Residual host

A delicate balance between host and donor effector cells is necessary, and residual host-versus-graft effects may lead to graft failure, which is also known as graft rejection. Graft failure is defined as the lack of functional hematopoiesis after HCT and can occur early (i.e., lack of initial hematopoietic... 

Karyology and Tumorigenicity May be required to test for safety of cell fine for those products with no cells, karyology and tumorgenic-ity not necessary but demonstration of residual host cell DNA is required for those products with presence of live cells, karyology and tumorgenicity required... 

The potential for toxicity resulting from any accessory parts of the product such as chemical linkers or carriers should be addressed. The occurrence of proteins derived from the production system, generally referred to as residual host proteins, is another factor that should be considered when investigating the potential for toxicity. 

Lupker, J. H. Residual host cell protein from continuous cell lines. Dev Bio Stand 93 61-64 (1998). 

As the trap is made deeper the intensity spreads more widely over the levels of the band. In treating deep traps it is convenient to begin with the hypothetical limit of the infinitely deep trap, based on the wave functions (17) of the residual host, and to consider transitions to them from the ground state. The transition... 

There are zero projections for / = 2 and 4 on account of symmetry. The squares of the other projections are given in the last line of Table II. The fractional intensities of transitions to levels of the host add up to five-sixths, the remaining one-sixth appearing in the transition to the trap molecule. For the other cases in Table II intensities have been calculated by perturbation theory based on the residual host wave functions (17) and the free guest wave function. 

The residual host cell DNA may represent a different threat as an impurity for each product, since it depends on the host organism and the purification process. The control of residual DNA is a measure of efficacy and consistency in the purification process, as well as the product quality. The levels of DNA should be quantified using methods of an adequate sensitivity. Among the techniques used, the following can be mentioned. 

Lupker JH (1998), Residual host cell protein from continuous cell lines effect on the safety of protein pharmaceuticals, In Brown F, Griffths E, Horaud F, Petricciani JC (Eds) Safety of Biological Products Prepared from Mammalian Cell Culture, vol. 93, Dev. Biol. Stand., Karger, Basel, pp. 61 -64. 

O Brien TC, Maloney CJ, Tauraso NM. Quantitation of residual host protein in chicken embryo-derived vaccines by radial immunodiffusion. Appl Microbiol 1971 21(4) 780-2. 

The crude viral harvest was tested for adventitious agents as needed to comply with current regulatory guidelines. Purified virus was tested to confirm the absence of RCAs, residual host ceU proteins and DNA, endotoxin, and to quantify total and infectious vector particles and thus, the in-fectivity ratio. Bulk virus lots were released after meeting specifications which included one or more endotoxin unit mL and infectivity ratios of > 2% (infectious ti-ter/total viral particles). 

Typically, biotechnology products have been produced in cell lines not of human origin. In such cases, residual host cell proteins (HCP) are perceived as a safety concern to the patient. In the case of... 

Two methods were used to quantitate residual host cell (HEK 293) DNA in AdSFGF-4 preparations. The first, utilizing membrane hybridization of an oligonucleotide probe followed by chemiluminescence detection, was based on a previously de-... 

Table 6.1 Residual host cell DNA in Ad5FGF-4 samples...

DEVELOPMENT AND OPTIMIZATION OF A QUANTITATIVE WESTERN BLOT AND DOT BLOT PROCEDURE FOR THE DETERMINATION OF RESIDUAL HOST CELL PROTEINS PRESENT IN INACTIVATED POLIO VACCINE USING A GZU BASED SIGNAL REAGENT... 

Dagouassat, N., Haeuw, J.F., Robillard, V., Damien, F., Libon, C., Corvaia, N., Lawny, F., Nguyen, T.N., Bomiefoy, J.Y. and Beck, A., 2001a, Development of a quantitative assay for residual host cell proteins in a recombinant subunit vaccine against human respiratory syncytial virus. J. Immunol. Methods 251 151-159. 

Host-cell DNA is an upstream-derived process-related impurity in drug substances derived from a cell culture process, often the result of cell lysis, or rupture resulting from physical exertion (e.g., shear forces, excessive air bubbling, etc.) in a culture vat or cell pelleting or removal during harvest. The guidelines outlined by the WHO surest that up to 10 ng of residual host-cell DNA per purified dose is considered acceptable. It has been suggested that whenever possible, the level is no more than 100 pg of cellular DNA per dose. 

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