Did you know that seven in ten Americans is on at least one prescription? We live in a time where health consciousness is on the rise, and there seems to be a pill for everything. How do scientists get from disease to cure, and how are drugs formulated?
If you’ve ever wondered how drugs and pharmaceuticals are developed, here’s a detailed look at drug formulation and delivery systems from end to end!
Drug Formulation From Start to Finish
How are drugs made? It’s a complex question that usually begins with identifying a clinical problem. That health issue might be cancer, an allergic reaction, bone density issues, epilepsy: anything of clinical relevance. Sometimes different pharmaceutical companies specialize with creating treatments for specific health issues, while others may work more broadly.
Once the company decides what issue to look for, they’ll develop a lab (or several labs) all staffed with highly-educated scientists and technicians to study the target health concern. This is usually an expensive proposition, as the equipment to start a wet lab can easily run into the tens of millions of dollars, and depending on the nature of the issue they’re studying, the chemicals and everyday disposable materials needed to research can cost thousands of dollars per day, even before the salaries of the professionals doing the research.
Researching the Problem
Generally, research progresses in one of three ways: in vitro, in vivo, and ex vitro.
In Vivo Research
In vivo research happens when scientists and physicians study the clinical issue as it happens in people or animals. Most often, work is conducted on animals according to strict FDA guidelines, as there are strict government regulations about the kinds of research which can be done on people, and especially at the beginning stages medical research is often a black box, oriented towards studying the pathogen or condition before developing possible treatments.
But there’s another important reason in vivo research happens on animals first. Most people have a lot of genetic and microbiome diversity, which means that the application of medicines and treatments can result in a wide variety of efficacy outcomes. In the medical profession, most of the animals used for research are specifically bred by scientists to represent the least amount of genetic diversity possible, that way the study of the disease and treatments can progress with the least amount of confounding factors. It allows scientists to test a variety of possible treatments and select the most effective, minimizing outliers.
Many of these animals are also genetically engineered or selected to make them easy to study. For example, some types of fish are used primarily in the study of certain genetic diseases; while labs studying gastric cancer may need to use specific strains of gerbil, because the pathogens which cause stomach cancer in humans don’t cause cancer in many other animals.
In vivo research may study the course of pathogenesis, looking for early markers of a condition or disease. Or it may look for genetic or environmental clues about what causes the conditions. It can also be used as a means to safely harvest tissues for in vitro or ex vivo research,
In Vitro Research
In vitro research studies the condition (or the pathogen or genetic mutation which creates the condition) outside of the organism. This means that scientists may be working with tissue samples, or the inert pathogen. Often, chemistry, crystallography, genetics, statistics, and many other scientific disciplines are applied here.
For example, scientists may study harvested tissue to see if its chemical composition differs from healthy tissue, and then analyze those different chemicals to ascertain how they relate to pathogenesis. They may study the genetics of different strains of pathogen, and try to discover what genes within the pathogen indicate increased pathogenesis. Or they may study the chemical composition of the structural elements of the pathogen, to find out the mechanics of how it might behave in vivo.
But they might also engage in ‘dry’ work as well, using strictly computational analysis in the cases when there is already enough data about the pathogen, condition, or populations affected to run statistical analysis. They might find that a specific kind of diet worsens the condition, or that some segments of a population are more at risk than others, gaining more critical information to provide physicians and to guide research.
Ex Vitro Research
Ex vitro research is a bit of a combination between the two: generally, studying living pathogens outside of a host organism. This can be useful because you can study how a pathogen behaves, and get a detailed look at its life cycle, but results can often be confounded by the lack of a living environment.
Ex vitro research often combines elements of both other disciplines. For example, rather than using animal subjects, many scientists must carefully simulate the correct environment for the pathogen using cell line cultures or specially-designed media. But microscopy, genetics, chemistry, and many other disciplines are all brought into play as well, while scientists study what kinds of environmental conditions might reduce the risk of pathogenesis, analyze the secretions of the pathogen to find their chemical composition, and study what microbiome factors might help the body or other more helpful organisms out-compete the pathogen.
Drug Composition & Manufacture
The molecule, compound, or compound mixture eventually selected as a treatment or cure is often tested at the research stage, on small, non-human cases of the clinical problem. But sometimes getting enough of the drug to treat a human can pose a problem, especially if it’s a complex protein or other biological.
Often, scientists must find or design a way to harvest the compound. This may mean harvesting the compound from organisms which produce it naturally. For example, Premarin (an estrogen drug sometimes sold under the names Premphase, Premelle, or Prempac) uses an estrogen compound harvested from pregnant mare urine. In other cases, scientists might bio-engineer bacteria to secrete compounds, as they do with insulin.
This is because complex biologicals are extremely difficult (or, more often, simply impossible) to synthesize with existing technology.
The goal of the research will eventually be to find a drug mechanism which can deliver a molecule or compound into the body which alleviates symptoms or treats the condition. In general, any delivered drug is meant to affect either the patient or the pathogen, and different delivery systems affect how fast the drug is metabolized and the locality of its delivery.
The primary delivery systems of drugs include injection, swallowing a pill, inhalation, or even absorption through the skin. And while in most cases the delivery system is necessitated by the kind of molecule or compound that has been selected as a treatment, they might also be localized with dissolvable patches or injections.
Analyzing the Information
Most pharmaceutical companies will have labs which focus on each of the above kinds of research, and in some cases, a large lab may do all three. Often, the research aspect can take years- even decades- before enough information is gathered to indicate possible treatments. Any possible experiment must be duplicated, often multiple times, before its results can be trusted, and many potentially promising leads can turn up as dead ends. For example, a chemical compound which effectively treats a pathogen or disease might be faintly toxic to humans in the quantities needed to be an effective treatment.
But when a promising cure or treatment is found, often the pharmaceutical company has spent hundreds of millions of dollars. And at that point, new teams are brought in to analyze the results, triple-checking the work of the scientific teams. The financial costs of human trial treatments are calculated, as well as costs to produce the drug during its limited patent life, compared to likely sales.
Since human trials are necessary for FDA approval, but exhorbitantly costly to undertake, some pharmaceutical companies halt the process there, and continue looking for alternative drugs if other costs and risks are too great. And for certain rare conditions, it is virtually impossible to get enough people to trial the drug for it to reach FDA approval, and special measures must be considered.
If the company paying for the research thinks that the drug can recoup its costs and earn profit even after paying for expensive human trials, at this point they will move forward and the drug will be patented. Most drug patents will have only a few short years left after completing human trials, which is in great part why many brand-name drugs are so expensive: under the current FDA framework, pharmaceutical companies will spend hundreds of millions on research, dead ends, and trials before finding a worthy solution to a medical problem, and must then make the drug expensive enough to recoup all those costs and make profit before the patent expires and the drug may be made by competing companies without penalty.