Tag: <span>safety</span>

With the continued progress of adenoviral vectors in gene therapy studies it is increasingly evident that a more formalized approach to the characterization and analysis of these viral vectors is urgently needed. Today, adenoviral vectors are beginning to be considered “well characterized biologics,” as shown by numerous publications describing sophisticated analytical approaches for recombinant adenovirus product candidates. Because the analytical definitions of adenoviral vectors currently lack comparison to a common standard, the problem for regulatory agencies is how to objectively evaluate safety in relation to the administered dose. This well-recognized need for an adenovirus standard has been addressed by a consortium of representatives from regulatory agencies, industry, and academic organizations — the Adenoviral Reference Material (ARM) Working Group. Its work has come to fruition in the recent public availability of the ARM, a purified wild type 5 adenovirus. Many aspects of the history, production, and characterization of the ARM have been published in detail…

Regulatory Viral Reference Materials Viral Vectors

Tissue engineering is an emerging area of biotechnology that will provide replacement tissues for patients, as well as complex, functional biological systems for research and testing in the pharmaceutical industry. A new research area of tissue engineering is the investigation of how living cells interact with and respond to synthetic biomaterial surfaces. The clinical developments that underlie that research include a number of novel tissue-engineered medical products (TEMPs)…

Biologics Production Research

Electron microscopy (EM) provides data for viral clearance studies, information on the presence and quantitation of endogenous retroviruses, and the detection and characterization of other potential contaminants. The technique is favored in this field because it is simple, reliable, and can give reliable quantitation for risk assessments. This article describes the main EM techniques currently used for testing cell cultures, culture supernatants, and bulk harvests. It also includes an in-depth description of a thin sectioning technique used to estimate virus titre in culture supernatants and bulk harvests…

Biologics Production Risk Analysis and Management

As product development proceeds in the field of cellular therapies, adequate product characterization remains a challenge for both IND Sponsors and FDA/CBER. Cellular therapy products are not considered to be well-defined products, and therefore the control and characterization of each stage of the production process helps to ensure product safety and consistency. Product characterization of cellular products includes demonstration of safety, plus determination of identity, purity, potency, and product stability. Development of appropriate specifications for each of these parameters is necessary for lot release, and also provides an important database of knowledge for addressing regulatory issues, such as lot-to-lot consistency and potential issues with product comparability, should the manufacturing process, or other aspects of product development, change over time…

Cell & Gene Therapy Regulatory

Viral safety and viral clearance evaluation are high-profile areas for product safety. Regulators are keenly focused on viral safety and expect high-quality data to support it, particularly for IND and BLA approvals. Familiarity with process and regulatory requirements, as well as expertise in the key areas of viral clearance, are essential for strategic planning and can yield savings in time, effort, and money…

Biologics Production Manufacturing Regulatory

Various systems are used for production of biopharmaceuticals, including bacteria, yeast, mouse ascites, and animal cell culture. Each production system has its own set of risk factors for infection by viruses and their potential transmission in the final product. Viral contamination in products can arise from the animals themselves, from environmental sources, from the starting cells, or from materials introduced during the production and purification procedures. Methods have been developed for the prevention and control of these risks. The strategy used to minimize the risk of viral contamination combines several levels of viral safety…

Biologics Production Risk Analysis and Management

As development proceeds for adenoviral vectors in gene transfer clinical trials, it becomes increasingly important that these products demonstrate a good safety profile, and thereby build confidence in those who must make decisions about risk/benefit ratios, dose escalation, and efficacy. Currently, safety and efficacy are based predominantly upon the analysis of data generated by non-standardized methods, resulting in inconsistent values being reported for virus titer and particle counts…

Risk Analysis and Management Viral Reference Materials

Recombinant adeno-associated viral (rAAV) vectors are known to be efficient vehicles for gene transfer in animal models. The attractive feature of this vector system consists primarily of long-term gene expression with little or no associated toxicities following administration to a variety of tissues. Previous and ongoing clinical trials in humans demonstrate a very good overall safety profile, but problems persist due to the lack of any systematic method for normalizing doses administered to animals and humans. To date, most of the work involves AAV serotype 2 vectors, but vector systems based on other AAV serotypes continue to develop rapidly. Administered doses are usually based on titer, but the defective nature of AAV makes determining vector infectious units difficult. Titering methods based on vector genomes (using hybridization, real-time PCR, or spectrophotometry) are more reliable, but give no information as to the infectivity of the vector. Determining infectious titer is critical, as the ratio of infectious virions to vector genome-containing virions helps to determine the dose, potency, and strength of the vector preparation…

Viral Reference Materials Viral Vectors

The baculovirus expression system promises to revolutionize the production of recombinant proteins for use as clinical products. The technology is robust, efficient, and low-cost when compared to other cell based systems. The technique may also present an advantage in producing safer products versus the equivalent materials made with mammalian cells. Proteins can be produced in insect cells without animal supplements such as fetal calf serum. In the current climate of concerns over Bovine Spongiform Encephalopathies, and bovine viral risks, this method offers a significant safety, as well as cost advantage, over other production methods…

Baculovirus Expression Technology Regulatory

The development of reference testing reagents has been used successfully in the past to standardize measurements among laboratories, particularly for biological products such as recombinant cytokines. This approach was recommended by many parties with a stake in adenovirus vector delivery in order to address the fact that particle units and infectious units are not standardized in the field. This has made interpretation of preclinical and clinical data, as it relates to the amount of adenovirus vector administered, difficult to compare across the field. An Adenovirus Reference Material is being developed to define the particle unit and infectious unit for adenovirus gene vectors, and create a commonality for comparisons, especially for data related to vector safety…

Viral Reference Materials Viral Vectors