The near-term future (i.e., over the next one to two years) is not discussed in this chapter. The midterm future (i.e., from two to 12 or so years, which is the time necessary to develop drugs that have already been discovered) may be assessed with some assurances, and several aspects of this period are discussed. The more distant long-term future cannot be visualized and predicted with as much clarity, but this is the major period described in this chapter. No conclusions will be reached about what distant future environments will be like (e.g., in the year 2020 and beyond). A number of trends that will influence the distant future world of drug discovery and development are already under way and will be discussed.

Two general types of answers are usually given to this question, revolutionary and evolutionary. The type of future forecast that any particular scientist, clinician, or marketer favors undoubtedly says more about their own personality and beliefs than about the likelihood of one of these scenarios being closer to the truth. The revolutionary view is most often held by optimistic upbeat managers and the evolutionary view by conservative and more pragmatic and skeptical managers. As an aside, the author believes the future will be closer to the evolutionary answer.

Numerous individuals and groups predicted a new revolution in drug discovery and treatment of many diseases in the 1980s (Wells 1983; Faust 1984a; Faust 1984b; Taylor and Voivodas 1987; Unger 1987), and at least an equal number of groups and scientists are currently predicting a revolution in the future treatment of disease. Current predictions are generally based on advances in genomics and proteomics as well as new biologicals, whereas the predictions in the 1980s were based primarily on biotechnology derived products…. A representative quote of the revolutionary style is taken from Unger (1987): “Sometime in the early part of the next century [i.e., the 21st century], it is generally felt that we will be relatively free of disease and that the new drug development research will focus more on cures and on the correction of deficiencies … Drugs will be ‘engineered’ rather than ‘discovered,’ and therefore the process will be more efficient … It seems likely that virtually any receptor or enzyme will be able to be characterized (both functionally and structurally) by the year 2000.”

The temptation to predict widespread changes in the future is based on a few assumptions:

The problem with the first assumption is that great discoveries do not occur according to a time schedule. Just because one can usually know with reasonable certainty that the next generation of an electronic device or computer hardware or software is possible to design and build, it does not mean that truly novel drugs are going to be found at a predetermined rate. This lack of predictability, however, means that changes and discoveries may occur either faster or slower than anticipated. The ability to extrapolate from past successes (and failures) in drug discovery to major long-term future discoveries is obviously unknown. Almost any scenario could be vigorously defended with many facts and figures. Nonetheless, such extrapolations are actually made using personal judgment and guesswork.

The problem about the potential of recombinant and other methods of biotechnology to supply new drugs (second assumption) is that, at present, this potential cannot yet be evaluated accurately. For one thing, these techniques are primarily applied to protein drugs, which must be used parenterally (primarily intravenously). Many biologics of proteins and polypeptides will only be therapeutically useful until smaller molecules are discovered that are clinically equivalent and may be taken orally. Alternatively, scientists will discover ways of getting proteins absorbed orally, a possibility that is currently under intense investigation.

The third assumption is one that holds great promise for a true revolution but no one knows whether this will occur in five, ten or thirty years from now. Increasing the number of targets for drug discovery will undoubtedly have a major effect, but even that may occur in an evolutionary or revolutionary process.

The fourth assumption is difficult to assess, except that there is little reason to believe that the current intensity of competition between pharmaceutical companies will diminish, unless the pharmaceutical industry in certain countries is nationalized or prices are controlled in the United States. Therefore, every attempt will be made by companies to exploit both potential and actual opportunities for drug discovery, development, and marketing advantages.

If it is possible to combine biotechnology with electronics and create a new hybrid, then a new revolution would be at hand. The marriage of microchips and biochips would have potential that is difficult to fully imagine. At this time, we must consider this possibility as remote and only unfettered speculation. Having said that, the author read in today’s newsletters that General Electric is working with at least two major pharmaceutical companies on this very project.

The evolutionary answer to predicting the future is based on the belief that the rate of discovery of important new “miracle” drugs will remain about the same as that over the past two decades or will decline slightly. Drugs with small but real improvements will gradually replace some older drugs. Although new types of drug delivery forms (e.g., edible whips, transdermal patches that are electrically stimulated) will be found useful for some drugs, they will not be used for most drugs. Capsules, tablets, and intravenous solutions will still remain the most common types of drugs.

The single aspect that will probably have the greatest influence on drug discovery from today through the year 2020 is the additional scientific and medical knowledge gained about health, disease, and functions of cells and organs. Research scientists in academic, industrial, and government laboratories seek this knowledge every day. This information is critical to the future success of the research-based pharmaceutical industry because scientific breakthroughs are often converted into new approaches for drug discovery.

There are multiple environments in which drugs are developed and which in turn influence drug development. These environments include the (a) internal environment or milieu within a company; (b) commercial and business environment outside a company in which drugs are manufactured, distributed, and sold; (c) regulatory environment in which drugs must be approved and in which their progress is monitored; (d) social and political environments in which drugs are developed and sold; e) academic and private practice environments in which drugs are clinically evaluated; and (f) medical and healthcare environments in which drugs are used. Each of these six environments is discussed below. Several factors that will influence future environments are then discussed. Additional information and perspectives on the future of drug development may be obtained in older books such as Pharmaceuticals in the Year 2000 (Bezold 1983), The Second Pharmacological Revolution (Wells 1983), and newer books listed in the references at the end of the text about the pharmaceutical industry.

Competition among companies is intense in many disease areas. This competition results from many factors such as generics and multiple brands available in some drug classes. Profits are being squeezed by cost containment measures and increased research budgets. These and other reasons are raising pressures on pharmaceutical companies to succeed or possibly face buyout or extinction. This pressure is squarely placed on R and D in research-based companies as well as on the marketing unit.

Most research-based companies are working at the frontiers of knowledge and are competing with each other. When drugs are discovered and are undergoing development, the competitive intensity heats up. The intensity of competition that has always been strong in the marketing area is becoming stronger during the drug development period. One reason is that the first drug to reach the market usually is able to retain the greatest market share, even after other chemically similar drugs are approved and marketed. Threats of therapeutic substitution and actual generic substitution add fuel to this fire of competition. See Chapter 34 for an additional discussion of competition between companies.

There are an extremely large number of disease areas where new drugs may be discovered and developed. Nonetheless, most companies are searching for new drugs in a relatively small number of disease areas. There are several reasons why most companies are concentrating on a limited number of therapeutic areas. First, there is a lack of suitable animal models in many areas and also a lack of sufficient scientific information about cellular problems and the causes of many diseases (i.e., a limited number of targets to study). A third reason that reduces the number of areas in which most pharmaceutical companies are active is that the potential for profit is limited in many therapeutic areas. Few companies are willing to invest and risk tens of millions of dollars, pounds, or euros looking for beneficial drugs unless there is a reasonable expectation of profit.

There has been a long-term trend toward decreasing numbers of large research-based pharmaceutical companies. This trend has been more apparent in some countries than others but has been fairly universal in industrialized countries for more than 35 years. The trend toward decreasing numbers of manufacturers of drugs has not been as consistent. The former trend will probably continue despite the fact that many biotechnology companies have started from scratch in the past two decades and several have been very successful. Mergers, large equity positions, and acquisitions of biotechnology companies by major pharmaceutical companies will reduce the number of independent biotechnology companies. This trend is already apparent, as is their relatively high failure rate. Japanese pharmaceutical companies are expected to become more active in international markets in the future.

The impact of fewer research-based pharmaceutical companies on drug discovery and development is not clear. A smaller number of companies may employ the same number of professionals employed currently, although it is more likely that the total number will be reduced. It is impossible to know how successful these larger sized companies will be at discovering new drugs. Many different scenarios could be hypothesized.

The factors that are primarily responsible for the overall trend toward fewer research-based pharmaceutical companies include: (a) increased costs of discovering and developing a drug, (b) decreasing life of patent protection for most drugs, and (c) decreasing economic return from sales because of generic manufacturers, cost containment, and price controls. These latter issues force pharmaceutical companies to deal more with health maintenance organizations (HMOs), preferred provider organizations (PPOs), and mail-order companies to sell their drugs, rather than with physicians who prescribe them. The erosion of a drug’s sales to generic competition is occurring more rapidly today than in the past. Two decades ago, it took about ten years for a brand name drug to lose most of its market. Today, because of more rapid entry by generics onto the market and more substitution within pharmacies, markets are being lost within a single year in many cases. Other factors include progressively restrictive government regulations of those agencies that approve and control drugs used. These factors also place a greater emphasis on the need for pharmaceutical companies to discover new chemical entities with commercial value to remain in business. This tends to pressure most research-based companies to explore the same therapeutic areas, many times using the same animal models and biological endpoints.

Adverse event reporting requirements for marketed drugs currently differ in many countries, whether they involve results from clinical studies or from voluntary/spontaneous reports from healthcare practitioners. No matter the source, however, it is incumbent on companies to provide relevant information on safety experiences to all regulators in whose countries the drug is on the market or still under development.

In spite of impressive advancements in the harmonization of requirements for reporting safety data to regulatory authorities, especially under the ICH process, there still remain differences in the forms, definitions, and timing for reports so that it is not yet possible to “do it once in the same way at the same time for everyone.” One ambitious objective is to have a single, global electronic safety database which all authorized parties are able to access, whether for entry of data or to review the data. Such a system has actually been proposed and could become a reality once regulatory agencies and companies understand and accept the benefits it would bring in eliminating unnecessary duplication and differences in the way safety data are managed today. Clearly, all of the risks for industry will have to be carefully considered and assessed before this can become a reality. Whether or not this will occur within the next one or two decades is pure conjecture.

There is a growing trend for national regulatory agencies to communicate more with each other and to share more information than ever before. This is taking place both prior to and subsequent to the time of drug approval. A trend toward increasing uniformity among regulatory agencies is noted in the efforts of the European Union to standardize applications for drug approval in their member countries. This European Union procedure was originally implemented over a decade ago and has been periodically revised. It seems that the Pan European system is one that is constantly evolving and one has to wonder if Europe will ever “arrive” at a uniform system that is workable. The trend toward greater harmonization of regulatory requirements and possibly a single regulatory dossier for most countries seems inevitable. Nonetheless, this trend is currently moving at a rather slow rate. The ICH CTD and its electronic form was merely a standardization of the format for a regulatory submission, and even that took many years to reach agreement, and the final CTD has provisions for region specific requirements, so that the final format is not completely harmonized. Nonetheless, that was an important step forward in the correct direction that industry and regulators agree upon.