Social Aspects of Drug Discovery, Development and Commercialization

By Odilia Osakwe and Syed A.A. Rizvi

Social Aspects of Drug Discovery, Development and Commercialization provides an insightful analysis of the drug discovery and development landscape as it relates to society. This book examines the scientific, legal, philosophical, economic, political, ethical and cultural factors that contribute to drug development. The pharmaceutical industry is under scrutiny to develop safer and more effective drugs in a quicker and more affordable manner. Recent criticism and debates have emphasized varying opinions on the issues concerning the drug discovery and development process.

This book provides thoughtful and valuable discussions and analysis of the social challenges and potential opportunities through all stages of the pharmaceutical process, from inception through marketing. With a unique focus on the social factors that increasingly play a role in how drug development is planned, structured, and executed throughout the drug product lifecycle, this is an essential resource for students, professors, and researchers who seek a better understanding of the interface between the pharmaceutical industry, health care systems, and society.

• Organized in a sequence of interrelated theories and principles that provide the foundation for increased understanding of the relevant social aspects
• Includes analysis of important new advances, key scientific and strategic issues, and overviews of recent progress in drug development
• Provides a global perspective with examples from developed areas, such as the US, Japan, Canada and Europe, as well as faster-growing and emerging economies including Brazil, Russia, India, and China
• Serves as an essential resource for students, professors, and researchers who seek a better understanding of the interface between the pharmaceutical industry, health care systems, and society

• Language: English
• Publisher: Academic Press
• Release date: Feb 18, 2016
• ISBN: 9780128024973

Odilia Osakwe

Dr. Odilia Osakwe has published 25 titles, including 1 book (edited), 24 articles in peer reviewed platform including journal articles, scholarly magazines, newsletters and technical notes. And has authored 10 papers/posters and oral presentations in major international professional meetings. Odilia has reviewed numerous manuscripts for different academic journals. Aside from those activities, she served as an editorial board member with Pharmaceutical Science Group of Canada for 3 years reviewing and editing articles with active contribution towards several of the published front cover topics. Odilia received her undergraduate degree from Abia state University and her Masters in Chemistry from Tennessee State University. Within this period, she worked with the Tennessee State Department of Laboratory Services. Following completion of a Master Degree in Chemistry, she took on a two-year post graduate fellowship, which was granted by Vanderbilt University, Nashville, Tennessee; completed in the department of pharmacology of Vanderbilt University Medical Centre. She joined a doctoral program with the department of pharmaceutical Sciences of Mercer University, Atlanta, Georgia and earned a PhD degree. During much of this period, starting from the second year into the doctoral program, she joined the Georgia Perimeter College, Atlanta, Georgia, teaching Chemistry courses for two years till the end of the program. During the all-but-dissertation stage, (ABD), Odilia received a Student Research Fellowship with the Centers for Disease Control and Prevention (CDC), Atlanta, Georgia where she worked as a researcher with the immunology laboratories of National Center for Immunization and Respiratory Diseases (NCIRD) in the Division of Bacterial Diseases (DBD), using the state-of-the-art instrumentation for validation of immunological assays. Further on, Odilia received a competitive National Science and Engineering Research Council of Canada (NSERC) award for Industrial Research and Development Postdoctoral Fellowship (IRDF-NSERC). The two-year training was accomplished at the University of Toronto Hospital Network, Industrial BioDevelopment Laboratory (IBDL) department where she took the lead of the Research and Development activities which include technical oversight and training of the University of Toronto undergraduates on various projects, with published results. Odilia works with Devik Pharma Inc., also a board member of the North American Institute of Pharmaceutical Technology, Scarborough, Ontario, Canada where she undertakes administrative and scholarly duties in the industrial pharmaceutical sector. She is an Adjunct Faculty with Ryerson University, Toronto, Ontario, Canada and Seneca College of Arts and Technology, Toronto, Ontario, Canada, teaching several courses in the Industrial Pharmaceutical Technology program.

Book preview

Social Aspects of Drug Discovery, Development and Commercialization

Odilia Osakwe MS, PhD

Industrial BioDevelopment Laboratory, UHN-MaRS Centre

Toronto Medical Discovery Tower and Ryerson University, Toronto, Canada

Syed A. A. Rizvi MSc, MBA, MS, PhD (Pharm), PhD (Chem), MRSC

Department of Pharmaceutical Sciences, Nova Southeastern University, Fort Lauderdale, FL, USA

Table of Contents

Cover

Title page

Copyright

Dedication

Preface

Introduction

Section I: Pharmaceutical Industry, Society, and Governance

Chapter 1: Pharmaceutical Regulation: The Role of Government in the Business of Drug Discovery

Abstract

1.1. Introduction

1.2. The legal instruments

1.3. The National Regulatory Authorities and Administration

1.4. Analytical framework for regulatory approval: benefit–risk assessment

1.5. The pharmaceutical product life cycle

1.6. The global pharmaceutical industry: harmonization and partnerships

1.7. Modernization of the global pharmaceutical systems: regulatory strategies, roadmap initiatives, and partnerships

Chapter 2: Trends in Innovation and the Business of Drug Discovery

Abstract

2.1. Introduction

2.2. Evolutionary trends in pharmaceutical innovation

2.3. Advances in pharmaceutical innovation technology

2.4. Select medical milestones of 2014

2.5. Factors contributing to pharmaceutical innovation setback

2.6. Case: challenges in antimicrobial drug discovery

2.7. Consequence of innovation setback

2.8. Strategies and approaches to addressing innovation failure

2.9. Concluding remarks

Chapter 3: Cash Flow Valley of Death: A Pitfall in Drug Discovery

Abstract

3.1. Introduction

3.2. Product valuation as an investment decision-making tool

3.3. Challenges associated with the valley of death

3.4. Firms involved in the pharmaceutical value chain

3.5. Strategies for bridging the Valley of Death and innovation failure

3.6. Funding models

3.7. Nongovernmental funding models

3.8. Other financial concepts

3.9. Private–public sector groups

Section II: Drug Discovery Cycle I: Discovery and Preclinical Drug Development

Chapter 4: Prediscovery Research: Challenges and Opportunities

Abstract

4.1. Introduction

4.2. Models of human disease biology

4.3. Diseases considered in biopharmaceutical research and development

4.4. Modern trends in drug discovery

4.5. Current challenges in early drug discovery

Chapter 5: The Significance of Discovery Screening and Structure Optimization Studies

Abstract

5.1. Introduction

5.2. Screening tools in drug discovery

5.3. In silico models in drug discovery and design

5.4. From hit to lead: summary of compound optimization in drug discovery

Chapter 6: Preclinical In Vitro Studies: Development and Applicability

Abstract

6.1. Introduction

6.2. Predictability of preclinical disease models

6.3. Trends in preclinical drug development

6.4. Relevance of ADME/PK studies

6.5. Experimental tools used in preclinical development

6.6. Drug eliminating agents and mechanisms

6.7. Application of zebrafish as a model whole organism: a landmark in preclinical development

Chapter 7: Animal Utilization in Drug Development: Clinical, Legal, and Ethical Dimensions

Abstract

7.1. Introduction

7.2. The scientific value of animal studies: pharmacology objectives

7.3. Laboratory animals model in the frontiers of drug discovery

7.4. Relationships in animal taxonomy and implications in pharmaceutical research and development

7.5. The effect of species differences on study results

7.6. How reliable is the animal toxicity information generated across the animal species?

7.7. Landmarks in preclinical development: species selection and rationale

7.8. Animal models in the development of biopharmaceuticals: the exceptional use of nonhuman primates

7.9. Legal accommodations on the use of animals in pharmaceutical research and development

7.10. Animal alternatives in drug development: replacing, reducing, and refinement of animals

Chapter 8: Pharmaceutical Formulation and Manufacturing Development: Strategies and Issues

Abstract

8.1. Introduction

8.2. Regulatory aspects of pharmaceutical development

8.3. Formulation and manufacturing in pharmaceutical development

8.4. Clinical trials materials

8.5. Concepts used in pharmaceutical development

8.6. Drug shortages

8.7. Manufacturing problems leading to drug shortages

8.8. Addressing drug shortages: strategies

Section III: The Drug Discovery Cycle II: Clinical Development

Chapter 9: Clinical Development: Ethics and Realities

Abstract

Part I.

Part II. Clinical development of candidate drugs

Part III. Clinical trial ethics

Chapter 10: Pharmacogenomics in Drug Discovery, Prospects and Clinical Applicability

Abstract

10.1. Introduction

10.2. Genetic variations and implications in drug development

10.3. The effectiveness of clinical implementation of pharmacogenomics

10.4. Promising outcomes associated with clinical application pharmacogenomics: cases

10.5. Economic and social implications of pharmacogenomics application

10.6. National regulatory agencies on pharmacogenomics implementation

Section IV: The Drug Discovery Cycle III: Authorization and Marketing

Chapter 11: Patents, Exclusivities, and Evergreening Strategies

Abstract

11.1. Introduction: patents and exclusive marketing rights

11.2. US Patent Law Amendments Act of 1984

11.3. The interplay of patents and exclusivities during the product lifecycle

11.4. Patents in the global pharmaceutical market place

11.5. Evergreening

11.6. Conclusions

Chapter 12: Drug Pricing and Control for Pharmaceutical Drugs

Abstract

12.1. Introduction

12.2. Drug assessment and pricing in various geographical locations

12.3. Pharmaceutical drug pricing and ethics

Chapter 13: Direct-to-Consumer Advertising

Abstract

13.1. Introduction

13.2. Ethics and relevance of pharmaceutical advertising

13.3. Pharmaceutical advertising and government control

13.4. Prescription medicine advertising codes

13.5. Conclusions

Index

Copyright

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Dedication

To

Philomena and Chioma

Preface

A considerable number of textbooks have delivered substantial information on the scientific and technological aspects of drug discovery and development, but very few have touched upon the social aspects. The idea of writing this book was stimulated by this necessity along with an emergent notion, which grew out of my experience as a lecturer on this subject, in Ryerson University.

The Social Aspects of Drug Discovery, Development and Commercialization presents a holistic overview of the entire drug discovery process, as it transitions from inception, to a pill in the hands of the patient. It explains the importance for it to be addressed comprehensively, to include all areas that interact with the society. This will enable a proper understanding of the workings of the pharmaceutical enterprise, from which springs forth the medical products that are supplied to the wide public. This will serve as a knowledge base to streamline ideas and perspectives about how drugs are created and distributed; for a regular citizen, an investor in the pharmaceutical business, or students or professionals who need to be updated on pharmaceutical affairs. In other words, this information helps the reader in decision making on the proper approach to healthcare and its products; and provides for the scholar or professional, a strong grounding in this subject area.

One outstanding characteristic of this textbook is that, it provides definitions and explanations of the relevant background information to serve as a framework for understanding the social aspects, making it a user-friendly resource for a wide range of readers. It details the key participants, relationships, and processes involved in the full drug discovery programs that span the pharmaceutical product lifecycle that are necessary for creating the medical solutions delivered to the public, as represented in the pharmaceutical ecosystems. Analysis of the paths of pharmaceutical innovation is within the context of the pharmaceutical ecosystem. For example, pharmaceutical policy and laws have emanated from extensive debate by a hierarchy of government-appointed groups, agencies, social groups, such as patient representative groups, representatives of charities and consumer associations, pharmaceutical and allied professionals, and other groups from various strata of the healthcare systems who are the voice of command in these decision making activities. Pharmaceutical ecosystems embrace the stakeholders, the processes, and technologies whose cross-interactions strengthen the drug discovery programs.

What type of knowledge is gained by the readers of this book?

The introductory chapter gives a general overview of the whole process, which serves as a foundation for the rest of the 13 chapters. Every chapter sequentially builds from the previous and all of which represent a progressive pathway in the discovery of an investigational drug molecule as it morphs into a full drug product that is accessed by the public.

This book attempts to answer certain exemplary questions. Chapter 1: What is the origin, meaning, and relevance of the pharmaceutical laws and regulations? Chapter 2: What is the pharmaceutical productivity landscape? Is pharmaceutical innovation sustainable? What is the technological flow, applicability, and effectiveness? What is the economic landscape for emerging pharmaceutical firms? What are the prospects and trend over the years? Chapter 3: What is responsible for hiatus or demise of the drug discovery pipeline in the initial stages of the drug discovery events? What are the relationships between the emerging and the big pharmaceutical companies? Chapters 4-6: How is the drug discovery pipeline advancing toward providing the needed medical solutions to diseases, especially the deadly ones? What are the hopes of families that have to grapple with life-threatening diseases? What is new in finding disease pathways and new drug molecules? Chapter 7: The animals chosen for testing of drug candidates, does this decision directly correlate with therapy pursued or are animals over utilized? How do the different species differ in pharmacological response? Chapters 8 and 9: Are drugs manufactured to precision? What is the reason for drug recalls? Chapter 9: Are clinical trials conducted to reflect specific public interests? What are the patients’ rights as participants in clinical trials? What are the opportunities and setbacks in multinational clinical trials? Chapter 10: Why are certain drugs more compatible with certain individuals and the experienced adverse events in only certain individuals? What is the applicability of individualized or precision medicine? Chapter 11: How does patents alter drug accessibility? What are the legal factors that affect patents and emergence of generics? How fast could generics be reached? Chapter 12: How does drug marketing benefit the end user? Chapter 13: What is the flow of drug pricing around the globe?

This book could serve as a training tool or reference guide for students and professionals in most of health science and allied disciplines; pharmacy, pharmaceutical sciences, pharmacology, clinical and translational research, medicine, nursing, and more. This also applies to those in pharmaceutical law and policy, health policy and management, and pharmacoeconomics. It can also be a useful information base for students and professionals in regulatory affairs, who are expected to be thorough in the knowledge of drug discovery.

The text is delivered in a concise, direct, and soft language to stimulate interest and enliven your readership.

I would like to extend my personal gratitude to Dr Syed A.A. Rizvi for his valued contribution to this work. Most and foremost, my hearty thanks goes to He who is the pillar of my life and who supplied the knowledge, courage, and strength that carried me throughout this process.

Introduction

1. Trends in drug discovery

The pharmaceutical industry is of tremendous value to society, mainly because of the active discovery and development of pharmaceuticals, which have increased quality of life through both ameliorating pain and suffering, and the treatment of diseases.

Major landmarks in drug discovery that preceded the thalidomide tragedy in the 1950s have led to a total overhaul of regulatory systems. Extensive federal governance has been deemed necessary to address the unsatisfactory efficacy and safety standards that characterized earlier drug manufacturing systems, which underlie the high standards imposed on companies that manufacture and distribute drugs to the public. Since then, increasingly innovative breakthroughs have contributed immensely to the changing pharmaceutical landscape.

The first major historical accomplishment was the innovation boon of the 1990s, a period marked by a rise in the production of blockbuster drugs that has contributed to more than one-third of the total pharmaceutical revenues, totaling US$149 billion [1]. Market growth rate skyrocketed due to expansion of the number of high selling drugs, which lifted the position of the pharmaceutical industry in the global economy [2]. Products from the leading five pharmaceutical companies – Pfizer, Roche, AstraZeneca, Merck & Co., and Novartis – topped the list of the best-selling drugs, such as Prozac, an antidepressant drug; Lipitor® (atorvastatin), which is used to treat blood cholesterol; and Plavix® (clopidogrel), which inhibits the formation of blood clots following myocardial infarction. Many of these drugs attract interest, particularly because they target chronic diseases. Large financial returns generated from just a handful of these drugs sustain the research and development (R&D) for emerging drugs. However, this business model is no longer very promising because patents are expiring. Diversification to niche market drugs is increasingly being expected so as to shift focus from the blockbuster drugs market to those drugs that target other diseases in demand of medical therapy. Thus, today’s R&D is largely driven by new medical discoveries associated with a high probability of economic and technical risk. These types of diseases require discovery of difficult targets that limit innovation speed and cash flow with a high price of unpredictability. For example, the emergence of HIV/AIDS points to the need to expect a therapy that has hitherto been a distant reality.

Incremental shifts in the configuration of the industry over time culminated in the technological breakthroughs of the early twentieth century when interpretation and understanding of molecular biology changed drastically. Groundbreaking biological techniques like proteomics and genomics emerged along with more sophisticated techniques that utilize advanced statistical and mathematical platforms coupled with computer-based strategies in biology and chemistry. Most of these are molecular modeling, simulations, combinatorial chemistry, high-throughput technology, and high-performance computing. Dynamic models created a framework to integrate the knowledge base within the functional areas and, most importantly, the high technology applications further facilitated a better handling of the rapidly growing volume of big data to scale down the complicated R&D processes for a better workflow and output. The omics revolution represents an advancement in molecular science that improved understanding of the molecular linkage of cause and function of diseases to enable the finding of the networks of pathways and, ultimately, the disease targets [3–5]. A model mechanism of drug action enables the drug discovery and development team to understand how drugs act in whole body systems, organs, and at a subcellular level. There is a growing technical competence in targeting smaller patient populations to narrower therapeutic areas for personalized medicine – a greater selectivity offered by genomics.

The Orphan Drug Act was intended to advance treatments for rare disease. This is increasingly leading to new drugs that are effective on smaller defined patient populations that fall into the orphans category, with a foreknowledge furnished by an increased understanding of the causes of the diseases. This presents an opportunity for companies to specialize in particular aspects of the drug development process, which is a more promising pathway to innovation success.

These revolutionary scientific and technological discoveries have brought changes that underscore a dynamic society undergoing major transformation – a change encompassing all the varied levels of the complex processes. This dynamic society requires an integrated framework to bring together all the processes within and across all aspects of the pre- and postdrug launch of candidate drugs. A robust pharmaceutical innovation system that would promote effective cooperation and communication among the stakeholders is highly desirable.

2. The pharmaceutical ecosystem

The pharmaceutical ecosystem refers to the interdependent relationships among levels of interacting stakeholder networks in connection with processes, tools, and infrastructures that are controlled by policies, laws, and opinions. The stakeholder groups are the discovery and development team, academia, physicians, healthcare providers, payers, patients, advocacy groups, consumers groups, and the public or civic society. All these players have unique perspectives about the pharmaceutical industry in connection with the needs, values, and preferences of the area of the public they represent. The infrastructure is the technological platform and core facilities used to drive the drug product from concept to access. The strategic issues – regulatory structures and reform, local and national cultures, politics, federal laws, economic and reimbursement policies, intellectual property and patent policies, product factors, and marketing dynamics – are also the tools for streamlining the utility of medicines during the pre- and postmarketing stages. This is the pivot upon which the pharmaceutical industry rotates. That is to say, all the R&D operations that are the core aspect of drug discovery and development are extensively affected and controlled by these social values. The definition mentioned earlier implies that all aspects of the ecosystem contribute toward most or all of that which translates into a new medical product. A functional ecosystem is characterized by uniform interdependent relationships, which is critical for the continuation of the system. Thus, a pharmaceutical industry that exhibits a functional ecosystem will be more efficient in satisfying its anticipated intended purpose. Figure 1 shows the relatedness of all the players in the pharmaceutical value chain leading to a functional pharmaceutical ecosystem with inference to the drug product.

Figure 1   Cross-Functional Interactions in the Pharmaceutical Ecosystem.

The pharmaceutical value chain is the totality of functions that are performed within big pharmaceutical companies until product phase-out.

There are networks of multichannel interactions at various levels around the development of a pharmaceutical product. This explains the enormous complexity of pharmaceutical innovation. Meaningful cooperation among all the elements offers the promise of high-performance collaboration, processes, and utility of tools and infrastructure [6].

The pharmaceutical ecosystem could be defined as the convergence of networks of cross-interacting subsystems across the drug product pipeline, which has a stake in the efficiency of the drug development and access to the marketed drug.

3. Aspects of the pharmaceutical systems and the stakeholders

3.1. Government and Policies

The government provides revolutionary policies that improve the entire pharmaceutical environment, such as federal laws, economic/reimbursement policies, intellectual property and patent policies, and health policies. The major national regulatory authorities are the Food and Drug Administration (FDA) for United States, the European Medicines Authority (EMA) for Europe, and the Pharmaceuticals and Medical Devices Agency (PMDA, KIKO) for Japan.

3.2. Drug Discovery Research and Development

Target identification through the optimization stage involves biochemists, pharmacologists, systems biologists, cell biologists, immunologists, and bioinformaticians, as well as synthetic, medicinal, analytical, and computational chemists, biotechnologists, and therapeutic area specialists. The preclinical R&D stage involves quality assurance professionals, assay development scientists, safety pharmacologists, and toxicologists. Those that study pharmacokinetics (PK) are the drug metabolism and PK scientists. Formulation and pharmaceutical scientists are involved in pharmaceutical development. Clinical R&D involves clinical research associates, pharmacologists, biostatisticians, molecular biologists, pharmacovigilance professionals, and drug safety scientists.

3.3. Economics Models

Economics models attempt to address scarcity of resources by evaluating economic outcomes of pharmaceuticals and their impacts on people, organizations, and society. Economics modeling involves business experts that implement product strategies to further their corporate objectives. The sales and marketing department partakes in market research to provide information about consumers, including the sales and prescriptions for an indication. Marketing communications provide projections of the anticipated sales trajectory of the drugs under development. The health outcomes are concerned with analysis of causes and effects of diseases, pricing and reimbursement, and economic value. Epidemiologists and strategic pricing executives are also part of this process. Patents cases are overseen by the patent attorneys.

3.4. The Civic Society

Civic society refers to the social groups, patient advocacy groups, consumer groups, other functional groups, and the public.

3.5. The Processes

Processes refer to the utilization of infrastructure and tools that convert knowledge and ideas into tangible products, marketing, and patient access. These include technical skills, machinery and equipment purposed for product innovation, process and product strategies and planning, protocol development, analysis, reporting, and data management.

Cross-functional interactions and coordination enable the pharmaceutical company to leverage knowledge across the value chain stream to optimize product innovation.

4. The mutual effect of the pharmaceutical systems and society

4.1. Pharmaceutical Policy and Regulation

Pharmaceutical policy is concerned with processes by which medicines are developed, approved, manufactured, distributed, and consumed, as well as the innovation tools for pricing access.

Policy could be defined as a means of furthering the administrative objectives and responsibilities of the government.

The regulators employ stringent strategies in their regulatory mechanisms, so as to always satisfy favorable risk–benefit requirements for safety and quality. The public expect the regulators will continue to exercise this mandate seamlessly. For instance, the regulators are expected to recognize the mutual implication of trying to emphasize access to therapies over safety or vice versa. As discussed by Miller and Henderson [7], a policy that focuses more on access to drugs at the expense of safety would lead to exposing the patient to a health risk. However, if access is preferably emphasized, it could affect costs and the ability of the patient to have life-saving medical therapy. Thus, in exercising its statutory authority, the regulator is expected to seek those interests that would promote the utility of a drug that benefits society. Pharmaceutical R&D is structured around governmental regulatory control for a drug product that is manufactured and distributed to the public [8].

Federal government policies provide financial sponsorships and incentives in support of biomedical/pharmaceutical-related research. The relevant organizations receive enormous funding from government agencies such as the National Institutes of Health (NIH) in the United States and the Canadian Institutes of Health Research (CIHR) of Canada. The Small Business Innovation Research and Small Business Technology Transfer programs of the NIH are a major financial funding source for innovative small companies with early-stage capital to engage in biomedical R&D that has a strong potential for commercialization. Over US$750 million was invested in 2014 alone (http://sbir.nih.gov/). About C$11.5 billion were issued between 2000 and 2014 by CIHR (http://www.cihr-irsc.gc.ca/).

A recent demonstration of interdependence among the social sectors of the pharmaceutical ecosystems in advancing drug discovery (Source: p. 24 CEN.ACS.ORG February 2, 2015).

4.1.1. Patent Linkage

Patents render exclusive permissions allowing the pioneering drug manufacturers monopoly of over sales of their drugs (preventing others from selling the drug) that have successfully passed through the drug approval cycles. Federal laws provide for linkages between the drug approval process and the registration of patents in most of North America and other countries spread over the globe. The prices of patented drugs are set by federal legislation that mandates the regulatory authority to the control of prices such that they are not excessive. There is a direct connection between drug prices and availability of generics in the sense that entry of a generic drug into the market accompanies a decrease in drug prices. Nevertheless, patent linkage is not a thriving strategy for the generic companies. The reason is because the lengthy procedure involved in drug approval was not considered when a generic company is permitted to initiate the application process only toward the end of the brand drug’s lifetime. This introduces delay in a drug entering the generic market and, as such, will also limit the low pricing effect [9].

4.1.2. Political Interests

Political activists, lobbyists, and special interests groups impress upon the government a need to accommodate their own interests in decision making. These could lead to controversy and uncertainties. If the applicable laws are not implemented, private interests surge and escalate leading to calls for action. This kind of social movement has dire consequences for the pharmaceutical industry [10–14].

4.2. Access to Drugs

Pharmaceuticals are expected to be readily available, effective, safe, and accessible. The drug discovery process is very complex, costing up to $1 billion with extensive development time of up to 15 years, and has been blamed on scientific, economic, and regulatory uncertainties. Efficiencies in drug discovery R&D are strictly dependent on the ability to provide a confirmatory evidence of robust experimental outcomes that satisfy the efficacy, safety, and quality mandate. But sometimes unforeseen biological activities undermine the clinical utility of the developmental drug. Such an encounter is not uncommon because it has often led to innovation failure, to the detriment of both the drug maker and the public. For example, a drug molecule might exhibit toxic off-target activities that were not determined in the early discovery research and during clinical development. This underlying toxicity might only manifest during the postmarketing period leading to drug recalls and revenue loss for the pharmaceutical company. In such a situation, there has been a tendency to resort to proceeds from other thriving pipeline drugs to sustain its R&D, and which translates into high prices for the drugs intended for the public.

Access to pharmaceuticals can be defined as the timely availability, subject to economic and physical conditions, of quality, safe, and effective medicines to those patients who need them. Many intertwined factors determine the level of access to quality medicines, such as the availability of financial resources, government policies, infrastructure conditions, private and public sector insurance programs, appropriate use, supply management, and manufacturing capacity¹.

4.3. Drug Pricing and Payment

The ability to receive discounted drugs and adequate coverage is a top priority. But commercialization goals need to be met, which more often have been pursued through established pricing mechanisms for cost recovery – the high cost of prescription drugs has been blamed on these huge pipeline expenditures. Revenue generated by the pharmaceutical company is partly dependent on what the third party is willing to pay. However, third party payers would want to reduce costs by excluding sales of highly costly drugs that are listed in the formularies and permit therapeutic substitution. Highly priced prescription drugs are largely unattractive especially those that are extensions of already marketed products that offer only marginal improvement in therapeutic value. To the lawmaker, the need for unrestricted access would sometimes necessitate the industry to compromise its high profitability intentions and operate like a not-for-profit business. Yet, the firm’s owner’s ultimate desire is to maximize wealth. In general, increasing the cost of drugs affects access to drugs, screening off those who are unable to afford pricey drugs and consequently jeopardizing their quality of health.

4.4. Communication

Communicating crucial information, risks, costs, and complexities to the public enables an understanding of all the hurdles of drug development risks and prices. Intuitively, the public relies on the drug firms to decide what data to disclose [15–17]. As such, common interests need to be communicated seamlessly. Trudo Lemmens in his publication Pharmaceutical knowledge governance: a human rights perspective expressed a growing concern over the extent of industry control of pharmaceutical data that it produces and how it impacts the therapeutic quality of the approved drug and public health. The report emphasized how dissemination of promotion, prescription, and consumption of pharmaceuticals and medical devices, and the adverse reporting system information, should take into consideration the protection and promotion of public health [18]. Advances in technology innovation drives the discovery of new drugs and these trends need to be communicated among the advisory bodies and regulatory authorities, investment and funding agencies, public health officials, medical societies, health professionals, public and private payers, and the general public. The purpose is to communicate values, opportunities, and challenges that will help transform the future of public health worldwide. Media influence arises when reports emphasize excessive profits and unethical behavior or promotional information, knowing that favorable remarks will not attract public attention.

4.4.1. Direct-to-Consumer Advertising/Gift Giving

The act of advertising is meant to help the consumer achieve positive health outcomes, to increase awareness of available options, and to build trust in the industry’s marketed products. The societal norms of right to health relates to the right to receive all the information that is crucial to health and freedom of expression. The drug company is expected to dispense candid information during an advertisement without commercial preference or deception. Advertising for marketing gains is a noncompliant gesture, which draws complaints and misgivings from the public. Quite often, elaborate funding has been invested toward advertising at the expense of the end user who indirectly pays for these practices through the purchase of drugs with built-in advertisement expenditures on price tags [19]. Funding of patient advocacy organizations has resulted in the protection of the interest of the funding partners. This sometimes overshadows its own objectives, leading to conflicts of interest and loss of confidence from the patients they represent [20]. The European Medicines Agency (EMA)’s Patients’ and Consumers’ Working Party is the platform for interaction of patients and with EMA. A group of representatives from patients’ and consumers’ organizations provide recommendations to the Agency and its human scientific committees on issues that align with the patient’s medical needs.

4.5. Drug Repositioning or Repurposing

Drug repositioning or repurposing is intended to find alternative uses for a pioneering drug or a drug that is made by another innovator. It mostly involves developing approved or failed compounds. Drug repositioning is expanding in the area of rare and neglected diseases. It is a new way of approaching drug compounds and targets that have been derisked during the development stages, which accelerates the process and thus saves money, because the drug could be produced with less effort and marketed with a huge profit margin. Drug repositioning has helped to mitigate failures in drug discovery and has been associated with therapeutic breakthroughs. For example, the thalidomide medicine that had deleterious effects in the past has found a new indication. This is a growth opportunity that brings value to society. However, there are divided interests over the choice of the repurposed drug and the objective of such an endeavor [21].

4.6. Stratified/Personalized Medicine

Stratified/personalized medicine holds the promise of a more precise and effective standard of care when medications are targeted to the responsive patient population who show fewer adverse reactions.

5. Cyclical interactions in the pharmaceutical ecosystem

Cyclical interactions within the pharmaceutical ecosystem are due to cross-relationships among the various aspects of the pharmaceutical ecosystems as detailed in Figure 1. Networks of interactions across the subsystems emphasize the interdependence of the industry and society (Figure 2). The cyclical interactions are as follows:

Government/Industry

Consultation: In the initial stages of the drug development program, the drug regulatory authority, such as FDA, issues guidance that defines the content of the drug product development plan to ascertain that it does not deviate from its intended purpose. Thus, communication between the sponsor/drug maker and the regulatory body is necessary at the initial stage. The agenda for such a meeting would be patient driven because it incorporates discussions that promote well-informed decisions for clinical trial design and the preclinical development program in support of the intended clinical trial design and therapeutic application [22,23].

Industry/Public Community

Consultation: The drug development program is often initiated in consultation with the stakeholders: physicians, patients, and payers to enable a well-informed clinical trial design. The obtained information is essential in identifying the product characteristics that promotes its commercial suitability [24,25].

Figure 2   Cyclical Interactions of the Pharmaceutical Subsystems.

Decisions made by one subsystem affect the other in a feedforward and feedback fashion. For example, patient/public values predispose the scientific or medical rationale to R&D portfolio prioritization