Change Control Initiation

Enhanced turn-over package Installation qualification protocols Operational qualification protocols Change control initiation Cycle development Performance qualification protocol Process validation protocols Validation final reports Validation package Certificate for use in manufacturing Required protocols and procedures for dry production Required protocols and procedures for liquid and semisolid products... 

The roles and responsibilities of the transfer lab and the receiving lab as well as an outline describing deliverables and timelines should be defined clearly at the initiation of the assay transfer process. Once a transfer protocol is defined, any deviation from the protocol during execution should be discussed in the transfer report. Explanations as to why the deviation is acceptable should be included in the report. The transfer report should also be approved by relevant functional departments. Due to the complexity of multi-site involvement, having a good change control system in place is important for making SOP modifications or updates. 

One practical example of the consequences of change control is that in the regime of system/instrument change control, hardware, software and operational aspects such as routine operation, maintenance and data integrity are locked down in fixed configurations. Any modification that has not been anticipated in the initial qualification requires testing and documentation. 

In this overview we focus on the elastodynamical aspects of the transformation and intentionally exclude phase changes controlled by diffusion of heat or constituent. To emphasize ideas we use a one dimensional model which reduces to a nonlinear wave equation. Following Ericksen (1975) and James (1980), we interpret the behavior of transforming material as associated with the nonconvexity of elastic energy and demonstrate that a simplest initial value problem for the wave equation with a non-monotone stress-strain relation exhibits massive failure of uniqueness associated with the phenomena of nucleation and growth. 

Qualification of equipment and validation of computer systems are not one-time events. They start with the definition of the product or project and setting user requirement specifications and cover the vendor selection process, installation, initial operation, ongoing use, and change control. 

Change control is absent or inadequate. Most errors are introduced into a system after changes are made without authorization, documentation, and revalidation. For example, FDA s principles of software validation [3] state in Paragraph 2.4 Of those software related recalls, 79% were caused by software defects that were introduced when changes were made to the software after its initial production and distribution. 21 CFR Part 11 validation guidance also states the following ... 

This is a commonsense argument for change control, not only because the product we produce is pharmaceutical, but also because change control applies to other industries as well, including airlines, automotive, and electronics. As a matter of fact, many industries have this requirement, and where they do not, they are looking for ways to implement it. The ISO series and Six Sigma are two examples of current quality and business improvement initiatives, which both improve the processes involved and implement change control to keep the process consistent. 

An unspecified process had been operated for 20 years using synthetic sodium carbonate powder (soda-ash) to neutralise the hydrogen chloride as it was formed by interaction of the amine and chloro compound in a non-aqueous (and probably flammable) solvent in a steel reactor. Substitution of the powdered sodium carbonate by the crystalline sodium carbonate—sodium hydrogencarbonate double salt ( trona, natural soda ) caused a reduction in the rate of neutralisation, the reaction mixture became more acid, and attack on the steel vessel led to contamination by iron. These changed conditions initiated exothermic side reactions, which eventually ran out of control and caused failure of the reactor. Subsequent laboratory work confirmed this sequence and showed that presence of dissolved iron(III) was necessary to catalyse the side reactions. 

After the system has been released for operation, system maintenance activities take over. The importance of such activities is characterized by recent FDA remarks related to the lack of change control management by regulated organizations. The FDA s analysis of 3140 medical device recalls conducted between 1992 and 1998 reveals that 242 of them (7.7%) are attributable to software failures. Of those software related recalls, 192 (or 79%) were caused by software defects introduced when changes were made to the software, after its initial production and distribution. 

The analytical predictor, as well as the other dead-time compensation techniques, requires a mathematical model of the process for implementation. The block diagram of the analytical predictor control strategy, applied to the problem of conversion control in an emulsion polymerization, is illustrated in Figure 2(a). In this application, the current measured values of monomer conversion and initiator feed rate are input into the mathematical model which then calculates the value of conversion T units of time in the future assuming no changes in initiator flow or reactor conditions occur during this time. 

The empirical model of equation (11) predicted the response of the mechanistic model to a step change in initiator flow very closely (the average absolute deviation between the empirical model and mechanistic model was 0.8% of the response). Three algorithms have been considered for control of the downstream reactor modeled by equation (11). 

Describe or reference the change control system that will be used to maintain the validated state of the VUS after the initial qualification. 

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