Biotechnology Research Articles

Industry sponsorship bias in cost effectiveness analysis: registry based analysis

ObjectiveTo assess the association between industry sponsorship (drug, medical device, and biotechnology companies) and cost effectiveness results in cost effectiveness analysis (CEA).DesignRegistry based analysisData sourceThe Tufts Cost-Effectiveness Analysis Registry was...

Global Investigative Site Personnel Diversity and Its Relationship with Study Participant Diversity.

Background There is little to no empirical data on the race and ethnicity of the global community of professionals conducting clinical trials funded by pharmaceutical and biotechnology companies and little empirical evidence on the relationship between the race and ethnicity of investigative site personnel and the overall and corresponding diversity of participants enrolled.MethodsA global online survey conducted in mid-2021 gathered responses from 3462 clinical research professionals representing approximately 3300 distinct investigative sites.ResultsWorldwide, including all research settings, the majority (64%) of investigative site personnel are White, 20% are LatinX, 6% are Black, 7% are Asian and 3% are other races and ethnicities (e.g., indigenous peoples, Pacific Islander, Middle Eastern, etc.). The representation of non-white site personnel is significantly higher in North America and Rest of World (ROW) compared to Europe. The highest levels of personnel diversity are found in private community-based practices, investigative sites and site networks. A significant correlation (p < 0.001) was found between site personnel diversity and patient enrollment diversity worldwide. As the mix of site personnel by race and ethnicity increases, the diversity of patients enrolled—except for Asian patients in sites outside of North America—also increases. A significant relationship was also found between the proportion of a given race or ethnicity of investigative site personnel and the corresponding race and ethnicity of patients enrolled.ConclusionsAn opportunity exists to address under-representation in clinical trials through identifying, hiring and supporting investigative site personnel to best reflect the patient communities that they serve.

Driving stem cell innovation

Brock Reeve has been the Executive Director of the Harvard Stem Cell Institute since 2006. In partnership with the Faculty Directors, he has overall responsibility for the operations and strategy of the Institute which is comprised of the schools of Harvard University and its affiliated hospitals and research institutions. Under the leadership of its Executive Committee, HSCI invests in scientific research and its faculty has grown to include over 370 Principal and Affiliated members. The Institute is engaged with several leading pharmaceutical companies and foundations in joint research projects and its faculty have founded over 40 stem cell-related startup companies and serve on leading Scientific Advisory Boards. Brock came to HSCI from the commercial sector with extensive experience in both management consulting and operations for technology-based companies, with a focus on life sciences. Prior to Harvard, Brock was COO and Managing Director of Life Science Insights a consulting and market research firm specializing in information technology in life sciences. As a consultant, Brock has additional experience in the healthcare/life sciences market with IBM, Viant Corp. and SRI Consulting, where his clients included some of the leading pharmaceutical, biotechnology and medical device companies. Brock received a BA and MPhil from Yale University and an MBA from Harvard Business School.

Current Aspects of Xenotransplantation in Human

Xenotransplantation is an approach which will be able to support the increasing demand of organ donation since the organ does not need to come from humans. Up till now, xenotransplantation is still barely performed since its risk and chance of success are still not proven to be safe. One of the biggest obstacles is rejection which may lead to xenograft failure and can occur in certain types and from certain causes. However, the risk of rejection can be minimized by the process of genetic engineering and applying anti-rejection drugs in which scientists and researchers are developing so that the procedure becomes safer in the future. Although the patient who was considered as the first successful xenotransplantation in human case had died a few months after the surgery and the cause of death still remains unsolved, the field of xenotransplantation still keeps developing by researchers, medical universities, and biotechnology companies since they all agree that xenotransplantation will produce lots of advantages and will be a big step of the medical treatment field. Despite the fact that xenotransplantation is a procedure that is risky and raises public concerns and ethical issues, the procedure is still believed to give more benefits towards the patient and medical development since serious problems like organ shortage and high number of deaths on the waiting list will be solved.

ProFound to tap trove of human proteins

Flagship Pioneering, which conceives of and launches biotech companies, has formed ProFound Therapeutics with an initial backing of $75 million. ProFound says it will identify new protein-based drug targets among tens of thousands of previously unlogged proteins that its technology has uncovered. The Human Genome Project had an overly constrained definition of a protein, according to ProFound. By expanding what it looked for, the company says, it has identified many more proteins that could be therapeutic targets.

Increasing the Reuse of Protein Non-Naïve Nonhuman Primates in Pharmaceutical Drug Discovery and Development: An Overview and Industry Position on the Challenges and Benefits.

The IQ Consortium NHP Reuse Working Group (WG) comprises members from 15 pharmaceutical and biotechnology companies. In 2020, the WG developed and distributed a detailed questionnaire on protein non-naïve NHP reuse to the WG member companies. The WG received responses from key stakeholders including principal investigators, facility managers, animal welfare officers and research scientists. This paper's content reflects the consolidated opinion of the WG members and the questionnaire responses on the subject of NHP reuse within nonclinical programs at all stages of research and development. Many of the pharmaceutical companies represented in the working group or participating in the questionnaire have already achieved some level of NHP reuse in their nonclinical programs, but the survey results suggested that there is significant potential to increase NHP reuse further and a need to understand the considerations involved in reuse more clearly. The WG has also focused carefully on the inherent concerns and risks of implementing protein non-naive NHP reuse and has evaluated the best methods of risk assessment and decision-making. This paper presents a discussion on the challenges and opportunities surrounding protein non-naïve NHP reuse and aims to stimulate further industry dialogue on the subject and provide guidance for pharmaceutical companies to establish roadmaps and decision trees enabling increased protein non-naïve NHP reuse. In addition, this paper represents a solid basis for collaborative engagement between pharmaceutical and biotechnology companies with contract research organizations (CROs) to discuss how the availability of protein non-naïve NHP within CROs can be better leveraged for their use within nonclinical studies.

Moo-re Gene-edited Animals Get Regulatory Clearance: U.S. FDA Approves Genetically Engineered Cattle for Human Consumption

Moo-re Gene-edited Animals Get Regulatory Clearance: U.S. FDA Approves Genetically Engineered Cattle for Human Consumption

Prototype precision oncology learning ecosystem: Norwegian precision cancer medicine implementation initiative.

e13634 Background: Norway, a country with a publicly funded health care system, was in 2018-19 lagging behind with respect to implementation of precision cancer medicine (PCM). Methods: Our approach mid-2019 was very simple and set out three aims: i) To establish access to advanced molecular diagnostics to allow identification and stratification of cancer patients into clinical trials; ii) To increase the volume of clinical trials with a PCM approach to gain experience and build competence; and iii) In parallel work for implementation of PCM into standard of care. Results: In a trans-disciplinary project we worked along four lines: i) Gathered support to have oncologists, hematologists, pathologists and cancer researchers join a nation-wide, bottom-up initiative with a few common priorities; ii) Liaised with executives and regulators in regional health care systems, The Ministry of Health and other public stakeholders and charities to have the top-down approaches meet the bottom-up initiative; iii) Aligned with industry to explore the possibility of a public-private partnership and iv) Coordinated with other PCM initiatives internationally. Over the past two years we have thus built and raised funding for: a) The InPreD-Norway national infrastructure delivering precision cancer diagnostics for patient identification and stratification into clinical trials (publicly reimbursed) and operating the national molecular tumor board; b) the IMPRESS-Norway national researcher-initiated PCM intervention trial (https://impressnorway.com), which opened for inclusion Q2 2021 and runs at all hospitals that treat cancer patients (18 hospitals). The trial is modelled on and coordinated with the Dutch DRUP trial and aligned with similar trials in the Nordic countries; c) the INSIGHT/INCLUDE projects for research on control cohorts, use of real world evidence (RWE), health economics and reimbursement models, and ethics, legal aspects and governance; and d) the CONNECT public-private partnership (https://www.connectnorway.org) for PCM implementation with 29 partners (14 pharma &amp; biotech companies, 9 public partners and 4 NGOs) for interaction with InPreD and IMPRESS initiatives and providing a forum that includes regulators and payors for policy discussions of reimbursement models and regulatory framework. Conclusions: Our experience could serve as a model for building a functioning ecosystem for implementation of PCM. Unique aspects include the nation-wide initiative, the population effect of the diagnostics to be offered and the integration of a public-private partnership.

The Evolution of CRISPR Technology from Editing to Diagnostics

The Evolution of CRISPR Technology from Editing to Diagnostics

Assessment of Oxidative Stress and Metabolic Risks With Machine Learning Algorithms in Ethnically Diverse Population: Cross-Sectional Data in Korea and the Netherlands

ObjectivesThe underlying mechanisms for the development of chronic lifestyle-related diseases result from enhanced oxidative stress, and method for quantifying in healthy adult individuals have been investigated in the previous study. However, this predictor targeted the Korean population, and it is currently unclear how to evaluate oxidative stress in diverse ethnicities. On top of that, impaired metabolism is another major process, which is closely related to cellular, organ, and organism levels interacting with oxidative stress to initiate these diseases. Therefore, this study is aimed to develop and validate a predictor to quantify oxidative stress and metabolic risks across the ethnicity. MethodsThis study was conducted using cross-sectional data of the Nutrition Questionnaires plus (NQ plus) study in the Netherlands (n = 618) and the Korea National Health and Nutrition Examination Survey (KNHANES) (n = 6,387). To merge these two separate population data equally, propensity score matching was applied. Based on health space statistical methodology, each axis was obtained from two different binary samples: healthy controls (n = 324) versus oxidative disease cases (n = 391) and metabolic syndrome cases (n = 73). The model development was carried out in 10-fold cross-validation of ridge, elastic-net, and LASSO (least absolute shrinkage and selection operator) regularized regression. Evaluating the predictive accuracy of the fine-tuned model was validated by unmatched data after propensity score matching. ResultsA total of 22 and 18 features were selected in fine-tuned models to distinguish oxidative stress and metabolic risks from healthy controls respectively. The performance of the prediction was assessed with the area under the receiver operating characteristic curve of 0.972 (CI 0.967 to 0.976) and of 0.962 (CI 0.954 to 0.97). ConclusionsThese practical composite biomarkers appear useful to stratify oxidative stress and metabolic risks in healthy adults beyond differences between populations. Further external validation is required to ensure prognostic value and general applicability in longitudinal cohorts. Funding SourcesThis research was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Ministry of Science & ICT(2012M3A9C4048761).

Biopharma Is Going Digital … Bit by Bit

Biopharma Is Going Digital … Bit by Bit

Yeast Sequencing

This paper examines the model of network genomics pioneered in the late 1980s and adopted in the European Commission-led Yeast Genome Sequencing Project (YGSP). It contrasted with the burgeoning large-scale center model being developed in the United States to sequence the yeast genome, chiefly as a pilot for tackling the human genome. We investigate the operation and connections of the two models by exploring a co-authorship network that captures different types of sequencing practices. In our network analysis, we focus on institutions that bridge both the European and American yeast whole-genome sequencing projects, and such concerted projects with non-concerted sequencing of yeast DNA. The institutions include two German biotechnology companies and Biozentrum, a research institute at Universität Basel that adopted yeast as a model to investigate cell biochemistry and molecular biology. Through assessing these bridging institutions, we formulate two analytical distinctions: between proximate and distal, and directed and undirected sequencing. Proximate and distal refer to the extent that intended users of DNA sequence data are connected to the generators of that data. Directed and undirected capture the extent to which sequencing was part of a specific research program. The networked European model, as mobilized in the YGSP, enabled the coexistence and cooperation of institutions exhibiting different combinations of these characteristics in contrast with the more uniformly distal and undirected large-scale centers. This contributes to broadening the historical boundaries of genomics and presenting a thicker historiography, one that inextricably meshes genomics with the trajectories of biotechnology and cell biology. This essay is part of a special issue entitled The Sequences and the Sequencers: A New Approach to Investigating the Emergence of Yeast, Human, and Pig Genomics, edited by Miguel García-Sancho and James Lowe.

A diversity profile of total bacteria (culturable and unculturable) as aquaculture marine water source of in central marine bio industry (BBIL) Mataram, Indonesia

The bacterial community plays a pivotal role in the quality of water sources for aquaculture activities, affecting the survival of cultured animals. In the present study, bacteria inhabiting seawater in Mataram were analyzed using culturable and unculturable analysis. Total bacteria cultured in SWC (seawater complete) medium had an abundance of 4.5 × 107 CFU mL-1. Nitrifying, denitrifying, and DNRA (dissimilative nitrate reduction to ammonium) bacteria were found in an abundance of 1.15 × 107 CFU mL-1, 7.7 × 106 CFU mL-1, and 5.6 × 106 CFU mL-1, respectively. Analysis of total bacteria performed by the Illumina MiSeq platform using the V3–V4 hypervariable regions of 16S rRNA gene indicated that the majority of the bacterial sequences related to Proteobacteria (84.2%), followed by Firmicutes (10.2%), Acidobacteria (1.5%), Bacteroidetes (1.4%), and Chloroflexi (1%). Family Piscirickettsiaceae, belonging to the order Thriotrichales, was observed as the most prevalent group accounting for 20.9%. In this study, Proteobacteria, the most common phylum, was dominated by Gammaproteobacteria. At the genus level, Alteromonas, Marinobacterium, and Methylophaga appeared as the top three prevalent groups inhabiting seawater in Mataram. Meanwhile, the top five bacterial species in seawater were Alteromonas bacterium, Methylophaga sp., Nautella italic, Ruegeria mobilis, and Pseudoalteromonas phenolica.

An integrated valuation model for payer and investor

ABSTRACT Background In order to optimize positioning and associated drug price for both payer and investor, it is for a company essential to forecast the potential market access attractiveness for the new drug for different indications at the early onset of the clinical development program. This analysis must include the constraints from the perspective of the payer, but also the biotech companies, who require a minimum drug price to satisfy their investors. This paper aims to provide an Integrated Valuation Model for payer and investor, bridging concepts from health economics and economic valuation reflecting the perspectives of the payer and the investor for a drug in early clinical development phase. The concept is illustrated for a new hypothetical drug (Product X) in advanced breast cancer in 1-line, 2-line, and 3-line position. Methods The Integrated Valuation Model includes the outcomes of the budget impact model, pricing matrix model, and cost-effectiveness model reflecting the payer’s perspective. These models are interacted and linked with a discounted cash flow model in order to reflect also the economic value from the investor’s perspective. Results The maximum price in 1-line position is €269.7 for the payer and the minimum price is €14.7 for the investor, which are unit prices per administration corresponding with treatment regimens for the comparative treatments. In 2-line position, the maximum price is €274.1 for the payer and the minimum price for the investor increases to €184.5 for the investor because of the smaller market size in 2-line position, which leads to a smaller pricing corridor to satisfy both payer and investor. Consequently, Product X has market access attractiveness for both payer and investor in 1-line and 2-line position. However, the minimum price €942.7 in 3-line position for the investor is higher than the maximum price €283.3 for the payer, which means there is no market potential. Conclusion The practical strategic application of the Integrated Valuation Model is optimization of positioning and price of Product X. Hence, it can be a transparent tool in early-stage development of a compound based on upfront assessment of market access attractiveness for the payer and the investor.

Discussion: The Importance of Protecting the Structure and Viability of Adipose Tissue for Fat Grafting

New Orleans, La. From Obatala Sciences, Inc. Received for publication July 6, 2021; accepted September 30, 2021. Disclosure:The author is a co-founder, co-owner, and chief scientific officer of Obatala Sciences, Inc., and LaCell, LLC, for-profit biotechnology companies focusing on the clinical translation of adipose-derived cells and extracellular matrix products for regenerative medicine. He is also a co-owner and co-founder of Talaria Antibodies, Inc., and the inventor on patents related to adipose and stromal/stem cell research applications. Jeffrey M. Gimble, M.D., Ph.D., Obatala Sciences, Inc., 2000 Lakeshore Drive, Suite 4020, New Orleans, La. 70122 [email protected]

AAV vector characterization best practices

David McCall, Commissioning Editor, Cell &amp; Gene Therapy Insights, speaks to Ga&#235;l Stephant, Senior CMC Project Leader, Vivet Therapeutics.Ga&#235;l St&#233;phant graduated from the Arts et M&#233;tiers CNAM, Paris III in 2008 as Engineer in biology, after working a few years as a technician. M. St&#233;phant joined innovative cell therapy company, Celogos in 2005 to develop an animal component free cell culture media designed to increase cell growth as well as reducing risk for patient. In 2008, he set up the cell culture laboratory Xentech (CRO company) for preclinical in vitro/ex vivo cancer model development. In 2012, he was hired as head of vector bioproduction unit at Theravectys. He then started in 2015, a first CMC Project leader r&#244;le at Yposkezy (formerly Genethon CDMO) followed by 3 years at Gensight Biologics, a biotech company where he was in charge of the production of AAV vector batches to be used in phases I and II clinical trials, as well as the preparation towards commercial phase. He then changed environment and joigned the pharmaceutical company Servier, to lead the CMC team of the CART cell/gene therapy development. Since 2021, M.St&#233;phant works for Vivet Therapeutics, a biotech company, where he manages the CMC activities for recombinant proteins and gene therapy products.

Overcoming the immune-related shortfalls of AAV

Genine Winslow is the CEO and co-founder of Chameleon Biosciences, a biotechnology company she founded in 2017 focused on safer, more effective gene therapies. At Chameleon, Genine combines her backgrounds in both immunology and gene therapy to engineer a next generation AAV based vector for systemic repeat dosing for children and adults who today cannot be treated with conventional gene therapies. Prior to Chameleon, Winslow has led gene therapy scientific initiatives at multiple companies including Audentes Therapeutics, BioMarin, BlueBird Bio, and Cell Genesys. On March 30th 2022, David McCall, Editor, Cell and Gene Therapy Insights spoke to Genine Winslow about overcoming the immune-related shortfalls of AAV. This article has been written based on that interview.

Trends and considerations in cell and gene therapy M&amp;A, partnering and IP

David McCall, Editor,&#160;Cell and Gene Therapy Insightsspeaks to Ewan Townsend, Partner, Arnold &amp; PorterEwan Townsend’s practice at Arnold &amp; Porter focusses on the commercial transactions involved in the development, exploitation and commercialization of medicinal products, representing many of the world’s most sophisticated biotechnology and pharmaceutical companies. His experience includes structuring, drafting and negotiating licence and collaboration agreements, manufacturing, distribution and supply agreements, material transfer agreements, clinical trial agreements, services agreements, co-promotion/co-development alliances, pharmacovigilance and quality agreements. Ewan also advises on the regulatory issues that frequently arise in the context of those transactions and throughout the medicinal product life cycle, particularly in relation to marketing authorizations, manufacturing, distribution, advertising, pricing and reimbursement.

2021 White Paper on Recent Issues in Bioanalysis: TAb/NAb, Viral Vector CDx, Shedding Assays; CRISPR/Cas9 & CAR-T Immunogenicity; PCR & Vaccine Assay Performance; ADA Assay Comparability & Cut Point Appropriateness(Part 3 - Recommendations on Gene Therapy, Cell Therapy, Vaccine Assays; Immunogenicity of Biotherapeutics and Novel Modalities; Integrated Summary of Immunogenicity Harmonization).

The 15th edition of the Workshop on Recent Issues in Bioanalysis (15th WRIB) was held on 27 September to 1 October 2021. Even with a last-minute move from in-person to virtual, an overwhelmingly high number of nearly 900 professionals representing pharma and biotech companies, contract research organizations (CROs), and multiple regulatory agencies still eagerly convened to actively discuss the most current topics of interest in bioanalysis. The 15th WRIB included 3 Main Workshops and 7 Specialized Workshops that together spanned 1week in order to allow exhaustive and thorough coverage of all major issues in bioanalysis, biomarkers, immunogenicity, gene therapy, cell therapy and vaccines. Moreover, in-depth workshops on biomarker assay development and validation (BAV) (focused on clarifying the confusion created by the increased use of the term "Context of Use - COU"); mass spectrometry of proteins (therapeutic, biomarker and transgene); state-of-the-art cytometry innovation and validation; and, critical reagent and positive control generation were the special features of the 15th edition. This 2021 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop, and is aimed to provide the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2021 edition of this comprehensive White Paper has been divided into three parts for editorial reasons. This publication (Part 3) covers the recommendations on TAb/NAb, Viral Vector CDx, Shedding Assays; CRISPR/Cas9 & CAR-T Immunogenicity; PCR & Vaccine Assay Performance; ADA Assay Comparability & Cut Point Appropriateness. Part 1A (Endogenous Compounds, Small Molecules, Complex Methods, Regulated Mass Spec of Large Molecules, Small Molecule, PoC), Part 1B (Regulatory Agencies' Inputs on Bioanalysis, Biomarkers, Immunogenicity, Gene & Cell Therapy and Vaccine) and Part 2 (ISR for Biomarkers, Liquid Biopsies, Spectral Cytometry, Inhalation/Oral & Multispecific Biotherapeutics, Accuracy/LLOQ for Flow Cytometry) are published in volume 14 of Bioanalysis, issues 9 and 10 (2022), respectively.

Grapevine Xylem Sap Is a Potent Elicitor of Antibiotic Production in Streptomyces spp.

Streptomyces bacteria produce a wide number of antibiotics and antitumor compounds that have attracted the attention of pharmaceutical and biotech companies. In this study, we provide evidence showing that the xylem sap from grapevines has a positive effect on the production of different antibiotics by several Streptomyces species, including S. ambofaciens ATCC 23877 and S. argillaceus ATCC 12596 among others. The production of several already known compounds was induced: actinomycin D, chromomycin A3, fungichromin B, mithramycin A, etc., and four compounds with molecular formulas not included in the Dictionary of Natural Products (DNP v28.2) were also produced. The molecules present in the xylem sap that acts as elicitors were smaller than 3 kDa and soluble in water and insoluble in ether, ethyl acetate, or methanol. A combination of potassium citrate and di-D-fructose dianhydrides (related to levanbiose or inulobiose) seemed to be the main effectors identified from the active fraction. However, the level of induction obtained in the presence of these compounds mix was weaker and delayed with respect to the one got when using the whole xylem sap or the 3 kDa sap fraction, suggesting that another, not identified, elicitor must be also implied in this induction.