The reason that a new paradigm of drug development is needed is due to the huge pressures on the industry. Some of the most important ones are industry’s ability to develop drugs is constantly under threat by the Food and Drug Administration’s (FDA) increasing standards, both technical and non-technical. These standards occasionally increase to the degree that they become unrealistic in several respects:

Furthermore, the FDA‘s political reactions sometimes trump their internal scientific standards (e.g., Plan B’s delays in being switched to over-the-counter status). This results in the unwillingness by most division directors (or office directors) to overrule reviewers (or division directors) whose judgment is overly conservative or outside the thinking of the medical mainstream on a particular issue.

Intellectual property protection is vital for new inventions, and yet is under attack from those (particularly in underdeveloped
countries) who view patents as a developed country’s method to prevent their country from exercising free choice about which products it wishes to pirate. Protecting intellectual property requires continued vigilance by industry and governments and a strong proactive program to ensure its health, which is critical to ensure that pharmaceutical companies can protect the rights to their inventions and can remain in business. Without patents, there would be almost no new drugs invented.

The assumption that the current blockbuster mentality (paradigm) of drug development within large and most medium pharmaceutical companies can continue indefinitely is just that, an assumption. An objective assessment of the limitations of this assumption would recognize that if another development paradigm is available then it should be seriously considered.

Another element is whether a global-based free market economy without the price controls currently in place in many countries will ever come about. The international trend in price controls is on the contrary, toward greater and greater controls on prices. Given that the prices of many new drugs exceed the averages of those previously developed by orders of magnitude, it appears necessary for industry to seek other ways to protect its future ability to develop and market drugs that may not be reimbursed to the price levels they wish to set. The greatest threat to the industry in this regard is the issue of whether price controls will be initiated in the United States, and if so, in what ways. While the industry has a great deal of power and influence at the national legislative level in the United States the public discontent about drug prices has been gradually escalating. While one aspect of this concerns re-importation of drugs from Canada, it is not a big step for the public and legislators to seek direct controls on prices of new drugs in the United States. However, price controls in the United States would have a chilling effect on the amount of money companies would likely spend on research essentially killing the goose that laid the golden egg.

It is becoming more and more challenging to maintain a positive biomedical research environment both within a company and within the overall industry because of how the industry is perceived. The industry has joined the tobacco and oil industries as the most disliked by the public. There are ever-increasing attacks directed against pharmaceutical research in the press, legislatures, and public forums. This attitude even takes violent forms, targeting our companies through animal rights groups and groups against cloning, use of stem cells, genetically modified excipients or foods, tissue usage, or use of fetal cells, and many other similar groups.

Lastly, there are the ethical issues and values that must be respected as the society seeks to deal with the many perspectives on all the above issues. The public is demanding to be involved in the decision-making process of the FDA and, in response, the agency has been going out of its way to accommodate and solicit public input on these and many other issues. All of the above factors suggest that the industry needs to be aware of, and ready to adopt, any new paradigms of drug development which may be in the industry’s interest to adopt.

Companies have been forced by the economics of drug discovery, development, and marketing to focus their efforts on bringing to market only those drugs that have large economic returns. These pressures are growing stronger on companies, and one can easily observe rapidly escalating hurdle rates (i.e., minimal expected sales of a drug required to put a compound into development, or sometimes to keep it in development) over the past several decades. For the largest companies, the minimum sales numbers to be achieved in the third year after marketing a new drug often range from $250 to $500 million per year to make its development feasible. For midsized companies, the minimum estimated third-year sales are approximately $75 million, and for smaller companies, the minimum sales numbers for a new product are less, often in the range of $5 to $15 million in the third year.

In their discovery and development activities, most companies are competing in the same therapeutic area, and often in the same disease. Discovery efforts aimed at finding new drugs involve only about 500 targets, which is a small number when it must serve the entire pharmaceutical industry and its continuous need to produce novel and medically valuable treatments. More than 200 of these targets are enzymes. Other targets include ion channels, cell nucleus receptors, hormones, cell growth factors, DNA, and cell membrane receptors. Everyone can appreciate how important it is when a scientist in academia or elsewhere describes a new receptor or protein with biological applications that serves as a new target. The research-based industry would wither away and possibly perish if the flow of new targets stopped.