POST-DELIVERY MODIFICATIONS

During the operational phase, it is necessary to ensure that the functional safety of the computer based system is maintained both during and after modifications. As mentioned in para. 4.24, adequate change control procedures which deal specifically with plant safety issues should therefore be in place. It is also important that the safety impact of the modifications be analysed by personnel from appropriate disciplines. In this respect, modifications to computer based systems are no different from other plant modifications. However, there are certain specific issues that apply uniquely to computer based systems and their software, and these are addressed in this section. 

The plant designers and operators should ensure that adequate change control procedures are in place, including appropriate procedures and organizational stractures for the review and approval of the safety aspects of the modification. These procedures shoirld be in place from the start of the project. 

All modifications shoirld be considered and classified according to their significance for safety. Those of the highest safety significance may need to be submitted to the regulatory authority, in particular those modifications that would alter previously approved operational limits and conditions. 

A procedure should be in place by which experts independent of the designers and developers of the modifieation should assess the adequacy of the proposed 

The change procedures should ensure that a safety justification is provided for each modification (see para. 15.3). 

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The licensee (i.e. the user of the computer system) shorrld establish an appropriate stracture to deal with operational and maintertance issues. Occasionally, the licensee may need its own team to perform post-delivery modifications on the software. This team shorrld have the same level of corrrpetence arrd equipmerrt as would have been provided by the original producer. 

Strict configuration control of the computer system (hardware and software) should be maintained dming the commissioning programme. Any changes required in this phase should be subjected to a formally documented change process (see Section 15 on post-delivery modifications). 

One major advantage of monoclonal antibodies from plants is the potential low cost of large-scale production. There are commercial companies (such as EPIcyte Pharmaceutical Inc) who are planning clinical dials for plant-produced secretory antibodies for human therapy. These so-called plantibodies can be produced at an estimated cost of 0.01 to 0.1/mg as opposed to 1 to 5/mg for production from cell culture processing of animal-derived hybridomas. The cost of microbial fermentation is lower than that of mammalian cell culture but bacteria lack the ability for efficient multimeric protein assembly and of any post-translational modification. A further potential advantage of the plantibodies is delivery by consumption of plant tissue and thus avoiding any need of purification. These possibilities are particularly applicable in certain cases such as the previously shown ability of a plant-produced... 

Selective post-polymerization modification of tertiary amine-containing polymers affords polysulfobetaines which are pH responsive [105, 106], Biocompatible drug delivery vehicles have been made from the copolymers of phosphobeta-ine and pH-responsive alkyl methacrylates [88]. The well-controlled micelles exhibit pH-modulated drug uptake and release. 

Keywords Amphipathic polymers Bifunctionalized homopolymers Dual-func-timial polymers Poly(glycidyl methacrylate) Post-polymerization modification Sequential reactions siRNA delivery Thiol-epoxy reaction... 

These two studies in particular are important. They demonstrate that not only can Pn peptide self-assembly be adjusted by sequence modification to suit a particular ionic strength and pH (e.g. conditions found in vitro or in vivo) but that it can be also made reversible and responsive. This raises the possibility that these peptides can be used in drug delivery, or as therapeutics that self-assemble post-injection. 

Several amine functionalized hyperbranched PGs have been reported as potential gene delivery systems after a proper surface group functionalization. In comparison to other dendritic structures, these scaffolds have the added advantage of being open, flexible, and possessing a polyether backbone which keeps the toxicity profile low. Different systems have been studied by post-modification of the hydroxyl groups... 

Modification of mesoporous silica nanoparticles using the bifunctional strategy, post-synthesis grafting, and backfilling strategy in order to make them suitable for drug delivery applications was reported (Lu et al. 2007). The modified nanoparticles were able to deliver the water insoluble drug camptothecin into different types of human cancer cells (Johansson et al. 2008). 

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