State of Validation

Once the system has been released for operation, the computer system maintenance activities take over. The maintenance activities must be governed by the same procedures followed during the development period. 

The maintenance of computer systems becomes an essential issue, particularly when a new version of the supplier-supplied standard software is updated. A change control procedure must be implemented whereby changes in the software and computer hardware may be evaluated, approved, and installed. 

Security is a key component for maintaining the trustworthiness of a computer system and associated records. Security is an ongoing element to consider, subject to continuous improvement. The security measurements that are implemented on a computer system may be obsolete after several years. 

Representative characteristics Phased rollouts Corrective, adaptive, perfective, and preventive maintenance Maintainability issues of obsolete technology (e.g., access to electronic records)  

Key Problem reporting and Operational audit Periodic review 

---

After visiting and inspecting the supplier, the information obtained is analyzed against the acceptance criteria, current company requirements for the validation of computer systems, and the regulatory expectations for computing environments. A report is produced that documents the audit process, provides information on the current state of validation of the supplier and what may be needed for compliance and, based on the audit findings, provides a recommendation on whether the supplier can be used. 

As with any computerized system, it is important that the implementation of the electronic submissions system be documented and validated. Changes to the system must be controlled in order to maintain the system s state of validation. Refer to Chap. 7 for an extensive overview of computer validation. 

The following section describes challenges presented to scientists involved in the analysis of drug candidates and final products, including the current state of validating a chromatographic method. 

The compliance gap is calculated by subtracting the state of validation score from the maximum possible risk assessment score for that system s level of risk. The maximum possible risk assessment scores for LOW, MEDIUM, and HIGH risk systems are 35,49, and 63, respectively. To avoid negative scores the state of validation assessment should be designed so that its maximum score is equal to or less than the maximum possible risk assessment score for a LOW risk system. The compliance-gap score can be included in the system inventory. The priority attached to validation should be based on tackling the systems with the highest compliance-gap scores first. 

Change Control will be written to ensure that systems and processes remain in a state of validation. The procedure outlines steps to follow when a change is proposed. The change control program ensures that proposed changes are reviewed and approved by appropriate departmental representatives prior to initiating changes. The review also defines the required tests and documentation to be performed to verify that the system, equipment, and process remain in a validated state. 

S = 1/2 states are valid for any three-eleetron situation however, some of the determinental funetions vanish if doubly oeeupied orbitals oeeur as for ls 2s. In partieular, the lsalsa2sa and... 

To reiterate, the development of these relations, (2.1)-(2.3), expresses conservation of mass, momentum, and energy across a planar shock discontinuity between an initial and a final uniform state. They are frequently called the jump conditions" because the initial values jump to the final values as the idealized shock wave passes by. It should be pointed out that the assumption of a discontinuity was not required to derive them. They are equally valid for any steady compression wave, connecting two uniform states, whose profile does not change with time. It is important to note that the initial and final states achieved through the shock transition must be states of mechanical equilibrium for these relations to be valid. The time required to reach such equilibrium is arbitrary, providing the transition wave is steady. For a more rigorous discussion of steady compression waves, see Courant and Friedrichs (1948). 

Steady wave A propagating transition region that connects two uniform states of a material. The wave velocities of all parts of the disturbance are the same, so the profile does not change with time, and the assumptions that go into the jump conditions are valid. 

If a reaction system consists of more than one elementary reversible reaction, there will be more than one relaxation time in general, the number of relaxation times is equal to the number of states of the system minus one. (However, even for multistep reactions, only a single relaxation time will be observed if all intermediates are present at vanishingly low concentrations, that is, if the steady-state approximation is valid.) The relaxation times are coupled, in that each relaxation time includes contributions from all of the system rate constants. A system of more than... 

The various solutions to Equation 3 correspond to different stationary states of the particle (molecule). The one with the lowest energy is called the ground stale. Equation 3 is a non-relativistic description of the system which is not valid when the velocities of particles approach the speed of light. Thus, Equation 3 does not give an accurate description of the core electrons in large nuclei. 

While significant amounts of experimental data are available on the side-chain tautomerism of the functionalized azoles, most are of qualitative character and not fully systematic. No accurate structural correlations which would allow rehable predictions of the energy preferences of a specific tautomer or the state of a tautomeric equilibrium at given conditions have been developed. Nevertheless, trends can be discerned, some of which have previously been formulated [76AHC(S1), pp. 386-391, 443-446]. More recent studies discussed in this section have confirmed the validity of the following ... 

The fact that the hygrometric state of the air influences the sense of smell is probably more validly explained by the fact that moist air is capable of carrjdng a larger proportion of tbe vapour of a volatile substance than is dry air. 

The guideline states that the objective of validation is to demonstrate that an analytical method is fit for its purpose and summarizes the characteristics required of tests for identification, control of impurities and assay procedures (Table 13-2). As such, it applies to chiral drug substances as to any other active ingredients. Requirements for other analytical procedures may be added in due course. 

---