Licensing factors

The regulatory factors that control initiation of replication of chromosomal DNA are the replication licensing factors (RTFs), which consist of two major components. 

Glozak MA, Seto E (2009) Acetylation/deacetylation modulates the stability of DNA replication licensing factor Cdtl. J Biol Chem 284(17) 11446-11453... 

How is replication tied to cell division Replication is tied to cell division by several proteins including the origin recognition complex, replication activator protein, and rep-hcation licensing factors. The process is controlled by cyclins, proteins produced during the Gj and S phases that bind to cyclin-dependent kinases and activate replication. 

Reflect and Apply What are replication licensing factors How did they get their name ... 

Replication licensing factors (RLFs) are proteins that bind to eukaryotic DNA. They get their name from the fact that replication cannot proceed until they are bound. Some of the RLF proteins have been found to be cytosolic. They have access to the chromosome only when the nuclear membrane dissolves during mitosis. Until they are bound, replication cannot occur. This property links eukaryotic DNA replication and the cell cycle. Once RLFs have bound, the DNA is then competent for replication. 

Other factors include available resources in terms of money and manpower to develop the system in-house, outsource, or purchase from e-clinical proprietary vendors, reliability, flexibility, and security. Some coordinating centers have chosen OSS/FS over proprietary vendors based on the criteria of cost, reliability, flexibility, and security [38]. The rationale is that although both have service comparability, proprietary software licensing costs, both for initial purchases and annual licensing, are significant. 

Compliance with the principles of GMP is one of the major factors considered by the Licensing Authority when examining an applicahon for a licence to manufacture under the Medicines Act (1968). Similar codes exist in the USA and other countries. 

The absence of mandatory manufacturer licensing in Cypms is believed to be a factor in the establishment of small packaging units to bypass price-fixing procedures. Moreover, the procedure for issuing a licence to manufacture a product is, to a certain degree, retrospective, since the application is submitted after the manufacturer has built the facility. Ensuring that any requested modification of the facility is carried out is therefore difficult. 

The impact of licensing and inspection on the quality of products is also realized through multi-stage causal links, as shown below (Figure 11.3). Once again, those factors which can be influenced by regulation have been shown in bold type. 

Consequently, measurement of the impact of licensing and inspection on the final outcomes (quality of product and quality of use) is complicated by other factors. The question then becomes how can we measure the effectiveness of licensing and inspection Two approaches are possible a) checking whether the necessary structures for licensing and inspection activities exist or b) using indicators that provide information about the intermediate outcomes of licensing and inspection. 

Many factors have to be considered when developing combination vaccines. First the selected components need to be given on a similar schedule and all components should already be licensed in the United States. The excipients contained in the individual vaccines may interfere with another component when combined, altering a component s immunogenicity. Finally, the immunogenicity of the combination must be similar (within 10%) to the immune response when the components are administered separately. This has been problematic with combinations containing Haemophilus influenza type b vaccine, for which the immune response has been significantly blunted in some combinations.13... 

Mammalian cell suspension cultures are the preferred choice for large-scale recombinant protein production in stirred-tank bioreactors. The most widely used systems are Chinese hamster ovary (CHO) cells and the murine myeloma fines NSO and SP2/0. In half of the biological license approvals from 1996-2000, CHO cells were used for the production of monoclonal antibodies and other recombinant glycosylated proteins, including tPA (tissue plasminogen activator) and an IgGl fusion with the tumor necrosis factor (TNF) receptor, the latter marketed as Enbrel [7]. 

Molex A version of the Sorbex process, for separating linear aliphatic hydrocarbons from branched-chain and cyclic hydrocarbons in naphtha, kerosene, or gas oil. The process operates in the liquid phase and the adsorbent is a modified 5A zeolite the pores in this zeolite will admit only the linear hydrocarbons, so the separation factor is very large. First commercialized in 1964 by 1992, 33 plants had been licensed worldwide. See also Parex (2). 

The demonstration of genotoxic activity in a pharmaceutical molecule may not necessarily translate into discontinuation of development and ultimate licensing of the product to be marketed. A survey of the Physicians Desk Reference reveals many examples of pharmaceutical products that have been shown to elicit genotoxic activity in one or more gene-tox assays.41 This observation indicates that other factors (such as risk, benefit, seriousness of ailment, target patient population, dosage, and frequency of administration, among others) are taken into consideration. 

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