(10q) Generic drugs - and the cost to develop the real stuff

This is an older text (from around 2013-2014) that I didn't publish earlier, among other reasons because my internet was down and afterwards the moment was gone, hence some links to older articles. But now it seems to be another moment to publish the updated article as part of my miniseries about the pharmaceutical sector to show it is much more than "only for the money" although I acknowledge there are excesses. As a reminder: 

- The first article was about the obligations pharmaceutical companies have to continue to monitor the safety of their products after commercialisation and if needed companies must update the product information, a cost for the companies. 

- The second article described how the product information of codeine-containing products had major updates long after it was first used because new data became available as a result of its use in clinical practice and because it can interfere with new drugs. 

- This third article describes the process from the design of new drugs and the research on its efficacy and safety before the commercialisation of these drugs but also repeats briefly what happens when it is on the markets. This is a timely procedure, certainly in the past when our knowledge about our body and the action of drugs on our body was still limited and thus medicines were developed and even discovered based upon their effect on reducing symptoms and/or their ability to heal illnesses. As this information continues to grow, today scientists can develop drugs more directed towards a certain goal.

A few years ago, the pharmaceutical company Novartis lost a court case in India that was celebrated by many people and organisations (see Novartis India case). In short, Novartis developed a new product that is quite similar to a previous version while it tried to stop the commercialisation of a generic product on the Indian market but failed; people celebrated this court decision because they say the ruling is good for poor countries. As a result, a much cheaper product can be used to threat chronic myeloid leukaemia and other cancers ($175 for generic product instead of $2600 a month for Novartis' product) although Novartis claimed their new product is superior; but that is useless when you can't afford the expensive drug. 

Also in Belgium there was a case that a very expensive drug is needed to treat a boy with a rare kidney disease and the difficulties it caused. This was not the last case and many more followed so both governments and private companies need to intervene while health insurance funds question whether very expensive treatments should be repaid, certainly when they don't heal - these cases contribute to the current distrust towards the pharmaceutical sector. And no, it is not that only recently companies became interested to invest in very rare diseases but their first attention was for common diseases as that benefits more people while it takes time to research diseases, certainly when they are rare and underlying mechanisms are not yet understood. 

Further, the price of generics that are already lower than that of the original product (originator) decreased further as doctors and pharmacists are encouraged to provide patients with the cheapest generic products. Still, when more manufacturers produce generic products and thus more competition, prices may drop further until a bottom price is reached whereby companies in low-pay countries may be able to reduce costs sufficiently more to out-compete companies in richer countries while fewer of the original product will be sold in case they remain more expensive so the reference product may disappear from the market. In addition, when markets are small such as for very rare diseases, it may become unprofitable for companies to invest in new products when other manufacturers may produce cheaper generics. Thus, I think a new system that benefits those who develop drugs and generics may be needed so investments in new medicines and techniques can continue while they can be marketed at sufficiently low prices so they are affordable for patients and still be profitable for companies.

Of course, from the inventor's perspective, it is unacceptable that the difference in price between a generic and original product is too big. But, there is a reason for this price difference because companies will naturally sell a similar product but developed at much lower costs than the original at a lower price, certainly when there is competition. Pharmaceutical companies argue that the original drugs are so expensive because the companies need to generate income for the development of newer drugs or they can no longer develop them; however, many people do not accept this. Still, as a comparison, most people accept that movie and pop stars and related industries earn millions and people are prepared to spend money on them but pharmaceutical companies are not allowed to make profits, even when they employ hundred of thousands of people worldwide to develop ever better products to improve our lives. Indeed, sometimes companies exaggerate their prices and thus it is good there is competition and government control, but we have to understand these companies need money so they are able to continue their research. 

In this article I will describe why developing drugs is expensive for the company and why generic products are in general much cheaper. I will also reason for another method than used today to generate money for the companies that develop drugs while it may allow that other companies can also sell the treatment. A new method of generating income for companies and universities may be needed now new types of treatments become common practice.

Comparison with the art world: music industry as an example

> Music industry

In the music industry (but this can be expanded to the movie and even sports industry), one or a few people write a song, now maybe on a computer but the cheaper paper is still possible; later the music can be performed before an audience and needs to be recorded before it can be sold. Thus, one needs paper and pen or a computer, some music instruments although these can now be simulated on a computer and a recording studio. Also good salespersons are needed to promote the music in the hope more people buy, although musicians may promote their music themselves if they allow more time to be discovered by the masses (certainly the internet is a good tool for self-promotion and so are live-performances) while during this period more songs can be written. When artists tour, they may need to employ musicians and dancers and stage directors, so employees need to be paid. They may need to rent a stage although they can also be invited to perform at a festival and receive payment for this. And yes, we should not forget that societies invests in culture so lesser known artists who have potential are given chances to be heard and seen.

When people like the music, the musicians start selling to whoever wants to buy the music and thus they start to earn money while when people don't like the music or the artist, people will not buy and thus artists will earn little if anything. This means that, when artists become better known, not only will they sell more records but in addition they can demand higher prices for CDs and concerts that many people are willing to pay, even when it sometimes concerns hundreds of euros for tickets, travel costs and housing. In addition, the music will be played in the media and clubs that earn artists money, even without performing.

If artists are bad housekeepers, than their manager will earn most; still, in general musicians will receive royalties via the copyright on their music, giving the creator and/or performers of an original work exclusive rights for a limited time, although this can last decades after the artists' dead during which their family receive the royalties (often destroying families as they quarrel over who has the rights); an example is the writer George Orwell who died 70 years ago and finally his work is out of copyright, although... . Because of copyrights by which we recognise the intellectual property of the creator, no-one is allowed to use the songs or words except when the musician/family agree and then they will receive royalties from the artists who made newer versions. In case a (young) musician may produce something similar, it is possible this person has to pay copyright to the original artist. Finally, today on social media when people post e.g. the opening dance at a wedding, the sound can be blocked because of possible copyright infringement instead of considering it as free advertisement - I accept it cannot be used for free by someone who wants to earn money by using music to improve a commercial.

Thus, for relatively little investment, artists (whether musicians, movie and theater stars, writers, painters and sculptors, ...) and athletes can earn lots of money if successful; becoming millionaires and even multimillionaires. And I acknowledge, production houses employ many people as long as the house can make money. Of course, many people who try will say it is not that easy, but maybe they should question themselves why they are not very successful. Maybe they are not very good or too uncompromising or just too compromising? Change may help their career while they shouldn't forget that many people who try to start a business remain small or go bankrupt while working for someone else is also not always easy, the reason why many try to start their own business or hope for their retirement.

> The making of medicines

Compare the above with the development of drugs by pharmaceutical companies. Many people are involved such as chemists who design and make molecules and determine their characteristics while other scientists, assistants and doctors (within the companies or at universities and hospitals) test the molecules on cells, animals and finally humans before the molecules can be approved as medicines by government medicine agencies and be marketed by the company. But even after the medicines is commercialised, potential problems are reported that can result in changes in the product information and in the worse case can result in the withdrawal of the medicine from the markets as discussed before. This shows that over a period of many years, molecules can be refused during many steps because they have either no effect or have too many side effects and thus those refused molecules will not result in any profit for the developing companies, only in loses. 

To be able to do the research, (expensive) specialist equipment is used for e.g. chromatography, microscopy, PCR, ... to collect data but also to fabricate the drugs that are successful and this according very strict regulation to guarantee safe products are developed. This shows lots of money are needed before one molecule out of many molecules can be sold as a medicine and even afterwards companies need to invest in more safety measures if needed, including developing better drugs. Still, due to the large numbers of molecules developed over the past decades and our growing understanding of how our bodies function, it is now possible for pharmaceutical companies to screen their database with molecules to find those that may be a solution for an illness that we now understand because of research over decades.

    Development of original medicine (drug), also called originator or reference product

Chemistry

Let's have a closer look at the different steps during the development of a medicine. The first step involves chemistry in the search for new molecules that can potentially become the active substance in a medicine. Chemists develop new molecules using chemical reactions or extract molecules from animals and plants or increasingly use molecular biology to produce the desired molecules. They can do this randomly or with a specific disease in mind whereby they use as a model a molecule in our body that has a certain actions and make modifications in the hope this mimics or stops the actions of the natural molecule in our body. 

Further, the chemists determine the characteristics of the newly developed molecule such as its stability and solubility but also techniques to upgrade the production of the new chemical in case it is successful and can be used as a new drug. This upgrading of production from the initial few milligrams produced in a laboratory to many thousands of kilos is not as straightforward as people think and is important to determine the price of the drug: does this require a few or many steps; is purification easy or difficult, ...? 

Finally, as active substances are mostly used in very little amounts in medicines such as 500 mg (that is only half a gram!!!), chemists also need to investigate whether the active molecule can be mixed with certain excipients (which are defined by EMA as any constituents of a medicinal product, other than the active substance and the packaging material) that are best inert, i.e. they should have no to very little action on their own in patients while the excipients cannot react with the active molecule although may increase the molecule's stability. Different molecules can be used but certain excipients are known to have negative effects for certain users (an example are sugars such as lactose that should be avoided by patients with known lactose intolerance); these excipients with known effect are listed in an annex with information that needs to be present in the product information of the scientific and public leaflets; this list is also regularly updated when new data becomes known. This shows it is good when many manufacturers produce medicines with the same active substance but different excipients so something is available for everyone.

Preclinical studies

After the molecule is synthesised, preclinical (or nonclinical) studies are done. During these studies, a lot of data are collected that are useful before test in humans can be done. The first studies collect data mainly from experiments done on cell cultures or organs but outside a living creature (in vitro tests, see Figure 1), partly because this lowers the costs and allows experiments in more controlled environment to receive faster answers to certain questions, but also to reduce the need to use animals. Later when molecules look promising, they will be tested in living plants and animals, so-called in vivo tests. 

An example of preclinical tests are products that are intended for use in eyes. These products can be tested in vitro on the eyes of slaughtered animals to check quickly whether the product damages the cornea and makes it opaque so the molecule cannot be used in human eyes. Still, these tests cannot yet replace all animal testing to avoid the risk that when no effect is observed on the eyes of dead animals, the molecule may still damage the eyes of living humans. But, scientists search for reliable alternatives to replace animal testing and they will be found.

Another example from my years in research was to study the effects of molecules on the stomach of pigs that were slaughtered at an abattoir and compare the results with the effects of the same molecules on human stomachs that were removed because of cancer. This would answer the question whether pig stomachs can be used as a model to study the effects of drugs on the human stomach. Thus, these were nonclinical studies as the research was done on stomachs outside the body.

Thus, first, molecules are screened for their activity (do they have any effect?) and toxicity (do they harm?) and initially this can be done on cell cultures. During this step, many molecules fail because they have no effect or they are toxic (e.g. cells die) while promising molecules will be tested in more details involving both in vitro and in vivo testing to answer following questions:

• How does the molecule act (e.g. it binds on what kind of receptors and/or activates which signaling pathway such as G-proteins) and does it have unwanted effects on other parts of the body (= pharmacodynamics or PD)? Thus, PD tries to answer the question how a molecule influences our body.
• What does the body do with the molecule such as speed of absorption by, distribution over and elimination from the body as well as how (fast) does bodies change the molecule such as the metabolism of codeine into morphine (= pharmacokinetics or PK)? Thus, PK tries to answer the question what does a body do with a molecule.
• Is the molecule harmful, immediately or after longer use such as weeks or even years? What is the maximum dose that can be used before the molecule causes harm or even kills; this harmful dose should preferably be far above the therapeutic dose when the molecule has its positive effect (= toxicity testing)? Thus, this tries to answer the question what is likely a safe but also effective dose when used in humans?

Although many questions can be answered using cell cultures and organs, animals are also needed to collect data about effects of the drug on different organs (e.g. a molecule may cure liver problems but may cause kidney problems), whether it may cause cancer and birth defects and whether it is excreted via the milk so it may harm nursing babies. It can also determine the dose when animals become ill and the molecule kills and this should be much higher than the therapeutic dose; this may differ from the results in cell cultures when the drug is toxic for a certain organ.

Indeed, animal studies are done before the product can be given to humans although companies limit their use if possible because they are expensive as animals need food and good housing conditions as required by laws. Further, animal studies result in more variable results than in vitro tests due to stress levels and fat that differ between individual animals, similar as in humans, factors that can influence the effect of the drugs. Therefore, laws force companies to test molecules in living animals to simulate real-life situation to maximise that drugs are safe when tests start on humans .

Figure 1: Examples of in vitro tests with a short incomplete explanation.
(A) BHK (Baby Hamster Kidney) cell line, the upper picture shows how we see them with the naked eye while for the lower picture a fluorescence microscope shows those cells that express a Green Fluorescent Protein (GFP).
(B) Dorsal Root Ganglia (DRG) are shown whereby the drawing shows the position of these ganglia in our body, a thickening just outside the spinal cord that is a collection of many sensory nerve cell bodies and each have one incoming and one outgoing nerve cell fibre. Below the drawing, thin individual nerve cell fibers can be seen coming out the end of a nerve that is attached with the DRG. Next the drawing, individual nerve cell bodies (bolls) that are normally within the DRG with their attached nerve cell fibers can be seen. The * indicates the presence of a fibroblast. Cells are green as they expressed GFP while red shows nerve cells and their fibers. Yellow are nerve cells that are both green and red.
(C) This shows the result of DNA that has been cut by enzymes and run on a gel to visualise the result. Also specific markers are run to know the approximate length of the DNA.

Once a molecule is potentially successful, technical procedures are developed to make the medicine in larger quantities (see also higher under "Chemistry"). Indeed, if for instance the molecule for injection can only be dissolved in a toxic solution, than a good molecule is useless when the solvent may kill. Therefore, even during the testing of molecules, chemists already look into problems that may prevent the use of the molecule as a medicine.

Finally, the molecule needs to be approved and registered as an Investigational New Drug (IND) by a government regulatory medicine agency before it can be used to test in humans.


Clinical studies
Indeed, before a drug can be sold, it needs to be tested in humans during in vivo clinical trials. Before these tests can start, they need to be approved by regulatory medicine agencies (such as Belgium's FAMHP) and Ethics Committees. First the safety is investigated in a small group of healthy volunteers during Phase 1 studies before the efficacy is tested during Phase 2 studies on a larger group of selected patients. If the results are encouraging, than the medicine can be studied on a group of thousands of patients during Phase 3 studies during which it is also compared with other already used treatments to test whether it is at least as efficient and safe as the other product (see also Table 1 to see the different development steps of a molecule before it becomes a medicine). 

These clinical studies are very expensive and time consuming as the test persons, often volunteers, receive a contribution for their time and potential risk while also doctors and nurses who perform the tests and scientists who analyse the data are paid. And yes, also insurance companies need to be paid so volunteers can receive compensations in case something goes wrong. During these so-called double-blinded studies, volunteers are divided in a control and test group whereby both the volunteers and doctors and nurses don't know who receive the test or control product and what should be expected to avoid placebo effects interfere with the results.

Table 1: The development and investigation of drugs or medicines, from the moment the molecule has to be invented and made until the medicine is sold on the markets; after commercialisation, pharmaceutical companies continue to investigate their drugs safety such as side-effects and interference with other drugs and updating the product information if needed.

At the end of the above described processes that take on average 7-8 years, a new medicine can come on the markets. During these processes, many molecules will be considered unsafe or not effective or cannot be produced in a safe way and thus only a small number of molecules will make it to the end. In addition, also packaging materials need to be designed (see Figure 2) that are safe and don't interact with the medicines. Also the storage conditions need to be checked before the drug can be mass produced to be sold. 

The final steps are control medicine agencies such as the European Medicine Agency (EMA) and national agencies that will finally decide whether a drug can be approved and thus sold or not. Even when scientists at pharmaceutical companies are convinced their drug is safe, medicine agencies may ask questions and even refuse the new medicine. During the registration, medicine agencies set limitations such as whether medicines can be sold over the counter or need to be prescribed by doctors and specialists for certain illnesses, limiting the number of people who can buy the drugs and thus limiting the income for the company. 

Figure 2: A few examples of medicines that can be different kinds of tablets packed in containers or blisters. Other medicines are liquids such as noise spray in a dark bottle to protect from light while we also know solutions for injection that can be in bottles, plastic bags and syringes.
Apart from medicines, also medical devices are important such as tape to prevent that wounds become infected with pathogens.

In addition and as described in my two previous articles of series 10, even after the authorisation (= post-marketing) and throughout the life-cycle of the drug, more data concerning the medicines their safety, benefits and optimal use (such as intake together with other medicines) are collected by companies during post-marketing Phase 4 studies or via spontaneous reporting of side effects by doctors and patients or via scientific publications. This is the followup of drug safety or pharmacovigilance and any concerns need to be reported to medicine agencies in order that (very rare) side-effects that were not seen during phase 3 studies or interactions with other medicines will be investigated. These are extra costs for the companies, including the update of the product information, and potentially the authorisation can be removed and the product taken from the market. In addition, any changes to the production process, such as a change in the excipients and upscaling of the production needs to be reported with medicine control agencies.

During the procedure, companies ask a patent when they register the new product that will last about 20 years during which period only the company that developed the drug can sell it. But, the 20 year period starts the moment the molecule is licensed, and thus after the clinical trials and approval of the drug, mostly only between 8 and 12 years are left for the company to sell the medicine with exclusivity. The total costs for pharmaceutical companies to develop a drug can be many tens and even hundreds of millions of euros (remember, thousands of people are directly involved in the development and commercialisation who need to be paid (see Table 2) while also volunteers, investors and insurance companies cost money) and there are further costs for as long as the medicine will be on the market. Thus, during a relatively short patent period, the company needs to recuperate the development costs and make profits to repay any debts and investors while monitor the safety of the product and invest in the development of new drugs; we should not forget to remain also competitive. After the patent period, other companies are allowed to sell generic drugs that have the same active substance as the medicine that was originally protected by a patent, resulting in more competition and thus a reduced price and income for the inventor.

Table 2: Listing of the 13 largest pharmaceutical companies according the above-mentioned sources. The companies are not listed according revenue but according the numbers of people they employed in 2020. When these 1,071,345 people earn only €35,000, the combined cost is nearly €37.5 billion.
In addition, these companies work together with universities, hospitals and other companies, pay volunteers in clinical studies, continue to investigate the safety of commercialised products and report changes in the production process while investors want a dividend.

The above shows it takes many years of hard work for companies before a medicine is developed and can be sold to a limited number of people. Thus, one can imagine that, in order to allow a return of the investment for companies because the development of drugs is very expensive, either the market is large so drug prices can be low such as for painkillers paracetamol and ibuprofen (although not too cheap to prevent abuse), or prices are high, certainly when illnesses are very rare and few products can be sold. 

And I didn't mention yet the many independent scientists, paid by government grants but also by pharmaceutical companies, who publish fundamental research (for instance about the kind of receptors and downstream signaling pathways that can be found in an organ), information that companies can use for the development of more specific drugs with fewer side-effects. Indeed, fundamental research is something that can also be done at universities and hospitals to increase the prestige of those institutions. Therefore, many companies work together with universities and pay (part of) the research that is done in return for knowledge while society invests in fundamental research at universities but also in the industry. Indeed, society and pharmaceutical industries interact with each other.

COVID-19 vaccines

Although I mention it takes many years to develop and test the efficacy and safety of medicines and vaccines, within less than one year after the start of the coronavirus pandemic, vaccines are developed and already administered to people and thus it is understandable that people are uneasy to be vaccinated. How is this rapid development possible and acceptable? 

First, there is the urgency as it concerns a pandemic that kills people around the world so a shortening of the clinical trial periods were accepted although, because of our good healthcare system, fewer people are dying than would have died in the past. Further, pharmaceutical companies have experience with vaccines while current technologies allow rapid production of new vaccines although mRNA COVID-19 vaccines are used for the first time. And yes, the long-term effects of the vaccines are still unknown. These are reasons why many people feel unsure as they think. Therefore, I think first people who want to be vaccinated should receive the vaccine so when people see it causes no harm more people will be willing to be vaccinated. 

    Generic drugs

After the above mentioned 20-years period, the patent expires and other companies are allowed to sell generic drugs, or generics. A generics is defined as a drug product that must contain the same active ingredient(s) and is comparable in dosage form, strength, route of administration, quality, performance and intended use as the reference drug. 

A generic drug also needs approval by regulatory medicine agencies before it can be marketed whereby companies have to prove their drug is comparable with the original drug according to above-mentioned criteria in green. Still, one can understand that proving something is similar as the original product is less expensive than first developing the drug before proving it works and is safe. As a result, once similar generics are approved that can be sold cheaper due to lower development costs, the price of the original product often lowers to survive competition so the company gets less return as patients, pharmacists and doctors can chose the cheapest product. The use of generics is even stimulated by governments to lower healthcare costs, certainly after a financial or healthcare crisis as the original drug is more expensive. This isn't such a problem when many people buy and lower prices still generates sufficient return but may create a problem for the company that invested in the development of a drug to treat an illness that is very rare and other companies sell a cheaper similar product - see Novartis India case in introduction.

Still, often patients prefer the (more expensive) original drug instead of the cheaper generic product because they believe the original drug works better or because they don't like to change something that has proven to work. And although this is considered a placebo effect whereby patients think a more expensive or original or familiar product works better, it is accepted that placebo effects are important whereby the effects of a drug may be stronger when people believe a drug is better. Further, one different excipient may cause a different response by a patient. 

    Summary of the above two chapters

Table 3: Comparison of the music industry for which many people accept to spend lots of money and worship very rich artists versus pharmaceutical companies that spend fortunes to develop medicines and vaccines and keep them safe by updating the product information but are told their life-saving products are too expensive.

The above shows that patents and copyrights are important tools to generate income for the developer, whether companies or artists, that allow them an income but also the ability to develop more products, buy equipment and create work for other people.

But, I think there is a problem when people are willing to spend lots of their own money on products such as music and films and sometimes spend hundreds of euros on festivals that benefit a relatively small group of people although indirectly other persons; still, it result in some of the best paid people in any business (i.e. musicians and actors), a business that is not really life-saving although important for people their well-being. Because many of those people don't accept that an industry that develops many useful and often life-saving products (such as treatments against cancer and vaccines to prevent illnesses), also demands a good income (i.e. profits). Instead, they condemn those companies for selling their products too expensive while these companies together create directly millions of jobs worldwide and indirectly by sponsoring research at universities but also because pharmacists, doctors and nurses sell their products to heal people. 

And yes, these companies also repay investors whose money made it possible to develop products. It is often the same: do good and people want it for free. That doesn't mean all is well in this sector because, like everywhere in society, it all became too much about making even more profits than last year or companies are punished by investors without a soul, those who are often united in hedge funds. 

Excesses do exist

Still, many useful products are sold at reasonable prices although then pharmaceutical companies are blamed they want to sell too easily medicines to make profits. But, I accept that certain products are very, too expensive as the examples in my introduction show, often because certain illnesses are very rare and complicated so the development of treatments took even more time and thus was more expensive while these prices anger people because it prevents that everyone has equal chances. Therefore, societies need to continue their financial support to develop products but demand in return that the price of finished products can be lower. And politicians and control agencies should also act against some extreme excesses such as Martin Shkreli, a former hedge fund manager whose company bought the rights to sell an antiparasitic drug and raised the price by a factor 56 - indeed, when (former) hedge funds managers are involved, be sure profits must be made, whatever the cost for society and whatever the damage to the reputation of the pharmaceutical sector and its employees of whom many are proud to find cures.

Still, not only pharmaceutical companies are guilty of excesses, also an unequal society whereby the very rich but also those with additional healthcare insurance drive prices upwards as there will be always someone who is able to pay the bill of medicines but also of doctors and specialists. Unless, indeed, prices rise above affordability and they become unfundable for anyone except the richest persons of whom many don't need those very expensive products as they concern very rare diseases that affects other people who can't afford them. But, when insurance companies may decide that costs become unacceptable and a platform has been reached, than the pharmaceutical companies but also hospitals will have to accept prices need to lower. Still, many years of development by many people need to earn the investment back or few will risks future investments in treatments of rare illnesses when other companies benefit most. 

Therefore, to keep healthcare products affordable for society while profitable for companies, I think that patents should last longer although in such a way that both inventors and other companies can sell at the lowest possible price that benefit society while all companies earn money; indeed, looking to a long-term return as we were used in the past with money that ordinary people invest and no longer that of hedge funds who can manipulate the shares as they wish and whereby people lose trust in the pharmaceutical companies as they think the companies are pressured to sell without adequate safety checks.

In conclusion, to make it clear after you read the above, I am not against artists who are successful and earn lots of money when their work brings joy to many as well as employment although I think some can charge less. But, I tried to place them against the context of the pharmaceutical industry and hope people will understand why sometimes drugs and more general treatment of illnesses can be very expensive. However, I agree that companies should not abuse their position or the mood of the public may turn against them, the reason for today's rise in anti-pharmaceutical company movements while this anger can even spill over to control agencies.

I also think we should rethink how to finance the whole system as it becomes too expensive for governments and the public but even for pharmaceutical companies to maintain an ever expanding inventory of which some products are sold in only small quantities while other products are still under development and a cost.

Whomever notice errors in my writing can leave a comment so I can improve the text. However, take into account that I tried to write it for a general public and, although long, it is not yet detailed enough to understand the whole picture.