Academic journal article Research-Technology Management

Linking Technological Change to Business Needs: Roadmapping Offers a Systematic Approach for the Pharmaceutical-Biotechnology Industry to Target Technology Investments in the Drug Delivery Process

Academic journal article Research-Technology Management

Linking Technological Change to Business Needs: Roadmapping Offers a Systematic Approach for the Pharmaceutical-Biotechnology Industry to Target Technology Investments in the Drug Delivery Process

Article excerpt

The field of genomics (the study of an organism's hereditary material, deoxyribonucleic acid) was created in 1990 when the Human Genome Project was initiated. The project has been compared in scope and complexity to the Manhattan project and the moon shot. However, genomics' greatest contribution will be to provide biologists new insights into the building blocks of life: genes and their corresponding products, proteins (1,2). This knowledge is obtained by sequencing DNA from human and model organisms (e.g., yeast, nematode, fruit fly, zebra fish). Comparing DNA sequences from a number of species enables scientists to study the function of a gene as it is expressed in different organisms (3, 4). Similarities in gene function between these organisms and humans enable pharmaceutical researchers to use these organisms to analyze the effect of new therapeutic agents on the biological function of specific proteins, i.e., target molecules (5).

Genomics technology was initially adopted by the pharmaceutical industry in 1993, when SmithKline Beecham announced a strategic alliance with Human Genome Sciences to use genomic tools to find new drug targets (6). (See "Formation of a Pharmaceutical-Biotechnology Network," next page). Human Genome Sciences, founded in 1992, funded the non-profit organization, The Institute for Genomic Research, and in return, obtained exclusive marketing rights to its inventions. The Institute, led by Craig Ventner, leveraged Ventner's research at the National Institutes of Health which allowed researchers to rapidly identify the genes expressed by different cell populations (6, 7). Differential gene expression enabled pharmaceutical researchers to identify potential drug targets by comparing expression profiles between different tissue or between diseased and "normal" cells (8,9).

The flood of genomic data has transformed biological research into an intensive information science. A new field was created, bioinformatics, to mine genomic data in public and private databases. Scientists in this field write programs to gain better insight into biological processes (10).

The completion of the "rough draft" of the human genome in February, 2001 (11) further accelerated this research by increased focus on the study of the structure and function of the proteins coded by genes (i.e., proteomics). Bioinformatics, linked to other new technologies, combinatorial chemistry and high throughput screening, has created a new paradigm for drug discovery. This technological change will move the industry from serendipitous discovery of new drugs to strategic management of markets and technology to improve healthcare for targeted diseases (12).

Technology management is critical to the pharmaceutical industry for a number of reasons. First, increased investment in pharmaceutical R&D has not resulted in a significant change in the number of new pharmaceutical agents introduced into the market (16,17). The cycle time for development of new drugs and R&D dollars spent per product has increased (9,16,18). This lack of R&D productivity is caused by many problems but among them are understanding the limitations of new drug discovery technologies (e.g., combinatorial chemistry, assays to validate targets), the unpredictable complexity of biological systems, and difficulty in making appropriate investments in technological areas that increase research productivity.

Second, many of the biotech companies that provide services to the pharmaceutical industry have moved to internal development of their own drugs either alone or in partnership with established companies (12). In a recent survey, it was estimated that approximately 50 percent of the drugs sold by the pharmaceutical industry were licensed in from other firms (9). Finally, the increase in the number of suppliers that provide services for specific aspects of the drug development value chain enables new entrants to partner with other companies to gain resources necessary for the commercialization process (19).

Roadmapping and the Drug Discovery Process

The pharmaceutical industry needs additional technology management tools to assess the potential value of new technologies to meet the challenges of the drug discovery process. Roadmapping can be applied at the industrial and corporate level to determine where new technology can be used to increase research productivity.

Roadmaps are defined as:

The view of a group of stakeholders as to how to get where they want to go--to achieve their desired objective. The purpose of a roadmap is to help the group make sure the right capabilities are in the right place at the right time to achieve this objective (20).

The unique feature of roadmaps versus traditional technology management tools is that they directly link technology to business needs by using a series of simple charts or graphs. The tool can be applied at any level where technology is a critical element of the analysis. The key issue raised in the construction of the roadmap is the availability and alignment of technology to meet the desired need.

The potential applications of roadmapping to industrial or corporate initiatives are described below. Development of a corporate roadmap is presented in more detail because of the wide breadth of application within an organization. In 'contrast, the scope of an industrial roadmapping initiative must be defined so that it does not violate antitrust law. Its focus will be at a pre-competitive level where all the parties that participate in the process do not gain an unfair competitive advantage.

Industrial roadmaps

Participants from several companies or a task force chartered by an industrial trade association, such as the Pharmaceutical Research and Manufacturers of America (PhRMA) or the Biotechnology Industry Organization, could form a committee to assess which R&D issues in the industry are impacting corporate profitability. This issue is addressed by answering several questions: Where are the bottlenecks in the drug development process? What is the estimated cost to the industry? Can these bottlenecks be resolved by having members work together at a pre-competitive level to address issues that face all companies in the industry? If consensus can be obtained on this issue, then member companies should provide the best talent with knowledge of the problem to work cooperatively on a defined project.

A format for a pharmaceutical industry roadmap is suggested in the diagram, above, which presents the different steps of the drug discovery value chain. There are three different levels of the roadmap, categorized as segment, program and project. Segments refer to different stages of the value chain, ensuring that any investment made in the project will benefit the member company. Programs are categories of technological methods under the segment and projects are initiatives which analyze in more detail a technology that addresses the specific problem.

For illustrative purposes, the technology identified for further investigation in the diagram is application of DNA microarrays to detect changes in expression profiles of selected genes which are predictive of an adverse host response to a chemical agent, such as a new drug. There is intense interest in this emerging field, termed toxicogenomics (21,22). Government initiatives, such as the National Center for Toxicogenomics, will serve to explore and develop the basic information required to build the foundation for this field. The pharmaceutical/biotech industry will adopt this knowledge and expand it to incorporate relevant technologies to improve productivity of the drug discovery process.

This approach to applying roadmaps as a tool to increase industry productivity and competitiveness is not new. In 1987, SEMATECH (Semiconductor Manufacturing Technology) was formed as a non-profit organization to stem the erosion of U.S. market share in the semiconductor industry by improving manufacturing technology. SEMATECH was funded jointly by the U.S. government and industry participants. The first National Technology Roadmap for Semiconductors was published in 1993 and these roadmaps have been updated to meet changing industrial needs.

The value of the roadmap to the semiconductor industry is reflected by the support SEMATECH continues to receive. In 1995, SEMATECH stopped receiving federal support and diversified its membership to include non-U.S. companies. In 2000, the name of the organization was changed to International SEMATECH to reflect the global nature of this industrial research consortium. Roadmaps play the central role in the organization as stated in the title of the 2000 Annual Report: Realize the Roadmap (23).

Corporate roadmaps

Similar activities can be initiated at the corporate level, but here the focus is on improving internal processes which may need improvement to increase R&D productivity or to upgrade a step in the drug discovery process that has fallen behind "industry standards." The roadmapping process can be divided into five steps: Team Formation, Focus, Technology/Workflow Analysis, Implementation, and Review.

Team formation.--The roadmapping team must be interdisciplinary to ensure that the relevant "voices" of the organization have input into this critical process. The team, in addition to R&D and technology management personnel, should also include members from business development, representatives from finance, and core staff members from functions such as medicinal chemistry, high throughput screening, regulatory, and safety studies. The first priority is to establish a common understanding of the process and the terminology employed in the analysis. Taking this step will minimize the confusion that can potentially arise during the roadmapping process.

Focus.--After Team Formation, team members must begin to develop a detailed analysis of the drug discovery process. Technology is a critical element of the analysis but it must be placed in its proper perspective. Introduction of new technology is important but valued only if it results in improvement in the efficiency and effectiveness of the process. One approach to develop a systematic analysis is to apply Goldratt's Theory of Constraints (24). This theory was developed for analysis of manufacturing processes. Goldratt defines a system constraint as "anything that limits a system from achieving higher performance versus its goal." Key assumptions in this theory are: 1) any system has at least one constraint, i.e., the chain is only as strong as its weakest link; 2) constraints dictate the performance of an organization to reach its goal; 3) once a weak link is strengthened, a new weak link will show itself.

In the drug discovery process, application of this theory must be modified based on limitation of technology and knowledge of biological systems. In the process of performing this analysis, the team must decide the metrics/ factors required to evaluate each step in the process. Issues to consider are costs, predictability of outcome, internal competencies in the organization, and opportunities for technology improvement. Upon completion of the analysis, a model can be created to identify steps in the process that have the greatest potential impact on increasing research productivity.

Technology/workflow analysis.--The deliverable from the Focus step is the identification of a specific step in the process for improvement based on technology availability and the probability of obtaining a successful outcome. The value of technologies in the specific process step is dependent on the degree of their alignment with the needs of the process. Rigorous evaluation of this alignment must be performed to understand the limitations and benefits of the technology.

Application of quality functional deployment (25) is useful in performing this analysis. The simplest way to use this tool is to develop a matrix in which the process needs are listed on the left side of the matrix and along the top are listed the assays/technologies used to address these needs. The degree of alignment is rated (i.e., high, medium, low) with regard to how well the assay/ technology meets the need. This exercise, combined with workflow analysis (26), will stimulate the team to develop innovative solutions to improve the efficiency and cost effectiveness of the process. At the completion of this step, team recommendations must include a list of actions and metrics to determine whether the process improvements had an impact on productivity.

Implementation.--The requirements for implementation must be identified and addressed if the recommendations are to have an impact on the research productivity. Support from management regarding appropriate personnel and budget investment is critical. Additionally, one of the benefits of the roadmapping process is the higher probability that implementation goes according to plan, since multiple functional areas were involved in the formulation of the roadmap and provided expert input to ensure its success.

Review.--Any systematic improvement to a process requires that the team members learn whether the process modification led to the desired outcome and, if appropriate, take further corrective actions. The Deming Cycle (plan-do-check-act) is a useful tool for reviewing the results from any process improvement. The check step permits the review of the agreed-upon metrics to determine whether they have met the goals of the roadmapping effort. If modifications are required, the appropriate members of the team should meet and define a revised action plan. In some cases, this may require modifying an existing technology/process or finding a new technology.

The benefit of using a defined, systematic process is that it sensitizes the participants to the critical elements needed to improve the process step. Inclusion of technology management personnel on the team ensures that team learning is not lost and can be applied if new technology is developed in the market that meets the needs of the organization.

Potential Benefits

The potential benefits of using this tool are that it: 1) provides a simple method to present complicated issues; 2) focuses discussion around specific steps of the process, enabling cross-functional understanding of complicated issues; 3) sensitizes those involved in the analysis to critical issues regarding alignment of technologies to meet needs; 4) enables faster and superior assessment of emerging technologies from the learning obtained in the roadmapping process.

The value of applying roadmapping to the drug discovery process is illustrated by results from a market research survey and by evaluating the strategic approach of Millennium Pharmaceuticals to the drug discovery process.

A market research survey sponsored by R&D Magazine polled pharmaceutical researchers about the drug development process (27). This survey showed that respondents believed that the majority of drug candidates failed because of undesirable biological effects and poor results in clinical trials. Respondents also indicated that technologies that could reduce these bottlenecks were earlier determination of toxicological properties of drug candidates and faster drug screening. The survey also found that better communication among co-workers, more researchers to solve understaffing, better screening of drug candidates, and better toxicological testing were more important than introduction of new technologies or just spending more money.

These results are consistent with the conclusions from a 1999 survey of the drug discovery process which stated that companies adopting new operating models for drug discovery "are now looking at how to optimize end-to-end performance and proactively manage pipeline bottlenecks" (17). These studies support the thesis above that in spite of technology advancement in genomics and proteomics, researchers must critically evaluate the steps in the drug discovery process and find the best solution in this dynamic environment to improve research productivity.

Millennium Pharmaceuticals, for example, has aggressively analyzed and improved the drug discovery process. Its progress in this area is best summarized by quotes in two investment analysis reports:

Millennium is revolutionizing the drug discovery and development process to tackle the most critical issue facing the pharmaceutical industry today--productivity. By examining every step in the process, Millennium is identifying the bottlenecks in the process and addressing them (28).

What we rather find unique about management's approach is its determination to gradually yet dramatically increase the efficiency of pharmaceutical research and discovery. To accomplish this, the company has brought in highly accomplished process engineers, who are applying some of the concepts used for decades by car makers, steel producers, etc...., to automate the drug discovery and development process (29).

Millennium's industrialization of the drug discovery process is driven by a Technology division that provides cutting-edge genomics and drug discovery technologies to Millennium's Pharmaceuticals division and other subsidiaries, Millennium Bio Therapeutics and Millennium Predictive Medicine (28). Ultimately, Millennium believes that within a four-year period they will be able to develop drugs at a cost and cycle time that is half of what it is (30).

Millennium's improvement to the drug discovery process is valued by the market, as demonstrated by renewal of collaborations with Bayer and Wyeth-Ayerst and by a large proportion of the upfront payments made by Bayer and Aventis to transfer Millennium' s technologies and drug discovery process into their companies. Indirectly, these agreements push those in Millennium's Technology division to set higher goals, resulting in new benchmarks for the pharmaceutical industry.

Summing Up

The growth of genomics and proteomics over the past ten years has led to optimistic predictions of revolution in the healthcare industry. This paradigm shift in biological science will ultimately fulfill many of these promises provided management of pharmaceutical R&D can be significantly improved. Companies must develop more efficient approaches to speed the identification and development of therapeutics that capitalize on the genomics/proteomics revolution. Roadmapping provides one method to ensure that throughout this technological revolution, any significant action or investment in this emerging area of science will be properly evaluated to link technology implementation to business needs in a focused, coordinated approach.

References

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(2.) Fields, Stanley. "Proteomics in Genomeland." Science 291 (2001); pp. 1221-1224.

(3.) Brown, Kathryn. "The Human Genome Business Today." Scientific American, July 2000, pp. 50-55.

(4.) Gene Ontology Consortium. "Gene Ontology: Tool for the Unification of Biology." Nature Genetics 25 (2000); pp. 25-29.

(5.) "A Creeping Success." The Economist, 5 June 1999, pp. 77-78.

(6.) Cohen, Jon. "The Genomics Gamble." Science 275 (1997); pp. 767-772.

(7.) Wickelgren, Ingrid. "Mining the Genome for Drugs." Science (1999); pp. 998-1001.

(8.) Ohlstein, Eliot H.; Ruffolo, Robert R.; and Elliott, John D. "Drug Discovery in the Next Millenium." Annual Reviews in Pharmacology and Toxicology 40 (2000); pp. 177-191.

(9.) "The Pharmaceutical Industry." The Economist. 21 February 1998, pp. 3-18.

(10.) Howard, Ken. "The Bioinformatics Gold Rush." Scientific American, July 2000, pp. 58-63.

(11.) International Genome Sequencing Consortium. "Initial Sequencing and Analysis of the Human Genome." Nature 409 (2001); pp. 860-921.

(12.) Goldsbrough, Peter; Lawyer, Pete; and Sondhi, Gayatri. "The Pharmaceutical Industry into its Second Century: From Serendipity to Strategy." Boston Consulting Group, Boston, Massachusetts, 1999.

(13.) PhRMA Annual Report 2000-2001, July 2000. http://www. phrma.org

(14.) Womack, James P.; Jones, Daniel T.; and Roos, Daniel. The Machine that Changed the World. New York.: HarperPerennial, 1990.

(15.) Harris, Gardiner. "Drug Firms Stymied in the Lab Become Marketing Machines." Wall Street Journal, 6 July 2000, sec. A, p. 1.

(16.) Harris, Gardiner. "Why Drug Makers are Failing in Search for New Blockbusters." Wall Street Journal, 18 April 2002, sec. A, p. 1.

(17.) "Drug Discovery/Part 1: A Path to New Diagnostic Opportunities?". In Vivo, July 1999, pp. 10-22.

(18.) DiMasi, Joseph A. "Trends in Drug Development Costs, Times, and Risks." Drug Information Journal 29 (1995); pp. 375-384.

(19.) Birch, Steve. "The Pharmaceutical Outsourcing Outlook, 1998-2003." Datamonitor PLC. 1999.

(20.) Probert, David and Radnor, Michael. "Technology Roadmapping." Research * Technology Management, this issue, p. 27.

(21.) Lovett, Richard A. "Toxicologists Brace for the Genomics Revolution." Science 289 (2000); pp. 536-537.

(22.) Hamadeh, Hisham K.; Amin, Rupesh P.; Paules, Richard S.; Afshari, Cynthia A. "An Overview of Toxicogenomics." Current Issues in Molecular Biology 4 (2002); pp. 45-56.

(23.) International SEMATECH 2000 Annual Report. http://www. sematech.org

(24.) Goldratt, Eliyahu M. Theory of Constraints. Croton-on-Hudson, NY: North River Press, 1990.

(25.) Cohen, Lou. Quality Functional Deployment, How to Make QFD Work for You. Reading, Massachusetts: Addison-Wesley Publishing Company, 1995.

(26.) Rother, Mike and Shook, John. Learning to See. Brookline, Massachusetts: Lean Enterprise Institute, 1998.

(27.) Studt, Tim. "Drug Development Bottlenecks Not Cured by Technology Alone." R&D Magazine, January 1999, pp. 40-41.

(28.) Lind, Douglas D; Copithorne, Caroline L.; and Bedard, Carla C. "Millennium Pharmaceuticals: At Its Core, an Integrator." Morgan Stanley Dean Witter, 26 October 2000.

(29.) Chovav, Meirav. "Millennium Pharmaceuticals (MLNM)." SolomonSmithBamey, 25 September 2000.

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RELATED ARTICLE: Formation of a pharmaceutical-biotechnology network.

The SmithKline Beecham--Human Genome Science alliance provided a new role for biotech companies in the pharmaceutical industry. A pharmaceutical-biotech network was created in which biotech companies that had developed novel technologies and/or information could partner with pharmaceutical firms to apply their competencies to different steps in the drug discovery value chain (see diagram, next page). Drug development now moved to a knowledge-based industry where technologies and information created by members of the network were captured for use in the commercialization process. This structural change in drug discovery led to an increased number of formal relationships between established pharmaceutical firms and biotech companies to fill this technology gap. In addition, funding of pharmaceutical R&D increased to meet this technological change, with a higher proportion of budgets used to support external research programs (12,13).

This new pharmaceutical-biotech network extends beyond companies meeting the immediate needs of the pharmaceutical industry. Another level of suppliers has formed where companies with valued reagents and instrument platforms serve the needs of all participants in the network. This extended structure can be compared to supplier networks that have been established in other industries (14,15). The primary role of the "brand" manufacturer is for commercialization and support of the final product. Tier 1 pharmaceutical suppliers provide products and services that directly bring value to these manufacturers while Tier 2 suppliers provide new instrument platforms and reagents which both pharmaceutical and biotech companies rely on to generate the data and information required for the new drug discovery process. This structure benefits the pharmaceutical industry by providing options to outsource components of the drug discovery value chain. Pharmaceutical firms can perform a "develop or buy" analysis to assess whether they want to integrate new technologies in an effort to improve research productivity. Tier 1 companies benefit by receiving revenues from pharmaceutical firms for offering valued products/services. Tier 2 companies benefit by selling innovative product/ service offerings to other members of the network.--R.C.M.

Robert McCarthy is a member of the Foresight Catalyst Group, LLC, a consulting company that provides services for companies seeking to improve technology management and integration into new products/services for the biotechnology and healthcare industry. For the past six years at Roche Diagnostics, he focused on the application of new technology management tools to evaluate industrial and technological changes that are occurring in life science research with the advent of the genomics/ proteomics revolution. He received a Ph.D. in microbiology from Indiana University and postdoctoral training in immunology and clinical chemistry at the Mayo Clinic in Rochester, Minnesota. bob@foresightcatalyst.com.

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