Gotowa bibliografia na temat „Biopharmaceutical CMO Market Share”

Biopharmaceutical products are of great importance in the treatment or prevention of many diseases and represent a growing share of the global pharmaceutical market. The usual technology for protein synthesis (cell-based expression) faces certain obstacles, especially with ‘difficult-to-express’ proteins. Cell-free protein synthesis (CFPS) can overcome the main bottlenecks of cell-based expression. This review aims to present recent advances in the production process of biologic products by CFPS. First, key aspects of CFPS systems are summarized. A description of several biologic products that have been successfully produced using the CFPS system is provided. Finally, the CFPS system's ability to scale up and scale down, its main limitations and its application for biologics production are discussed.

SCIENTIFIC RELEVANCE. Russia is pursuing a consistent government policy of import substitution and increasing the localisation of pharmaceutical manufacturing. The Strategy for the Development of the Pharmaceutical Industry until 2030 (Pharma-2030) includes the target share of medicinal products from the List of Strategic Medicines that should be fully localised. Since biotechnological medicinal products have high consumption growth rates and are listed as strategic medicines, it is a priority to study their production localisation process.AIM. This study aimed to analyse the degree of biopharmaceutical manufacturing localisation in Russia, considering the country of origin of active pharmaceutical ingredients (APIs).MATERIALS AND METHODS. The study used the State Register of Medicines and sales data of the DSM Group marketing agency. The authors used custom software for the Node.js® platform to determine the degree of production localisation.RESULTS. The analysis showed that the production process was fully localised for 25.6% (in packages) and 26.6% (in roubles) of all biotechnological medicinal products consumed in Russia in 2022. Imported medicinal products dominated the consumption structure, with a share of 33.9% in packages and 31.3% in roubles. Medicinal products with localised secondary packaging accounted for 5.8% in packages and 25.9% in roubles. Finished dosage forms produced using imported APIs had a significant share of 23.7% in packages and 6.2% in roubles. Russian APIs were used to produce 79% of the biotechnological medicinal products listed as strategic medicines, which corresponded to the full localisation of a share of the consumption structure of 10.8% in packages and 32.3% in roubles.CONCLUSIONS. The Russian biotechnological market remains heavily dependent on imported finished medicinal products and APIs. Although the Pharma-2030 target for the production of strategic biotechnological products has been achieved, the quantitative indicators show the necessity to increase output and localisation.

The continuous innovation of the biopharmaceutical industry has led to development of a new category of biopharmaceuticals i.e. Biobetters or Biosuperiors. Biobetters may have better efficacy, a longer half-life, lower dosing frequency, a reduced risk of immunogenicity, reduced toxicity and side effects along with lower early-stage research risk and development costs. Biobetters rather than biosimilars may capture significant share of market and are the next wave for companies to ride on. Although it sounds intuitive, biobetters will have to face various ordeals like identification of the apparent unmet need, quantification of the potential market opportunity, expensive investment in clinical trials, challenging regulatory approval, pressures of price erosion and patent litigations. Thus, development of biobetters truly requires the right balance between providing life-changing medical management for patients and maintaining an innovative pipeline for continued business success. This review will focus on technical and regulatory prospects of biobetters.

In recent years, monoclonal antibodies (mAbs) are gaining a wide market share as the most impactful bioproducts. The development of mAbs requires extensive experimental campaigns which may last several years and cost billions of dollars. Following the paradigm of Industry 4.0 digitalization, data-driven methodologies are now used to accelerate the development of new biopharmaceutical products. For instance, predictive models can be built to forecast the productivity of the cell lines in the culture in such a way as to anticipate the identification of the cell lines to be progressed in the scale-up exercise. However, the number of experiments that can be performed decreases dramatically as the process scale increases, due to the resources required for each experimental run. This limits the availability of experimental data and, accordingly, the applicability of data-driven methodologies to support the process development. To address this issue in this work we propose the use of digital models to generate in silico data and augment the amount of data available from real (i.e., in vivo) experimental runs, accordingly. In particular, we propose two strategies for in silico data generation to estimate the endpoint product titer in mAbs manufacturing: one based on a first principles model and one on a hybrid semi-parametric model. As a proof of concept, the effect of in silico data generation was investigated on a simulated biopharmaceutical process for the production of mAbs. We obtained very promising results: the digital model effectively supports the identification of high-productive cell lines (i.e., high mAb titer) even when a very low number of real experimental batches (two or three) is available.

In the life sciences, many graduate students and postdoctoral fellows find it challenging to enter the non-academic workforce after completing their programs. Through experiential learning, trainees can develop the knowledge, technical skills, soft skills, and project portfolio that employers value, and compete effectively in the job market. In this article, we share design considerations for developing a job simulation program based on our experience over five years with the Industry Team Case Study program at the University of Toronto. In this program, which is focused on the biopharmaceutical sector, trainees identify a business or policy challenge, conduct in-depth research, develop a solution to address the problem, and present their findings to industry professionals. For mentorship and coaching, trainees are matched with industry professionals. This article covers four areas of program development: starting the program, recruiting advisors and trainees, designing the program and project framework, and evaluating program effectiveness. Academic institutions and student organizations can use this information to start their own job simulation programs focused on their employment sector of interest. Employers can participate in these programs to develop and scout talent.

In the US, there is a vigorous public debate on the merits of biopharmaceutical innovations and their diffusion. There is virtual unanimity about the importance of maintaining a steady stream of biopharmaceutical innovations, to which patients should have timely access. However, the debate’s participants are cognizant that the effects of innovation and diffusion on health outcomes, health care spending, and incentives for future innovation, must be weighed against one another. First, we performed a Medline literature review to map the innovation diffusion process, combining the search terms “innovation,” “diffusion,” and “pharmaceutical.” Second, we conducted a survey of 190 physicians to examine their valuation of the innovativeness and rate of diffusion of 20 new molecular entities (NMEs). Third, we collected data from the Centers for Medicare and Medicaid Services (CMS) Formulary Finder to assess payers’ valuation of the innovativeness of the 20 NMEs in question. Based on our literature review, we identified the key stakeholders involved in the innovation diffusion process. Furthermore, we highlighted the changing landscape of translational movers and shakers, tracing the emergence of T2 barriers, emanating largely from third party payer formulary management. Our empirical analysis suggests payers are exerting influence on physicians’ prescribing decisions, while the role of patients and pharmaceutical firms has diminished somewhat. Payers directly affect prescribing decisions through the use of formularies, and indirectly by funding evidence-based continuing medical education. On average, across the 20 drugs we sampled, the time from approval to first prescription was 33 months, which indicates a slow diffusion process. Our data analysis shows a gap in perception of innovativeness between physicians and payers, with physicians ranking drugs as more innovative on average than payers. And, our findings suggest the more innovative a drug is perceived by physicians and payers the higher market share it has. Striking an appropriate balance on access to and cost of biopharmaceuticals will require policy adjustments on the part of payers. In cases in which there is a large degree of uncertainty or the fiscal impact is particularly high, coverage could be made subject to a policy of coverage with evidence development (CED). Here, coverage would be conditional on development and capture of outcome data. A CED policy could be combined with a risk-sharing arrangement in which financial risk is shared between payers and the biopharmaceutical industry.

The advent of biopharmaceuticals in modern medicine brought enormous benefits to the treatment of numerous human diseases and improved the well-being of many people worldwide. First introduced in the market in the early 1980s, the number of approved biopharmaceutical products has been steadily increasing, with therapeutic proteins, antibodies, and their derivatives accounting for most of the generated revenues. The success of pharmaceutical biotechnology is closely linked with remarkable developments in DNA recombinant technology, which has enabled the production of proteins with high specificity. Among promising biopharmaceuticals are interferons, first described by Isaacs and Lindenmann in 1957 and approved for clinical use in humans nearly thirty years later. Interferons are secreted autocrine and paracrine proteins, which by regulating several biochemical pathways have a spectrum of clinical effectiveness against viral infections, malignant diseases, and multiple sclerosis. Given their relevance and sustained market share, this review provides an overview on the evolution of interferon manufacture, comprising their production, purification, and formulation stages. Remarkable developments achieved in the last decades are herein discussed in three main sections: (i) an upstream stage, including genetically engineered genes, vectors, and hosts, and optimization of culture conditions (culture media, induction temperature, type and concentration of inducer, induction regimens, and scale); (ii) a downstream stage, focusing on single- and multiple-step chromatography, and emerging alternatives (e.g., aqueous two-phase systems); and (iii) formulation and delivery, providing an overview of improved bioactivities and extended half-lives and targeted delivery to the site of action. This review ends with an outlook and foreseeable prospects for underdeveloped aspects of biopharma research involving human interferons.

The World Health Organization (WHO), with the scientific support of the International Pharmaceutical Federation (FIP), guides the development of multisource pharmaceutical products for market authorization using in vivo bioequivalence studies or, where applicable, in vitro biowaiver strategies based on the Biopharmaceutical Classification System (BCS). A review of the regulatory framework guiding generic medicines approval in Latin American countries revealed that less than 50% of regional health authorities offer a generic medicines development pathway utilizing a BCS-based biowaiver strategy. Aligned with the ONE FIP Strategy to facilitate access to medicines, a regional case study was carried out to implement and harmonize BCS-based biowaiver knowledge in Latin American countries. A steering committee involving regional representatives from health authorities, the pharmaceutical industry, and universities were established to coordinate to develop activities. A series of digital engagement events were held in Spanish and English with representatives from Latin America to share knowledge on BCS-based regulatory strategy, promote collaborations, and explore the alignment of biowaiver approval and regulatory pathways among Latin American countries. Feedback from diverse Latin American stakeholders demonstrated inconsistent implementation of bioequivalence testing within the region. However, there is support for a synergistic approach among countries to reduce duplication and increase efficiency in market authorization for generic medicines. This includes alignment with the WHO Prequalification of Medicines program as well as the development of a computational database for the classification of active pharmaceutical ingredients to demonstrate therapeutic interchangeability of immediate-release oral dosage forms according to the BCS. FIP-facilitated digital learning opportunities raised awareness of the BCS-based biowaiver regulatory strategy among Latin American stakeholders. It resulted in a plan to continually strengthen collaborative efforts in the region to harmonize regulations relevant to drug development generics medicines to introduce cost-effective medicines products that benefit public health.

Type II diabetes is a global pandemic, as evidenced by data from a study by the International Diabetes Federation. The disease is a chronic, progressive process with a special metabolic condition that is characterized by hyperglycemia. Therapeutic effects should be aimed at eliminating the main causes of type II diabetes mellitus: insulin secretion dysfunction, a decrease in tissue resistance to insulin, or a combination of these. The aim of the work was to study the range of oral antidiabetic drugs on the pharmaceutical market of Ukraine for the treatment of type II diabetes. The objects of study were drugs used in the treatment of type II diabetes. Studies were conducted using content analysis of official sources of information. In the course of the work, the range of antidiabetic drugs, classification, mechanism of action, cost, main advantages and disadvantages of use were established. It is established that the most common dosage form for the treatment of diabetes are tablets, which occupy more than 90% of the total range of drugs. The lack of modern types of dosage forms in the group A10B is the basis for the creation of new drugs with improved biopharmaceutical and consumer properties. The data obtained indicate a strong dependence of the pharmaceutical market of antidiabetic drugs of Ukraine on imports, with the exception of insulin (А10В). The share of imports in the market in quantitative terms for the period under review amounted to more than 75.86% of the total market volume. It has been established that the use of drugs of the A10B A, A10B F groups with an affordable cost with active therapy contributes to a lower rate of development of diabetes mellitus type II and a high degree of regression to normal glucose, without affecting the fluctuations in body weight. Preparations of the new generation (A10B H, A10B J, A10B X) are highly effective with an insufficient safety profile. The high cost of drugs of these groups makes them inaccessible to the general population. It has been shown that only metformin and voglibosis have a positive effect on body mass fluctuation rates, which will ensure safe and effective glycemic control with minimal risk of hypoglycemia and without weight gain in the treatment of type II diabetes.

Background Biopharmaceutical products have become an important sector of the pharmaceutical industry in the United States (U.S.). This fast-growing sector is in a critical position in which therapeutic biological products represent over a third of all new drugs in clinical trials or awaiting approval from the U.S. Food and Drug Administration (FDA) (International Trade Administration, n.d.). The development and review of a new therapeutic biological product is a complex process that requires considerable monetary and time investment. This process takes, on average, twelve years, and the estimated average cost of taking a new drug from concept to market exceeds $1 billion (Van Norman, 2016a). After the significant expenditure of manufacturer time and resources, many drugs fail to achieve FDA approval late in the process. Criticism has arisen from the fact that the increasingly complex regulatory environment and expense associated with drug development have caused a lag in the release of new pharmaceuticals to the drug market. Advocacy groups and experts in the area are demanding a more rapid approval and release of new products because they consider the current process to be risk averse, slow, and inefficient (Ty Williams, 2016; Van Norman, 2016a). The FDA has created programs to expedite the approval of drugs and biological products (FDA, 2018). Despite all of these efforts, FDA scrutiny remains a long, costly, and risky process. The goal of this work is the exploration of the factors and gaps relevant to the FDA review and approval process which contribute to process inefficiencies, as well as proposed methods and solutions to address such gaps. Review Findings Researchers who investigated the FDA review and approval operations have identified challenges and constraints in the process (e.g. Baylor, 2014; Conner et al., 2014; Kinch, 2016; Ty Williams, 2016; Van Norman, 2016a, 2016b). Van Norman (2016a) and Ty Williams (2016) emphasizes that the main challenges for the pharmaceuticals are in terms of cost and time. Complexities in the flow of information and the communications network have been identified due to the fact that the process involves multiple FDA resources and constant communication with the applicant. Additionally, complexities could arise from the review team not only having to deal with the flow of new submissions but also with the flow of resubmitted applications, which puts a strain on FDA normal operations by having to share resources between both types of submissions. Other relevant challenges are in terms of bias due to the user fees collected from sponsors and drug manufacturers to support the drug approval process (Ty Williams, 2016) and lack of transparency of non-published drug trial data (Van Norman, 2016b). The review of methods and solutions to address such challenges and constraints has identified a lack of research activity in studying the approval process from the regulatory agency point of view (i.e. from FDA internal operations). Most research efforts are directed toward the incorporation of modeling tools to the drugs development and production practices (e.g. Gernaey & Gani, 2010; Horner, Joshi, & Waghmare, 2017). Reform models to the current FDA review and approval process have been published with the purpose of providing flexible approaches to change the way medical products are brought to market (Thierer & Wilt, 2016; Williams, Joffe, & Slonim, 2016; Klein & Tabarrok, 2016; Conko & Madden, 2000; Gulfo, Briggeman, & Roberts, 2016). The implementation of any of these reform models may imply a shift in the responsibilities of the FDA and therefore may change the organizational structure of the regulatory agency – something that must be addressed and measured for effectiveness. Conclusions Suggesting changes to the review and approval of therapeutic biological products is a challenging task. To the best of our knowledge, none of the academic articles identified in this scoping review have modeled the FDA review and approval process to address issues related to the robustness, reliability and efficiency of its operations from an internal point of view. The reform models identified in the literature are limited in several aspects. For example, there is a general lack of application of scientific methodologies and modeling techniques in understanding FDA as a complex sociotechnical system. In addition, tools and methods to assess their efficacy before implementation are largely absent. Findings from this scoping review suggest an opportunity to employ Model-Based Systems Engineering (MBSE) approaches to provide a systems-oriented descriptive model of the FDA approval process for therapeutic biological products as a service network, with the objective of providing a method to support individual, team, and organizational decision-making to balance the process structure in terms of enforcement and in-formation. This holistic approach will serve several investigative purposes: (1) identify influential sources of variability that cause major delays including individual, team, and organiza-tional decision-making, (2) identify the human-system bottle-necks, (3) identify areas of opportunity for design-driven im-provements, (4) study the effect of induced changes in the sys-tem, and (5) assess the robustness of the structure of the FDA approval process in terms of enforcement and information sym-metry.