USP〈1047〉 GENE THERAPY PRODUCTS

Introduction

The manufacturing of gene therapy products has been divided into two sections. This section discusses five topics that apply to manufacturing of all gene therapy products: 1) raw materials, 2) characterization of banked materials, 3) in-process controls, 4) specifications, and 5) validation considerations. The second section, Manufacturing of Gene Therapy Products, addresses manufacturing of gene therapy vectors, both viral and nonviral, and discusses the design of gene vectors in detail.

All the general principles of current good manufacturing practice (cGMP) outlined by the FDA in 21 Code of Federal Regulations (CFR) 210, 211, 600s (especially 21 CFR 610), and 820, as well as other USP chapters apply to the manufacturing of gene therapy products. The manufacturing facility, equipment and process, raw materials, quality systems, and trained personnel are some of the key elements of cGMP. cGMPs are applied throughout clinical development. Typically, the extent of control increases as clinical development progresses, and full cGMP compliance is expected by initiation of manufacturing in support of Phase III clinical trial(s). The facility and equipment should be carefully designed, built, and validated to support the manufacturing process and to maintain the required product/facility segregation. Preventive maintenance and calibration should be performed routinely on critical equipment. Incubators, bioreactors, and freezers should be fitted with alarm systems that can remotely signal failure. Quality systems should be established to ensure manufacturing is consistent and in control. Systems include but are not limited to the following: change control, document control, environmental monitoring, training, validation master plans, raw material testing and release, vendor approval, product testing and release, stability testing, and corrective/preventive action (CAPA).

Ancillary Materials

A wide variety of raw materials, including ancillary materials, may be used in manufacturing. Raw materials may include complex substances such as cells, tissues, biological fluids, growth factors, and monoclonal antibodies. Some of these materials may remain in the final therapeutic product as active substances, cryoprotectants, or excipients. An ancillary material exerts an effect on a therapeutic material (for example, a cytokine may activate a population of cells) but is not intended to be present in the final therapeutic product. The quality of raw materials used in the production of a gene therapy product can affect the safety, potency, and purity of the product. Therefore, qualification of this type of materials is necessary to ensure the consistency and quality of all gene therapy products. Activities involved with raw material qualification will change as products move through various stages of clinical development and on to licensure and commercialization. A well-designed qualification program becomes more comprehensive as product development progresses. A qualification program for raw materials used in the manufacturing of gene therapy products should address each of the following areas: 1) identification and selection, 2) suitability for use, 3) characterization, 4) animal-derived components, and 5) quality assurance. For all raw materials, it must be considered when and where each is used in the manufacturing process because this can help define selection criteria. Ancillary Materials for Cell, Gene, and Tissue-Engineered Products 〈1043〉 should be consulted for specific information about implementing an appropriate qualification program for these materials. Other USP chapters provide information about the qualification and standards of specific ancillary materials (e.g., Bovine Serum 〈1024〉, Fetal Bovine Serum—Quality Attributes and Functionality Tests 〈90〉, and Growth Factors and Cytokines Used in Cell Therapy Manufacturing 〈92〉).

Source from USP and Please refer to USP for details:

https://online.uspnf.com/uspnf/document/2_GUID-BB4ED358-C717-4023-AD39-36A0144F41D8_20101_en-US?source=TOC

Polymer Vial for cell and gene therapies

RTU(ready to use) 2ml COP vial