Ron Najafi explains how nitrosamines form in drugs from secondary amines and nitrosating agents, and traces the regulatory history from the late 1970s through the 2018 resurgence. He covers Emory Pharma's analytical work on Valsartan, Losartan, and ranitidine, including the NDMA findings that led to Zantac's FDA withdrawal.
Chapters
Welcome to Emory Pharma speaker series. We have a very special guest here today, our very own CEO of Emory Pharma, Dr. Ron Najafi. He's a serial entrepreneur. He's founded many other companies like cplab Safety, which is a laboratory safety product manufacturer, Novavay Pharmaceuticals, where he took that company public, and now Emory Pharma. For those of you who don't know, he's the passionate director behind our YouTube channel, our speaker series, and many of the videos that go on our Emory Pharma website today. He has a very interesting presentation on nitrosamines and their role in pharmaceutical drug development. He's a chemist, entrepreneur, inventor, my personal mentor and someone I admire a lot. He also actually happens to be my father. So please join us in welcoming him.
Thank you, Anna. So today I want to tell you a little bit about nitrosamines and the role they play in pharmaceutical development. And really there's been a lot of anxiety and questions around nitrosamine. And this has been going on since the late 1970s and then it died down in the 80s and 90s and now it's picked up again. So I want to kind of show you a little bit of a chemistry. So don't get scared. This is really high school chemistry. It is really. We're showing an amine here, a nitrosonium ion here, very powerful electrophile reacting with an amine, in this case a secondary amine. So you form a nitrosamine, nitrosamine. Or you call some nomenclature, you can say N nitrosamine. And this here is your amine, here is a nitroso. So that's how the terminology in nomenclature works. So nitroso, nitrosonium ion. And NO plus is a nitrosating agent and it's also called nitronium ion. And it's often produced, not always, but often produced by the reaction of sodium nitrite and HCl. Having said that, you know, obviously since 2018, there's been a huge again, uproar of nitrosamine scare around literature. All you have to do is Google it and you'll see FDA's expectation from the industry is pharmaceutical industry has to be responsible for understanding potential of forming nitrosamine. They need to understand the impurities that are being formed around nitrosamine. They need to know how to manufacture a product. They need to expect potential problem, nitrosamine formation and so forth and so on. So these are, and European medical authority is very similar to this. You can look at that look that up as an expectation. So what is Emery Pharma's role? Since 2018, we've been dealing with nitrosamine, initially from the Angiotensin II receptors, Valsartan Losartan, various blood pressure medication. And in fact, when this came up, my mother was taking Valsartan Losartan and so it was like, it was really personal to me. Want to know what's going on? We were contacted by a number of people, wanted to know what the situation was. So we got involved in doing some nitrosamine analysis using gas chromatography, which is really the go to instrument for detection of these highly volatile nitrosamines. And of course we got involved with Zantac and that's been detailed at length on our website and in the literature and everything. We've also filed a petition with the FDA where we recognize that ranitidine, which is also known as Zantac, if subjected to heat or moisture, can fall into a degradation pathway, which is not very well understood, but we know it produces ndma. And so Emery Pharma was one of the very first companies that recognized that. And on January 2nd, we filed a petition explaining the NDMA formation. And as a result of that, within 90 days, FDA decided to officially withdraw the product off the market. So we know a lot about ndma and since then we've actually done a lot of investigation. Some of our team members that I want to acknowledge, Dr. Rakesh Jain, Dr. Neil Bose, Dr. Ryan Chu, they have all been involved in nitrosamine analysis and investigation. So in many ways, you know, this investigation for us is personal. We want to make sure. I know people were taking Zantac for many years. I know a lot of people taking Valsartan. So we want to have safe drugs. So how do we ensure safety of a drug? You know, so to ensure safety of a drug, it's just not, oh, let's synthesize the drug. Compound A could go to B, to go to C, various things. And then here is a final product. We put it in the pharmacy shelf. It's more complicated than that. And one really has to do it right. And to be able to properly assess pharmaceutical safety, you need to have control on a lot of different things. So your supply chain needs to be controlled. Your supply chain are your components you're using for your drug, your solvents, your. Are you using recycled solvent? If so, do you have any control around impurities that could be within your recycled solvent? Are you, what kind of packaging are you using?
