Tag: <span>contaminant control</span>

On January 31, 2003, FDA under the leadership of Commissioner Dr. Mark McClellan, issued a report entitled “Improving Innovation in Medical Technology: Beyond 2002.” One of the goals described in this report is to “speed potentially important emerging technologies to the market by reducing regulatory uncertainty and increasing the predictability of product development.” The technology areas of cell therapy and gene therapy were specifically identified. This article highlights some of the challenges for manufacturers and regulators of these products and describes ongoing efforts at FDA — as well as opportunities to partner with FDA — to improve the product development process for cell therapy and gene therapy products…

Cell & Gene Therapy Manufacturing Regulatory

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

The use of animal products, such as bovine serum, in the manufacture of biologics is a common practice. The United States’ Code of Federal Regulations, part nine (9CFR), dictates mandatory testing for viruses. In the last few years, we have learned that certain viruses undetected in industry standard tests, like the 9CFR assay, can cause significant contamination of bovine products. Last year in Europe, new guidelines from the Committee for Veterinary Medicinal Products (CVMP), and draft guidelines from the Committee for Proprietary Medicinal Products (CPMP), were published to address testing requirements for bovine serum. The use of these European Guidelines for bovine serum testing broadens the ability to detect viral contamination…

Biologics Production Manufacturing

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

The Adenovirus Reference Material (ARM) is a purified and well-characterized wild type adenovirus (Ad5) now available to researchers worldwide. Due to the need for a common reference material, the ARM was produced with the purpose of validating assay methods and internal standards for use in developing recombinant adenovirus for gene therapy. Analysis of ARM by RP-HPLC, however, detected the presence of a contaminant peak with a distinctive A240 local wavelength maximum. The contaminant was found in all of the vials, with some variability in amount between vials. It appears that the contaminant is not associated with the virus and it is unlikely that it will interfere with the use of the ARM as a reference material. The source of the contaminant was probably a leachate or plasticizer from the tubing or containers used during the final processing step…

Viral Reference Materials