Biopharmaceutical Characterization Services

PTMs of proteins, refer to the covalent addition of functional groups or proteins, the regulation of the proteolytic cleavage of subunits and the degradation of the entire protein, which can increase the functional diversity of the proteome and impact their structure, stability, function, interacting partners, and localization within the cell. PTMs have a critical role in many cellular processes such as cellular differentiation, protein degradation, signaling and regulatory processes, regulation of gene expression, and protein-protein interactions. The most common PTMs can be phosphorylation, glycosylation, ubiquitination, nitrosylation, methylation, acetylation, lipidation and proteolysis. Although identification of PTMs is characterized with extreme tedious, an advanced analytical platform at Alfa Chemistry can provide you a high quality characterization service of various post-translational modifications. To meet your specificity, sensitivity, and small sample requirement, our experts can provide highly sensitive target phosphoprotein expression analysis using a variety of technique methods such as western blots, ELISAs, and mass spectrometry. Based on your product's specific structural characteristics, a strategic analytical program will be further designed by our scientists under the industry guidance such as ICH Q6B. As a PTM analysis service provider, Alfa Chemistry is specialized in mass spectrometry (Orbitrap and QToF) analysis and providing high-resolution, accurate-mass (HRAM) data to our clients. In addition, a range of chromatographic techniques are available at our laboratory and can be used to define your product acceptance criteria or supporting process validation activities.

Protein isoforms, also known as protein variants, represent the members of a variety of highly similar proteins that are structurally heterogeneous and mainly formed by alternative splicing, charge variants, truncations, amino acid substitutions, polymorphism and post-translation modifications (PTMs). Accumulating evidences demonstrated that protein isoforms have critical roles in various biological processes such as heart hypertrophy, autoimmune diseases, diabetes, and they impact thyroid pathological conditions which are closely related to many of cancer. Besides, these changes can also markedly impact the stability and activity of protein products, even cause immunologically adverse reactions. Given the significant role of protein isoforms in various stages in a number of pathologies, detection of the isoforms is supposed to be an efficient biomarker or therapeutic targets. With decades of analysis experience and unique expertise in the field of protein testing services, experts from Alfa Chemistry can offer you the best protein isoform detection services using our advanced technologies and several novel methods. To present the accuracy and reliability for protein isoform differentiation, many up-to-date analytical platforms which are based on mass spectrometry (MS) have been developed. Combining our expertise in protein identification with other advanced approaches such as electrospray ionization (ESI), hydrophobic interaction chromatography (HIC) and two-dimensional difference gel electrophoresis (2-D DIGE) to further ensure a far higher reliability and confidence protein analysis for you.

Glycosylation, a form of co-translational and post-translational modification, is generally produced by attachment of sugar moieties to other functional group of another molecule. Biology glycosylation represents the enzymatic process in which glycans are attached to proteins, lipids, or other organic molecules. It has been proved that biology glycosylation has a vital effect on a wide range of biological processes such as cell attachment to the extracellular matrix and protein–ligand interactions in the cell. Besides, glycans produced by glycosylation are also essential in membrane and secreted proteins for their various structural and functional roles. Glycan profiling, refers to the investigation of the glycan structures, is an invaluable tool for biopharmaceutical development, control of protein biological functions, pharmacokinetics, antibody effector functions and biomolecular interactions. However, glycosylation analysis is always challenged by the complexity and the isobaric nature of attached glycans. Alfa Chemistry can offer the customers around the world with high through-put analytical services to supporting their needs for glycosylation profiling as well as other biomolecules, cells and tissues. With rapid mass spectrometric glycan profiling and full structural analysis of glycans, our scientists are specialized in providing the qualitative and quantitative information of glycan structures.

Peptides and proteins are the main components of biopharmaceutical products. Using the N-terminal Edman sequencing and amino acid analysis can determine the amino acid composition or content of proteins, peptides or other biopharmaceutical products. N-terminal Edman sequencing can also be termed as Edman degradation, which represents the sequential cleavage of amino acids from the N-terminal end of a protein and identification of individual amino acids. As a cyclic procedure, the N-terminal Edman sequencing service can provide you the detailed information about the N-terminal amino acid sequence of protein by using microbore HPLC. At Alfa Chemistry , N-terminal sequencing of proteins or peptides will be offered as lyophilized samples, in solution or blotted on PVDF membrane as fee-for-service. Importantly, your protein or peptide products are able to be sequenced 5 to 40 steps, which is depending on the total amount, purity and amino acid sequence of your samples and your requirements. Finally, a comprehensive report of the N-terminal sequence analysis will be provided by our staff for determination of the amino acid sequence of your products. For amino acid analysis, various advanced technique platforms such as ion-exchange liquid chromatography with post-column Ninhydrin derivatisation and photometric detection and HPLC-UV/FLU are available for our experts. With the world-class expertise in (glycol) protein analysis, we can provide you with optical density measurement, peptide or protein content and molar ratio analysis, and extinction coefficient determination services.

As one of the most important components of drug industry, biopharmaceuticals include therapeutic proteins, fusion proteins, and monoclonal antibodies have exhibited many treatment advantages. However, the degradants caused by oxidation, deamination, truncations and other reasons lead to a significant concern about the safety, efficacy, quality, purity and potency of the biopharmaceutical product. In this case, efficient and accurate identification and characterization of degradants plays an essential role in the biopharmaceutical product development. Alfa Chemistry is dedicated to offer high-quality biopharmaceutical characterization services for global clients. Our extensive expertise and superior equipment can provide you a comprehensive analytical method for degradant characterization for your biotech and biological products. By utilizing a broad range of techniques include glycosylation analysis by mass spectrometry, liquid chromatography, SEC-MALS, cIEF/ IEF and analytical ultracentrifugation, Alfa Chemistry can provide characterization services for various biological degradants such as modified forms, truncated forms and product aggregates. The scientists in our laboratory are capable enough to conduct a series of biologic tests that can be applied for determination of a range of degradants and other contaminants.

Disulfide linkage is a single covalent bond that formed between the sulfur atoms of cysteines. At tertiary structure level, such bonds are formed inside the protein subunit and are critical to the folding and stability of these proteins since proteins are secreted to the extracellular medium such as antibodies, growth factors and peptide hormones. In contrast, the disulfide linkages are formed between two protein subunits at quartenary structure level, which has an important effect on biasing protein towards the folded topology. At this level, the disulfide bond is supposed to be able to elevate the effective local concentration of protein residues and down-regulate the effective local concentration of water molecules. Given the ability of stabilizing overall structure of proteins, cross-linked disulfide linkages in many commercialized biopharmaceutical products are widely applied in industrial processes or to protect protein-based therapeutics. An established highly sensitive HPLC-MS/MS platform at our laboratory can meet your any requirements of disulfide linkages analysis. Furthermore, optimized protocol can be offered by our experienced analysts to enable more fast and sensitive site mapping service. Other advanced techniques such as Matrix-assisted laser (LC/ESI-MS, Q-TOF) can be further applied to provide serial of analysis of sulfhydryl groups and disulfide bonds for our clients.

Biomarker or biological marker, can be used to indicate the biological processes, pathogenic processes and the pharmacologic responses to a therapeutic intervention, and it can be served as the surrogate endpoints that are able to measure the effects of investigational compounds and monitor disease progression. Although the process of biomarkers analysis are highly complex and time-consuming, the experts of Alfa Chemistry who have extensive experience in biopharmaceutical characterization and development are able to provide you an efficient analytical strategy with high efficacy and accuracy. With manual and/or automated methods, we can provide the most suitable solutions to meet any special detection requirements. At Alfa Chemistry , various multifunctional equipment and dedicated laboratory spaces enable our clients to access services of monitoring several biomarkers in parallel. Additionally, for supporting our clients' regulatory reports, a fully consultative and comprehensive assay validation services will be offered by our scientists under the up-to-date industry guidelines.

As a biological preparation, vaccine can be used as a prophylactic treatment to prevent future infections or as a therapeutic agent. Materials that are applied to produce vaccines are well-defined such as purified protein antigens of natural origin, rDNA, polysaccharides, semi-synthetic poly- or oligosaccharide-protein conjugates and novel nucleic acid constructs. Furthermore, viral vector-based products or virus-like particles (VLPs) are the vaccines technologies that act as vaccine carriers and adjuvants. The vaccines development support teams from Alfa Chemistry will work with our clients to evaluate the various components of vaccines such as carbohydrate, lipopolysaccharide, lipid, protein, glycoprotein, and lipoprotein components. With a comprehensive suite of methods, the experts of our laboratory can provide high quality services to meet the requirements from our vaccine manufacturers and researchers throughout the vaccine development process. Finally, to support your regulatory reports, fully proof of identity, efficacy and purity of the vaccines can be provided by our team. Alfa Chemistry have decades of experience in delivering quality analytical data for our clients. We offer analytical support services such as viral analysis and characterization, recombinant DNA vaccines and aggregation state characterization for vaccine analysis. Through the solid-state circular dichroism (ssCD) analytical technique, our experts can determine the specific structure of biopharmaceutical antigens contained in colloidal particulate vaccines. Besides, other methods such as specialized orthogonal analytical techniques can be utilized to offer you an increased range of vaccine analysis, formulation, and stability testing services according to your requirements.

Immunochemistry, also known as the large molecule bioanalysis, represents an efficient technique to determine the efficacy, safety, disease state or mechanism of action of your product, and provide you with useful feedback data to support your important decisions during biologic drug development. As a professional company specialized in a wide variety of immunoassay-related services, Alfa Chemistry provides immunochemistry services including but not limited to immunoassays, biomarker assays, cell-based neutralization assays, immunogenicity assays and ligand-binding assays. Besides, with comprehensive suite of immunochemistry techniques, our laboratory is able to perform antibody purification, antibody characterization/quantification, antibody modification and labeling. Various advanced techniques and methods such as BSI uses luminex technology will further be provided for your monoclonal and polyclonal antibody development. For supporting your toxicokinetics (TK) and pharmacokinetics (PK) studies, immunogenicity and biomarker studies, our industry-leading expertise in immunochemistry can provide development and validation of proprietary assays, implemention and validation of existing methods, optimization methods, and validation of existing immunoassay kits (ELISA and ECL platforms).

Ligand binding assays represents the process of quantifying an analyte for a ligand, which relies on the binding of ligand molecules to antigens, receptors, antibodies and other macromolecules. This kind of procedure is used primarily in pharmacology for producing drugs that are selective or mimic the endogenously found cellular components. The main aspects of ligand-receptor binding interactions include binding affinity and kinetics, conformations of targets, binding thermodynamics and ligand efficiency. The effective clinical effect of a biotherapeutics mainly depends on the specific binding activities. In this case, matching the binding activities of a biosimilar candidate to those of the reference product plays a central role in the development of biosimilar drugs.

Alfa Chemistry can offer the ligand-binding and activity assays such as labeled, label-free, structure-based, thermodynamic, and whole cell ligand-binding assays with various sophisticated analytical platforms and methods such as automated ELISA systems, MSD, LC-MS/MS, hybrid hybrid assays, oligonucleotides, luminex? technologies and high-resolution mass spectrometry. Besides, other advanced techniques such as radioimmunoassay (RIA), enzyme immunoassay (EIA), fluorescence immunoassay (FIA) and immunoradiometric assay (IRMA) can be offered by our laboratory to determine your macromolecular drug therapeutics, immunogenicity screening, and biomarkers in biological matrices. It should be noted that in order to support your bioanalysis, the pertinent solutions and interpretations that are customized to your requirements for molecule or other investigation will be delivered by our biological analyst and our immunogenicity, pharmacokinetic and statistical specialists.

Covalent attachment of one or more poly(ethylene glycol) (PEG) chains or certain polymers to some of therapeutic agents can be used to improve the pharmacokinetic (PK) profile of a drug such as significantly extend the drug's half-life in the body. However, conventional bioanalytical techniques have been demonstrated to be insufficient in PEGylated drug analysis due to the complexity and increasing molecular size of the PEGylated or polymer-linked drugs. The Good Laboratory Practice (GLP) compliant laboratories of Alfa Chemistry are adept at developing and validating bioanalytical methods which are competent for supporting your PEGylated and other polymer-linked drug assays. With the validated innovative bioanalytical technique platform, our scientists can provide you a packaging bioanalytical method to quantify your compounds which cover a variety of biological matrices and species. Additionally, by using advanced approaches such as nuclear magnetic resonance spectroscopy (NMR), full range of services for bioanalysis of pegylated and other polymer-linked drug assays such as egylated small molecule bioanalysis and pegylated large molecule bioanalysis are placed on a strategy position at Alfa Chemistry to support your iopharmaceutical or biologic medicine developments.

Antibody-drug conjugates (ADCs), the monoclonal antibodies chemically linked to biologically active small molecule drugs, represents a new class of biotherapeutics that have a rapidly growing portion of the drug discovery pipeline in pharmaceutical companies. Drug/Antibody Ratio (DAR) is defined as the average number of drugs conjugated to the antibodies and is an important attribute of ADCs, which has an obvious effect on the efficacy of drug products. For example, low drug loading can lead to a reduced potency while high drug loading is closely related to toxicity and inferior pharmacokinetics. To measure the DAR of your drug products, Alfa Chemistry will work with our clients throughout all stage of your drug development, using various advanced analytical methods such as UV/Vis spectroscopy, HIC, RP-HPLC, LC-ESI-MS and other advanced instrumentation. Additionally, our scientists are specialized in the field of novel therapeutics development and have extensive experience in antibody-drug conjugate (ADC) chemistry. Summary, we are proud and confident in providing high quality DAR analysis services for our customers across the world.