Chapter 9B Autologous Chondrocyte Implantation
Quality Assurance of Cells for Chondrogenic Implantation
Introduction
High-quality chondrocytes are essential for successful autologous chondrocyte implantation (ACI) outcomes. Cell therapy manufacturers must comply with good manufacturing practices (GMPs), which are enforced by national authorities in most countries. The goal of GMPs is to ensure that products are safe, pure, and effective. The GMPs require that manufacturers establish quality systems for the design, manufacture, packaging, labeling, and storage of products commercially distributed for human use. In many countries, regulatory agencies have also issued guidance documents that pertain specifically to additional requirements for cellular therapeutics. It is the responsibility of the manufacturer to validate the manufacturing process and establish product release specifications. Products cannot be shipped unless all release specifications have been met. At a minimum, product release assays should assess cell number and viability, test for adventitious agents, and evaluate purity (i.e., endotoxin). Recently, the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMEA) have begun requiring that cell therapy manufacturers also develop identity and potency assays for their products. Each of these assays is defined in the following section. For detailed descriptions of quality control and quality assurance systems for cell therapy manufacturing, the reader is referred to Kielpinski et al.1 and Mayhew et al.2
Quality Assessment of Chondrocytes
Viability
Viability is defined as the percentage of live cells in the product. Viability is easily measured for cells in suspension using trypan blue or other well-established assays.
The measurement of viable cells in a matrix or on a membrane requires a customized approach. For example, Wang et al.3 developed a novel assay to accurately and precisely measure viability in matrix-induced autologous chondrocyte implanation (MACI) implants because the collagen membrane caused interference in all conventional assay techniques that were tested.
Sterility
Sterility assays typically take 14 days to perform. Therefore, it is common to test prerelease samples of the product. A rapid microbial test, the BacT/Alert System (Genzyme Biosurgery, Cambridge, Mass.), has been validated for sterility testing of Carticel and MACI implants.4 This system usually provides test results in a matter of hours. Regardless of the system used, product samples must be negative for microbial growth. The aseptic process must be validated using media fills.
Identity
The purpose of an identity assay is to confirm the identity of a culture as consisting of chondrocytes and to assess heterogeneity, if any. Historically this has been done by assessing cell morphology. Recently, two novel assays that can distinguish cultured chondrocytes from closely related synoviocytes on the basis of genetic markers have been described.5,6 The assay developed by Rapko and colleagues has been validated as a chondrocyte identity assay and approved by the F&A as a Carticel lot release assay.5 This is the first genetic marker-based chondrocyte identity assay approved for use in the United States.
Related posts:
Cartilage Morphology
Bone Grafting around an Articular Joint
Autologous Chondrocyte Implantation: ACI First and Second Generation
Bone Marrow Stimulating Techniques: Carbon Fiber Resurfacing
Fixation of Osteochondral Fragments
Autologous Chondrocyte Implantation: Transarthroscopic Implantation of Hyalograft (Hyaff 11) with Autologous Chondrocytes
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