Gene Therapy Formulation Specific Process-Related Residual Testing

The development and production of gene therapy formulations involve complex processes that often introduce various exogenous substances for assisted production, purification and stabilization, and the residues of these exogenous substances in the formulations can affect the safety and efficacy of the products. Therefore, strict monitoring of process-related residues has become an important part of product quality control in gene therapy.

CD Formulation is an industry leader in gene therapy formulation development and quality control assays, and with our extensive quality control experience, we can provide our customers with a comprehensive range of process-related residue testing services to ensure the purity, safety and compliance of gene therapy formulations.

The Importance of Gene Therapy Formulation Specific Process-Related Residual Testing

Indispensable to the development and manufacture of gene therapy formulations is the introduction of a range of exogenous chemicals that are specifically designed to facilitate the construction of gene vectors, refinement, and enhancement of the durability of the final product. These substances, which we may call process-related residues, can potentially affect the safety of gene therapy products by remaining in the finished product. The presence of these trace impurities not only triggers an unintended response from the human immune system but also exhibits cytotoxicity, which can lead to a range of adverse health effects. Failure of the manufacturing process to remove all excess ingredients may result in compromising the efficacy and long-term storage stability of the gene therapy product. Therefore, testing for process-related residues is critical, and systematic testing can verify product purity and ensure compliance with stringent requirements from regulatory agencies.

Explore Our Gene Therapy Formulation Specific Process-Related Residual Testing

The determination of process-specific relevant residues is critical to ensure the safety and efficacy of gene therapy formulations. The impact of these residues on the final product can be minimized through accurate determination and stringent quality control. Below is a list of several common process-related residues that we can assay for that is not limited to the following residues.

Tween 20

In the development of gene therapy formulations, viruses need to be lysed using lysing agents. Tween is a commonly used viral lysing agent that disrupts the lipid membranes or lipids of viruses, causing the proteins or encapsidated proteins to be solubilized and purified for use. The extensive use of these lysing agents not only pollutes the environment, but their residues may also have an impact on the subsequent production process. We accurately quantify Tween 20 in the production process of gene therapy preparations to ensure the safety, stability, and efficacy of gene therapy formulations.

Affinity ligands

Affinity ligands, as indispensable tools, play a crucial role in the refining process of gene therapy products, especially in adeno-associated virus (AAV) vector purification. Such ligands form specific binding with target molecules through their unique chemical structures, thus realizing efficient separation. However, it is worth noting that some affinity ligands carry residues that may stimulate a response from the body's immune system, which poses a potential challenge for ensuring the safety and efficacy of gene therapy formulations. Therefore, accurate determination and optimization of affinity ligands in gene therapy formulations is important for the development of high-quality gene therapy formulations.

Detergents

In the field of gene therapy, specific types of detergents play a crucial role, especially during the breakdown and purification of viral vectors. However, the traces left behind by these chemicals have the potential to adversely affect cells and even entire tissues, especially notable at higher treatment doses. We can help researchers delve into and precisely regulate the conditions of use to overcome the dosage of specific types of detergents in the development of gene therapy formulations.

Transfection agents

To improve the transfection efficiency of gene vectors in cells, different types of transfection reagents are usually added during the preparation process. Residues of these chemicals can adversely affect the efficacy and safety of gene therapy products and must therefore be strictly monitored.

For example, PEIpro is a polymeric transfection reagent that condenses DNA into positively charged particles. These particles adhere to negatively charged cell surface residues and enter the cell via cytosis, and the complex formed by PEIpro and DNA then undergoes osmotic expansion into the cytoplasm, where the DNA is free to fuse into the nucleus upon cleavage of the complex. Therefore, PEIpro can be used to produce recombinant proteins by transient gene expression in the development and production of gene therapy agents, and it can also be used to produce viral vectors by using adherent cell lines cultured in a serum-free medium. However, PEIpro is highly cytotoxic and may cause cell death by disrupting cell membranes or apoptosis by disrupting mitochondrial membranes after cytosolization. Therefore, it is important to accurately determine the content of transfection agent PEIpro for gene therapy preparations.

Our Technologies for Gene Therapy Formulation Residual Testing

Highlights of Our Gene Therapy Formulation Residual Testing

• We have many years of experience in gene therapy formulation development and quality control, so clients can work with us with confidence.
• We can quickly respond to client needs, provide scientifically sound assays, and support clients at all stages of gene therapy formulation development.
• Our quality control meets regulatory requirements to ensure reliable technical support services for every stage of our client's project progress.
• We combine customer needs and project characteristics with our best solutions to ensure the most suitable, customized solution for our clients.

Published Data

Journal: Gene Ther

IF: 4.3

Published: 2001

This article describes the authors' efforts to maintain gene therapy vector viability during transport and storage at remote testing sites. Formulation and processing factors that affect viral formulation stability, such as the selection of appropriate buffer systems, cryoprotectants, and storage conditions, were identified. Adenovirus and adeno-associated virus expressing Escherichia coli β-galactosidase (lacZ) were suspended in a mixture of complex carbohydrates, cyclodextrin, and various surfactants. Infectious titers of all formulations were determined using X-gal staining of 293 and 84-31 cells. The authors provide a solution for vector viability preservation in lyophilized formulations for gene therapy by identifying appropriate buffer systems, cryoprotectants, and storage conditions.

CD Formulation provides efficient and reliable process-specific residue testing services for quality control of gene therapy formulations. If you are interested in us, please feel free to contact us.