Expectations for Phase-Appropriate Drug Substance and Drug Product Specifications for Early-Stage Protein Therapeutics

2019 ◽  
Vol 108 (4) ◽  
pp. 1442-1452 ◽  
Author(s):  
Juliana Kretsinger ◽  
Neha Frantz ◽  
Scott A. Hart ◽  
Wayne P. Kelley ◽  
Bob Kitchen ◽  
...  
Keyword(s):  
Drug Product ◽  
Early Stage ◽  
Protein Therapeutics ◽  
Drug Substance ◽  
Product Specifications

scholarly journals Manufacturing Bacteriophages (Part 2 of 2): Formulation, Analytics and Quality Control Considerations

2021 ◽  
Vol 14 (9) ◽  
pp. 895
Author(s):  
Carolina Moraes de Souza ◽  
Tayfun Tanir ◽  
Marvin Orellana ◽  
Aster Escalante ◽  
Michael Sandor Koeris
Keyword(s):  
Quality Control ◽  
Product Development ◽  
Analytical Methods ◽  
Drug Product ◽  
Early Stage ◽  
Drug Substance ◽  
Performance Parameters ◽  
Entire Spectrum ◽  
Pharmaceutical Development ◽  
Made In

Within this second piece of the two-part series of phage manufacturing considerations, we are examining the creation of a drug product from a drug substance in the form of formulation, through to fill-finish. Formulation of a drug product, in the case of bacteriophage products, is often considered only after many choices have been made in the development and manufacture of a drug substance, increasing the final product development timeline and difficulty of achieving necessary performance parameters. As with the preceding review in this sequence, we aim to provide the reader with a framework to be able to consider pharmaceutical development choices for the formulation of a bacteriophage-based drug product. The intent is to sensitize and highlight the tradeoffs that are necessary in the development of a finished drug product, and to be able to take the entire spectrum of tradeoffs into account, starting with early-stage R&D efforts. Furthermore, we are arming the reader with an overview of historical and current analytical methods with a special emphasis on most relevant and most widely available methods. Bacteriophages pose some challenges that are related to but also separate from eukaryotic viruses. Last, but not least, we close this two-part series by briefly discussing quality control (QC) aspects of a bacteriophage-based product, taking into consideration the opportunities and challenges that engineered bacteriophages uniquely present and offer.

scholarly journals Current hurdles to the translation of nanomedicines from bench to the clinic

2021 ◽  
Author(s):  
Snežana Đorđević ◽  
María Medel Gonzalez ◽  
Inmaculada Conejos-Sánchez ◽  
Barbara Carreira ◽  
Sabina Pozzi ◽  
...  
Keyword(s):  
Drug Product ◽  
Early Stage ◽  
Regulatory Agencies ◽  
Important Process ◽  
Close Collaboration ◽  
Critical Quality Attributes ◽  
Research Areas ◽  
Physical Chemical ◽  
Clinical Models ◽  
Further Development

AbstractThe field of nanomedicine has significantly influenced research areas such as drug delivery, diagnostics, theranostics, and regenerative medicine; however, the further development of this field will face significant challenges at the regulatory level if related guidance remains unclear and unconsolidated. This review describes those features and pathways crucial to the clinical translation of nanomedicine and highlights considerations for early-stage product development. These include identifying those critical quality attributes of the drug product essential for activity and safety, appropriate analytical methods (physical, chemical, biological) for characterization, important process parameters, and adequate pre-clinical models. Additional concerns include the evaluation of batch-to-batch consistency and considerations regarding scaling up that will ensure a successful reproducible manufacturing process. Furthermore, we advise close collaboration with regulatory agencies from the early stages of development to assure an aligned position to accelerate the development of future nanomedicines. Graphical abstract

scholarly journals Understanding and Kinetic Modeling of Complex Degradation Pathways in the Solid Dosage Form: The Case of Saxagliptin

Pharmaceutics ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 452 ◽  
Author(s):  
Robnik ◽  
Likozar ◽  
Wang ◽  
Stanić Ljubin ◽  
Časar
Keyword(s):  
Relative Humidity ◽  
Degradation Product ◽  
Degradation Products ◽  
Drug Product ◽  
Degradation Kinetics ◽  
Dosage Forms ◽  
Drug Substance ◽  
Polymer Composition ◽  
Solid Dosage Forms ◽  
Solid Dosage

Drug substance degradation kinetics in solid dosage forms is rarely mechanistically modeled due to several potential micro-environmental and manufacturing related effects that need to be integrated into rate laws. The aim of our work was to construct a model capable of predicting individual degradation product concentrations, taking into account also formulation composition parameters. A comprehensive study was done on active film-coated tablets, manufactured by layering of the drug substance, a primary amine compound saxagliptin, onto inert tablet cores. Formulation variables like polyethylene glycol (PEG) 6000 amount and film-coat polymer composition are incorporated into the model, and are connected to saxagliptin degradation, via formation of reactive impurities. Derived reaction equations are based on mechanisms supported by ab initio calculations of individual reaction activation energies. Alongside temperature, relative humidity, and reactant concentration, the drug substance impurity profile is dependent on micro-environmental pH, altered by formation of acidic PEG degradation products. A consequence of pH lowering, due to formation of formic acid, is lower formation of main saxagliptin degradation product epi-cyclic amidine, a better resistance of formulation to high relative humidity conditions, and satisfactory tablet appearance. Discovered insights enhance the understanding of degradational behavior of similarly composed solid dosage forms on overall drug product quality and may be adopted by pharmaceutical scientists for the design of a stable formulation.

Justification of Drug Product Dissolution Rate and Drug Substance Particle Size Specifications Based on Absorption PBPK Modeling for Lesinurad Immediate Release Tablets

2016 ◽  
Vol 13 (9) ◽  
pp. 3256-3269 ◽  
Author(s):  
Xavier J. H. Pepin ◽  
Talia R. Flanagan ◽  
David J. Holt ◽  
Anna Eidelman ◽  
Don Treacy ◽  
...  
Keyword(s):  
Particle Size ◽  
Dissolution Rate ◽  
Drug Product ◽  
Immediate Release ◽  
Drug Substance ◽  
Pbpk Modeling

Application of high throughput technologies to drug substance and drug product development

2004 ◽  
Vol 28 (6-7) ◽  
pp. 943-953 ◽  
Author(s):  
Colin R Gardner ◽  
Orn Almarsson ◽  
Hongming Chen ◽  
Sherry Morissette ◽  
Matt Peterson ◽  
...  
Keyword(s):  
Product Development ◽  
High Throughput ◽  
Drug Product ◽  
Drug Substance

scholarly journals Annual Product Quality Review

2020 ◽  
Vol 11 (2) ◽  
pp. 1862-1869
Author(s):  
Manjunath D.N. ◽  
Shailesh T. ◽  
Gowrav M.P.
Keyword(s):  
Product Quality ◽  
Drug Product ◽  
Pharmaceutical Product ◽  
Regulatory Requirements ◽  
Quality Review ◽  
Control Procedures ◽  
Release Data ◽  
Pharmaceutical Production ◽  
Product Specifications

Annual Product Quality Review (APQR) is an estimation prepared according to the Current Goods Manufacturing Practice (CGMP) requirements of different regulatory authorities. A Goods  Manufacturing Practice (GMP) ensures that the products are constantly produced and controlled according to quality standards. APQR is not only required for GMP but also required for the quality improvement of the pharmaceutical product. APQR is an evaluation carried out annually to measure the standard of quality of each drug with an intention to verify the constancy of current process and to check the correctness of current specifications and to highlight any trend in order to determine the need to change any drug product specifications or the manufacturing processes or control procedures. It is a written report that is required for every drug, based on the data that was collected in the previous year. It is designed to minimize the risks involved in any pharmaceutical production that cannot be eliminated through testing the finished product. The APQR is globally accepted by the industry and the contents should specify a list of manufactured batches, release data and reviews of deviations, complaints, recall and returned goods. This article gives brief overview of regulatory aspects and regulatory requirements for Annual Product Quality Review of pharmaceutical product. It mainly focusses on the documentation  required for the preparation of Annual Product Quality Review. Thus the article is based on the regulatory requirements or standards to manufacture and maintain the quality of any pharmaceutical product.

scholarly journals Identification, Isolation and Origin of Potential Dimer Impurities of Dichlorphenamide: A Carbonic Anhydrase Inhibitor Drug (Antiglaucoma)

2021 ◽  
Vol 33 (6) ◽  
pp. 1249-1252
Author(s):  
T. Purendar Reddy ◽  
Nageshwar Dussa ◽  
Srinivas Mamidi ◽  
Mahesh Panasa ◽  
Ramadas Chavakula ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Drug Product ◽  
Carbonic Anhydrase Inhibitor ◽  
Drug Substance ◽  
Substantial Impact ◽  
Isolation And Characterization ◽  
New Process ◽  
Inhibitor Drug

Present work describes the identification, isolation and characterization of two new process related dimeric impurities of dichlorphenamide (1). During the synthesis of dichlorphenamide, the formation of two new dimeric impurities namely 2,3-dichloro-5-(3,4-dichloro-5-sulfamoyl-phenyl)sulfonylbenzenesulfonamide (2) (1,1Œ-dichlorphenamide dimer) and 2,3-dichloro-5-(2,3-dichloro-5-sulfamoylphenyl) sulfonyl-benzenesulfonamide (3) (1,3Œ-dichlorphenamide dimer) was observed. In addition, origin and the strategies adapted to control these potential dimer impurities were also described. These impurities have a substantial impact on the quality of the drug substance as well as drug product.

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