Guide to Cell Therapy GxP

Quality Standards in the Development of Cell-Based Medicines in Non-pharmaceutical Environments
 
 
Academic Press
  • 1. Auflage
  • |
  • erschienen am 24. Juli 2015
  • |
  • 266 Seiten
 
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978-0-12-803116-2 (ISBN)
 

Guide to Cell Therapy GxP: Quality Standards in the Development of Cell-Based Medicines in Non-Pharmaceutical Environments provides a practical guide to the implementation of quality assurance systems for successful performance of all cell-based clinical trials.

The book includes all information that should be used in investigational medicinal product dossier (IMPD), the launching point for any clinical investigation, and beyond, bridging the gap in knowledge with the inclusion of examples of design of GLP-compliant preclinical studies, design of bioprocesses for autologous/allogeneic therapies, risk-based assessment of GMP-compliant processes for the production of cell-based therapies, and instructions on how to implement GLP/GMP standards in centers accredited with other quality assurance standards (JACIE; FACT/NETCORD, ISO9001, and others).


  • Provides easy access to important information on current regulations, state-of-the-art techniques, and recent advances otherwise scattered on various funding websites, within conference proceedings, or maintained in local knowledge
  • Features protocols, techniques for trouble-shooting common problems, and an explanation of the advantages and limitations of a technique in generating conclusive data
  • Includes practical examples of successful implementation of quality standards


Dr. Vives has specialties in GLP/GMP implementation, the development of (stem) cell-based products for regenerative medicine, and design, execution and analysis of non-clinical studies. He was a post-doctoral Fellow at University of Edinburgh and moved to Stem Cell Sciences Ltd in the UK where he became Head of Research. Six years ago, he became Head of Preclinical Studies at XCELIA, a biopharmaceutical company formed from The Catalan Blood and Tissue Service (Banc de Sang i Teixits) devoted to the development of advanced therapy medicine. As the Quality manager at XCelia, Dr. Vives secured the facility as the first GLP-compliant laboratory in Spain dedicated to the development of advanced cell therapies. He is now Director of R&D, responsible for technology transfer of innovative experimental bioprocesses into GMP-compliant production environments. He also manages GLP test facilities and relationships with Health Regulatory Agencies among other compliance responsibilities.
  • Englisch
  • San Diego
  • |
  • USA
Elsevier Science
  • 4,77 MB
978-0-12-803116-2 (9780128031162)
0128031166 (0128031166)
weitere Ausgaben werden ermittelt
  • Front Cover
  • Guide to Cell Therapy GxP
  • Copyright
  • Contents
  • List of Contributors
  • Foreword
  • Preface
  • 1 - Overview of the Development Program of a Cell-Based Medicine
  • 1. Introduction
  • 2. Key Pharmaceutical Factors to Consider in Early Development Stages
  • 3. TPP: Beginning with the End in Mind
  • 4. Stages of Drug Development
  • 5. Considering Stakeholders
  • 6. Product Lifecycle and Portfolio Management
  • 7. Performance Management and the Check Point Value
  • 8. Conclusions
  • References
  • Glossary
  • List of Acronyms and Abbreviations
  • 2 - European Regulatory Framework for the Development of Cell-Based Medicines
  • 1. Introduction
  • 2. What Cell-Based Products are Considered as Medicinal Products??The Legal Definitions and Main Regulations Applying to Cell-Ba...
  • 3. An Introduction to Cell-Based Medicine Development: Roadmap
  • 4. Regional and National Institutions Supporting Cell Therapy Translational Research
  • 5. European Regulation for Advanced Therapy Medicinal Products Not Intended?to be Placed on the Market: Hospital Exemption and I...
  • 6. Conclusions
  • References
  • 3 - Nonclinical Studies for Cell-Based Medicines
  • 1. Introduction
  • 2. Types of Cell-Based Advanced Therapy Medicinal Products and their Safety Considerations
  • 3. Regulations and Nonclinical Studies
  • 4. Nonclinical Assessment-The Risk-Based Approach
  • 5. The Requirement for Good Laboratory Practice
  • 6. General Study Design Considerations
  • 7. Specific Nonclinical Safety Considerations
  • 8. Conclusions
  • References
  • Glossary
  • List of Acronyms and Abbreviations
  • 4 - Good Manufacturing Practice Compliance in the Manufacture of Cell-Based Medicines
  • 1. Outline of the Chapter
  • 2. Quality Management
  • 3. Documentation
  • 4. Qualification and Validation
  • 5. Premises and Equipment
  • 6. Personnel and Hygiene
  • 7. Manufacturing
  • 8. Quality Control
  • 9. Inspections, Audits, Complaints, Recalls, and Returns
  • 10. Conclusion
  • Acknowledgment
  • References
  • List of Abbreviations
  • 5 - Good Clinical Practice in Nonprofit Institutions
  • 1. Introduction
  • 2. The Elements of GCP Compliance
  • 3. The Clinical Trial Protocol
  • 4. The Investigator's Brochure
  • 5. The Informed Consent
  • 6. Essential Documents for Clinical Trial
  • 7. Clinical Trial Files
  • 8. Sponsor' Study Audit and Inspections
  • 9. Conclusion
  • References
  • Glossary
  • List of Acronyms and Abbreviations
  • 6 - Compatibility of GxP with Existing Cell Therapy Quality Standards
  • 1. Quality Standards in Cell Therapy
  • 2. Adaptation of Existing Standards to GxP
  • 3. Impact of GxP Implementation
  • 4. Quality by Design
  • 5. Recommendations for Optimizing Integration of QA Systems
  • 6. Conclusions
  • References
  • Glossary
  • List of Abbreviations
  • Index
1

Overview of the Development Program of a Cell-Based Medicine


Arnau Pla     CELLAB, Barcelona, Spain

Abstract


The success in bringing to the market a new medicine in a timely and cost-effective manner relies on a proper product development strategy. Public institutions lead the development of cell-based therapeutics up to early stage clinical trials without the resources found in biotech and pharma industries. This may explain the reduced number of cell therapies approved and their disastrous financial performance in terms of revenues. Apart from understanding the whole development process, there are a couple of basic tools (such as the target product profile) and important concepts (e.g., freedom to operate) that can help to improve the early development process in a nonpharma environment and make it sound to investors for further developments up to regulatory approval for commercialization. In this chapter, we will present and discuss the series of milestones required to make an academic achievement into an approved clinical therapy.

Keywords


Advanced therapy medicinal product; Cell-based medicine; Licensing; Product development; Product lifecycle; Target product profile

Chapter Outline

1. Introduction 1

2. Key Pharmaceutical Factors to Consider in Early Development Stages 4

3. TPP: Beginning with the End in Mind 5

4. Stages of Drug Development 6

5. Considering Stakeholders 8

6. Product Lifecycle and Portfolio Management 9

7. Performance Management and the Check Point Value 10

8. Conclusions 11

References 12

Glossary 13

List of Acronyms and Abbreviations 13

1. Introduction


The goal of pharmaceutical product development is to establish the formulation composition and define its manufacturing process to consistently deliver a drug product. This drug product has to meet appropriate quality attributes required for its intended efficacy and safety profile. In addition to basic quality requirements, the commercial success of a drug product, and by extension its lifecycle, is determined by other key parameters such as patents, market, prices competence, regulatory changes, and others that must be carefully considered during early development stages. Pharmaceutical and biopharmaceutical industries have developed systematic approaches to fulfill these complex requirements. In contrast, the newborn cell therapy industry, closely linked to academia, should develop novel approaches to address this major challenge [1]. Although there are extensive resources and efforts devoted by many companies, to date, there are few cell therapy products licensed in Europe and in the United States (Table 1). This fact reflects the great complexity of developing such type of treatments. However, great hopes are invested in the emerging field of regenerative medicine and the use of cells as therapeutic agents. The term advanced therapy medicinal product (ATMP) covers the following medicinal products for human use (http://www.ema.europa.eu/ema/):

Table 1

Approved Human Cell-Based Therapeutics

In the United States: Provenge®; Autologous cellular immunotherapy Dendreon Corporation Laviv®; Autologous cultured fibroblasts Fibrocell Technologies, Inc. Carticel®; Autologous cultured chondrocytes Genzyme BioSurgery Gintuit®; Allogeneic cultured keratinocytes and fibroblasts in bovine collagen Organogenesis, Inc. Allocord®; HPC from cord blood SSM Cardinal Glennon Children's Medical Center Hemacord®; Allogeneic HPC from cord blood New York Blood Center Ducord®; HPC from cord blood Duke University School of Medicine HPC from cord blood Clinimmune Labs, University of Colorado Cord Blood Bank HPC from cord blood LifeSouth Community Blood Centers, Inc. In Europe: Chondrocelect®; Autologous cultured chondrocytes TIGenix MACI®; matrix-induced autologous chondrocyte implantation Genzyme Provenge®; Autologous cellular immunotherapy Dendreon Corporation Holoclar®; Autologous limbal stem cells Chiesi Farmaceutici S.p.A. In Canada and New Zealand [12]: Prochymal®; Adult human MSC Osiris Therapeutics, Inc. In Japan [12]: JACE®; Autologous cultured epidermis Japan Tissue Engineering Company (J-TEC) JACC®; Autologous cultured cartilage Japan Tissue Engineering Company (J-TEC) In Korea [12]: Hearticellgram-AMI®; Autologous bone marrow-derived MSC Pharmicell Cartistem®; MSC for the treatment of osteoarthritis Medipost

With the exception of blood products, the rest include a substantial manipulation in their manufacture. Only approved human cell-based medicines were included. HPC = hematopoietic progenitor cells; MSC = mesenchymal stromal cells.

Gene-therapy medicines: These contain genes that lead to a therapeutic effect. They work by inserting recombinant genes into cells, usually to treat a variety of diseases, including genetic disorders, cancer, or long-term diseases. Somatic-cell therapy medicines: These contain cells or tissues that have been manipulated to change their biological characteristics. Tissue-engineered medicines: These contain cells or tissues that have been modified so that they can be used to repair, regenerate, or replace tissue. Combined advanced therapy medicines: These are medicines that contain one or more medical devices as an integral part of the medicine. Cell therapy-based medicinal products (CTMPs) are defined as medicinal products when there is more than minimal manipulation of the cellular component or where the intended use of the cells is different from their normal function in the body. Much attention had been paid to the potential of novel stem cell- and tissue engineering-based therapies following a number of relevant scientific milestones and media news of potential new cures [2,3]. These therapies have become the focus of many biopharmaceutical developments, which face a number of major challenges in translating these scientific advances into Food and Drug Administration (FDA)/European Medicines Agency (EMA)-approved medical products. ATMPs, including cell therapy and tissue engineering products, are considered as medicines in the European Union [4]. ATMPs are at the forefront of scientific innovation in medicine; consequently, specific regulatory framework has been developed and implemented in Europe and in the United States. In this regard, the Regulation (EC) N° 1394/2007 on ATMPs was drafted and came into force in December 2008. The Regulation laid down specific rules concerning centralized authorization and pharmacovigilance of the ATMPs. This regulatory framework has a crucial influence in the development of such ATMPs. As a consequence, the teams involved in the ATMP development must take into account the FDA/EMA scientific and regulatory guidelines that provide a detailed description of the safety, efficacy, and quality issues for CTMPs [5,6]. As we can see in Box 1, cell therapy and tissue engineering products are very clearly defined by regulatory agencies. Box 1 What are Cell Therapy and Tissue Engineering Products? Cell therapies and tissue engineering products are considered as medicines when the following are true: Cell-based product: Substantial manipulation of cells or not intended to be used for the same essential function(s) Administered to human beings with a view to treating, preventing, or diagnosing a disease through the pharmacological, immunological, or metabolic action Tissue-engineered product: Substantial manipulation of tissues or not intended to be used for the same essential function(s) Engineered cells or tissues Administered to human beings with a view to regenerating, repairing, or replacing a human tissue

2. Key Pharmaceutical Factors to Consider in Early Development Stages


Several technical obstacles must be overcome during the stages of product conception and design, before cell and tissue engineering therapies move out from basic research laboratories to clinical phases of investigation. There are many challenges...

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