Analysing stratified medicine business models and value systems: innovation-regulation interactions

Stratified medicine offers both opportunities and challenges to the conventional business models that drive pharmaceutical R&D. Given the increasingly unsustainable blockbuster model of drug development, due in part to maturing product pipelines, alongside increasing demands from regulators, healthcare providers and patients for higher standards of safety, efficacy and cost-effectiveness of new therapies, stratified medicine promises a range of benefits to pharmaceutical and diagnostic firms as well as healthcare providers and patients. However, the transition from 'blockbusters' to what might now be termed 'niche-busters' will require the adoption of new, innovative business models, the identification of different and perhaps novel types of value along the R&D pathway, and a smarter approach to regulation to facilitate innovation in this area. In this paper we apply the Innogen Centre's interdisciplinary ALSIS methodology, which we have developed for the analysis of life science innovation systems in contexts where the value creation process is lengthy, expensive and highly uncertain, to this emerging field of stratified medicine. In doing so, we consider the complex collaboration, timing, coordination and regulatory interactions that shape business models, value chains and value systems relevant to stratified medicine. More specifically, we explore in some depth two convergence models for co-development of a therapy and diagnostic before market authorisation, highlighting the regulatory requirements and policy initiatives within the broader value system environment that have a key role in determining the probable success and sustainability of these models.     

Driving adoption of new technologies in biopharmaceutical manufacturing

The challenge of introducing new technologies into established industries is not a problem unique to the biopharmaceutical industry. However, it may be critical to the long-term competitiveness of individual manufacturers and, more importantly, the ability to deliver therapies to patients. This is especially true for new treatment modalities including cell and gene therapies. We review several barriers to technology adoption which have been identified in various public forums including business, regulatory, technology, and people-driven concerns. We also summarize suitable enablers addressing one or more of these barriers along with suggestions for developing synergies or connections between innovation in product discovery and manufacturing or across the supplier, discovery, manufacturing, and regulatory arms of the holistic innovation engine.     

The signs of life in architecture

Engineers, designers and architects often look to nature for inspiration. The research on 'natural constructions' is aiming at innovation and the improvement of architectural quality. The introduction of life sciences terminology in the context of architecture delivers new perspectives towards innovation in architecture and design. The investigation is focused on the analogies between nature and architecture. Apart from other principles that are found in living nature, an interpretation of the so-called 'signs of life', which characterize living systems, in architecture is presented. Selected architectural projects that have applied specific characteristics of life, whether on purpose or not, will show the state of development in this field and open up future challenges. The survey will include famous built architecture as well as students' design programs, which were carried out under supervision of the author at the Department of Design and Building Construction at the Vienna University of Technology.     

A Novel T-type Overhangs Improve the Enzyme-Free Cloning of PCR Products

PCR product cloning is the foundational technology for almost all fields in the life sciences. Numerous innovative methods have been designed during the past few decades. Enzyme-free cloning is the only one that avoids post-amplification enzymatic treatments, making the technique reliable and cost effective. However, the complementary staggered overhangs used in enzyme-free cloning tend to result in self-ligation of the vector under some circumstances. Here, we describe a “T-type” enzyme-free cloning method: instead of designing the complementary staggered overhangs used in conventional enzyme-free cloning, we create “T-type” overhangs that reduce the possibility of self-ligation and are more convenient for multi-vector cloning. In this study, we systematically optimize “T-type” enzyme-free cloning, compare its cloning background with that in conventional enzyme-free cloning, and demonstrate a promising application of this technique in multi-vector cloning. Our method simplifies post-amplification procedures and greatly reduces cost, offering a competitive option for PCR product cloning.     

The biological sciences in India: Aiming high for the future

India is gearing up to become an international player in the life sciences, powered by its recent economic growth and a desire to add biotechnology to its portfolio. In this article, we present the history, current state, and projected future growth of biological research in India. To fulfill its aspirations, India''s greatest challenge will be in educating, recruiting, and supporting its next generation of scientists. Such challenges are faced by the US/Europe, but are particularly acute in developing countries that are racing to achieve scientific excellence, perhaps faster than their present educational and faculty support systems will allow.India, like China, has been riding a rising economic wave. At the time of writing this article, four Indians rank among the ten wealthiest individuals in the world, and the middle class is projected to rise to 40% of the population by 2025 (Farrell and Beinhocker, 2007). Even with the present global economic setbacks, India''s economy is expected to grow to become the third largest in the world. India''s recent economic boom has been driven largely by its service and information technology industries, fueled to a large extent by jobs provided by multinational companies. However, this “outsourcing” model is unlikely to persist indefinitely. India''s future must rely upon its own capacity for innovation, which will require considerable investment in education and research.Biotechnology represents a potential sector of economic growth and an important component in India''s national health agenda. Appreciating the important role that biology will play in this century, the Indian government is expanding as well as starting several new biological research institutes, which will open up many new positions for life science researchers. Funds also are becoming available for state-of-the-art equipment, thus decreasing the earlier large disparity in support facilities between the top research institutes in India and the US/Europe. India is becoming an increasingly viable location to conduct biological research and a fertile ground for new biotechnology companies. However, success need not rise in proportion to money invested, unless India attracts and supports its best young people to do research.Many academic centers and industries in the US/Europe are beginning to have an eye on India, the world''s largest democratic country, for possible collaborations. Western institutions have long benefited from having Indian scientists on their faculty or postdoctoral fellows/graduate students in their laboratories (perhaps benefitting more than India itself). However, Western scientists, by and large, know very little about the scientific and educational systems in India. (As was true of authors of this article before we began our 8-month sabbatical at the National Center for Biological Sciences in Bangalore). The goal of this article is to provide a brief historical and contemporary view of the biological sciences in India. We also provide an editorial perspective on the upcoming challenges for the Indian life sciences, with a particular emphasis on how India will grow and support its next generation of scientific leaders.     

The varied lives of organisms: variation in the historiography of the biological sciences

This paper emphasizes the crucial role of variation, at several different levels, for a detailed historical understanding of the development of the biomedical sciences. Going beyond valuable recent studies that focus on model organisms, experimental systems and instruments, we argue that all of these categories can be accommodated within our approach, which pays special attention to organismal and cultural variation. Our empirical examples are drawn in particular from recent historical studies of nineteenth- and early twentieth-century genetics and physiology. Based on the quasi-paradoxical conclusion that biological and cultural variation both constrains and enables innovation in the biomedical sciences, we argue that more attention should be paid to variation as an analytical category in the historiography of the life sciences.     

Opportunities and challenges for the life sciences community

Twenty-first century life sciences have transformed into data-enabled (also called data-intensive, data-driven, or big data) sciences. They principally depend on data-, computation-, and instrumentation-intensive approaches to seek comprehensive understanding of complex biological processes and systems (e.g., ecosystems, complex diseases, environmental, and health challenges). Federal agencies including the National Science Foundation (NSF) have played and continue to play an exceptional leadership role by innovatively addressing the challenges of data-enabled life sciences. Yet even more is required not only to keep up with the current developments, but also to pro-actively enable future research needs. Straightforward access to data, computing, and analysis resources will enable true democratization of research competitions; thus investigators will compete based on the merits and broader impact of their ideas and approaches rather than on the scale of their institutional resources. This is the Final Report for Data-Intensive Science Workshops DISW1 and DISW2. The first NSF-funded Data Intensive Science Workshop (DISW1, Seattle, WA, September 19-20, 2010) overviewed the status of the data-enabled life sciences and identified their challenges and opportunities. This served as a baseline for the second NSF-funded DIS workshop (DISW2, Washington, DC, May 16-17, 2011). Based on the findings of DISW2 the following overarching recommendation to the NSF was proposed: establish a community alliance to be the voice and framework of the data-enabled life sciences. After this Final Report was finished, Data-Enabled Life Sciences Alliance (DELSA, www.delsall.org ) was formed to become a Digital Commons for the life sciences community.     

The computational challenges of applying comparative-based computational methods to whole genomes

The explosion in genomic sequence available in public databases has resulted in an unprecedented opportunity for computational whole genome analyses. A number of promising comparative-based approaches have been developed for gene finding, regulatory element discovery and other purposes, and it is clear that these tools will play a fundamental role in analysing the enormous amount of new data that is currently being generated. The synthesis of computationally intensive comparative computational approaches with the requirement for whole genome analysis represents both an unprecedented challenge and opportunity for computational scientists. We focus on a few of these challenges, using by way of example the problems of alignment, gene finding and regulatory element discovery, and discuss the issues that have arisen in attempts to solve these problems in the context of whole genome analysis pipelines.     

Bridging the gap

Therapeutic monoclonal antibodies (mAbs) currently dominate the biologics marketplace. Development of a new therapeutic mAb candidate is a complex, multistep process and early stages of development typically begin in an academic research environment. Recently, a number of facilities and initiatives have been launched to aid researchers along this difficult path and facilitate progression of the next mAb blockbuster. Complementing this, there has been a renewed interest from the pharmaceutical industry to reconnect with academia in order to boost dwindling pipelines and encourage innovation. In this review, we examine the steps required to take a therapeutic mAb from discovery through early stage preclinical development and toward becoming a feasible clinical candidate. Discussion of the technologies used for mAb discovery, production in mammalian cells and innovations in single-use bioprocessing is included. We also examine regulatory requirements for product quality and characterization that should be considered at the earliest stages of mAb development. We provide details on the facilities available to help researchers and small-biotech build value into early stage product development, and include examples from within our own facility of how technologies are utilized and an analysis of our client base.     

From genes to therapeutics: educating the government and the public on biomedical sciences-a Singapore experience

Singapore has a highly developed economy and has been recognized to have one of the best business environments in Asia. Her success is based largely on focused developments of key industries in traded services and manufacturing sectors. The challenge for Singapore is to utilize her small human resource to transform the present economy to a more knowledge-intensive economy. Singapore has recently embarked on the ambitious goal of developing Biomedical Sciences as an industry. Educating the government and the public on various aspects of this new industry was identified as one of the essential steps towards this goal. The challenge was to inspire non-biologists to embrace the life sciences. This review describes how a series of workshops were developed to address the needs and the challenges of educating the public and the government.     

Biology and data-intensive scientific discovery in the beginning of the 21st century

The life sciences are poised at the beginning of a paradigm-changing evolution in the way scientific questions are answered. Data-Intensive Science (DIS) promise to provide new ways of approaching scientific challenges and answering questions. This article is a summary of the life sciences issues and challenges as discussed in the DIS workshop in Seattle, September 19-20, 2010.     

Tissue engineering applications and stem cell approaches to the skin, nerves and blood vessels

Tissue engineering applies the principles of life sciences and engineering to the development of biological substitutes to restore, maintain or improve tissue function. Developments in this multidisciplinary field have yielded advances in the reconstruction of skin, peripheral nerves and blood vessels. In this review we highlight the fundamental principles and challenges of engineering products which can mimic both the structure and function of these tissues in their healthy state. We discuss the recent progress in the field with its implications for revolutionising healthcare in the future.     

Bioprospecting in plants for engineered proteins

For more than two decades, bioengineered plants have produced protein therapeutics for human and animal use. Almost all proteins produced by other existing systems, including antibodies, vaccines and plasma proteins, have now been manufactured in plants. Considering the limitations of microbial and mammalian reactor-based protein-production technologies and the impending bottleneck in manufacturing capacity, plants are now emerging as an attractive alternative system with which to supply the growing need for protein-based therapeutics. However, full realization of the promise of plant-derived engineered proteins requires that we confront the dual challenges of bioequivalence and product consistency, challenges that are largely related to post-translational protein modifications (PTMs) that are crucial to the structure and function of most eukaryotic proteins. Among the protein PTMs, the foremost challenge for bioactivity and acceptance by the pharmaceutical and biotechnology industries and regulatory agencies is glycosylation. Advances made in recent years that 'humanize' plant glycosylation pathways combined with the discovery of terminal sialic acids (SAs) in plants now make feasible the bioengineering in plants of glycoproteins that have mammalian-like glycosylation.     

Ethnographic Critique and Technoscientific Narratives: The Old Mole, Ethical Plateaux, and the Governance of Emergent Biosocial Polities

A reading of the puzzle novel ViennaBlood, by Adrian Mathews, is juxtaposed tothree ethnographic sketches of contemporaryethical plateaus or domains of ethicalchallenge – the challenges of informed publicconsent to new technologies, the seductions todo whatever is medically possible (sometimes atthe expense of quality of life or the `gooddeath'), and the power of money in driving thebiotechnological industries. ViennaBlood deals with precautionary germplasmmodification and chemical camouflage justifiedas protection against ethnically-targetedbiological warfare, and touches on a series oftechnologies such as new reproductivetechnologies, genetic engineering, andcryptographic attacks and defenses, as well asthe ability to evade regulatory controls. Suchtechnoscientifically informed novels are usefulas cautionary tales, in exploring thecomplexity and interaction among newtechnologies, and the phantasmagoria that helpdrive new technologies. They are not so good atthinking through institutional development: achallenge for ethnography and new socialtheory. Ethnography, like novels, can functionas checks on the mechanisms of abstraction anduniversalization that frequently bedevil thenon-anthropological, non-cross-culturally orcross-temporally comparative, social sciences.Questions are raised about new or emergentbiosocialities, forms of governance, and formsof cultural critique.     

Perspectives on functional genomics

As the first assembly of the human genome was announced on June 26, 2000, we have entered post genome era. The genome sequence represents a new starting point for science and medicine with possible impact on research across the life sciences. In this review I tried to offer brief summaries of history and progress of the Human Genome Project and two major challenges ahead, functional genomics and DNA sequence variation research.     

Bridging the gap: Facilities and technologies for development of early stage therapeutic mAb candidates

Therapeutic monoclonal antibodies (mAbs) currently dominate the biologics marketplace. Development of a new therapeutic mAb candidate is a complex, multistep process and early stages of development typically begin in an academic research environment. Recently, a number of facilities and initiatives have been launched to aid researchers along this difficult path and facilitate progression of the next mAb blockbuster. Complementing this, there has been a renewed interest from the pharmaceutical industry to reconnect with academia in order to boost dwindling pipelines and encourage innovation. In this review, we examine the steps required to take a therapeutic mAb from discovery through early stage preclinical development and toward becoming a feasible clinical candidate. Discussion of the technologies used for mAb discovery, production in mammalian cells and innovations in single-use bioprocessing is included. We also examine regulatory requirements for product quality and characterization that should be considered at the earliest stages of mAb development. We provide details on the facilities available to help researchers and small-biotech build value into early stage product development, and include examples from within our own facility of how technologies are utilized and an analysis of our client base.Key words: monoclonal antibody, preclinical development, biologics, CHO cells, cell culture     

Biosimilars advancements: Moving on to the future

Many patents for the first biologicals derived from recombinant technology and, more recently, monoclonal antibodies (mAbs) are expiring. Naturally, biosimilars are becoming an increasingly important area of interest for the pharmaceutical industry worldwide, not only for emergent countries that need to import biologic products. This review shows the evolution of biosimilar development regarding regulatory, manufacturing bioprocess, comparability, and marketing. The regulatory landscape is evolving globally, whereas analytical structure and functional analyses provide the foundation of a biosimilar development program. The challenges to develop and demonstrate biosimilarity should overcome the inherent differences in the bioprocess manufacturing and physicochemical and biological characterization of a biosimilar compared to several lots of the reference product. The implementation of approaches, such as Quality by Design (QbD), will provide products with defined specifications in relation to quality, purity, safety, and efficacy that were not possible when the reference product was developed. Actually, the need to prove comparability to the reference product by the biosimilar industry has increased the knowledge about the product and the production‐process associated by the use of powerful analytical tools. The technological challenges to make copies of biologic products while attending regulatory and market demands are expected to help innovation in the direction of attaining more productive manufacturing processes. © 2015 American Institute of Chemical Engineers Biotechnol. Prog., 31:1139–1149, 2015     

Future-proofing regulation for rapidly changing biotechnologies

Our understanding of DNA structure and how it interacts with the environment to give form and function at the organism level is growing at an unprecedented pace which shows no sign of slowing. These developments have already led to many new products and will continue to underpin as yet unpredicted future developments in biotechnology. However, this potential will not be realised unless the mechanisms for risk assessment, regulatory approval, product claims and labelling etc. are fit for purpose, have the confidence of all stakeholders and are sufficiently agile to support this rapidly changing field. The sectors that are making particular advances in biotechnological processes include agriculture, pharmaceuticals, food, chemical and human diagnostics and therapeutics. In many of these areas the research, investment and innovation pipeline is operating well as evidenced by the many marketed products. However, developments in plant breeding methods have posed particular challenges for regulators which in turn is stifling R&D and innovation, particularly in the EU. In rapidly moving areas of research and development, it is imperative that regulatory frameworks are future-proofed by design.

     

Genetic contributions to agricultural sustainability

The current tools of enquiry into the structure and operation of the plant genome have provided us with an understanding of plant development and function far beyond the state of knowledge that we had previously. We know about key genetic controls repressing or stimulating the cascades of gene expression that move a plant through stages in its life cycle, facilitating the morphogenesis of vegetative and reproductive tissues and organs. The new technologies are enabling the identification of key gene activity responses to the range of biotic and abiotic challenges experienced by plants. In the past, plant breeders produced new varieties with changes in the phases of development, modifications of plant architecture and improved levels of tolerance and resistance to environmental and biotic challenges by identifying the required phenotypes in a few plants among the large numbers of plants in a breeding population. Now our increased knowledge and powerful gene sequence-based diagnostics provide plant breeders with more precise selection objectives and assays to operate in rationally planned crop improvement programmes. We can expect yield potential to increase and harvested product quality portfolios to better fit an increasing diversity of market requirements. The new genetics will connect agriculture to sectors beyond the food, feed and fibre industries; agri-business will contribute to public health and will provide high-value products to the pharmaceutical industry as well as to industries previously based on petroleum feedstocks and chemical modification processes.     

Biosecurity in the age of Big Data: a conversation with the FBI

New scientific frontiers and emerging technologies within the life sciences pose many global challenges to society. Big Data is a premier example, especially with respect to individual, national, and international security. Here a Special Agent of the Federal Bureau of Investigation discusses the security implications of Big Data and the need for security in the life sciences.