Stuart R. Gallant, MD, PhD In Danielle Ofri’s recent column in The New York Times “My Patients Used to Be Enthusiastic About the Covid Vaccine. What Changed?,” Dr. Ofri offers some strategies to discuss Covid-19 vaccination hesitance, including [1]: In this week’s post, PharmaTopa asks the question, what is known about the best strategies for…
Stuart R. Gallant, MD, PhD Before there was a pharmaceutical industry, humans looked to plants as source of medicines. Today’s post focuses on medicines derived from plants and how they are different and unique. Drug Discovery From Plants There are two chief methods of drug discovery from plants: However, the ways that chemicals from plants…
Stuart R. Gallant, MD, PhD CAVEAT: THIS POST INCLUDES PHOTOGRAPHS OF TISSUE INJURIES AND MAY CAUSE SOME READERS DISCOMFORT. An 81-year-old, retired accountant is on a walk with friends. He overestimates his agility crossing a rickety bridge over a stream and ends up waist deep in the murky water. Fortunately, he does not strike his…
Stuart R. Gallant, MD, PhD Humans have been smoking tobacco for more than 10,000 years, but e-cigarettes (“vapes”) have only existed for less than two decades [1]. In the US population, tobacco smoking peaked in the mid-1950s at 45% of adults. By 2021, smoking had dropped to 16% of the US population, a long-term decline…
Stuart R. Gallant, MD, PhD I was talking with one of my nieces recently. In her school, she and several of her friends have a project to build a small greenhouse to grow mushrooms. I am writing this post in the hopes it will be helpful to her, not just for her current science project,…
Stuart R. Gallant, MD, PhD Twenty to fifty percent of international travelers develop travelers’ diarrhea—sudden onset of loose stools while traveling. While some of these cases resolve quickly, others may have serious health effects, particularly if medical care is not near at hand. One of the challenges to travelers and to those leading international travel…
Stuart R. Gallant, MD, PhD Sooner or later, something goes wrong in our work lives. In pharmaceutical manufacturing, errors or “deviations” are common events, and there is a lot at stake. When I started working at Bayer AG, just after my graduation, there was an informal group called the “million-dollar club.” You joined the club…
Stuart R. Gallant, MD, PhD Consultation—offering your professional services to companies on a time-limited basis—can be a rewarding type of work. It is gratifying to be introduced to a project that is behind schedule and threatening a company’s future—and within a short period of time be able to put the “car back on the road.”…
Stuart R. Gallant, MD, PhD In today’s post, some important aspects of development and manufacture of combination products with pharmaceutical autoinjectors are considered. Pharmaceutical autoinjectors provide three key advantages over individual vial and syringe delivery of intramuscular and subcutaneous parenteral drugs: These advantages go a long way to explaining the size of the $60B autoinjector…
Stuart R. Gallant, MD, PhD In today’s post, we will look at subcutaneous suspensions as a way of meeting difficult drug delivery challenges. To decide whether a subcutaneous suspension might be appropriate for a small molecule drug product, three screening questions must be considered (see Venn diagram above): How Do Subcutaneous Suspensions Perform Pharmacokinetically? Before…
Stuart R. Gallant, MD, PhD The Washington Post just published an article by Andrew Van Dam, “How much money do doctors really make and why is it such a lot?” The author leads the story with the line, ”The average U.S. physician earns $350,000 a year.” He then lists the standard knocks on physician salaries: …
Stuart R. Gallant, MD, PhD In the last two decades, startup pharmaceutical companies have become increasingly frugal with investment capital. One of the ways to save a bunch of money is by picking the right location to establish a laboratory. Today’s post presents some of the options, along with issues to bear in mind when…
Stuart R. Gallant, MD, PhD People reach a peak bone mass and muscle mass in their early 20s. After that, any increase in weight typically means an increase in fat. Ideally, our weight would stabilize as we reach adulthood and remain fairly constant until we naturally started losing muscle and bone mass in our elderly…
Stuart R. Gallant, MD, PhD PharmaTopo recently posted on the topic of founding a pharmaceutical startup. Today’s post looks at pharmaceutical startups from the investor’s point of view. There are many ways to invest in the pharmaceutical sector (pharma focused mutual funds, venture capital funds, angel investments). This post looks at angel investing and friends…
Stuart R. Gallant, MD, PhD In the late 1950s, electronics scientists and engineers like Robert Noyce, Gordon Moore, and Eugene Kleiner invented the idea that technically minded people could do more than work for a corporation, they could own it (or at least a piece of it). They shook up the assumptions about how business…
Stuart R. Gallant, MD, PhD Steroid hormone replacement therapy (HRT) is a topic that has been in the scientific and popular press a lot recently. Your primary care physician has a wealth of information about the benefits and risks of HRT. Also, tucked between the cryotherapy spas, high-end golf cart dealers, and discount jewelry outlets…
Stuart R. Gallant, MD, PhD Steroid hormones are frequently in the news—sometimes in infamy, as in the case of sports doping, but also in many medical uses (for example, hormone blocking therapies for cancer and hormone replacement therapies for hormone deficiency). In the first part of this two-part post, we will look at the pharmacology…
Stuart R. Gallant, MD, PhD Our skin does so much for us. Skin protects us against infection and dehydration. Skin allows us to be in contact with the world via its many nerve endings. Skin allows us to grip objects securely by its many tiny ridges, but it also allows us to let things slide…
Stuart R. Gallant, MD, PhD Imagine that you have an infection, and you need a common antibiotic, but you cannot find a drugstore that is able to provide it. Or, imagine that your young son has been doing great in school, and his recent prescription for methylphenidate has been helping him concentrate, but his supply…
Stuart R. Gallant, MD, PhD Proteins and peptides are commonly delivered subcutaneously and by infusion; however, these approaches have disadvantages. Among the chief problems are: discomfort at the injection site, inconvenience of administration at a medical office or infusion center, and added expense of an autoinjector or other administration supplies. For protein drugs, the dream…
Stuart R. Gallant, MD, PhD The focus of today’s post is oral drug release—immediate, delayed, and extended. Many technologies exist for controlling drug release—the focus of this post is on the interaction of gastrointestinal anatomy and oral dosage forms to understand how drug release can be manipulated. Bioavailability Bioavailability is typically depicted as a concentration…
Stuart R. Gallant, MD, PhD The Convention on Pharmaceutical Ingredients (CPhI) was just held in Frankfurt. As the self-described “leading networking event for pharmaceutical industry,” the CPhI events are great places to meet and learn about contract manufacturing organizations (CMOs) [1]. Today’s post is about selecting and working with a contract manufacturer. To simplify the…
Stuart R. Gallant, MD, PhD In 1991, Helmut and Erika Simon, two German tourists hiking in the Alps near the Austrian/Italian border when they saw a body lodged in the snow and ice. Initially thought to be corpse of a modern-day mountaineer, the body turned out to be much older. “Ötzi,” as he became known,…
Stuart R. Gallant, MD, PhD Above is a photo from the 1947 launch of the M.V. St. Essylt at J.L. Thompson and Sons was a shipyard at Sunderland in the north of England. She had a gracefully raked funnel and first-class accommodations for 12 passengers in addition to her crew and cargo. Judging from the…
Stuart R. Gallant, MD, PhD I have a weakness for old Hollywood movies. The movie still that appears above this paragraph depicts John Carradine in the role of the undertaker in the 1976 film The Shootist. It’s a small role, but Carradine absolutely nails it as the scheming foil to John Wayne’s character, the gunslinger…
Stuart R. Gallant, MD, PhD When I think of patent law, I am reminded of a line from the play A Man for All Seasons. Discussing the thickets of English law, Sir Thomas More asks Will Roper rhetorically, “And when the last law was down, and the Devil turned round on you where would you…
Stuart R. Gallant, MD, PhD Back in April, PharmaTopo posted on lipid nanoparticle formulations for Covid-19 vaccines [1]. Because the Moderna bivalent vaccine recently arrived in clinics, I thought it would be nice to look at what makes the bivalent booster special. Covid 19 Infection Before discussing the vaccine booster, a quick review of Covid-19…
Stuart R. Gallant, MD, PhD In the first part of this post, we looked at urokinase. In the second part, we will look at tissue plasminogen activator (tPA)—urokinase’s more successful cousin. A Tale of Two Kinases—Second Chapter: Tissue Plasminogen Activator In 1979, Professor Désiré Collen of University of Leuven was the first person to isolate…
Stuart R. Gallant, MD, PhD This November will be the 35th anniversary of the approval of tissue plasminogen activator (tPA, alteplase) a leading treatment for heart attack, ischemic stroke, and severe pulmonary embolism—and the first licensed treatment to be produced in Chinese hamster ovary (CHO) cells. During all three of these events (heart attack, ischemic…
Stuart R. Gallant, MD, PhD I was intrigued by Amazon’s recent purchase of One Medical for $3.9B in cash. Amazon is implementing a strategy to move into healthcare which focuses on pharmacy and pharmacy benefit management (PBM). (Several months ago, PharmaTopo posted on PBMs [1].) Before looking at the details of Amazon’s strategy, let’s look…
Stuart R. Gallant, MD, PhD As pharmaceutical supply chains have become global, the risk management of drug supply has become increasingly complex. Recently, I was discussing selection of a drug product manufacturing site with a colleague. He paused in our conversation of the technical and financial issues to ask, “Exactly, how close is the facility…
Stuart R. Gallant, MD, PhD Within pharmaceutical development, there are two types of go-no-go decisions: 1) clinical and 2) financial. These decisions are linked together by the drug development plan. This post touches on both types of decisions but focusses particularly on the financial. Clinical Decision Making The drug development timeline is marked with milestones…
Stuart R. Gallant, MD, PhD I am sure many of you are so done with Covid 19 that you could not imagine wearing a mask without a government mandate. Hold that thought and listen. I have a friend—let’s call him Joe. Joe is in sales, and he recently attended an industry conference. He flew to…
Stuart R. Gallant, MD, PhD Having discussed the pathological processes of Alzheimer’s disease in the first part of this post, the current status of Alzheimer’s drug development is the subject of the second part. Licensed Treatments—Non-Course-Altering Ideally, the time to develop Alzheimer’s disease could be increased. Since it is rare to develop symptoms prior to…
Stuart R. Gallant, MD, PhD One of the most useful words in medicine is “multifactorial.” Commonly, in science and medicine, we struggle to find a single root cause or principle of each problem we study. However, humans are complex and frequently resist attempts to find simple explanations for their afflictions. Some diseases (for example, lysosomal…
Stuart R. Gallant, MD, PhD Eventually, all of us need to talk to a doctor or a nurse, maybe about a headache, flu symptoms, or something more severe. Ideally, we would like that to be a conversation in which our medical professional was fully present and focused on us—rather than glancing up from time to…
Stuart R. Gallant, MD, PhD In Pharmaceutical manufacturing, frequently process development uses designed plays—just like in American football. In football, the play caller looks at the situation (first down, short yardage, red zone, etc.) and picks from a small number of options. For instance, if there is less than a yard to go on a…
Stuart R. Gallant, MD, PhD Hopefully, you have received your Covid-19 vaccine. If you did, there’s a pretty good chance it was delivered in lipid nanoparticles. Both Moderna Spikevax and Pfizer–BioNTech Comirnaty are formulated in lipid nanoparticles. Today’s post looks at lipid nanoparticles formulations and what we know about them. In PharmaTopo’s post on Factor…
Stuart R. Gallant, MD, PhD The United States has a mixed public and private insurance system for health care. Payments for pharmaceuticals are provided through a complex interconnected payment system. I thought the topic of payment for pharmaceuticals would make a nice post. Health Care Payments in the 1960s Before we get into how the…
Stuart R. Gallant, MD, PhD In the first part of this two-part post, we looked at the biochemistry of clotting factor Factor VIII and the production of Factor VIII by plasma fractionation. We have now reached the late 1970’s, and the era of recombinant DNA technology. Our story continues… Recombinant Factor VIII Pharmaceutical companies had…
Stuart R. Gallant, MD, PhD Today’s post is a big story involving genetic engineering, pharmaceuticals, intellectual property, and economics. You will recall from the first installment of Pharmaceutical Design Focus that Genentech was founded in 1976 and expressed its first commercial protein (insulin) in E. coli in 1979. Genentech could have spent a few decades…
Stuart R. Gallant, MD, PhD This post is the first in an occasional PharmaTopoTM series called “Technology Focus.” Today, we look at supercritical fluid chromatography (SFC). The most important point in this post is that if you have a background in liquid chromatography, most of the ideas in this post should be fairly intuitive. In…
Stuart R. Gallant, MD, PhD In the second part of this two-part post, the topic of valuation will be discussed, followed by how some of these financial metrics affect and are affected by market strategy. G. Valuation Dividend Payout Percent (dividend/net income) is a traditional measure of value. In the past few decades, investors changed…
Stuart R. Gallant, MD, PhD This two-part post looks at pharmaceutical companies and how they are financially structured to survive in a competitive market, to deliver value to their investors, and to manufacture quality pharmaceuticals for the patients they serve. I look at companies which fall in the categories of mature, diversified pharmaceutical companies, generic…
Stuart R. Gallant, MD, PhD Okay, here’s the premise of today’s post: you have contracted with a company outside the US (maybe in Germany, China, or India) to manufacture your company’s active pharmaceutical ingredient (API), and now you need that API in the US to manufacture your company’s drug product (DP). After you manufacture the…
Stuart R. Gallant, MD, PhD Insulin is a subject on a lot of people’s minds—C&E News just came out with a cover story on insulin [1]. This post focuses on the manufacturing and marketing of insulin. It’s part of an occasional PharmaTopoTM series called “Pharmaceutical Design Focus.” Manufacturing Insulin 43 years ago, a team assembled…
Stuart R. Gallant, MD, PhD The first part of this two-post series addressed knowledge management and knowledge mapping. In this second part, the use of these tools will be discussed. The Knowledge Base In the first part, a knowledge map for CMC activities was provided: Here are some thoughts on the use of this type…
Stuart R. Gallant, MD, PhD Any successful drug development program generates a massive amount of information. Just the NDA can run to more than 100,000 pages [1]. And of course, what goes in front of the regulators represents a tiny fraction of the data generated within the development program. In this two-part post, the topic…
Stuart R. Gallant, MD, PhD In the first post of this series, raw materials risk analysis was discussed. In the second post of this series, raw materials testing, starting materials, and contact materials are discussed. Testing, Release, and Audits The starting point of release raw materials for GMP manufacturing is the manufacturer’s specification. This can…
Stuart R. Gallant, MD, PhD One of the first steps in a pharmaceutical development project is selection of chemicals. For the development team, it may be an almost unconscious decision, “What sodium chloride brand do we have in the lab right now? We are starting an experiment today.” Or, it may be a carefully thought…
Stuart R. Gallant, MD, PhD This is the second post in a two-part series on the value of medications. In this post, we bite the bullet and look at cost-effectiveness data in units of dollars per QALY, bearing in mind that there are some significant theoretical and practical problems of this type of analysis. An…
Stuart R. Gallant, MD, PhD This post is the first in a two-part series on the value medications. “The Value of Medications” is a bit of a misnomer. Medications don’t have one value (“The Value”). Medications have different values, depending on how they are evaluated. These values can be depicted as spheres, as in the…
Stuart R. Gallant, MD, PhD Some readers may not have had the opportunity to be deposed by the opposing counsel from a pharmaceutical company. Here is what that experience is like, and here is what you can do to protect yourself and your company. Think of this post as taking a lesson from Noah—build your…
Stuart R. Gallant, MD, PhD How A Drug Development Plan Originates Keller and Schnell suggest that there are five challenges to a pharmaceutical startup: 1) gathering clinical evidence, 2) transforming data and features into a value proposition, 3) ensuring market access and sufficient funding, 4) designing a profit-optimal pricing and contracting scheme, and 5) preparing…
Stuart R. Gallant, MD, PhD Non-clinical development has two chief goals: 1) to develop safety data enabling the entry of the medicine into human clinical trials and 2) to manufacture and release one or more lots of the medicine to supply the clinical trials. The data from these two activities are provided in regulatory filings…
Stuart R. Gallant, MD, PhD Licensors and Licensees As discussed in Part 1 of this three-part series, drug development and licensing has taken on the characteristics of a soccer match with full backs (universities and startup firms developing and patenting drug concepts) passing to midfielders (startups who undertake initial drug product development and early phase…
Stuart R. Gallant, MD, PhD In the last three decades, how pharmaceutical drug development occurs has changed dramatically. Prior to this change, a significant share of new drugs was developed by integrated pharmaceutical firms, companies like Pfizer and Johnson & Johnson in the United States and Bayer in Europe. Drug development occurred in a stage-gate…
Stuart R. Gallant, MD, PhD The Biden administration has announced that it plans to invest billions of dollars in Covid-19 vaccine manufacturing capacity [1]. What’s the likely effect of Covid-19 on pharmaceutical manufacturing? Parenteral Drug Manufacture: In 2019, before the pandemic, worldwide revenue from parenteral drugs (also known as sterile or injectable drugs) was $450…
Stuart R. Gallant, MD, PhD In Danielle Ofri’s recent column in The New York Times “My Patients Used to Be Enthusiastic About the Covid Vaccine. What Changed?,” Dr. Ofri offers some strategies to discuss Covid-19 vaccination hesitance, including [1]: In this week’s post, PharmaTopa asks the question, what is known about the best strategies for…
Stuart R. Gallant, MD, PhD Before there was a pharmaceutical industry, humans looked to plants as source of medicines. Today’s post focuses on medicines derived from plants and how they are different and unique. Drug Discovery From Plants There are two chief methods of drug discovery from plants: However, the ways that chemicals from plants…
Stuart R. Gallant, MD, PhD CAVEAT: THIS POST INCLUDES PHOTOGRAPHS OF TISSUE INJURIES AND MAY CAUSE SOME READERS DISCOMFORT. An 81-year-old, retired accountant is on a walk with friends. He overestimates his agility crossing a rickety bridge over a stream and ends up waist deep in the murky water. Fortunately, he does not strike his…
Stuart R. Gallant, MD, PhD Humans have been smoking tobacco for more than 10,000 years, but e-cigarettes (“vapes”) have only existed for less than two decades [1]. In the US population, tobacco smoking peaked in the mid-1950s at 45% of adults. By 2021, smoking had dropped to 16% of the US population, a long-term decline…
Stuart R. Gallant, MD, PhD I was talking with one of my nieces recently. In her school, she and several of her friends have a project to build a small greenhouse to grow mushrooms. I am writing this post in the hopes it will be helpful to her, not just for her current science project,…
Stuart R. Gallant, MD, PhD Twenty to fifty percent of international travelers develop travelers’ diarrhea—sudden onset of loose stools while traveling. While some of these cases resolve quickly, others may have serious health effects, particularly if medical care is not near at hand. One of the challenges to travelers and to those leading international travel…
Stuart R. Gallant, MD, PhD Sooner or later, something goes wrong in our work lives. In pharmaceutical manufacturing, errors or “deviations” are common events, and there is a lot at stake. When I started working at Bayer AG, just after my graduation, there was an informal group called the “million-dollar club.” You joined the club…
Stuart R. Gallant, MD, PhD Consultation—offering your professional services to companies on a time-limited basis—can be a rewarding type of work. It is gratifying to be introduced to a project that is behind schedule and threatening a company’s future—and within a short period of time be able to put the “car back on the road.”…
Stuart R. Gallant, MD, PhD In today’s post, some important aspects of development and manufacture of combination products with pharmaceutical autoinjectors are considered. Pharmaceutical autoinjectors provide three key advantages over individual vial and syringe delivery of intramuscular and subcutaneous parenteral drugs: These advantages go a long way to explaining the size of the $60B autoinjector…
Stuart R. Gallant, MD, PhD In today’s post, we will look at subcutaneous suspensions as a way of meeting difficult drug delivery challenges. To decide whether a subcutaneous suspension might be appropriate for a small molecule drug product, three screening questions must be considered (see Venn diagram above): How Do Subcutaneous Suspensions Perform Pharmacokinetically? Before…
Stuart R. Gallant, MD, PhD The Washington Post just published an article by Andrew Van Dam, “How much money do doctors really make and why is it such a lot?” The author leads the story with the line, ”The average U.S. physician earns $350,000 a year.” He then lists the standard knocks on physician salaries: …
Stuart R. Gallant, MD, PhD In the last two decades, startup pharmaceutical companies have become increasingly frugal with investment capital. One of the ways to save a bunch of money is by picking the right location to establish a laboratory. Today’s post presents some of the options, along with issues to bear in mind when…
Stuart R. Gallant, MD, PhD People reach a peak bone mass and muscle mass in their early 20s. After that, any increase in weight typically means an increase in fat. Ideally, our weight would stabilize as we reach adulthood and remain fairly constant until we naturally started losing muscle and bone mass in our elderly…
Stuart R. Gallant, MD, PhD PharmaTopo recently posted on the topic of founding a pharmaceutical startup. Today’s post looks at pharmaceutical startups from the investor’s point of view. There are many ways to invest in the pharmaceutical sector (pharma focused mutual funds, venture capital funds, angel investments). This post looks at angel investing and friends…
Stuart R. Gallant, MD, PhD In the late 1950s, electronics scientists and engineers like Robert Noyce, Gordon Moore, and Eugene Kleiner invented the idea that technically minded people could do more than work for a corporation, they could own it (or at least a piece of it). They shook up the assumptions about how business…
Stuart R. Gallant, MD, PhD Steroid hormone replacement therapy (HRT) is a topic that has been in the scientific and popular press a lot recently. Your primary care physician has a wealth of information about the benefits and risks of HRT. Also, tucked between the cryotherapy spas, high-end golf cart dealers, and discount jewelry outlets…
Stuart R. Gallant, MD, PhD Steroid hormones are frequently in the news—sometimes in infamy, as in the case of sports doping, but also in many medical uses (for example, hormone blocking therapies for cancer and hormone replacement therapies for hormone deficiency). In the first part of this two-part post, we will look at the pharmacology…
Stuart R. Gallant, MD, PhD Our skin does so much for us. Skin protects us against infection and dehydration. Skin allows us to be in contact with the world via its many nerve endings. Skin allows us to grip objects securely by its many tiny ridges, but it also allows us to let things slide…
Stuart R. Gallant, MD, PhD Imagine that you have an infection, and you need a common antibiotic, but you cannot find a drugstore that is able to provide it. Or, imagine that your young son has been doing great in school, and his recent prescription for methylphenidate has been helping him concentrate, but his supply…
Stuart R. Gallant, MD, PhD Proteins and peptides are commonly delivered subcutaneously and by infusion; however, these approaches have disadvantages. Among the chief problems are: discomfort at the injection site, inconvenience of administration at a medical office or infusion center, and added expense of an autoinjector or other administration supplies. For protein drugs, the dream…
Stuart R. Gallant, MD, PhD The focus of today’s post is oral drug release—immediate, delayed, and extended. Many technologies exist for controlling drug release—the focus of this post is on the interaction of gastrointestinal anatomy and oral dosage forms to understand how drug release can be manipulated. Bioavailability Bioavailability is typically depicted as a concentration…
Stuart R. Gallant, MD, PhD The Convention on Pharmaceutical Ingredients (CPhI) was just held in Frankfurt. As the self-described “leading networking event for pharmaceutical industry,” the CPhI events are great places to meet and learn about contract manufacturing organizations (CMOs) [1]. Today’s post is about selecting and working with a contract manufacturer. To simplify the…
Stuart R. Gallant, MD, PhD In 1991, Helmut and Erika Simon, two German tourists hiking in the Alps near the Austrian/Italian border when they saw a body lodged in the snow and ice. Initially thought to be corpse of a modern-day mountaineer, the body turned out to be much older. “Ötzi,” as he became known,…
Stuart R. Gallant, MD, PhD Above is a photo from the 1947 launch of the M.V. St. Essylt at J.L. Thompson and Sons was a shipyard at Sunderland in the north of England. She had a gracefully raked funnel and first-class accommodations for 12 passengers in addition to her crew and cargo. Judging from the…
Stuart R. Gallant, MD, PhD I have a weakness for old Hollywood movies. The movie still that appears above this paragraph depicts John Carradine in the role of the undertaker in the 1976 film The Shootist. It’s a small role, but Carradine absolutely nails it as the scheming foil to John Wayne’s character, the gunslinger…
Stuart R. Gallant, MD, PhD When I think of patent law, I am reminded of a line from the play A Man for All Seasons. Discussing the thickets of English law, Sir Thomas More asks Will Roper rhetorically, “And when the last law was down, and the Devil turned round on you where would you…
Stuart R. Gallant, MD, PhD Back in April, PharmaTopo posted on lipid nanoparticle formulations for Covid-19 vaccines [1]. Because the Moderna bivalent vaccine recently arrived in clinics, I thought it would be nice to look at what makes the bivalent booster special. Covid 19 Infection Before discussing the vaccine booster, a quick review of Covid-19…
Stuart R. Gallant, MD, PhD In the first part of this post, we looked at urokinase. In the second part, we will look at tissue plasminogen activator (tPA)—urokinase’s more successful cousin. A Tale of Two Kinases—Second Chapter: Tissue Plasminogen Activator In 1979, Professor Désiré Collen of University of Leuven was the first person to isolate…
Stuart R. Gallant, MD, PhD This November will be the 35th anniversary of the approval of tissue plasminogen activator (tPA, alteplase) a leading treatment for heart attack, ischemic stroke, and severe pulmonary embolism—and the first licensed treatment to be produced in Chinese hamster ovary (CHO) cells. During all three of these events (heart attack, ischemic…
Stuart R. Gallant, MD, PhD I was intrigued by Amazon’s recent purchase of One Medical for $3.9B in cash. Amazon is implementing a strategy to move into healthcare which focuses on pharmacy and pharmacy benefit management (PBM). (Several months ago, PharmaTopo posted on PBMs [1].) Before looking at the details of Amazon’s strategy, let’s look…
Stuart R. Gallant, MD, PhD As pharmaceutical supply chains have become global, the risk management of drug supply has become increasingly complex. Recently, I was discussing selection of a drug product manufacturing site with a colleague. He paused in our conversation of the technical and financial issues to ask, “Exactly, how close is the facility…
Stuart R. Gallant, MD, PhD Within pharmaceutical development, there are two types of go-no-go decisions: 1) clinical and 2) financial. These decisions are linked together by the drug development plan. This post touches on both types of decisions but focusses particularly on the financial. Clinical Decision Making The drug development timeline is marked with milestones…
Stuart R. Gallant, MD, PhD I am sure many of you are so done with Covid 19 that you could not imagine wearing a mask without a government mandate. Hold that thought and listen. I have a friend—let’s call him Joe. Joe is in sales, and he recently attended an industry conference. He flew to…
Stuart R. Gallant, MD, PhD Having discussed the pathological processes of Alzheimer’s disease in the first part of this post, the current status of Alzheimer’s drug development is the subject of the second part. Licensed Treatments—Non-Course-Altering Ideally, the time to develop Alzheimer’s disease could be increased. Since it is rare to develop symptoms prior to…
Stuart R. Gallant, MD, PhD One of the most useful words in medicine is “multifactorial.” Commonly, in science and medicine, we struggle to find a single root cause or principle of each problem we study. However, humans are complex and frequently resist attempts to find simple explanations for their afflictions. Some diseases (for example, lysosomal…
Stuart R. Gallant, MD, PhD Eventually, all of us need to talk to a doctor or a nurse, maybe about a headache, flu symptoms, or something more severe. Ideally, we would like that to be a conversation in which our medical professional was fully present and focused on us—rather than glancing up from time to…
Stuart R. Gallant, MD, PhD In Pharmaceutical manufacturing, frequently process development uses designed plays—just like in American football. In football, the play caller looks at the situation (first down, short yardage, red zone, etc.) and picks from a small number of options. For instance, if there is less than a yard to go on a…
Stuart R. Gallant, MD, PhD Hopefully, you have received your Covid-19 vaccine. If you did, there’s a pretty good chance it was delivered in lipid nanoparticles. Both Moderna Spikevax and Pfizer–BioNTech Comirnaty are formulated in lipid nanoparticles. Today’s post looks at lipid nanoparticles formulations and what we know about them. In PharmaTopo’s post on Factor…
Stuart R. Gallant, MD, PhD The United States has a mixed public and private insurance system for health care. Payments for pharmaceuticals are provided through a complex interconnected payment system. I thought the topic of payment for pharmaceuticals would make a nice post. Health Care Payments in the 1960s Before we get into how the…
Stuart R. Gallant, MD, PhD In the first part of this two-part post, we looked at the biochemistry of clotting factor Factor VIII and the production of Factor VIII by plasma fractionation. We have now reached the late 1970’s, and the era of recombinant DNA technology. Our story continues… Recombinant Factor VIII Pharmaceutical companies had…
Stuart R. Gallant, MD, PhD Today’s post is a big story involving genetic engineering, pharmaceuticals, intellectual property, and economics. You will recall from the first installment of Pharmaceutical Design Focus that Genentech was founded in 1976 and expressed its first commercial protein (insulin) in E. coli in 1979. Genentech could have spent a few decades…
Stuart R. Gallant, MD, PhD This post is the first in an occasional PharmaTopoTM series called “Technology Focus.” Today, we look at supercritical fluid chromatography (SFC). The most important point in this post is that if you have a background in liquid chromatography, most of the ideas in this post should be fairly intuitive. In…
Stuart R. Gallant, MD, PhD In the second part of this two-part post, the topic of valuation will be discussed, followed by how some of these financial metrics affect and are affected by market strategy. G. Valuation Dividend Payout Percent (dividend/net income) is a traditional measure of value. In the past few decades, investors changed…
Stuart R. Gallant, MD, PhD This two-part post looks at pharmaceutical companies and how they are financially structured to survive in a competitive market, to deliver value to their investors, and to manufacture quality pharmaceuticals for the patients they serve. I look at companies which fall in the categories of mature, diversified pharmaceutical companies, generic…
Stuart R. Gallant, MD, PhD Okay, here’s the premise of today’s post: you have contracted with a company outside the US (maybe in Germany, China, or India) to manufacture your company’s active pharmaceutical ingredient (API), and now you need that API in the US to manufacture your company’s drug product (DP). After you manufacture the…
Stuart R. Gallant, MD, PhD Insulin is a subject on a lot of people’s minds—C&E News just came out with a cover story on insulin [1]. This post focuses on the manufacturing and marketing of insulin. It’s part of an occasional PharmaTopoTM series called “Pharmaceutical Design Focus.” Manufacturing Insulin 43 years ago, a team assembled…
Stuart R. Gallant, MD, PhD The first part of this two-post series addressed knowledge management and knowledge mapping. In this second part, the use of these tools will be discussed. The Knowledge Base In the first part, a knowledge map for CMC activities was provided: Here are some thoughts on the use of this type…
Stuart R. Gallant, MD, PhD Any successful drug development program generates a massive amount of information. Just the NDA can run to more than 100,000 pages [1]. And of course, what goes in front of the regulators represents a tiny fraction of the data generated within the development program. In this two-part post, the topic…
Stuart R. Gallant, MD, PhD In the first post of this series, raw materials risk analysis was discussed. In the second post of this series, raw materials testing, starting materials, and contact materials are discussed. Testing, Release, and Audits The starting point of release raw materials for GMP manufacturing is the manufacturer’s specification. This can…
Stuart R. Gallant, MD, PhD One of the first steps in a pharmaceutical development project is selection of chemicals. For the development team, it may be an almost unconscious decision, “What sodium chloride brand do we have in the lab right now? We are starting an experiment today.” Or, it may be a carefully thought…
Stuart R. Gallant, MD, PhD This is the second post in a two-part series on the value of medications. In this post, we bite the bullet and look at cost-effectiveness data in units of dollars per QALY, bearing in mind that there are some significant theoretical and practical problems of this type of analysis. An…
Stuart R. Gallant, MD, PhD This post is the first in a two-part series on the value medications. “The Value of Medications” is a bit of a misnomer. Medications don’t have one value (“The Value”). Medications have different values, depending on how they are evaluated. These values can be depicted as spheres, as in the…
Stuart R. Gallant, MD, PhD Some readers may not have had the opportunity to be deposed by the opposing counsel from a pharmaceutical company. Here is what that experience is like, and here is what you can do to protect yourself and your company. Think of this post as taking a lesson from Noah—build your…
Stuart R. Gallant, MD, PhD How A Drug Development Plan Originates Keller and Schnell suggest that there are five challenges to a pharmaceutical startup: 1) gathering clinical evidence, 2) transforming data and features into a value proposition, 3) ensuring market access and sufficient funding, 4) designing a profit-optimal pricing and contracting scheme, and 5) preparing…
Stuart R. Gallant, MD, PhD Non-clinical development has two chief goals: 1) to develop safety data enabling the entry of the medicine into human clinical trials and 2) to manufacture and release one or more lots of the medicine to supply the clinical trials. The data from these two activities are provided in regulatory filings…
Stuart R. Gallant, MD, PhD Licensors and Licensees As discussed in Part 1 of this three-part series, drug development and licensing has taken on the characteristics of a soccer match with full backs (universities and startup firms developing and patenting drug concepts) passing to midfielders (startups who undertake initial drug product development and early phase…
Stuart R. Gallant, MD, PhD In the last three decades, how pharmaceutical drug development occurs has changed dramatically. Prior to this change, a significant share of new drugs was developed by integrated pharmaceutical firms, companies like Pfizer and Johnson & Johnson in the United States and Bayer in Europe. Drug development occurred in a stage-gate…
Stuart R. Gallant, MD, PhD The Biden administration has announced that it plans to invest billions of dollars in Covid-19 vaccine manufacturing capacity [1]. What’s the likely effect of Covid-19 on pharmaceutical manufacturing? Parenteral Drug Manufacture: In 2019, before the pandemic, worldwide revenue from parenteral drugs (also known as sterile or injectable drugs) was $450…