Evidence functional control, computer

All of the areas of proof described above provide evidence concerning the current operations of the computer systems in place, but can those same controls be expected to continue to function over time Certainly a trend of control provides some presumption, and annual SOP review procedures provide a degree of assurance, but the most significant evidence of system reliability lies internal to the software and is documented only through a review of that source code itself. 

In our opinion, this book demonstrates clearly that the formalism of many-point particle densities based on the Kirkwood superposition approximation for decoupling the three-particle correlation functions is able to treat adequately all possible cases and reaction regimes studied in the book (including immobile/mobile reactants, correlated/random initial particle distributions, concentration decay/accumulation under permanent source, etc.). Results of most of analytical theories are checked by extensive computer simulations. (It should be reminded that many-particle effects under study were observed for the first time namely in computer simulations [22, 23].) Only few experimental evidences exist now for many-particle effects in bimolecular reactions, the two reliable examples are accumulation kinetics of immobile radiation defects at low temperatures in ionic solids (see [24] for experiments and [25] for their theoretical interpretation) and pseudo-first order reversible diffusion-controlled recombination of protons with excited dye molecules [26]. This is one of main reasons why we did not consider in detail some of very refined theories for the kinetics asymptotics as well as peculiarities of reactions on fractal structures ([27-29] and references therein). 

The FDA will consider the lack of computer validation as a significant inspection finding and log it as a 483 noncompliance citation. The MHRA may take a more lenient view depending on the criticality of the system on GxP operations. The lack of a detailed written description of an individual computer system (kept up to date with controls over changes), its functions, security and interactions (EU GMP Annex 11.4) a lack of evidence for the quality assurance of the software-developed process (EU GMP Annex 11.5), coupled with a lack of adequate validation evidence to support the use of GxP-related computer systems may very well be either a critical or major deficiency. Ranking will depend on the inspector s risk assessment. 

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