Development Of A Risk Management System For Consumables Used In Biopharmaceutical Manufacturing

Injectable drugs, like those manufactured by the BioPharmOps group of Novartis Pharmaceuticals AG, must conform to strict guidelines for purity and potency. Recent non-conformances of critical supplied consumables have revealed potential business and patient safety risks for biotechnology manufacturers worldwide. As a result, Novartis has launched a program to enhance control systems over all consumables and their suppliers. Within this program, the author has developed a system to identify, analyze, and mitigate the various risks which may impact the business due to non-conformances in supplied consumables. The first function of the system is the identification of key risks and their potential effects according to various failure modes that have been observed during the use of the consumables in production. This is accomplished with a standardized list of possible failure modes which can be applied to all consumables. The categorization allows the relative risk of each failure mode to be compared among consumables. Secondly, the risk of contamination is evaluated using a Failure Modes and Effects Analysis (FMEA) framework. The three dimensions of the FMEA framework are the severity, likelihood, and detectability of a failure. The severity of each failure mode is assessed by analyzing the quantitative and qualitative impact that a failure might have on the purity and potency of the drug. This calculation is based on the properties of each consumable and its use in the production system. The likelihood of failure events is assessed through an analysis of the complexity of the consumable and its supply chain, and a review of the quality systems at the supplier. Detectability analysis considers the tests and inspections in place at various stages including consumable manufacturing, receiving inspection, and in-process tests during drug manufacturing which could detect a non-conformance. The total risk level is evaluated as the product of these three dimensions and a threshold is defined for requiring additional mitigations for these risks. This risk assessment method is implemented in an automated worksheet to ensure consistency among users and efficient analysis. The third outcome of the system is the recommendation of mitigations to reduce total exposure to contamination risk. Mitigations may be internal (new tests and inspections) or implemented at the supplier (improved sampling rates, enhanced general quality systems, or new controls). The recommended mitigations provide guidance for the reduction of risks to an acceptable level, and when implemented, the impact and frequency of non-conformances will be diminished. Ultimately, this reduces Novartis' exposure to potential business loss and protects patients from injury caused by contamination.

Sets forth tested and proven risk management practices in drug manufacturing Risk management is essential for safe and efficient pharmaceutical and biopharmaceutical manufacturing, control, and distribution. With this book as their guide, readers involved in all facets of drug manufacturing have a single, expertly written, and organized resource to guide them through all facets of risk management and analysis. It sets forth a solid foundation in risk management concepts and then explains how these concepts are applied to drug manufacturing. Risk Management Applications in Pharmaceutical and Biopharmaceutical Manufacturing features contributions from leading international experts in risk management and drug manufacturing. These contributions reflect the latest research, practices, and industry standards as well as the authors' firsthand experience. Readers can turn to the book for: Basic foundation of risk management principles, practices, and applications Tested and proven tools and methods for managing risk in pharmaceutical and biopharmaceutical product manufacturing processes Recent FDA guidelines, EU regulations, and international standards governing the application of risk management to drug manufacturing Case studies and detailed examples demonstrating the use and results of applying risk management principles to drug product manufacturing Bibliography and extensive references leading to the literature and helpful resources in the field With its unique focus on the application of risk management to biopharmaceutical and pharmaceutical manufacturing, this book is an essential resource for pharmaceutical and process engineers as well as safety and compliance professionals involved in drug manufacturing.

The purpose of this new edition is to offer an updated view of the risk management field as it applies to medical products. Since the publication of the first edition (2012), the emphasis on risk-based processes has growth exponentially across all sectors, and risk management is now considered as significant as quality management. ISO 9001 was revised and now requires that top management promote the use of risk-based thinking. ISO 13485:2016, which specifies the requirements for a quality management system specific to the medical devices industry, also now shows a greater emphasis on risk management and risk-based decision making. In addition, the FDA Food Safety Modernization Act (FSMA) is the most important reform of U.S. food safety laws in more than 70 years. This indispensable book presents a systematic and comprehensive approach to quality risk management. It will assist medical and food product manufacturers with the integration of a risk management system or risk management principles and activities into their existing quality management system by providing practical explanations and examples. The appropriate use of quality risk management can facilitate compliance with regulatory requirements such as good manufacturing practice or good laboratory practice. All chapters have been updated and revised, and a new chapter has been added to discuss some of the most common pitfalls and misunderstandings regarding risk management, specifically those related to the use of FMEA as the only element of risk management programs. One of the appendices includes 12 case studies, and the companion CD-ROM contains dozens of U.S. FDA and European guidance documents as well as international harmonization documents (ICH and GHTF-IMDRF) related to risk management activities, as well as a 30-question exam (with answers) on the material discussed in the book.

Biopharmaceutical Processing: Development, Design, and Implementation of Manufacturing Processes covers bioprocessing from cell line development to bulk drug substances. The methods and strategies described are essential learning for every scientist, engineer or manager in the biopharmaceutical and vaccines industry. The integrity of the bioprocess ultimately determines the quality of the product in the biotherapeutics arena, and this book covers every stage including all technologies related to downstream purification and upstream processing fields. Economic considerations are included throughout, with recommendations for lowering costs and improving efficiencies. Designed for quick reference and easy accessibility of facts, calculations and guidelines, this book is an essential tool for industrial scientists and managers in the biopharmaceutical industry. Offers a comprehensive, go-to reference for daily work decisions Covers both upstream and downstream processes Includes case studies that emphasize financial outcomes Presents summaries, decision grids, graphs and overviews for quick reference

For quality professionals and manufacturers in the food safety and medical device industries, risk management is essential to ensuring organizations meet FDA regulations and requirements. Without these recognized standards, the lives of patients and consumers are placed in jeopardy. In this third edition of Quality Risk Management in the FDA-Regulated Industry, Jose Rodriguez-Perez provides an updated view of the risk management field as it applies to FDA-regulated products using risk-based thinking.

Sets forth tested and proven risk management practices in drug manufacturing Risk management is essential for safe and efficient pharmaceutical and biopharmaceutical manufacturing, control, and distribution. With this book as their guide, readers involved in all facets of drug manufacturing have a single, expertly written, and organized resource to guide them through all facets of risk management and analysis. It sets forth a solid foundation in risk management concepts and then explains how these concepts are applied to drug manufacturing. Risk Management Applications in Pharmaceutical and Biopharmaceutical Manufacturing features contributions from leading international experts in risk management and drug manufacturing. These contributions reflect the latest research, practices, and industry standards as well as the authors' firsthand experience. Readers can turn to the book for: Basic foundation of risk management principles, practices, and applications Tested and proven tools and methods for managing risk in pharmaceutical and biopharmaceutical product manufacturing processes Recent FDA guidelines, EU regulations, and international standards governing the application of risk management to drug manufacturing Case studies and detailed examples demonstrating the use and results of applying risk management principles to drug product manufacturing Bibliography and extensive references leading to the literature and helpful resources in the field With its unique focus on the application of risk management to biopharmaceutical and pharmaceutical manufacturing, this book is an essential resource for pharmaceutical and process engineers as well as safety and compliance professionals involved in drug manufacturing.

The fourth edition of Process Validation in Manufacturing of Biopharmaceuticals is a practical and comprehensive resource illustrating the different approaches for successful validation of biopharmaceutical processes. A pivotal text in its field, this new edition provides guidelines and current practices, contains industrial case studies, and is expanded to include in-depth analysis of the new Process Validation (PV) guidance from the US FDA. Key Features: Offers readers a thorough understanding of the key concepts that form the basis of a good process validation program for biopharmaceuticals. Includes case studies from the various industry leaders that demonstrate application of these concepts. Discusses the use of modern tools such as multivariate analysis for facilitating a process validation exercise. Covers process characterization techniques for scaling down unit operations in biopharmaceutical manufacturing, including chromatography, chemical modification reactions, ultrafiltration, and microfiltration, and practical methods to test raw materials and in-process samples. Providing a thorough understanding of the key concepts that form the basis of a good process validation program, this book will help readers ensure that PV is carried out and exceeds expectations. Fully illustrated, this is a much-needed practical guide for biopharmaceutical manufacturers.

Developing Solid Oral Dosage Forms: Pharmaceutical Theory and Practice, Second Edition illustrates how to develop high-quality, safe, and effective pharmaceutical products by discussing the latest techniques, tools, and scientific advances in preformulation investigation, formulation, process design, characterization, scale-up, and production operations. This book covers the essential principles of physical pharmacy, biopharmaceutics, and industrial pharmacy, and their application to the research and development process of oral dosage forms. Chapters have been added, combined, deleted, and completely revised as necessary to produce a comprehensive, well-organized, valuable reference for industry professionals and academics engaged in all aspects of the development process. New and important topics include spray drying, amorphous solid dispersion using hot-melt extrusion, modeling and simulation, bioequivalence of complex modified-released dosage forms, biowaivers, and much more. Written and edited by an international team of leading experts with experience and knowledge across industry, academia, and regulatory settings Includes new chapters covering the pharmaceutical applications of surface phenomenon, predictive biopharmaceutics and pharmacokinetics, the development of formulations for drug discovery support, and much more Presents new case studies throughout, and a section completely devoted to regulatory aspects, including global product regulation and international perspectives

The concepts, applications, and practical issues of Quality by Design Quality by Design (QbD) is a new framework currently being implemented by the FDA, as well as EU and Japanese regulatory agencies, to ensure better understanding of the process so as to yield a consistent and high-quality pharmaceutical product. QbD breaks from past approaches in assuming that drug quality cannot be tested into products; rather, it must be built into every step of the product creation process. Quality by Design: Perspectives and Case Studies presents the first systematic approach to QbD in the biotech industry. A comprehensive resource, it combines an in-depth explanation of basic concepts with real-life case studies that illustrate the practical aspects of QbD implementation. In this single source, leading authorities from the biotechnology industry and the FDA discuss such topics as: The understanding and development of the product's critical quality attributes (CQA) Development of the design space for a manufacturing process How to employ QbD to design a formulation process Raw material analysis and control strategy for QbD Process Analytical Technology (PAT) and how it relates to QbD Relevant PAT tools and applications for the pharmaceutical industry The uses of risk assessment and management in QbD Filing QbD information in regulatory documents The application of multivariate data analysis (MVDA) to QbD Filled with vivid case studies that illustrate QbD at work in companies today, Quality by Design is a core reference for scientists in the biopharmaceutical industry, regulatory agencies, and students.

Amgen is a leader in the biopharmaceutical industry. It manufacturers and provides human therapeutics that drastically improve lives. Amgen's reputation and brand, its goodwill, is an invaluable asset to its ability to succeed in an increasingly competitive landscape. Because of this, risk management, both in manufacturing and in supply chain arenas, are directly linked to continuing long-term sustainable growth. With an increasingly global market and expanding pipelines, biotechnology companies, like Amgen, face a supply chain challenge to manufacture and distribute products using economically feasible methods that ensure patient safety. Preventing product mix-ups plays a key role in ensuring that safety. Marking nude product that moves intra-Amgen or to contract manufacturers will provide a higher level of confidence that the right product is reaching the patient. Several solutions for marking nude vials and syringes immediately rise to the top of the strata of potential technologies. Despite being promising, each technological solution has key unknowns that must be answered by rigorous labscale testing to provide quantitative data to make the best decision on the future of this process within Amgen. Along with the testing, it is clear that the financial landscape of the different solutions varies a great deal. Each potential solution will be analyzed to determine its capital requirements as well as ongoing costs. Lastly, the solution must be realistic to implement into Amgen's current GMP. And thus, each technology will be evaluated as it relates to the overall complexity of implementation into an already tightly controlled process. From a more macroscopic industry perspective, the FDA, as well as other regulatory agencies, has been discussing this issue for several years. Strategically, biotechnology companies are all hesitant to invest in a particular solution at the moment for fear that the FDA will require a different solution in the near term. In reality, biotechnology companies risk billions in R&D and drug development and are therefore, in a way, naturally risk averse when it comes to their processes and operations. Inventory and manufacturing operations are more driven by risk management than by cost. Of course, the important factor to remember is that risk management is a precursor to drug quality and patient safety. The majority of the risks that are controlled are risks that would either prevent environmental contamination of the drugs or affect the quality of the drugs. Altruistic or not, this has profound long term business strategy implications in an ultra-competitive marketplace where another biotechnology firm would certainly oblige taking market share if Amgen were to suffer a reputation ruining event.