Interactions of formulation excipients with proteins in solution and in. Stability and characterization of human interleukin1s leo gu and jodi fausnaugh 1. Case histories the characterization, stabilization, and formulation of acidic fibroblast growth factor authors. Pdf parenteral formulations of proteins and peptides. The characterization and stability testing for oral peptide formulations. Screening approach to the characterization and formulation of biopharmaceuticals 173 sangeeta b. Formulation, characterization, and stability of protein drugs case. Formulation characterization and stability of protein drugs case histories. Formulation, characterization, and stability of protein drugs, rodney pearlman and y.
Request pdf formulation, stability, and characterization of protein and peptide drugs the evolution of recombinant dna technology and the advances in. Bansi zalavadia international journal of innovative pharmaceutical research,2010,14. Despite their therapeutic potential, peptides frequently pose drug delivery. Manning mc, patel k and borchardt rt, stability of protein pharmaceuticals, pharm res, 6, pp903918, 1989 2. 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. Formulated subcutaneous sc protein drugs must be stable and unaffected at very high protein concentrations over 100 mgml within their container closure, e. Stability characterization and formulation development of alteplase, a recombinant tissue plasminogen. It also involves extensive stability studies under stressed conditions. Stability and characterization of protein and peptide drugs. Scientific and commercial success of a pharmaceutical product. Case histories pp 181217 cite as the characterization, stabilization, and formulation of acidic fibroblast growth factor authors.
Stability of protein in cores in frozen storage 10, 20, 40c sec data. Proteins generally require a formulation excipients as a protein stabilizer in a liquid state. 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. Characterization and stability of peptides and proteins bioneer. 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. Protein drugs plastic screw cap losing backofftorque. 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. Leading scientists offer detailed profiles of ten protein drugs currently in development.
Extrinsic contributing factors include ph, osmolarity, protein concentration, formulation excipients, and exposure of a product to physical stress from. However, polymers possessing hydrophobic character, such as peg. Oral drug delivery, peptideprotein drugs, particulate delivery. When proteins become unstable, molecules unfold and aggregate. 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. Stability characterization and formulation development of. The indepth coverage includes a highly useful compendium of. A comprehensive guide to protein stability assay platforms. Current perspectives on stability of protein drug products.
Russell middaugh 9 fluorescence and phosphorescence methods to probe protein structure and stability in ice. Instability, stabilization, and formulation of liquid. Formulation, stability, and characterization of protein and peptide. Aggregated proteins incur immune responses that cause serious side effects, which makes protein stability an integral part of protein formulation.
Nonionic surfactants are often used in protein formulations to reduce interfacial stress and prevent protein denaturation, aggregation, and adsorption loss lee et al. Formulation, characterization, and stability of protein drugs. Characterization of particulate drug delivery systems for. Analysis of degradation products of polysorbate 20 in protein formulation by iecrp 2dlc 3. 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 during. Characterization of monoclonal antibody formulations.
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. The case histories of these important new compounds are described from the perspective of their formulation, characterization, and stability. Wang yj, pearlman r eds stability and characterization of protein and peptide drugs. Formulation, in vitro characterization and stability. Identification and characterization of major esters in polysorbate 20 2. Costeffective scaleup of the cell culture or fermentation process, and puri. Strambini 10 applications of sedimentation velocity analytical.
Size, molecular weight, polydispersity, viscosity, and interaction parameters can all. Characterization and stability of polysorbate 20 in. It simultaneously measures a range of stability parameters including protein unfolding transition temperature t m and aggregation onset temperature t agg. Characterization of protein and peptide drugs case histories edited by y. Instability, stabilization, and formulation of liquid protein pharmaceuticals instability, stabilization, and formulation of liquid protein pharmaceuticals wang, wei 19990820 00. Key formulation challenges of protein mab drugs sandeep nema, phd pfizer. This ready reference also features recent data and an abundance of previously unpublished information. Stability and characterization of human growth hormone.
Nguyen th, ward c 1993 stability characterization and formulation development of alteplase, a recombinant tissue type plasminogen activator. Stability and characterization of protein and peptide drugs case histories. A realworld guide to the production and manufacturing of biopharmaceuticals. Department of pharmacy, universitetsparken 2, 2100 copenhagen. Smallscale characterization studies should be conducted to evaluate protein stability under formulation conditions. Protein formulation an overview sciencedirect topics. These may include determination of isoelectric point pi of physical stability after concentration, aggregation and freezethaw. Fda recommendations for comparability studies to support. Stability of polysorbate 20 in protein drug product hydrophilic head group hydrophobic fatty. Case histories download more latest stuff visit english 460 pages springer. Formulation characterization and stability of protein. Farma has extensive experience in quantifying and determining the structure and stability of peptide or protein drugs. Protein stability is essential for drug efficacy and storage shelf life. Strambini 10 applications of sedimentation velocity.
Physicochemical and formulation developability assessment for. This ready reference also features recent data and an abundance. Biopharmaceutical product stability considerations, part. The focus in the development stage of recombinant protein drugs is the production and puri. The characterization, stabilization, and formulation of.
Mountain view, california plenum press new york and london. 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 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. Formulation and process development strategies for. 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. Protein stability depends on temperature, ph, concentration. Polysorbate 20 is a nonionic surfactant commonly used in the formulation of therapeutic monoclonal antibodies mab to prevent protein denaturation and aggregation. Candidate selection for developability with differential. Ft of mab and fusion protein drug substance formulation same as that of drug product 20 mm histidine buffer.
Characterization of particulate drug delivery systems for oral delivery of peptide and protein drugs volume. Formulation, characterization, and stability of protein drugs case histories edited by rodney pearlman megabios corporation v burlingame, california i and y. We provide a comprehensive range of highquality analytical assays to characterize protein therapeutics. Formulation development of protein products typically begins with characterization of the biomolecule to identify critical quality attributes of its physical and chemical stability. Download freecourseweb formulation, characterization. Characterization and stability study of polysorbate 20 in. Powell, godfrey amphlett, jerry cacia, william callahan, eleanor cannovadavis, byeong chang et al. Advanced protein formulations wiley online library. Please use one of the following formats to cite this article in your essay, paper or report. Stability testing of therapeutic proteins using dls and. Protein instability is one of the major reasons why protein. 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. Borchardt the university of kansas lawrence, kansas recent volumes in this series. Characterization and formulation considerations for recombinantly.
Formulation, characterization, and stability of protein. 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. Formulation, in vitro characterization and stability studies of self microemulsifying drug delivery systems of domperidone 1 presented by. 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. Physicochemical and formulation developability assessment. Rodney pearlman is the author of formulation, characterization, and stability of protein drugs 3. Characterization, stability, and formulations of basic. 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. Manvar college of pharmacy,dumiyani sudhanshu sharma and preeti k. Rodney pearlman author of formulation, characterization. Peptides are smaller than proteins and, as a result, may lack a single stable secondary structure. 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 accurate prediction of protein stability under pharmaceutical formulation conditions is.
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