Frequency: Quarterly E- ISSN: 2250-0286 P- ISSN: 2249-3573 IBI Factor 3.9 Abstracted/ Indexed in: Ulrich's International Periodical Directory, Google Scholar, SCIRUS, Genamics Journal Seek, PSOAR, getCITED, InfoBase Index, EBSCO Information Services
Quarterly published in print and online "Inventi Impact: Biosimilars & Biopharmaceuticals (Formerly Inventi Impact: Biosimilars)" publishes high quality unpublished as well as high impact pre-published research and reviews catering to the needs of researchers and professionals. This journal focuses on manufacture, development and usage of biopharmaceutical compounds considered similar to an innovator agent. The topics included are chemical composition and structure, quality and purity, patent issues, bioequivalence and interchangeability, clinical efficacy data, economic considerations etc.
Prior to the introduction of regulated process validation activities it was generally assumed that the production process for protein drugs per se is under control and appropriate for their generation, if the final product fulfils the criteria raised for the bioanalytical quality end control for therapeuticals. However nowadays, the production process is being considered in a much deeper and considerably more differentiated fashion. The use of in-process and on-/at-line controls and supervisions on a regular basis encompassing all critical parameters about the individual sub-processes and the emerging intermediary and side products is generally thought to significantly contribute to the demonstration that the production process is under control at the time point of the measurements and with high probability also thereafter. The deep understanding of the interrelationship between process and product can not completely eliminate but will considerably reduce the risk for the emergence of product variants, impurities and contaminants during critical sub-processes that may escape detection during final quality control for technical and/or economical reasons. The test systems required for elucidation of the multiple process-product interactions have to be chosen, validated and calibrated according to commonly accepted and approved criteria. In the near future novel platform technologies, such as protein chips and biosensors that are based on novel capturing/immobilising probes, e.g. glycosylphosphatidylinositol-anchored proteins, and detection probes, e.g. nanoparticles, will greatly contribute to the rapid and reliable measurement of many samples for multiple parameters in cell-free and cell-based assay configurations in parallel rather than consecutive fashion....
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The present study aimed to compare pharmacokinetic parameters of two pramipexole\n0.25 mg formulations in order to show bioequivalence. The study was conducted in a randomized,\nopen-label, two-period, two-sequence, and crossover design, involving 23 healthy volunteers. One of\nthe 0.25 mg formulations of pramipexole evaluated in the study was manufactured by PT Dexa\nMedica, Palembang, Indonesia, the other, used as the reference, by Boehringer Ingelheim Pharma\nGmbH & Co. KG, Ingelheim am Rhein, Germany. All eligible subjects were required to fast\nbefore each drug administration period, which was separated by a one-week washout period.\nPramipexole concentrations in plasma were assayed using a validated ultra performance liquid\nchromatography with mass spectrometry (UPLC-MS/MS) detector. The evaluated pharmacokinetic\nparameters included the area under the plasma concentration curve from time zero to the last observed\nmeasurable concentration (AUC0-t), the area under the plasma concentration curve extrapolated to\ninfinite time (AUC0-âË?ž), the maximum plasma concentration (Cmax), the time to reach Cmax (tmax),\nand the plasma concentration half-life (t1/2). To evaluate the bioequivalence of those two pramipexole\nformulations, 90% confidence intervals (CIs) for geometric mean ratios of both formulations were\ncalculated for AUC and Cmax parameters, while tmax and t1/2 differences were analyzed on the\nnon-transformed data using Wilcoxon matched-pairs and a Studentââ?¬â?¢s paired t-test, respectively.\nThe 90% CIs for the geometric mean ratios of the two pramipexole formulations were 95.89%\n(90.73%ââ?¬â??101.34%), 95.53% (89.75%ââ?¬â??101.68%), and 92.11% (84.35%ââ?¬â??100.58%) for AUC0-t, AUC0-âË?ž,\nand Cmax, respectively. There were no statistically significant differences for tmax and t1/2 between\nthe two pramipexole formulations. It is concluded that two pramipexole formulations in this study\nwere bioequivalent....
Antibody-drug conjugates (ADCs) have recently emerged as efficient and selective cancer\ntreatment therapeutics. Currently, alternative forms of drug carriers that can replace monoclonal\nantibodies are under intensive investigation. Here, a cytotoxic conjugate of an anti-HER2 (Human\nEpidermal Growth Factor Receptor 2) diaffibody with monomethyl-auristatin E (MMAE) is proposed\nas a potential anticancer therapeutic. The anti-HER2 diaffibody was based on the ZHER2:4 affibody\namino acid sequence. The anti-HER2 diaffibody has been expressed as a His-tagged protein in\nE. coli and purified by Ni-nitrilotriacetyl (Ni-NTA) agarose chromatography. The molecule was\nproperly folded, and the high affinity and specificity of its interaction with HER2 was confirmed\nby surface plasmon resonance (SPR) and flow cytometry, respectively. The (ZHER2:4)2DCS-MMAE\nconjugate was obtained by coupling the maleimide group linked with MMAE to cysteines, which\nwere introduced in a drug conjugation sequence (DCS). Cytotoxicity of the conjugate was evaluated\nusing the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide MTT assay and the\nxCELLigence Real-Time Cell Analyzer. Our experiments demonstrated that the conjugate delivered\nauristatin E specifically to HER2-positive tumor cells, which finally led to their death. These results\nindicate that the cytotoxic diaffibody conjugate is a highly potent molecule for the treatment of\nvarious types of cancer overexpressing HER2 receptors....
To develop a biosimilar product, it is necessary to demonstrate\nbiosimilarity between the proposed biosimilar product and the\nreference product in terms of the purity, potency, efficacy, and\nsafety. In this paper, clinical efficacy data required for establishing\nbiosimilarity are considered. Non-inferiority (NI) and equivalence\nmethods are commonly used for analyzing clinical trials to meet\nthis requirement. The equivalence approach often requires large,\ncostly, and lengthy clinical trials. The non-inferiority approach\nwhile requiring somewhat smaller trials are not accepted by all as\nadequately addressing the similarity issue between the proposed\nbiosimilar product and the reference product as they do not rule out\nthe prospect that the biosimilar product has increased activity which\nmight be associated with more adverse effects. To address some\nof the challenges faced by the use of non-inferiority or equivalence\nmethods, a constrained non-inferiority (cNI) approach is proposed\nto address both the clinical efficacy of the biosimilar product and\nthe similarity to the reference product. The performance of the\nproposed constrained non-inferiority approach for analyzing a\nbiosimilar trial is demonstrated through simulation and examples....
Therapeutics derived through application of modern biotechnology has become an essential component of contemporary pharmacology and clinical medicine. Biopharmaceuticals have given an unprecedented edge to humanity to treat many formidable diseases. It has been anticipated that biotechnological medicines will occupy 50% share of pharmaceutical market by next decade. The first ever biotech drug came into use by the advent of recombinant insulin in early 80ââ?¬â?¢s. Since then many biologics including recombinant human protein and monoclonal antibodies followed that changed the world of therapeutics. All these came through years and years of intensive research and at the cost of huge investments. Now we are passing through a time when some of the biologics have lost patent protection and many are moving towards it. ââ?¬Å?Patent Cliffââ?¬Â is a well noticed term nowadays in biopharmaceutical industry that opened the scope for ââ?¬Å?biosimilarsââ?¬Â entry into therapeutic market. This simply means that the expiry of patent protection for many original biopharmaceuticals or biologics has led to the development of newer versions of original products. These similar products are called ââ?¬Å?biosimilarsââ?¬Â or ââ?¬Å?non-original biologicsââ?¬Â. Biosimilars are also innovative biotechnology medicines but copy the original technology to obtain a therapeutic what is similar to the original one. However, there might be differences on a protein level depending on the biological process of manufacturing. Biosimilars represent the newer class of biotech medicinal products that have been anticipated to have significant impact on therapeutics market. Biosimilars development is currently one of the fastest growing areas in biopharmaceuticals industry because of incumbent patent expiry of top 12 best-selling biologics. In June 2013, worldââ?¬â?¢s first biosimilar of infliximab, RemsimaÃ?® (CT-P13) developed by Celltrion, was approved by the Committee for Medicinal Products for Human Use (CHMP) of European Medicine Agency (EMA). Many more biosimilars are in the pipeline and some are awaiting approval. Biosimilar approval has evoked a competition in global market targeting the blockbuster biologics. The underlying reason is that biosimilars will dramatically reduce the cost of treatments where biologics are predominating. Moreover, a recent advance in technology in biopharmaceutical industry allows showing similarity between originator and biosimilar product. Although biosimilars are emerging in the market and their market share is increasing although there are many issues raising the concerns such as safety, immunogenicity, regulatory processes, pharmacovigilance, automatic substitution, naming and labelling rules. Recent evidences have been able to demonstrate quality, efficacy, and safety of biosimilars whereas a lack of interchangeability and international standards has to be addressed. Here we provide a brief overview of biosimilars development, its increasing uses and market value as well as opportunities for emerging pharmaceutical industries....
Vascular cell adhesion molecule-1 (VCAM-1) is closely associated with tumor progression\nand metastasis. However, the relevance and role of VCAM-1 in lung cancer have not been clearly\nelucidated. In this study, we found that VCAM-1 was highly overexpressed in lung cancer tissue\ncompared with that of normal lung tissue, and high VCAM-1 expression correlated with poor survival\nin lung cancer patients. VCAM-1 knockdown reduced migration of A549 human lung cancer cells\ninto Matrigel, and competitive blocking experiments targeting the Ig-like domain 6 of VCAM-1\n(VCAM-1-D6) demonstrated that the VCAM-1-D6 domain was critical for VCAM-1 mediated A549\ncell migration into Matrigel. Next, we developed a human monoclonal antibody specific to human\nand mouse VCAM-1-D6 (VCAM-1-D6 huMab), which was isolated from a human synthetic antibody\nlibrary using phage display technology. Finally, we showed that VCAM-1-D6 huMab had a nanomolar\naffinity for VCAM-1-D6 and that it potently suppressed the migration of A549 and NCI-H1299 lung\ncancer cell lines into Matrigel. Taken together, these results suggest that VCAM-1-D6 is a key domain\nfor regulating VCAM-1-mediated lung cancer invasion and that our newly developed VCAM-1-D6\nhuMab will be a useful tool for inhibiting VCAM-1-expressing lung cancer cell invasion....
Abstract: PB10 IgG1, a monoclonal antibody (MAb) directed against an immunodominant epitope\non the enzymatic subunit (RTA) of ricin toxin (RT), has been shown to passively protect mice\nand non-human primates from an aerosolized lethal-dose RT challenge. However, it was\nrecently demonstrated that the therapeutic efficacy of PB10 IgG1 is significantly improved when\nco-administered with a second MAb, SylH3, targeting RTâ??s binding subunit (RTB). Here we report that\nthe PB10/SylH3 cocktail is also superior to PB10 alone when used as a pre-exposure prophylactic (PrEP)\nin a mouse model of intranasal RT challenge. The benefit of the PB10/SylH3 cocktail prompted us to\nengineer a humanized IgG1 version of SylH3 (huSylH3). The huPB10/huSylH3 cocktail proved highly\nefficacious in the mouse model, thereby opening the door to future testing in non-human primates....
Enalapril is an angiotensin-converting enzyme inhibitor used for treatment of hypertension and chronic heart disease. Enalaprilat\nis its active metabolite responsible for the activity. This study aimed to develop and validate a method for enalapril and enalaprilat\nanalysis and to determine the bioequivalence of two tablet formulae of enalapril. LC-MS/MS bioanalytical method was developed\nand validated and then applied to evaluate the bioavailability of two enalapril formulae. Antihyperglycemic sitagliptin was used as\ninternal standard (IS). The method was accurate for the within- and between-days analysis, and precise CV% was <5%, being linear\nover the calibration range 1.0ââ?¬â??200.0 ng/ml. Stability was >85%and the LODwas 0.907 and 0.910 ng/ml for enalapril and enalaprilat,\nrespectively, and LLOQ was 1 ng/ml. The pharmacokinetic parameters ...
Aim: Tauroursodeoxycholic acid (TUDCA) is a taurine conjugated form of ursodeoxycholic acid (UDCA) with higher hydrophility. To\nfurther evaluate the efficacy and safety of TUDCA for primary biliary cholangitis (PBC), we performed this study on Chinese patients.\nMethods: 199 PBC patients were randomly assigned to either 250mg TUDCA plus UDCA placebo or 250mg UDCA plus TUDCA\nplacebo, 3 times per day for 24 weeks. The primary endpoint was defined as percentage of patients achieving serum alkaline\nphosphatase (ALP) reduction of more than 25% from baseline.\nResults: At week 24, 75.97% of patients in the TUDCA group and 80.88% of patients in the UDCA group achieved a serum ALP\nreduction of more than 25% from baseline (P=0.453). The percentage of patients with serum ALP levels declined more than 40%\nfollowing 24 weeks of treatment was 55.81% in the TUDCA group and 52.94% in the UDCA group (P=0.699). Both groups showed\nsimilar improvement in serum levels of ALP, aspartate aminotransferase, and total bilirubin (P>0.05). The proportion of patients with\npruritus/scratch increased from 1.43% to 10.00% in UDCA group, while there�s no change in TUDCA group (P=0.023). Both drugs\nwere well tolerated, with comparable adverse event rates between the 2 groups.\nConclusions: TUDCA is safe and as efficacious as UDCA for the treatment of PBC, and may be better to relieve symptoms than\nUDCA....
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