Identifying Key Benefits in European Off-Patent Biologics and Biosimilar Markets: It is Not Only About Price!

Biosimilar medicines have shown similarity with the originator biologic and offer a similar clinical outcome generally at a lower cost. This paper identifies benefits of off-patent biologics and biosimilars, and illustrates these benefits with empirical data from Europe. We provide a narrative review of published literature on values and benefits of biosimilars in Europe. The results describe cost savings as the key driver stemming from the lower price of biosimilars, than that of originator products, and from price competition between biosimilar(s), originator, and next-generation products. Cost savings may then translate into a number of other associated benefits. The lower price of biosimilars and similar effectiveness to the originator biologics improve cost effectiveness, implying that reimbursement can be granted or extended to other pa

Dielectric relaxation in double-perovskite Ca2GdTaO6

The double perovskite oxide calcium gadolinium tantalate, Ca2GdTaO6 (CGT) is synthesized by solid-state reaction technique. The Rietveld refinement of the X-ray diffraction pattern of the sample shows monoclinic phase at room temperature. Fourier transform infrared (FTIR) spectrum shows two primary vibrational modes of the sample at around 378 and 566 cm-1. Dielectric spectroscopy is applied to investigate the ac electrical conductivity of CGT in the temperature range 303-673 K and frequency range 42 Hz-1 MHz. The modified Cole-Cole equation is used to describe the relaxation mechanism in CGT. The relaxation time corresponding to dielectric loss is found to obey the Arrhenius law with an activation energy of 0.26 eV. The impedance data has been modeled by an equivalent circuit consisting of two serially connected R-CPE units, one for the grain and the other for the grain boundary, each containing a resistor (R) and a constant phase element (CPE). The frequency dependent conductivity spectra follow the Jonscher power law

Identifying Key Benefits in European Off-Patent Biologics and Biosimilar Markets: It is Not Only About Price!

Biosimilar medicines have shown similarity with the originator biologic and offer a similar clinical outcome generally at a lower cost. This paper identifies benefits of off-patent biologics and biosimilars, and illustrates these benefits with empirical data from Europe. We provide a narrative review of published literature on values and benefits of biosimilars in Europe. The results describe cost savings as the key driver stemming from the lower price of biosimilars, than that of originator products, and from price competition between biosimilar(s), originator, and next-generation products. Cost savings may then translate into a number of other associated benefits. The lower price of biosimilars and similar effectiveness to the originator biologics improve cost effectiveness, implying that reimbursement can be granted or extended to other patient groups, or that the biologic therapy can be moved to an earlier line of treatment. Cost savings from biosimilars can be used to increase patient access to therapy or to increase the number of healthcare professionals. Finally, competition between off-patent biologics and biosimilars may stimulate an innovation in the formulation and development of next-generation biologics. Our paper illustrates that the benefit of off-patent biologics and biosimilars is not restricted to cost savings, but that these medicines may contribute to an expansion of medical treatment options for patients, hence concomitantly contributing to the long-term sustainability of the healthcare system. This review provides a broader view for clinical and economic decision makers and healthcare professionals on the added benefits of off-patent biologics and their use in clinical practice.status: publishe

Identifying Key Benefits in European Off-Patent Biologics and Biosimilar Markets: It is Not Only About Price!

Biosimilar medicines have shown similarity with the originator biologic and offer a similar clinical outcome generally at a lower cost. This paper identifies benefits of off-patent biologics and biosimilars, and illustrates these benefits with empirical data from Europe. We provide a narrative review of published literature on values and benefits of biosimilars in Europe. The results describe cost savings as the key driver stemming from the lower price of biosimilars, than that of originator products, and from price competition between biosimilar(s), originator, and next-generation products. Cost savings may then translate into a number of other associated benefits. The lower price of biosimilars and similar effectiveness to the originator biologics improve cost effectiveness, implying that reimbursement can be granted or extended to other patient groups, or that the biologic therapy can be moved to an earlier line of treatment. Cost savings from biosimilars can be used to increase patient access to therapy or to increase the number of healthcare professionals. Finally, competition between off-patent biologics and biosimilars may stimulate an innovation in the formulation and development of next-generation biologics. Our paper illustrates that the benefit of off-patent biologics and biosimilars is not restricted to cost savings, but that these medicines may contribute to an expansion of medical treatment options for patients, hence concomitantly contributing to the long-term sustainability of the healthcare system. This review provides a broader view for clinical and economic decision makers and healthcare professionals on the added benefits of off-patent biologics and their use in clinical practice

Dielectric relaxation in double-perovskite Ca₂GdTaO₆

125-133The double perovskite oxide calcium gadolinium tantalate, Ca2GdTaO6 (CGT) is synthesized by solid-state reaction technique. The Rietveld refinement of the X-ray diffraction pattern of the sample shows monoclinic phase at room temperature. Fourier transform infrared (FTIR) spectrum shows two primary vibrational modes of the sample at around 378 and 566 cm-1. Dielectric spectroscopy is applied to investigate the ac electrical conductivity of CGT in the temperature range 303-673 K and frequency range 42 Hz-1 MHz. The modified Cole-Cole equation is used to describe the relaxation mechanism in CGT. The relaxation time corresponding to dielectric loss is found to obey the Arrhenius law with an activation energy of 0.26 eV. The impedance data has been modeled by an equivalent circuit consisting of two serially connected R-CPE units, one for the grain and the other for the grain boundary, each containing a resistor (R) and a constant phase element (CPE). The frequency dependent conductivity spectra follow the Jonscher power law. </span

Cloning, Expression, Purification, and Immunocharacterization of Placental Protein-14

Human placental protein-14 (PP-14), a member of the lipocalin superfamily, shares homology at the level of the primary and secondary structures with bovine $\beta$-lactoglobulin. It is the most prominent endometrial protein synthesized by the glandular cells of endometrium under estrogen priming and progesterone stimulation. The temporal and spatial expression of PP-14 in the female reproductive tract combined with its biological activities ex vivo suggest that this glycoprotein probably plays an essential physiological role in the regulation of fertilization, implantation, and maintenance of pregnancy. We proposed to elucidate the molecular mechanisms involved in the function of this protein. A prerequisite to such investigations on any protein is the availability of sufficient amounts of the same in a homogenous form. Therefore, recombinant DNA technology was employed. The PP-14 cDNA was obtained from the first-trimester endometrial tissue RNA by RT-PCR using unique primers. After confirming the identity of the gene, the protein was expressed in Escherichia coli and purified to homogeneity. The gene was also cloned and expressed in Pichia pastoris to obtain the protein product in a glycosylated form. The recombinant proteins were immunocharacterized using a cross-reactive antibody raised to bovine $\beta$-lactoglobulin. Polyclonal antiserum raised to the E coli expressed PP-14 also bound to the native PP-14 from amniotic fluid suggesting that recombinant PP-14 may be exploited to elucidate functional aspects of the protein

The Contribution of Non-Conventional T Cells and NK Cells in the Mycobacterial-Specific IFNγ Response in Bacille Calmette-Guérin (BCG)-Immunized Infants

<div><p>Background</p><p>The <i>Mycobacterium bovis</i> Bacille Calmette-Guérin (BCG) vaccine is given to >120 million infants each year worldwide. Most studies investigating the immune response to BCG have focused on adaptive immunity. However the importance of TCR-gamma/delta (γδ) T cells and NK cells in the mycobacterial-specific immune response is of increasing interest.</p> <p>Methods</p><p>Participants in four age-groups were BCG-immunized. Ten weeks later, in vitro BCG-stimulated blood was analyzed for NK and T cell markers, and intracellular IFNgamma (IFNγ) by flow cytometry. Total functional IFNγ response was calculated using integrated median fluorescence intensity (iMFI).</p> <p>Results</p><p>In infants and children, CD4 and CD4-CD8- (double-negative (DN)) T cells were the main IFNγ-expressing cells representing 43-56% and 27-37% of total CD3+ IFNγ+ T cells respectively. The iMFI was higher in DN T cells compared to CD4 T cells in all age groups, with the greatest differences seen in infants immunized at birth (p=0.002) or 2 months of age (p<0.0001). When NK cells were included in the analysis, they accounted for the majority of total IFNγ-expressing cells and, together with DN Vδ2 γδ T cells, had the highest iMFI in infants immunized at birth or 2 months of age.</p> <p>Conclusion</p><p>In addition to CD4 T cells, NK cells and DN T cells, including Vδ2 γδ T cells, are the key populations producing IFNγ in response to BCG immunization in infants and children. This suggests that innate immunity and unconventional T cells play a greater role in the mycobacterial immune response than previously recognized and should be considered in the design and assessment of novel tuberculosis vaccines.</p> </div

CD4 and DN (CD4^-CD8^-) T cells are the main IFNγ-expressing subsets in blood taken from infants 10 weeks after BCG immunization.

<p>Box plots (with lower quartile, median and upper quartile, Tukey whiskers) of the proportion of DP, CD8, CD4, DN T cell subsets within the IFNγ⁺ expressing cells in individuals given BCG at birth (n=28), at 2 months of age (2m; n=27), between 10 and 24 months of age (10-24m; n=7) and in adulthood (n=5). DN: CD4^-CD8^- double negative T cells. DP: CD4⁺CD8⁺ double positive T cells.</p

NK, DN Vδ2 TCRγδ^- and DN Vδ2 TCRγδ⁺ T cells represent two-thirds of measured IFNγ-expressing cells in blood taken from infants 10 weeks after BCG immunization given at birth (n=20) or at 2 months of age (2m; n=23).

<p>Box plots (with lower quartile, median and upper quartile, Tukey whiskers) of the proportion of DP, CD8, CD4, DN Vδ2 TCRγδ^-, DN Vδ2 TCRγδ⁺ and NK cells within the combined NK IFNγ⁺ and CD3⁺ IFNγ⁺ population. DN: CD4^-CD8^- double negative T cells. DP: CD4⁺CD8⁺ double positive T cells.</p

DN (CD4^-CD8^-) T cells have a higher IFNγ functional response than CD4 T cells in blood taken from infants 10 weeks after BCG immunization.

<p>(A) Frequency and (B) median fluorescence intensity (MFI) of IFNγ-expressing CD4 (grey bars) and DN T cells (white bars), and (C) IFNγ total functional response (iMFI) in individuals given BCG at birth (n=28), at 2 months of age (2m; n=26), between 10 and 24 months of age (10-24m; n=7) and in adulthood (n=9). Box plots with lower quartile, median, upper quartile and Tukey whiskers are shown. **: p<0.001, ***: p<0.0001. DN: CD4^-CD8^- double negative T cells.</p