Applications of Single-Use Products in Cell and Gene Therapy (CGT)

In the description of the "Good Manufacturing Practice for Pharmaceutical Production" regarding the appendix for cell therapy products, it is clearly required that the facilities, equipment, and environment used in the production process must meet corresponding environmental standards. Additionally, measures should be taken during the production of cell products to minimize contamination and cross-contamination, thereby controlling quality risks.

Single-use products, due to their sterility, tightness, flexibility, and disposable characteristics that avoid cross-contamination risks, can fully comply with regulatory requirements and meet the needs for preparation, storage, and transportation in the relevant processes of cell and gene therapy products.

Quality Requirements of Single-Use Products in CGT Industry

Since single-use products come into direct or indirect contact with the production materials and the CGT products themselves, there is a heightened focus on the biocompatibility of single-use products (e.g., USP Class VI), the absence of animal-derived components, sterility (including endotoxin and pyrogen control), extractables and leachables (E&L), and the control standards for insoluble particles/contaminants. The following sections will elaborate on these focus areas and the control measures implemented by Cobetter:

1. Extractables and Leachables

SUS products come into direct or indirect contact with the CGT process materials or cell products, and the types and quantities of extractables may adversely affect the quality, safety, and production process of CGT products, potentially posing safety risks to patients receiving treatment. 

Therefore, it is essential to assess and control the extractables from single-use products used in the CGT field, including both potential and actual extractables.

Cobetter Single-Use Products E&L Control Measures:

• Raw Material Control: Stability of materials, extractables of materials, control of critical quality parameters, and production risk management.
• Product Validation: E&L validation of products, meeting the requirements of BPOG and USP665 regulations through various extraction agent validation tests.
• Additional Validation: Cobetter CNAS-certified laboratory can provide customers with individual E&L validation tests for their products and the single-use products they come into contact with, along with corresponding validation reports. Additionally, safety assessments and toxicological analyses can be conducted based on actual processes.

2. Control of Insoluble Particles/Visible Contaminants

The severity of risks caused by particulate contamination is often uncontrollable and is influenced by multiple factors, including the intended route of administration, dosage volume, particle characteristics (size, shape, composition, quantity), and the target location of the particles. Therefore, managing particulate matter in the production of CGT products is one of the challenges currently faced in this field. The effective control of particulate matter in disposable products and the standards for insoluble particles in the final products have received increased attention and higher requirements when applied to CGT products.

Cobetter Single-Use Products Particle Control Measures:

• Production Environment Control: Different cleanrooms are arranged for production based on various application process points to meet the requirements for visible contaminants and insoluble particles. This includes ISO Class 7 cleanrooms for component and tubing production, ISO Class 7 cleanrooms for bag production and tubing assembly, and ISO Class 4.8 cleanrooms for filling bags.
• Production Process: Self-produced blow-molded film production processes ensure that the inner layer of the film is very clean and free from contamination.
• Pre-Washing Componen: Washing production line meets WFI standards, using washing and drying equipment for tubing, and employing ultrasonic cleaning and class 100 ovens for connector components to ensure cleanliness.
• Personnel, Material, and Equipment Control: Increasing spraying, double-layer changing, equipment dusting, and static electricity elimination to reduce the impact of static adsorption of particulate matter.

Cobetter Single-Use Products—Supporting CGT Technology

Cell Culture: Cobetter Lifecask RW Single-Use Bioreactors / Lifecask RG Single-Use Bioreactors

These products exhibit no cytotoxicity and do not inhibit cell growth, demonstrating enhanced cell-friendliness. They are available in multiple volume specifications, and can meet customized customer needs. Our membrane materials and components are produced in-house, ensuring stable supply. They fully satisfy the cultivation and expansion requirements in non-specific therapies such as LAK (Lymphokine-Activated Killer cells) and CIK (Cytokine-Induced Killer cells), as well as specific therapies like CAR-T (Chimeric Antigen Receptor T cells) and TCR-T (T-cell Receptor T Cells).

Fluid Transfer and Filtration: Lifecube™ SA Transfer Sets

High flexibility, allow for the selection of various tubing materials and connector forms to achieve multiple process applications, providing in-depth customization services based on various applications. Including but not limited to media feeding, extension, transfer, filtration tubing, seed train transfer tubing, UF/DF connection tubing, media/buffer dispensing and filtration tubing, as well as intermediates filtration assembly tubing and dispensing systems. With a rich array of accessories and flexible customization options, Lifecube™ SA transfer sets fully satisfy the diverse process application needs for fluid transfer and filtration within the CGT industry.

Liquid Preparation, Storage, and Transportation: Cobetter Lifecube™ Single-Use Storage Bags / Sampling Bags / Mixing Bags

The products are manufactured in ISO Class 4.8 or ISO Class 7 cleanrooms, covering the entire process from raw material storage to product packaging. The production and quality management processes comply with the ISO 9001:2015 quality management system and adhere to CGMP requirements, ensuring stable and reliable product quality.

These bags can be confidently used in various process points, including media sampling and preparation, buffer sampling and preparation, storage of cells/intermediates, harvesting/purification/formulation of plasmid production, virus purification/storage, sampling of cell culture liquids, and cryopreservation of cell products. Customization requests can be quickly addressed, and comprehensive product validation is available. The production quality management is stringent, with multiple disposable system hardware options available for customization, fully meeting the fluid application needs of CGT processes.

Product Filling: Cobetter Lifecube™ Single-Use Final Filling Bags

High-purity final filling is conducted in dedicated workshops classified as ISO Class 4.8, strictly adhering to the ISO 9001:2015 quality management system. Product validation guidelines are provided, along with pre-cleaning of tubing and connector fittings, and rigorous particulate control measures. This ensures the provision of high-purity single-use filling bag products that meet the stringent filling requirements in the CGT field.