabis and cannabis derived compounds for drug development if they do not contain Delta-9-THC at more than 0.3% by dry weight. And this gives sponsors and investigators new options that do not involve NIDA.

Narrator: This is the DarshanTalks Podcast. Regulatory guy, irregular podcast, with host Darshan Kulkarni. You can find the show on Twitter @darshantalks or the show's website at darshantalks.com.

Darshan: Hey, everyone. Welcome to another episode of DarshanTalks. We have a really special guest with us. We have Syed Salim and Syed is... Syed, why don't you actually introduce yourself?

Syed: Wonderful. Thanks Darshan. Thanks for having me. My name is Syed Saleem. I am a pharmacist. I hold a doctorate of pharmacy and an MBA. I have a pharmacist license active in 24 States, United States. I also have some of the certifications, Six Sigma, Project Management, pharmaceutical specialist and a few other.

I do have a vast background in the compounding industry and the regulatory and compliance. And also formulation's, including 503A, 503B. I've been in the company industry prior to the DQSA, that is the Quality Safety Act, which came in around 2013. So I do have a wide range experience touching into production side of manufacturing, retail, hospital. Yeah, all those.

Darshan: So a really simple question, cause I have to ask this because, like you know, I'm a pharmacist as well. But you said you have licenses in 24 States, is it?

Syed: That is correct.

Darshan: So how difficult is it to maintain that?

Syed: It is pretty tedious because every state has their own CEs to be... certain CEs. Like some States do require you having a pain management sees CEs some States require your sterile compounding, non-sterile compounding. Each of these States has their own requirements. And I have to tell you, I have a good spreadsheet and then I do have reminders and yeah. A few of those tools. Yes.

Darshan: Have you found that to be useful in the compounding world?

Syed: Sure it is, because... And again, the regulatory requirements does need a pharmacist to be licensed onsite to have these licenses in those particular States. So for that reason, a pharmacist needs to have the licenses in those States. If the pharmacy or the 503B outsourcing facility need to do business in those particular States.

Darshan: So, if that's true, do you lined up at... Tell me about the type of work you do Syed.

Syed: Sure. I'm a pharmacist in charge/director role at the 503B facility, which also has a 503A though. So we hold a 503B FDA registered facility and also a pharmacy. But majority, I think that most of the business is on the 503B sides. We comply with our 503B requirement, which is basically following all the CGMP, following all the CFRs.

So it is pretty strict and it is well beyond the 797 requirements. So we need to have... it's like a mini pharma manufacturing, wherein we have a quality department, which is a completely independent. With their quality control quality assurance, a quality unit, with a quality manager who looks after that. Then we have a regulatory compliance department and then we have a production operations. So it's very organized. It's not a typical pharmacy or compounding pharmacy, which used to be before, we are evolving towards manufacturing.

So this facility we are, we build it brand new. I know a lot 503Bs struggle to transition from the old compounding pharmacy, but this facility, we had to build the ground up. Right from the DQ, it's design qualifications. Having all the instruments validated. I mean, pretty much everything what we do here represents a pharma manufacturing in a mini scale.

Darshan: That's the real question, right? So everyone talks about how 503Bs are pharmacies, and you talk about how they're really many manufacturing companies, or mini manufacturers. What is the distinction as you see it? What are the big mistakes people make?

Narrator: This is the DarshanTalks Podcast. Before this week's podcast, US privacy data shield is your GDPR compliance plan ruined, Darshan will introduce this episode with a recap for the week of Friday, July 31st, 2020.

Darshan: This week has been a little bit of a clinical trial heavy week. We've seen notices from the FDA where they've put out a guidance on how they want companies to deal with cannabis and CBD products, and they put our guidance on specifically how the clinical research should be done. They had some interesting ideas about where do you actually procure the hemp, if you will. This has been interesting in light of the actual farm bill. This is going to be interesting, because that speaks not only to the clinical research that's being done, but the enforcement efforts the FDA will expect as well in the context of promotion. So if you are manufacturing a product that does not meet FDA standards, or if you're making a product that does not meet FDA standards, but you're making claims that are drug-like claims, the FDA might start prosecuting based on that.

So that should be an interesting thing to look out for. Additionally, there is some news out there about how pharma is starting to work more with telehealth. So keep an eye out for that. You'll see that in the newsletter if you subscribe to it. I also am going to do a separate podcast on a CBD and the FDA's position on that. So keep an eye out for that as well. However, talking about telehealth and pharma, we've done several interviews on this so we know that this is an area that is of particular interest to companies right now, so obviously in the area of clinical research, there are companies that are now switching over to doing full blown remote studies. You combine that with telehealth, that's the Holton combination that companies are looking out for. In fact, there was a article that came out saying that clinical trials are rebounding after the COVID-19 crash.

Darshan: The question is, are patients going to continue coming in and participating in these studies, when it's evident that there is still a continuing fear about infection because of COVID. The last piece of information that I thought was kind of interesting is this article that I've seen pop up every so often, but the idea that drug companies are influencing academic conferences. We did an interview with Kelly Willenberg where we talked about how important the conferences are for a lot of the companies that are selling to drug companies or to sites. But the question of do drug companies actually use these conferences to influence physicians is really important. On one hand, obviously associations and groups like ASCO and conferences, like ASCO are really important to spread information, but if the information has been contaminated, that's not good. However, when is something contaminated? Is it when there's just no study done and the pharma happens to actually sponsor the conference, or is it in the actual writing of the study itself? Stay tuned. We'll probably keep exploring this as new news keeps coming out.

Narrator: This is the DarshanTalks Podcast. Regulatory guy, irregular podcast, with host Darshan Kulkarni. You can find the show on Twitter @darshantalks or the show's website at darshantalks.com.

Darshan: So the recent holding, talking about the US/EU privacy data shield, and I want to talk about that in the context of what's been happening. So let's start from what is GDPR. GDPR is the General Data Protection Regulation. Comes out of the European Union. It covers an individual's rights to basic identity information, such as name, address, ID numbers, web data, such as location, IP address, cookie data, RFID tags, health and genetic data, biometric data, racial or ethnic data,