Adopting a fully single-use process to improve speed to clinic: A leachables case study (original) (raw)
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Approaches to Quality Risk Management When Using Single-Use Systems in the Manufacture of Biologics
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Biologics manufacturing technology has made great progress in the last decade. One of the most promising new technologies is the single-use system, which has improved the efficiency of biologics manufacturing processes. To ensure safety of biologics when employing such single-use systems in the manufacturing process, various issues need to be considered including possible extractables/leachables and particles arising from the components used in single-use systems. Japanese pharmaceutical manufacturers, together with single-use suppliers, members of the academia and regulatory authorities have discussed the risks of using single-use systems and established control strategies for the quality assurance of biologics. In this study, we describe approaches for quality risk management when employing single-use systems in the manufacturing of biologics. We consider the potential impact of impurities related to single-use components on drug safety and the potential impact of the single-use s...
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Impact of process validation and equipment qualification in production of bio-therapeutics
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Production of therapeutic proteins like Biosimilars uses a complex cell based fermentation and purification process. There are chances of errors in these complex production processes due to complexities in the molecular pathway that every protein follows. Therefore to produce a desired therapeutic protein that elicit the correct immunological response in the patient, one need to ensure that it must have correct sequence, size, structure so that they are recognized by the specific receptors. The quality of these therapeutic proteins is characterized through standard assays and methods such as SDS PAGE (sodium dodecyl sulphate-polyacrylamide gel electrophoresis), IEF (Isoelectric focusing), Western Blot and other methods those are based on HPLC, Mass spectrometry and capillary electrophoresis to conform the desired molecular size, purity and identity of proteins. Thus in the process of validation of a method, equipment plays a critical role in ensuring the quality and safety of a biopharmaceutical product. It is always necessary to generate scientific data and information such as IQ (Installation qualification), OQ (Operational qualification) and PQ (Performance qualification) protocol and reports for each instrument employed in the process at the beginning and before the actual testing of the desired product. It is only after the completion of these activities, the product under different manufacturing steps can be characterized. Involvement of a software in conjunction to an equipment is also common and it is important that the software is in use with the equipment also meets the requirements of the CFR 21 FDA (Code of Federal Regulations, 21 Part 11 of US Food and Drug Administration), which is a legal requirement in a modern manufacturing process and hence it is important to comply with these rules as set of guidelines that will help to ensure the integrity and safety of data.
Biologics development represents a substantial advancement in the pharmaceutical industry because of their promise and huge success in the oncology, immunoscience, and cardiovascular disease areas. Prior to entering the marketed product development phase, each biopharmaceutical needs to go through series of stages that will allow or disallow the biologics asset to become a commercialized product. Each of those phases includes development planning and designing of studies to test relevant hypotheses to support the drug label if approved. The current thesis will focus on the principles, assumptions, and processes that are established to designate an asset (biologics) as a targeted first-in-human program. First-in-human studies are included under phase 1 trials, where initial human exposure is initiated to the investigational new drug (IND). Phase 1 is critical since it affirms if a compound’s mechanisms of action in humans and its development can result in a potentially new drug entity. Subsequently, step by step initiatives and processes from the perspective of different functional groups within the pharma will be revised to outline the staged procedures, methods, critical, and non-critical paths taken when a molecule is nominated as a clinical candidate. Overall alignment of deliverables will be presented between the different functional areas that partake in the first-in-human development. Strategic changes to the biologics development process, cell line development with multiple candidate sequences, initial platform fit assessment for a process, analytical and formulation will be acknowledged. Platform strategy for drug substance production, as well as, drug product composition will be outlined along with boilerplates for analytical method development to fit or not fit the platform approach. The functional groups that will be reviewed will be; Discovery, Cell line development, Drug Substance process development, Formulation development, Toxicology, Quality, Drug Substance manufacturing, Drug Product manufacturing, Stability and regulatory. Keywords: Fast to First in Human, Biologics, Development, Clinical.
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Food and Drug Administration's process analytical technology (PAT) initiative is a collaborative effort with industry to introduce new and efficient manufacturing technologies into the pharmaceutical industry. PAT's are systems for design, analysis, and control of manufacturing processes. 1 The Process Analytical Technology (PAT) initiative aims to move from a paradigm of 'testing quality into 'building quality in by design'. PAT tools are heavily applied in pharmaceutical workflows that underpin drug substance and dosage form development, scale-up, and manufacture. 2 This review introduced the concept of PAT, steps in PAT and it's applications. 3 INTRODUCTION:-Process analytical technology (PAT) is a key element of the "Pharmaceutical Current Good Manufacturing Practices (CGMPs) for the 21st Century-a Risk Based Approach" initiative announced by the FDA in August 2002 to improve and modernize pharmaceutical manufacturing. 4 FDA is issued guidance for industry entitled: "PAT, a framework for innovative pharmaceutical development, measurement and quality assurance" in order to catalyze improvements. 5 PAT forms a part of the Quality by Design (QbD) concept, also a regulatory-inspired methodology. 6
Advances in pharmaceutical materials and processing
Pharmaceutical Science and Technology Today, 1998
w In common with other industries, the pharmaceutical community is preparing itself for advancing into the year 2000 and beyond. Many innovations are taking place, both in the development of new drug delivery systems and the project plans for new drug development activities. All of these areas are important factors in the future of new drug products in any attempt to relieve current or future ailments. Advances in pharmaceutical materials and processing require new generations of pharmaceutical technologies, which in turn require an improved understanding of each step in the unit processes of dosage form development. The unit processes range from raw material qualification to final product release using process monitoring of critical steps. The authors illustrate some recent research trends in understanding and improving pharmaceutical materials and processing through the use of experience obtained within several research programs at Purdue University (West Lafayette, IN, USA). A systematic approach to the validation of monoclonal antibody manufacturing processes Christian A. Knaack and Anrhony M.J. Hawrylechko