During processing and formulation of the drug product, the protein is exposed to conditions that could have significant effects on its chemical and physical stability, and lead to aggregation and. Smallscale characterization studies should be conducted to evaluate protein stability under formulation conditions. Stability and characterization of protein and peptide drugs case histories. Current perspectives on stability of protein drug products during. Protein stability depends on temperature, ph, concentration. Formulation development of protein products typically begins with characterization of the biomolecule to identify critical quality attributes of its physical and chemical stability. Leading scientists offer detailed profiles of ten protein drugs currently in development. Nguyen th, ward c 1993 stability characterization and formulation development of alteplase, a recombinant tissue type plasminogen activator.
Proteins generally require a formulation excipients as a protein stabilizer in a liquid state. Download freecourseweb formulation, characterization. This ready reference also features recent data and an abundance. Key formulation challenges of protein mab drugs sandeep nema, phd pfizer. Characterization and stability study of polysorbate 20 in. Fda recommendations for comparability studies to support. Formulation, in vitro characterization and stability. Size, molecular weight, polydispersity, viscosity, and interaction parameters can all. Characterization, stability, and formulations of basic. Physicochemical and formulation developability assessment. We provide a comprehensive range of highquality analytical assays to characterize protein therapeutics. Advanced protein formulations wiley online library. Instability, stabilization, and formulation of liquid protein pharmaceuticals instability, stabilization, and formulation of liquid protein pharmaceuticals wang, wei 19990820 00. This ready reference also features recent data and an abundance of previously unpublished information.
Bansi zalavadia international journal of innovative pharmaceutical research,2010,14. Formulation, characterization, and stability of protein. With respect to drug product quality aspects, initial characterization of the physical and chemical stability liabilities of the peptide is typically completed via preformulation workup and hence known at the start of formulation development, though aggressive manufacturing processes can introduce unforeseen challenges in development. Stability characterization and formulation development of. Peptides are smaller than proteins and, as a result, may lack a single stable secondary structure. Stability and characterization of human growth hormone. It also involves extensive stability studies under stressed conditions. Mountain view, california plenum press new york and london. Protein stability is controlled by innumerable intrinsic and extrinsic factors, but the major ones are primary sequence, 3d structure, subunit associations, and posttranslational modifications. The characterization and stability testing for oral peptide formulations. A realworld guide to the production and manufacturing of biopharmaceuticals. Stability characterization and formulation development of alteplase, a recombinant tissue plasminogen.
These may include determination of isoelectric point pi of physical stability after concentration, aggregation and freezethaw. Please use one of the following formats to cite this article in your essay, paper or report. Powell, godfrey amphlett, jerry cacia, william callahan, eleanor cannovadavis, byeong chang et al. Formulated subcutaneous sc protein drugs must be stable and unaffected at very high protein concentrations over 100 mgml within their container closure, e. Formulation, in vitro characterization and stability studies of self microemulsifying drug delivery systems of domperidone 1 presented by. Formulation and process development strategies for. Protein formulation an overview sciencedirect topics. Strambini 10 applications of sedimentation velocity. It is critical to understand the molecular heterogeneity and stability of polysorbate 20 in mab formulations as polysorbate can gradually degrade in aqueous solution over time by multiple pathways losing surfactant functions and. Characterization of monoclonal antibody formulations during longterm storage introduction the development of the use of proteins, especially monoclonal antibodies mabs, as therapeutic molecules has provided many challenges.
Stability and characterization of human interleukin1s leo gu and jodi fausnaugh 1. Ft of mab and fusion protein drug substance formulation same as that of drug product 20 mm histidine buffer. Characterization and stability of polysorbate 20 in. Rodney pearlman is the author of formulation, characterization, and stability of protein drugs 3. It simultaneously measures a range of stability parameters including protein unfolding transition temperature t m and aggregation onset temperature t agg. Protein stabilization by a stabilizers can be achieved through the traditional preferential interaction mechanism 16 andor other proposed mechanisms such as nonspecific interaction with surface hydrophobic pockets 17 or charged amino acids, 18 specific. Formulation characterization and stability of protein drugs case histories. Case histories download more latest stuff visit english 460 pages springer. The accurate prediction of protein stability under pharmaceutical formulation conditions is.
Extrinsic contributing factors include ph, osmolarity, protein concentration, formulation excipients, and exposure of a product to physical stress from. The term formulation, fill and finish refers to the series of processing steps that are needed to turn a purified drug substance into the final dosage form, the finished product, for the market. Stability and characterization of protein and peptide drugs. Formulation, characterization, and stability of protein drugs case histories edited by rodney pearlman megabios corporation v burlingame, california i and y. The focus in the development stage of recombinant protein drugs is the production and puri. Characterization of protein and peptide drugs case histories edited by y. Characterization of monoclonal antibody formulations. Characterization and formulation considerations for recombinantly. Release testing and 3 months real time and accelerated stability data on at least one lot of drug product all process validation data for process b 10,000l scale trending of all historical data both process a and b clearly labeled including release, characterization, stability data. Instability, stabilization, and formulation of liquid. Whether characterizing the original or subsequent reference standards, evaluating production lots to those standards or performing comparability studies of biosimilars or biobetters, we have the fullrange of. Nonionic surfactants are often used in protein formulations to reduce interfacial stress and prevent protein denaturation, aggregation, and adsorption loss lee et al. Rodney pearlman author of formulation, characterization.
Stability of protein in cores in frozen storage 10, 20, 40c sec data. Department of pharmacy, universitetsparken 2, 2100 copenhagen. Protein stability is essential for drug efficacy and storage shelf life. Formulation, characterization, and stability of protein drugs. When proteins become unstable, molecules unfold and aggregate. Costeffective scaleup of the cell culture or fermentation process, and puri. Formulation, characterization, and stability of protein drugs case.
Request pdf formulation, stability, and characterization of protein and peptide drugs the evolution of recombinant dna technology and the advances in. A comprehensive guide to protein stability assay platforms. Physicochemical and formulation developability assessment for. Polysorbate 20 is a nonionic surfactant commonly used in the formulation of therapeutic monoclonal antibodies mab to prevent protein denaturation and aggregation. Characterization and stability of peptides and proteins bioneer. Pdf parenteral formulations of proteins and peptides.
Interactions of formulation excipients with proteins in solution and in. Analysis of degradation products of polysorbate 20 in protein formulation by iecrp 2dlc 3. Borchardt the university of kansas lawrence, kansas recent volumes in this series. However, polymers possessing hydrophobic character, such as peg. Protein drugs plastic screw cap losing backofftorque. Screening approach to the characterization and formulation of biopharmaceuticals 173 sangeeta b. Farma has extensive experience in quantifying and determining the structure and stability of peptide or protein drugs. Stability testing of therapeutic proteins using dls and. The case histories of these important new compounds are described from the perspective of their formulation, characterization, and stability. Topp em, zhang l, zhao h et al, chemical instability in peptide and protein pharmaceuticals, formulation and process development strategies for manufacturing of a biopharmaceuticaljameel f, hershenson s eds, wiley and sons, new york. Characterization of particulate drug delivery systems for oral delivery of peptide and protein drugs volume. Russell middaugh 9 fluorescence and phosphorescence methods to probe protein structure and stability in ice. Successful development of liquid biopharmaceutical formulations requires careful assessment of the biophysical properties of the protein in solution, primarily focused on achieving optimal conformational and colloidal stability of the drugsubstance molecule 111. Current perspectives on stability of protein drug products.
Formulation, characterization, and stability of protein drugs, rodney pearlman and y. Characterization of particulate drug delivery systems for. The formulation step involves taking the purified protein at the desired concentration and dispensing it with the correct excipients that can ensure product quality and integrity. Candidate selection for developability with differential. While much has been written about the science of biopharmaceuticals, there is a need for practical, uptodate information on key issues at all stages of developing and manufacturing commercially viable biopharmaceutical drug products. Despite their therapeutic potential, peptides frequently pose drug delivery.
Stability of polysorbate 20 in protein drug product hydrophilic head group hydrophobic fatty. Oral drug delivery, peptideprotein drugs, particulate delivery. The characterization, stabilization, and formulation of. Aggregated proteins incur immune responses that cause serious side effects, which makes protein stability an integral part of protein formulation. Formulation, stability, and characterization of protein and peptide. Case histories the characterization, stabilization, and formulation of acidic fibroblast growth factor authors. Manning mc, patel k and borchardt rt, stability of protein pharmaceuticals, pharm res, 6, pp903918, 1989 2.
Scientific and commercial success of a pharmaceutical product. Wang yj, pearlman r eds stability and characterization of protein and peptide drugs. Thus, if interfacial stress is a stability concern for a particular protein molecule, then use of a nonionic surfactant is a good first step in mitigating this problem. The indepth coverage includes a highly useful compendium of. Stability testing of pharmaceutical products is a complex set of procedures involving considerable cost, time consumption and scientific expertise in order to build in quality, efficacy and safety in a drug formulation. Case histories pp 181217 cite as the characterization, stabilization, and formulation of acidic fibroblast growth factor authors. Biopharmaceutical product stability considerations, part. Manvar college of pharmacy,dumiyani sudhanshu sharma and preeti k. Strambini 10 applications of sedimentation velocity analytical. Formulation characterization and stability of protein.
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