Biopharmaceutical Sector Research Articles

QSAR Implementation for HIC Retention Time Prediction of mAbs Using Fab Structure: A Comparison between Structural Representations.

Monoclonal antibodies (mAbs) constitute a rapidly growing biopharmaceutical sector. However, their growth is impeded by high failure rates originating from failed clinical trials and developability issues in process development. There is, therefore, a growing need for better in silico tools to aid in risk assessment of mAb candidates to promote early-stage screening of potentially problematic mAb candidates. In this study, a quantitative structure–activity relationship (QSAR) modelling workflow was designed for the prediction of hydrophobic interaction chromatography (HIC) retention times of mAbs. Three novel descriptor sets derived from primary sequence, homology modelling, and atomistic molecular dynamics (MD) simulations were developed and assessed to determine the necessary level of structural resolution needed to accurately capture the relationship between mAb structures and HIC retention times. The results showed that descriptors derived from 3D structures obtained after MD simulations were the most suitable for HIC retention time prediction with a R2 = 0.63 in an external test set. It was found that when using homology modelling, the resulting 3D structures became biased towards the used structural template. Performing an MD simulation therefore proved to be a necessary post-processing step for the mAb structures in order to relax the structures and allow them to attain a more natural conformation. Based on the results, the proposed workflow in this paper could therefore potentially contribute to aid in risk assessment of mAb candidates in early development.

Solid-Phase Protein Modifications: Towards Precision Protein Hybrids for Biological Applications.

Proteins have attracted increasing attention as biopharmaceutics and diagnostics due to their high specificity, biocompatibility, and biodegradability. The biopharmaceutical sector in particular is experiencing rapid growth, which has led to an increase in the production and sale of protein drugs and diagnostics over the last two decades. Since the first‐generation biopharmaceutics dominated by native proteins, both recombinant and chemical technologies have evolved and transformed the outlook of this rapidly developing field. This review article presents updates on the fabrication of covalent and supramolecular fusion hybrids, as well as protein‐polymer hybrids using solid‐phase approaches that hold great promise for preparing protein hybrids with precise control at the macromolecular level to incorporate additional features. In addition, the applications of the resultant protein hybrids in medicine and diagnostics are highlighted where possible.

Knowledge Management as a Pharmaceutical Quality System Enabler: How Enhanced Knowledge Transfer Can Help Close the ICH Q10 to ICH Q12 Gap.

Knowledge management (KM) is identified in ICH Q10 (Pharmaceutical Quality System), as a key enabler to the pharmaceutical quality system (PQS). ICH Q8 (Pharmaceutical Development), ICH Q11 (Development and Manufacture of Drug Substances), and ICH Q12 (Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management) each build on the expectation that knowledge will be managed effectively in order to support and improve the product and process across the pharmaceutical product life cycle. However, in spite of the fact that KM was introduced in ICH Q10 over 10 years ago, there is ample evidence that it is not yet a mature discipline within the biopharmaceutical sector, and the authors suggest that this could hinder full realization of the potential benefits of ICH Q8, ICH Q11, and ICH Q12. The Pharmaceutical Regulatory Science Team (PRST), a research team based at the Dublin Technological University (TU Dublin) in Ireland, has been conducting research on KM for several years, and this paper presents the next phase in this research. Specifically, the focus of this current research was to explore ways to offer practical solutions to improve the management of knowledge across the pharmaceutical product life cycle, starting with a focus on enhancing knowledge transfer during technology transfer projects. The typical challenges associated with ineffective knowledge transfer were presented and the high-level requirements needed to address these were identified through the research. From these requirements, a four-step framework was developed as a systematic means to enhance knowledge transfer. Accompanying the framework was a KM toolkit consisting of a range of KM practices (tools, processes, and behaviors) to facilitate more effective knowledge flow during technology transfer. It was then illustrated how such a framework can be extended across the entire pharmaceutical product life cycle, supporting the advancement of KM from an enabler in ICH Q10 to a key consideration (both technical and regulatory) in ICH Q12.

Spectroscopic and thermodynamic studies on binding behaviour of an ionic liquid, 2′,3′-Epoxypropyl-N-methyl-2-oxopyrrolidinium acetate, with bovine serum albumin (BSA)

Spectroscopic and thermodynamic investigation of molecular interactions in a binary mixture of 2′,3′-epoxypropyl-N-methyl-2-oxopyrrolidinium acetate ([EPMpyr][OAC]) ionic liquid (IL) with a bovine serum albumin (BSA) aqueous solution was carried out. The thermophysical properties of density (ρ) and speed of sound (u) were first measured for the binary mixture at different mole concentrations in the temperature range from 293.15–323.15 K at a 5 K interval at atmospheric pressure. Using the above data, the thermodynamic properties of excess molar volume (VmE), isentropic compressibility (ks), deviation in isentropic compressibility Δks and intermolecular free length Lf were derived. These thermodynamic parameters have been used to get more information about the interaction of IL with BSA. In addition, absorption, steady state emission, synchronous emission, three-dimensional (3D) emission and circular dichroism (CD) have been exploited to acquire an understanding of the binding mechanisms and binding strengths of the interactions between the IL and BSA. Emission quenching results clearly indicate that the effect of IL on trypthophan of BSA. This work was undertaken with the expectation of getting results which would cast light on the types of interactions occurring between [EPMpyr][OAC] and BSA molecule. Furthermore, the data emanating from this work may help researchers in the bio-pharmaceutical sector developing more active IL based drugs. Moreover, this work can provide valuable information of potential interest to researchers in biotechnology including drug bioengineering.

Aggregation-prone peptides modulate activity of bovine interferon gamma released from naturally occurring protein nanoparticles

Efficient protocols for the production of recombinant proteins are indispensable for the development of the biopharmaceutical sector. Accumulation of recombinant proteins in naturally-occurring protein aggregates is detrimental to biopharmaceutical development. In recent years, the view of protein aggregates has changed with the recognition that they are a valuable source of functional recombinant proteins. In this study, bovine interferon-gamma (rBoIFN-γ) was engineered to enhance the formation of protein aggregates, also known as protein nanoparticles (NPs), by the addition of aggregation-prone peptides (APPs) in the generally recognized as safe (GRAS) bacterial Lactococcus lactis expression system. The L6K2, HALRU and CYOB peptides were selected to assess their intrinsic aggregation capability to nucleate protein aggregation. These APPs enhanced the tendency of the resulting protein to aggregate at the expense of total protein yield. However, fine physico-chemical characterization of the resulting intracellular protein NPs, the protein released from them and the protein purified from the soluble cell fraction indicated that the compactability of protein conformations was directly related to the biological activity of variants of IFN-γ, used here as a model protein with therapeutic potential. APPs enhanced the aggregation tendency of fused rBoIFN-γ while increasing compactability of protein species. Biological activity of rBoIFN-γ was favored in more compacted conformations. Naturally-occurring protein aggregates can be produced in GRAS microorganisms as protein depots of releasable active protein. The addition of APPs to enhance the aggregation tendency has a positive impact in overall compactability and functionality of resulting protein conformers.

The role of frequent engagement in alliances in firm likelihood to patent

PurposeThe purpose of this paper is to explore the role of alliance experience in firm innovation; it argues that, while cumulative alliance experience has a marginally diminishing contribution to likelihood of firm innovation over time, frequent engagement in alliances and an expanding alliance portfolio inhabit an enhancing role. This reveals new dimensions to the role of alliance experience as an antecedent to firm learning in managing alliances and to the development of alliance capabilities.Design/methodology/approachThe paper estimates a range of models identifying the relationship between alliance experience and firm innovation. The panel data sample captures the full range of firms active in the UK bio-pharmaceuticals sector during the early stages of its development observing them from 1991 to 2001. An exploratory case study analysis is employed to shed light on the nuanced factors linking frequent engagement in alliances to the development of practices for efficient alliance management.FindingsThe paper shows that cumulative alliance experience has a marginally diminishing contribution to likelihood of firm innovation over time, while frequent engagement in alliances and the ensuing expansion of alliance portfolios enhance firm innovation. The exploratory case analysis demonstrates a link between frequent engagement in alliances and the development of processes for alliance management that could collectively reflect alliance capabilities.Originality/valueContribution derives from a longitudinal analysis of an original panel data set that maps the UK bio-pharmaceuticals sector over the initial period of its development. The paper sheds light on factors that can compel firms to form alliance capabilities, and extends a currently thin body of work on the foundations and antecedents to alliance and alliance portfolio capabilities.

Availability and Pharmacoeconomics of Insulin Therapy in Countries with the Largest Number of Diabetics

The aim of the review was to analyze the availability of insulin therapy and the ways to improve it in countries with the largest number of patients with diabetes. It was also aimed to assess the medical, social and economic importance of insulin therapy and industrial production of therapeutic recombinant insulin. Materials and methods. The analysis was based on the data taken from monographs and publications in peer-reviewed journals, reports of companies and medical organizations, and the information available in the Internet. The demand and supply in the market of recombinant therapeutic insulin, the insulin market segmentation, and the costs for insulin replacement therapy in countries with the largest number of patients with diabetes were studied. Results and discussion. The pro- and contra- arguments regarding the import of insulin and its impact on the national budget are presented. Technological specifics of recombinant insulin production are discussed; the funding and investments in the biopharmaceutical sector are analyzed. The benefits of industrial production of recombinant therapeutic insulin and its impact on the regional and national economy are demonstrated. Conclusion. The availability of therapeutic insulin in most countries with the largest number of diabetics is unsatisfactory and needs a radical improvement. By analyzing the economic aspects of diabetes and the pharmacoeconomics of insulin, it is advised to develop a modern management system for insulin replacement therapy, especially in countries with large numbers of diabetics. The use of innovative technologies will reduce the production costs of recombinant therapeutic insulin, increase the availability of insulin therapy and thereby improve the quality of life in diabetic patients. Evidence that the production of therapeutic insulin has a positive effect not only on the healthcare, but on the socio-economic situation in the region is also provided. Countries with a number of diabetics exceeding 5 million are encouraged to launch their own production of recombinant therapeutic insulin. The results of the present analysis confirm that half of them are able to manufacture adequate human insulin and/or its analogues.

Policy coherence as a demand for excellence in Iranian bio-production industry

PurposeThe Iranian bio-pharma industry was the first high-tech industry in the country, which had succeeded to develop innovative products. Despite past successes, there are bottlenecks preventing the industry from meeting the national standard and plans for excellence. The purpose of this paper is to find out the challenges impeding further innovation of the firms in the industry and find solution to the issues. Based on these findings, the authors recommend a set of policies that might be of interest to the new-comer countries in biotechnology.Design/methodology/approachThe institutional structure of the industry, its market situation and the players are studied using a qualitative method based on an institutional approach and an appreciative theory.FindingsTen challenges were found after examining the pyramid of technological capabilities. Moreover; conflicting approaches in the policies made for the national health system and industrial development are identified. Adoption of policy coherence has been highlighted as a necessary strategy to harmonize and integrate the approaches required to play a role in bio-production global market actively.Practical implicationsA unique focal point for the country’s strategic plans should be assigned, and the supply-side policies with demand-side policies must be balanced.Originality/valueThis paper is an evidence-based effort to bring policy coherence as an approach in sectoral level, while political settlement lies in governance level. The opportunities for improvement are highlighted in the Iranian bio-pharmaceutical sector, as a key technology. Moreover, the findings could be used as lessons-learned for new-comers countries.

Bioprocessing in the Digital Age: The Role of Process Models

In this age of technology, the vision of manufacturing industries built of smart factories is not a farfetched future. As a prerequisite for Industry 4.0, industrial sectors are moving towards digitalization and automation. Despite its tremendous growth reaching a sales value of worth $188 billion in 2017, the biopharmaceutical sector distinctly lags in this transition. Currently, the challenges are innovative market disruptions such as personalized medicine as well as increasing commercial pressure for faster and cheaper product manufacturing. Improvements in digitalization and data analytics have been identified as key strategic activities for the next years to face these challenges. Alongside, there is an emphasis by the regulatory authorities on the use of advanced technologies, proclaimed through initiatives such as Quality by Design (QbD) and Process Analytical Technology (PAT). In the manufacturing sector, the biopharmaceutical domain features some of the most complex and least understood processes. Thereby, process models that can transform process data into more valuable information, guide decision-making, and support the creation of digital and automated technologies are key enablers. This review summarizes the current state of model-based methods in different bioprocess related applications and presents the corresponding future vision for the biopharmaceutical industry to achieve the goals of Industry 4.0 while meeting the regulatory requirements.

Effective Knowledge Transfer During Biopharmaceutical Technology Transfer

While knowledge management (KM) has been widely applied in other sectors, the international biopharmaceutical sector has struggled with the meaningful and sustained application of effective KM practices. This is evident even though KM has been highlighted in regulatory guidance for over 10 years, and the positive business impact of KM is well recognized in other sectors. This paper focuses on the topic of KM as applied to biopharmaceutical technology transfer, introducing new research that explores the importance and effectiveness of knowledge transfer as an integral component of a biopharmaceutical product technology transfer. Results from multiple sources explored in this paper are well aligned in recognizing that knowledge transfer is very important to enable technology transfer, yet the biopharmaceutical sector is not very effective at this knowledge transfer. This is especially true of tacit knowledge transfer which is often reported to be ineffective. Additional research will further define the barriers to improve knowledge transfer effectiveness and how the biopharmaceutical sector might improve in this area.

Monitoring bioactive and total antibody concentrations for continuous process control by surface plasmon resonance spectroscopy.

Monoclonal antibodies have become an increasingly important part of fundamental research and medical applications. To meet the high market demand for monoclonal antibodies in the biopharmaceutical sector, industrial manufacturing needs to be achieved by large scale, highly productive and consistent production processes. These are subject to international guidelines and have to be monitored intensely due to high safety standards for medical applications. Surface plasmon resonance spectroscopy - a fast, real-time, and label-free bio-sensing method - represents an interesting alternative to the quantification of monoclonal antibody concentrations by enzyme-linked immunosorbent assay during monoclonal antibody production. For the application of monitoring bioactive and total monoclonal antibody concentrations in cell culture samples, a surface plasmon resonance assay using a target-monoclonal antibody model system was developed. In order to ensure the subsequent detection of bioactive monoclonal antibody concentrations, suitable immobilization strategies of the target were identified. A significant decrease of the limit of detection was achieved by using an adapted affinity method compared to the commonly used amine coupling. Furthermore, the system showed limit of detection in the low ng/mL range similar to control quantifications by enzyme-linked immunosorbent assay. Moreover, the comparison of total to bioactive monoclonal antibody concentrations allows analysis of antibody production efficiency. The development of an alternative quantification system to monitor monoclonal antibody production was accomplished using surface plasmon resonance with the advantage of low analyte volume, shorter assay time, and biosensor reusability by target-layer regeneration. The established method provides the basis for the technical development of a surface plasmon resonance-based system for continuous process monitoring.

On-park and off-park research spin-offs: some insights from an empirical investigation on Italy

Research spin-offs (RSOs) are recognised as an important opportunity for universities, and for enhancing entrepreneurship and growth. Several empirical investigations have been published in this field, and the debate on the relationship between RSOs and science parks/incubators is still open. This paper aims at contributing to this debate through an investigation of the role played by these structures for the growth and development of RSOs. The empirical analysis - descriptive statistics and econometric estimation - focuses on 155 respondents in a questionnaire investigation. It shows that on-park RSOs are smaller than off-park firms, they have an international attitude, and are specialised in the biopharmaceutical sector. The analysis reveals that RSOs are less prone to develop patents compared to off-park ones, and seem to be high value-added and innovative. RSOs require huge investments in equipment and laboratories in order to grow, facilities offered by structures like science parks and incubators.

Biopharmaceutical Entrepreneurship, Open Innovation, and the Knowledge Economy

This article focuses on the paradigm shift of the global biopharmaceutical sector’s utiliza- tion of open innovation models to optimize drug development. Leveraging four exemplars, this review highlights that traditionally propriety, non-collaborative biotechnology and pharmaceutical companies increasingly use principles, processes, and structures of open innovation to increase drug R&D effectiveness and efficiency. We discern three essential elements in the successful creation of open innovation partnerships: (i) culture, (ii) collaborative management skills, and (iii) strategic capability alignment. This analysis provides guidance for business leaders and scholars interested in the managerial and strategic dimensions of applying open innovation to the drug development environment. Theoretically, the article contributes to the growing stream of research integrating the concepts of knowledge economy, open innovation, and Enterprise 2.0. We discuss the specific ways in which open innovation holds potential to improve quality, increase speed, and lower costs and thus yield positive benefits for global health.

Are explicit knowledge transfers clustered or diffused in the U.S. biopharmaceutical market sector?

ABSTRACT The goal of this paper is to understand better the dynamics of explicit knowledge transfers in the U.S. biopharmaceutical market sector. We draw upon the entrepreneurship and economic geography literature to help explain activity in this sector. We specifically are interested in how location and other factors affect the means, geographic distance, and knowledge base distance of these transfers. We examine explicit knowledge transfers in the form of technologies and products. We examine transfers by private and publicly traded biopharmaceutical firms using a series of binary logistic regression analyses. We find that firms located in bio-clusters are more likely to transfer explicit knowledge locally compared to non-locally. We also find that private firms compared with publicly traded firms and biotechnology firms compared to pharmaceutical firms are more likely to transfer knowledge locally. Pharmaceutical firms are more likely to transfer knowledge via licensing than product acquisitions compared with biotechnology firms. Our study should be of interest to researchers, biopharmaceutical firms, entrepreneurs, and policy makers.

Mecanismos de transferencia de tecnología como elementos del fortalecimiento del conocimiento acumulado en la industria biofarmacéutica mexicana: El Caso de la UDIBI – IPN

Introducción: La literatura relacionada con la transferencia de tecnología (TT), ha colocado un mayor énfasis en las organizaciones una vez que han establecido un vínculo de colaboración con instituciones de educación superior (IES); sin embargo, existe escaso conocimiento que observe el efecto inverso, es decir, la TT al interior de una IES tras esta interacción. Este trabajo aborda el caso de un laboratorio de investigación y desarrollo (I&D) integrado a una universidad pública federal, que, además de generar ciencia básica para proyectos internos, ofrece servicios tecnológicos al sector biofarmacéutico nacional e internacional; cuyos ingresos, le permiten autofinanciar su operación, empleando de forma marginal el presupuesto federal. Bajo un enfoque organizacional e institucional, este artículo tiene como objetivo dar a conocer los mecanismos de TT que confluyen en este laboratorio, pero también, exponer la contribución de estos al fortalecimiento de su conocimiento acumulado.Método: Este estudio se realizó a partir de veintiocho entrevistas semiestructuradas con personal y agentes externos de la UDIBI, empleando cuestionarios diferenciados con preguntas abiertas, y otras, cerradas con escalas tipo Likert. De igual manera, fueron revisados diferentes convenios de colaboración sostenidos entre este laboratorio y otros actores de la industria con la finalidad de observar el objeto de su interrelación. El procesamiento de la información fue realizado empleado el software NVIVO, lo que favoreció a realizar un análisis más eficiente.Resultados. El laboratorio institucional estudiado requiere allegarse de conocimiento de última generación para desarrollar su operación crítica basada en la generación de ciencia básica y la oferta de servicios tecnológicos. Se encontró que al interior de esta entidad politécnica confluyen múltiples y variados mecanismos de TT (organizacionales como institucionales), cuyos productos se traducen en conocimiento de diversa naturaleza que complementa y potencia la base acumulada de conocimiento propio y es base para la explotación de productos científicos, tecnológicos y servicios de alto valor tanto para la academia como para la industria. Otro hallazgo identificado fue que no sólo estos mecanismos transfieren tecnología en un solo sentido; sino, que dada la contribución que hace este laboratorio a su fuente de conocimiento, el flujo se convierte en bidireccional.Discusión o Conclusión: Los diferentes mecanismos aquí presentados son el producto de la dinámica de la interacción que sostiene el laboratorio estudiado con actores externos e internos, donde, el conocimiento asimilado de estos, junto con el conocimiento propio; pero al mismo tiempo de una visión científica-comercial por parte de su directiva. Todos en conjunto, conforman una importante base de su actual desarrollo, expansión, e incluso, su autosostenimiento; representando así, uno de los escasos casos de excepción en México, de unidades científicas similares integradas a IES públicas que aspiran a trascender hacia un enfoque emprendedor de las universidades.

Sequences of learning types for organizational ambidexterity

PurposeThis paper aims to examine how distinct sequences of organizational learning types (experiential and vicarious) underpin processes of exploratory versus exploitative innovation.Design/methodology/approachData collection consists of 16 interviews conducted with senior personnel at two firms in the biopharmaceutical sector, with sequences of organizational learning types derived from the associated innovation projects. These sequences and their differential emphases on experiential or vicarious learning are used to construct a conceptual model. Propositions describe the structural differentiation and integration mechanisms useful to foster organizational ambidexterity.FindingsTechnological brokering emerges as a key means by which organizations can reconcile the learning sequences underlying exploration and exploitation. For exploration, a structure incorporating cross-industry technology brokerage during the initiation and development phases of innovation is posited. For exploitation, a structure harnessing intra-industry technology brokerage during the development phase of innovation is suggested. Integration of these projects can be accomplished through cross-unit interfaces incorporating both types of brokerage roles, with emphasis on their use during implementation.Originality/valueThis paper considers the ways in which organizations focus on separate types of organizational learning at different stages of the innovation process. Insights are provided into how firms mobilize internal and external knowledge to advance these projects independently, as well as to link these efforts and thereby facilitate ambidexterity.

Cross-Interaction Chromatography-Based QSAR Model for Early-Stage Screening to Facilitate Enhanced Developability of Monoclonal Antibody Therapeutics.

Monoclonal antibodies (mAbs) constitute a rapidly growing biopharmaceutical sector. However, their growth is impeded by developability issues such as polyspecificity and lack of solubility, which leads to attrition as well as manufacturing failures. In this study a multitool hybrid quantitative structure-activity relationship (QSAR) model development framework is described. This framework uses four novel datasets derived from the primary sequences of IgG1-κ-humanized mAbs with varying degrees of resolutions. Unsupervised pattern recognition is first performed on the descriptor sets to visualize any intrinsic property-based clustering, followed by regression of descriptors against cross-interaction chromatography (CIC) retention times. Model optimization is performed via unsupervised variable reduction followed by supervised variable selection. Finally, the models and datasets are benchmarked based on the regression model performance metrics such as R2 , Q2 , and RMSE. The results show that datasets containing localized descriptors rather than averaged value over the entire protein have better predictive performance of CIC retention behavior with R2 > 0.8 and RMSE < 0.3. Furthermore, the results indicate the physicochemical, electronic, and topological properties of hypervariable regions of antibodies that contribute most to the CIC retention times. The results of these studies could contribute to early-stage screening and better design of mAbs.

Quality Risk Management Competency Model-Case for the Need for QRM Competencies.

The Pharmaceutical Regulatory Science Team (PRST), a research team based at the Dublin Technological University (TU Dublin) in Ireland, recently conducted a Quality Risk Management (QRM) survey and a face-to-face focus group workshop to assess the level of formality of QRM roles in the biopharmaceutical sector. This was carried out as part of a research study, which identified the need for the development of QRM role-based competencies as fundamental to realizing QRM's benefits. The research study followed a hybrid Delphi research methodology composed of: (1) Survey 1, (2) focus group workshop, (3) Survey 2, and (4) competency model development. This paper presents the results of Survey 1 and the focus group workshop. Survey 1 explored the need for QRM role-based competencies and the subsequent face-to-face focus group workshop built on this to propose initial standard QRM roles, with a view to confirming these and developing associated competencies. This paper presents the findings from Survey 1 and the focus group workshop. The results of the follow-up research activities will be presented in a subsequent paper.LAY ABSTRACT: The publication of the ICH Q9 Quality Risk Management (QRM) guideline in 2005 has greatly impacted the biopharmaceutical sector. Fourteen years after Q9, the benefits of QRM are yet to be realized. The biopharmaceutical sector still struggles with the implementation of Q9 principles to effectively assess and manage product quality risks as a surrogate for patient safety.This paper looks at the need for standard QRM roles and the associated competencies for those roles.

Biosimilars and the Patent Law

Biopharmaceuticals are one of the most important recent medical innovations which revolutionised many areas of medicine. Dynamic development of the market for biopharmaceuticals in recent years is related to the expiration of the IP exclusive rights on original innovative biological medicinal products. This has resulted in introduction to the market of biosimilars. One of the greatest challenges concerning the emergence of biosimilars is modifying the law to ensure balance between the market development of biosimilars and access of patients to biological therapy. The development of biopharmaceutical inventions works hand in hand with the patent system. It should be underlined that IP rights in the biopharmaceutical sector are crucial for promoting innovation due to the very long time of product development. It is exactly the area in which patents make sense to fill the gap between innovation and the risk of imitation. However, the existing patent system is too expensive and slow for biotechnology development. It should be further adapted to the needs of biopharmaceuticals.

Self-Interaction of Human Serum Albumin: A Formulation Perspective.

In the present study, small-angle X-ray scattering (SAXS) and static light scattering (SLS) have been used to study the solution properties and self-interaction of recombinant human serum albumin (rHSA) molecules in three pharmaceutically relevant buffer systems. Measurements are carried out up to high protein concentrations and as a function of ionic strength by adding sodium chloride to probe the role of electrostatic interactions. The effective structure factors (Seff) as a function of the scattering vector magnitude q have been extracted from the scattering profiles and fit to the solution of the Ornstein–Zernike equation using a screened Yukawa potential to describe the double-layer force. Although only a limited q range is used, accurate fits required including an electrostatic repulsion element in the model at low ionic strength, while only a hard sphere model with a tunable diameter is necessary for fitting to high-ionic-strength data. The fit values of net charge agree with available data from potentiometric titrations. Osmotic compressibility data obtained by extrapolating the SAXS profiles or directly from SLS measurements has been fit to a 10-term virial expansion for hard spheres and an equation of state for hard biaxial ellipsoids. We show that modeling rHSA as an ellipsoid, rather than a sphere, provides a much more accurate fit for the thermodynamic data over the entire concentration range. Osmotic virial coefficient data, derived at low protein concentration, can be used to parameterize the model for predicting the behavior up to concentrations as high as 450 g/L. The findings are especially important for the biopharmaceutical sector, which require approaches for predicting concentrated protein solution behavior using minimal sample consumption.