We are at this moment in the middle of a crisis. Drug prices are simply out of control and superbugs are on the rise making drugs less effective. However, out of control prices are the first issue of concern right now because millions of people have to make do without the drugs they need because they cannot afford them. Enter generics, the low-cost option for those that cannot afford expensive brand name drugs. However, before we get super excited about generics we have to ask the question, do they work. On this episode of Lessons from the Screen, we are going to be looking primarily at that question, but we are also going to be digging into the process of how generics are made, approved, and brought to market.
The Generic Drug Industry, for many people, they are the answer to the problem of overpriced drugs. In the minds of many, they are the same as the brand drugs at a fraction of the price. The statements of many in the Food and Drug Administration, pharmacist, insurance companies, and generic manufacturing companies support this. However, all of them have a stake in making those statements.
The Food and Drug Administration would face major backlash and a loss of credibility if they stood in the way of a cheaper alternative to brand drugs. People would say they are working on the payroll of pharmaceutical companies, which is a problem they already face with the revolving door many top FDA officials go through as they transition from drug companies to the FDA and back again. The fact that most people do not really understand what the FDA actually does is not helping matters much in that regard. Nevertheless, as a regulatory agency backed by the US Government, maintaining public trust is paramount and the FDA will do anything to maintain that rapidly diminishing trust. Admitting that Generic drugs are not a cheaper copy of brand drugs after generics have been in use for so long would destroy the agencies credibility. This also explains why the agency has been so resistant to admitting any sort of mistakes on their end. The Ranbaxy situation is a prime example of this in which they finally after nearly a decade of investigating with clear evidence decided to hold the corporation criminally liable for its dangerous generic pharmaceuticals in 2013. The Wellbutrin XL recall in 2012 is another example of this as the FDA had been first notified about the problem with the generic drug more than 5 years before it took action.
Pharmacists also face a credibility crisis. For years, many of them have championed generic drugs as being the same as brands and they are regularly recognized as the experts on pills. While many pharmacists will change their minds and opinions when they notice a problem, many will not. There is currently a disagreement between pharmacists about the FDA regulations for generic drugs and how bioequivalence is measured. This is mostly a professional pride and ego deal however and nothing of the scope of the public pressure the FDA faces. However, one can only imagine the embarrassment the field would feel if generic drugs were not actually equivalent seeing as how they are viewed as the pill experts in society, a label that should probably be attached a little more to the chemist. They would however also face backlash from the activist community who would undoubtedly accuse them of being in bed with the pharmaceutical companies, a claim that they are already facing more and more although not to the extent of the FDA.
Insurance Companies are not worried about credibility. They are worried about profits and the truth is, the more people utilizing generics the less money insurance companies pay to pharmaceutical companies. This point is driven home by the fact that many insurance companies have created health plans that only provide generic drugs. The price points for these plans are often at a low enough level that you can reasonably surmise that they are targeting everyone that is not wealthy. Insurance companies absorb a chunk of the cost of brands into their operating expenses while also passing on a substantial portion to its customers in the form of increased premiums and co-pays. If the insurance company pays out less money to pharmaceutical companies by purchasing generics instead of brands then they keep more of their income as profit.
Finally, we have the generic manufacturing industry. They have a clear-cut and obvious stake in equalizing the thoughts people have when thinking about brands vs. generics. Since they make the generic drugs, the existence of the entire generic drug industry hinges on the public believing there is no difference between generics and brands.
On the other end, you have the brand name manufacturing companies. They are seemingly the only ones pushing back on this narrative on a large scale and they obviously are concerned about their own profits. The idea that brands and generics are essentially the same things hurts their industry just as much as it helps the generics. Seeing as how so many brand companies have raised the price of their drugs to such a disgusting and prohibitive level, it makes sense that they have become the bad guys in all of this. I am not going to suggest anything different; to be sure, they are definitely wrong for what they have been doing concerning pricing their drugs. However, they are not the only bad people here, and given the games being played on all sides of this issue, I’d say there are no good guys in both intention and activity to be seen.
When a drug is made, a company spends millions of dollars doing research on it. Money is spent figuring out what, where, how, and why of the particular disease in question. Over a period of many years to decades, a company and various independent researchers may study a disease before a breakthrough happens. When that breakthrough occurs, various trials are conducted to figure out the best way to turn this new knowledge into a working therapy starting with animals. This is significant because all medicines are toxic. If given in a dose that is too high all chemical medicine will kill you and so will most natural medicines. If given in a dose that is too low all medicines will be ineffective and will only serve to create new strands of bacteria that are resistant to the medicine being administered. If given on an elevated level that is not high enough to kill, you might still see some bad adverse effects. So animal trials are used to figure out dosages and fine-tune understanding of how medicine will interact with an illness in a living body. This could last for years to decades unless a condition of emergency is declared during which the restrictions on medications are severely reduced with the goal of bringing drugs to market faster. Before animal trials even begin companies patent all the chemicals and process that are used or could be used to make a drug so that they are the only ones that can make it.
Drugs made in the US at all stages of the production process are subject to unannounced, random and rigorous FDA inspections. Moreover, the guidelines for acceptable facilities, protocols, and employee behavior are tight. Complying with all of these regulations, performing all of these trials, doing all the necessary research, patenting the dozens of different chemical variations and manufacturing processes, and training employees all take a lot of money. These are the reasons brand name drugs give for why they charge so much, and while we should be fair and understanding about these expenses, they should not treat us as if we are stupid. We understand that it cost money to make the drugs, but we also understand that there is no reason why the top 10 Pharmaceutical CEOs make between 17.5 and 38 million dollars a year according to the Wall Street Journal. Number 25 on that list makes 7.25 million a year. Clearly, these companies have room to spare on their bottom lines.
Where it gets interesting is what happens as that patent nears expiration. Drug patents last for 20 years from the time of submission which is usually a years before the drug actually hits the market. Barring a number of maneuvers that would lengthen that patent, once it expires the drug becomes available to be genericided (that is not a word but it’s going to become one for this show).
In addition to having a patent on a drug, pharmaceutical companies are also given exclusivity by the FDA. Exclusivity means that only one company will get approval and permission to sell a drug in the US by the FDA effectively making it a monopoly and conferring additional protections to a drug. A company can have the patent and exclusivity or one or the other. Exclusivity protections are shorter in duration than patents, offer virtually no protection from things like reverse engineering, and process stealing. However, as soon as the patent expires, generic drug companies go to work. One thing to keep in mind here is that when a patent expires, companies are allowed to try to recreate a drug, but they are not given the recipe for making the drug. The data that is available shows them what is in the brand drug, not the quantities, temperatures, times, or pressures.
Leading up to the expiration of a patent, generic drug companies will be reverse engineering a brand drug in order to find out how it is put together. This process takes a lot of time and resources but not nearly as much as creating a new drug from scratch, which is what the lower prices are attributed to. After the patent has expired generic drug companies fill out forms and submit information to the FDA for approval to create a generic version of the brand drug whose patent has expired. If they are approved the generic company receives a brief period of exclusivity which is used to solidify profits for the company. Generic prices during this exclusive period or lowered but often times remain elevated somewhat for maximum profit.
In order for a generic to gain approval, it has to prove that it is pharmaceutically equivalent to the brand. Meaning it has to show that it has the same type of delivery (tablet or injection), time-release technology, and a similar effect in the body. The manufacturer has to show that they are capable of making the drug correctly and consistently. The active ingredient has to be the same and delivered to the proper place in the body. Inactive ingredients have to be safe. The drug has to be stable, meaning it will not break down over time. The container that the drug is shipped in and sold has to be appropriate. The label has to be the same as the brand name label, and all the relevant patents and exclusivities attached to the brand have to have expired.
All of that sounds great right, especially if everyone is being honest and transparent. Moreover, you would hope that is the case considering people's lives are on the line. Unfortunately, what a lot of researchers, regulators, and investigators are finding out is that not everyone is being honest and transparent. The book, Bottle of Lies by Katherine Eban, which I reviewed in the last show, is all about the dishonesty in the generic drug industry. She presents a strong argument built through 10 years of investigations that the generic drug industry is sacrificing health for profit and instead of learning how to operate in compliance with the FDA, they have learned how to appear as if they are. But what of the FDA’s regulation?
Well to start with, the corporations selling the drugs or the main ingredients present almost all of the data the FDA has on a given drug. The system is built on the honor system. The one check the FDA has to make sure that things are legit is its random and unannounced inspections. The problem with this is that the FDA only does these inspections in the USA. Foreign plants and corporations have announced visits usually planned out weeks or even months in advance and as has been the case in India and China, companies have taken that time to create elaborate systems to fool inspectors; this includes taking them to dummy sites that are not actually used to manufacture anything.
The equivalency data that the FDA relies on has on some occasions been shown to be the brand data resubmitted as the generic. Although those instances might be rare, there is a range of acceptability in generic therapeutic effects that seems to swing wildly depending on who you talk to. Some pharmacist and researchers say that a generic drug has to have a therapeutic effect between 80% and 125% of the brand, which is a wild 45% area of acceptability. This is wild because drugs are toxic and only provide medicinal effects in a limited range, as mentioned before, too much will kill you, too little won’t treat the issue and will cause resistant bacteria to form. However, others say that the range is only 10% once you perform the complex math necessary for the data checks. While 10% is definitely better than 45%, it is not the same. If someone is, 5% taller than someone else is you would not say that the two were the same height. Therefore, if a drug is 5% weaker than another drug you should not say they are the same drug. The FDA does not make its bioequivalence data available from what I could see, but given the fact that modern experts are still arguing about what they mean, I doubt me looking at them would help.
Time release is also an issue as we saw with Wellbutrin XL. Generic drugs do not always release their drugs in the same manner as brands concerning time. This could be do to the fact that generics don’t have to have the same release mechanism or the same excipients which are the non-active ingredients. While the non-active ingredients have to be safe, we cannot ignore the effect that they can have on the way the active ingredient may work in a given situation.
Doctors overseas have been compensating for lower strength generics by prescribing what would otherwise be considered insane amounts of drugs. Here in America, a growing list of concerns is being tabulated as people see negative side effects when they shift from brands to generics. Companies like Ranbaxy have been found guilty of felony crimes involving manufacturing drugs and distribution. In addition, as the brands push their drug prices higher, the demand for generics grows louder making regulators and well-meaning whistleblowers appear to be bad people. However, the fact is, there is a level of concern that is healthy when it comes to all medication. If we accept the idea that you get what you pay for or the idea that corporations are driven by greed and profit, then we should be looking extra closely at corporations that are willing to produce expensive drugs for very cheap. The drugs they produce are not the same as the brands, in some cases, its close enough. But brand or Generic, we should take care to thoroughly research the toxic substances that are being used to treat us. FDA inspections are public knowledge, and if a drug or its active ingredient was made out of the country at a plant that has not been inspected in a number of years, India or China should be especially concerning given the history of generic manufacturers in those parts of the world. The website to search inspections will be linked below. If you are interested in my personal takeaways about this situation, tune into the podcast.
is a lover of learning and analyzer of anything that can be analyzed, even if it probably shouldn't be.