The Impact of the COVID-19 Pandemic on the Future of Science Careers.

As COVID-19 swept across the world, it created a global pandemic and an unpredictable and challenging job market. This article discusses the future of the 2020-2021 job market in both academia and industry in the midst and aftermath of this pandemic.

Interchangeability Of Biological Drug Products-FDA Draft Guidance.

The Biological Price Competition and Innovation Act (BPCI Act) of 2009 established a pathway for the approval of biosimilars and interchangeable biosimilars in the United States. The Food Drug Administration (FDA) has issued several guidances on the development and assessment of biosimilars which implement the BPCI Act. In particular, a recent draft guidance on the interchangeability of biological products presents an overview of scientific considerations on the demonstration of interchangeability with a reference product. The present communication provides a general summary of the draft guidance and briefly observes a few current issues on interchangeability.

A Comparison of Coverage Restrictions for Biopharmaceuticals and Medical Procedures.

BACKGROUND: Differences in payer evaluation and coverage of pharmaceuticals and medical procedures suggest that coverage may differ for medications and procedures independent of their clinical benefit. We hypothesized that coverage for medications is more restricted than corresponding coverage for nonmedication interventions. METHODS: We included top-selling medications and highly utilized procedures. For each intervention-indication pair, we classified value in terms of cost-effectiveness (incremental cost per quality-adjusted life-year), as reported by the Tufts Medical Center Cost-Effectiveness Analysis Registry. For each intervention-indication pair and for each of 10 large payers, we classified coverage, when available, as either "more restrictive" or as "not more restrictive," compared with a benchmark. The benchmark reflected the US Food and Drug Administration label information, when available, or pertinent clinical guidelines. We compared coverage policies and the benchmark in terms of step edits and clinical restrictions. Finally, we regressed coverage restrictiveness against intervention type (medication or nonmedication), controlling for value (cost-effectiveness more or less favorable than a designated threshold). RESULTS: We identified 392 medication and 185 procedure coverage decisions. A total of 26.3% of the medication coverage and 38.4% of the procedure coverage decisions were more restrictive than their corresponding benchmarks. After controlling for value, the odds of being more restrictive were 42% lower for medications than for procedures. Including unfavorable tier placement in the definition of "more restrictive" greatly increased the proportion of medication coverage decisions classified as "more restrictive" and reversed our findings. CONCLUSIONS: Therapy access depends on factors other than cost and clinical benefit, suggesting potential health care system inefficiency.

Hubs to spread technology and save lives.

The patent on an expensive preventive treatment for respiratory syncytial virus infections expires this year. A WHO technology transfer hub in the Netherlands aims to help developing countries make the drug themselves. Gary Humphreys reports.

Biosimilars: where we were and where we are.

Recent progress in biosimilars development is overviewed, with attention to the history of issues and processes leading to current regulations, and to scientific considerations, including progress on design and operational implementation issues that arise and are peculiar to biosimilars trial design and implementation.

Multidisciplinary approach to R&D in vitiligo, a neglected skin disease.

A global interest in therapies for neglected diseases is rising, but traditional biopharma research and development (R&D) process is prohibitively expensive to justify cost of their development. Vitiligo is a multifactorial orphan disease that affects at minimum 35 million people worldwide, yet no therapeutic solutions exist. The present authors describe a budget-minded pursuit of the new therapy development for vitiligo, which includes a multidiscipline collaboration and effective bridging between academic research, biobanking, and bioinformatics. The present authors anticipate that the present authors' "theoretically induced and empirically guided" discovery process will enable development of more leads, with a much greater probability of success and under tighter budgets compared with those of the biopharma company. Ultimately, the multidisciplinary approach described below facilitates the collaborative development of personalized treatments for different patient subpopulations in vitiligo and other neglected diseases.

Emergence of biopharmaceutical innovators in China, India, Brazil, and South Africa as global competitors and collaborators.

Biopharmaceutical innovation has had a profound health and economic impact globally. Developed countries have traditionally been the source of most innovations as well as the destination for the resulting economic and health benefits. As a result, most prior research on this sector has focused on developed countries. This paper seeks to fill the gap in research on emerging markets by analyzing factors that influence innovative activity in the indigenous biopharmaceutical sectors of China, India, Brazil, and South Africa. Using qualitative research methodologies, this paper a) shows how biopharmaceutical innovation is taking place within the entrepreneurial sectors of these emerging markets, b) identifies common challenges that indigenous entrepreneurs face, c) highlights the key role played by the state, and d) reveals that the transition to innovation by companies in the emerging markets is characterized by increased global integration. It suggests that biopharmaceutical innovators in emerging markets are capitalizing on opportunities to participate in the drug development value chain and thus developing capabilities and relationships for competing globally both with and against established companies headquartered in developed countries.

Impact of Biopharmaceutics Classification System-based biowaivers.

The Biopharmaceutics Classification System (BCS) is employed to waive in vivo bioequivalence testing (i.e. provide "biowaivers") for new and generic drugs that are BCS class I. Granting biowaivers under systems such as the BCS eliminates unnecessary drug exposures to healthy subjects and provides economic relief, while maintaining the high public health standard for therapeutic equivalence. International scientific consensus suggests class III drugs are also eligible for biowaivers. The objective of this study was to estimate the economic impact of class I BCS-based biowaivers, along with the economic impact of a potential expansion to BCS class III. Methods consider the distribution of drugs across the four BCS classes, numbers of in vivo bioequivalence studies performed from a five year period, and effects of highly variable drugs (HVDs). Results indicate that 26% of all drugs are class I non-HVDs, 7% are class I HVDs, 27% are class III non-HVDs, and 3% are class III HVDs. An estimated 66 to 76 million dollars can be saved each year in clinical study costs if all class I compounds were granted biowaivers. Between 21 and 24 million dollars of this savings is from HVDs. If BCS class III compounds were also granted waivers, an additional direct savings of 62 to 71 million dollars would be realized, with 9 to 10 million dollars coming from HVDs.

An unofficial legislative history of the Biologics Price Competition and Innovation Act of 2009.

In March 2010, Congress passed the Biologics Price Competition and Innovation Act of 2009 (BPCIA). This law established a statutory pathway for approval of "biosimilars," follow-on versions of innovative biological products. This article traces the history of the BPCIA, beginning with a discussion of the origins of federal regulation of drugs and biologics, including passage of the Hatch-Waxman amendments, in Section I. Section I also describes the development of the European approval framework for biosimilars in the mid-2000s and how this increased interest in creation of a pathway in the United States. The article then provides, in Section II, an overview of early stakeholder discussions in the United States regarding legal and scientific issues relating to biosimilars, spanning the years 1998-2006. The legislative debate began in earnest in late 2006, when the first biosimilars bill was introduced. Section III of the article examines introduced bills, other legislative proposals, and related stakeholder discussion in detail, leading up to enactment of the BPCIA. Section IV describes the BPCIA as enacted, and the paper ends with the authors' concluding observations about the legislative negotiations and their implications for interpretation of the Act.

Alternative strategies for toxicity testing of species-specific biopharmaceuticals.

Although toxicology studies should always be conducted in pharmacologically relevant species, the specificity of many biopharmaceuticals can present challenges in identification of a relevant species. In certain cases, that is, when the clinical product is active only in humans or chimpanzees, or if the clinical candidate is active in other species but immunogenicity limits the ability to conduct a thorough safety assessment, alternative approaches to evaluating the safety of a biopharmaceutical must be considered. Alternative approaches, including animal models of disease, genetically modified mice, or use of surrogate molecules, may improve the predictive value of preclinical safety assessments of species-specific biopharmaceuticals, although many caveats associated with these models must be considered. Because of the many caveats that are discussed in this article, alternative approaches should only be used to evaluate safety when the clinical candidate cannot be readily tested in at least one relevant species to identify potential hazards.

Health economics of market access for biopharmaceuticals and biosimilars.

BACKGROUND AND SCOPE: This article discusses health economic challenges of research and development, registration, pricing and reimbursement of biopharmaceuticals and biosimilars. A literature search was carried out of PubMed, Centre for Reviews and Dissemination databases, Cochrane Database of Systematic Reviews and EconLit up to March 2009. FINDINGS: The development process of biopharmaceuticals is risky, lengthy, complex and expensive. Registration is complicated by the inherent variation between biopharmaceuticals. Also, as biopharmaceuticals are likely to be efficacious in a subgroup of the patient population, there is a need to select the most responsive target population and to identify biomarkers. To inform pricing and reimbursement decisions, the development process needs to collect comparative data to calculate the incremental cost effectiveness and budget impact of biopharmaceuticals. There is a role for innovative mechanisms such as risk-sharing arrangements to reimburse biopharmaceuticals. CONCLUSIONS: Given that biosimilars are similar, but not identical to the reference biopharmaceutical, the development process needs to generate clinical trial data in order to gain marketing authorisation. From a health economic perspective, the question arises whether inherent differences between biopharmaceuticals and biosimilars produce differences in safety, effectiveness and costs: to date, this question is unresolved. The early inclusion of health economics in the process of developing biopharmaceuticals and biosimilars is imperative with a view to demonstrating their relative (cost) effectiveness and informing registration, pricing and reimbursement decisions.

Biopharmaceutical innovation and industrial developments in South Korea, Singapore and Taiwan.

South Korea, Singapore and Taiwan are well known as export-oriented developmental states which for decades employed industrial policy to target particular industries for government support. In the past fifteen years, these three countries all identified the biopharmaceutical industry as a strategic sector. This article explores, through economic analysis, the rationale for this decision and the strategies chosen for linking into the global bio-economy with the objective of catching up in biopharmaceuticals. The paper identifies three comparative advantages enjoyed by these countries in the biopharma sector: (1) public investments in basic research; (2) private investments in phase 1 clinical trials; and (3) a potentially significant contract research industry managing latter-stage clinical trials. Governments employ a range of industrial policies, consistent with these comparative advantages, to promote the biopharmaceutical industry, including public investment in biomedical hubs, research funding and research and development (R&D) tax credits. We argue that the most important feature of the biopharmaceutical industry in these countries is the dominant role of the public sector. That these countries have made progress in innovative capabilities is illustrated by input measures such as R&D expenditure as share of gross domestic product, number of patents granted and clinical trials, and volume of foreign direct investment. In contrast, output indicators such as approval of new chemical entities suggest that the process of catching up has only just commenced. Pharmaceutical innovation is at the stage of mainly generating inputs to integrated processes controlled by the globally incumbent firms.

Implementation of Fully Integrated Continuous Antibody Processing: Effects on Productivity and COGm.

The changing landscape of the biopharmaceutical market is driving a paradigm shift toward continuous manufacturing. To date, integrated continuous bioprocessing has not been realized as enabling technologies are nascent. In this work, a fully integrated continuous process is successfully demonstrated from pilot scale bioreactor to drug substance. Comparable product quality is observed between the continuous process and a 500 L fed-batch conventional process. The continuous process generated material at a rate of 1 kg of purified mAb every 4 days, achieving a 4.6-fold increase in productivity compared to the fed-batch process A plant throughput analysis using BioSolve software shows that a fed-batch facility with 4 × 12 500 L stainless steel bioreactors and purification train of the corresponding scale can be replaced by a continuous facility consisting of 5 × 2000 L single use bioreactors and smaller purification train, with a cost reduction of 15%.

Recommendations for Comparison of Productivity Between Fed-Batch and Perfusion Processes.

Due to the growing interest in integrated continuous processing in the biopharmaceutical industry, productivity comparison of batch-based and continuous processes is considered a challenge. Integrated continuous manufacturing of biopharmaceuticals requires scientists and engineers to collaborate effectively. Differing definitions, for example, of volumetric productivity, may cause confusion in this interdisciplinary field. Therefore, the aim of this communication is to reiterate the standard definitions and their underlying assumptions. Applying them to an exemplary model scenario allows to demonstrate the differences and to develop recommendations for the comparison of productivity of different upstream processes.

The positive impacts of Real-World Data on the challenges facing the evolution of biopharma.

Demand for healthcare services is unprecedented. Society is struggling to afford the cost. Pricing of biopharmaceutical products is under scrutiny, especially by payers and Health Technology Assessment agencies. As we discuss here, rapidly advancing technologies, such as Real-World Data (RWD), are being utilized to increase understanding of disease. RWD, when captured and analyzed, produces the Real-World Evidence (RWE) that underpins the economic case for innovative medicines. Furthermore, RWD can inform the understanding of disease, help identify new therapeutic intervention points, and improve the efficiency of research and development (R&D), especially clinical trials. Pursuing precompetitive collaborations to define shared requirements for the use of RWD would equip service-providers with the specifications needed to implement cloud-based solutions for RWD acquisition, management and analysis. Only this approach would deliver cost-effective solutions to an industry-wide problem.

Monoclonal antibody "gold rush".

The market, sales and regulatory approval of new human medicines, during the past few years, indicates increasing number and share of new biologics and emergence of new multibillion dollar molecules. The global sale of monoclonal antibodies in 2006 were $20.6 billion. Remicade had annual sales gain of $1 billion during the past 3 years and five brands had similar increase in 2006. Rituxan with 2006 sales of $4.7 billion was the best selling monoclonal antibody and biological product and the 6th among the top selling medicinal brand. It may be the first biologic and monoclonal antibody to reach $10 billion annual sales in the near future. The strong demand from cancer and arthritis patients has surpassed almost all commercial market research reports and sales forecast. Seven monoclonal antibody brands in 2006 had sales exceeding $1 billion. Humanized or fully human monoclonal antibodies with low immunogenicity, enhanced antigen binding and reduced cellular toxicity provide better clinical efficacy. The higher technical and clinical success rate, overcoming of technical hurdles in large scale manufacturing, low cost of market entry and IND filing, use of fully human and humanized monoclonal antibodies has attracted funds and resources towards R&D. Review of industry research pipeline and sales data during the past 3 years indicate a real paradigm shift in industrial R&D from pharmaceutical to biologics and monoclonal antibodies. The antibody bandwagon has been joined by 200 companies with hundreds of new projects and targets and has attracted billions of dollars in R&D investment, acquisitions and licensing deals leading to the current Monoclonal Antibody Gold Rush.

Multiobjective long-term planning of biopharmaceutical manufacturing facilities.

Biopharmaceutical companies with large portfolios of clinical and commercial products typically need to allocate production across several multiproduct facilities, including third party contract manufacturers. This poses several capacity planning challenges which are further complicated by the need to satisfy different stakeholders often with conflicting objectives. This work addresses the question of how a biopharmaceutical manufacturer can make better long-term capacity planning decisions given multiple strategic criteria such as cost, risk, customer service level, and capacity utilization targets. A long-term planning model that allows for multiple facilities and accounts for multiple objectives via goal programming is developed. An industrial case study based on a large scale biopharmaceutical manufacturer is used to illustrate the functionality of the model. A single objective model is used to identify how best to use existing capacity so as to maximize profits for different demand scenarios. Mitigating risk due to unforeseen circumstances by including a dual facility constraint is shown to be a reasonable strategy at base case demand levels but unacceptable if demands are 150% higher than expected. The capacity analysis identifies where existing capacity fails to meet demands given the constraints. A multiobjective model is used to demonstrate how key performance measures change given different decision making policies where different weights are assigned to cost, customer service level, and utilization targets. The analysis demonstrates that a high profit can still be achieved while meeting key targets more closely. The sensitivity of the optimal solution to different limits on the targets is illustrated.