Vives / Carmona Guide to Cell Therapy GxP

Quality Standards in the Development of Cell-Based Medicines in Non-pharmaceutical Environments
1. Auflage 2015
ISBN: 978-0-12-803116-2
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: 6 - ePub Watermark

E-Book, Englisch, 266 Seiten

Guide to Cell Therapy GxP is a practical guide to the implementation of quality assurance systems for the successful performance of all cell-based clinical trials. The book covers all information that needs to be included in investigational medicinal product dossier (IMPD), the launching point for any clinical investigation, and beyond.ÿ Guide to Cell Therapy GxP bridges a knowledge gap with the inclusion of examples of design of GLP-compliant preclinical studies; design of bioprocesses for autologous/allogeneic therapies; and instruction on how to implement GLP/GMP standards in centers accredited with other quality assurance standards. Guide to Cell Therapy GxP is an essential resource for scientists and researchers in hospitals, transfusion centers, tissue banks, and other research institutes who may not be familiar with the good scientific practice regulations that were originally designed for product development in corporate environments. This book is also a thorough resource for PhD students, Post-docs, Principal Investigators, Quality Assurance Units, and Government Inspectors who want to learn more about how quality standards are implemented in public institutions developing cell-based products. - 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.

Autoren/Hrsg.

Vives, Joaquim

Carmona, Gloria

Leseproben

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...