Validation of Utility Systems

This chapter provides a summary of the key validation test functions and acceptance criteria for each utility system. These are provided as a guideline for those involved in the validation of ABC Pharmaceutical. Approval of this Master Plan neither provides approval of these test functions and acceptance criteria nor does it limit the test functions and acceptance criteria included in any protocol. Final approval of test functions and acceptance criteria is made by approval of the Installation, Operational, and where applicable, Performance Qualification protocols. 

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Validation of Utility Systems, Test Functions, and Acceptance Criteria... 

Validation of utility systems. Define test functions and acceptance criteria for the utilities, including workmanship. 

Civil work Drainage system Validation of utility systems Test functions and acceptance criteria... 

Design and qualification of critical support utilities Validation of computer systems, methods, manufacturing, and cleaning processes Labeling controls... 

The inspection should cover the evaluation and assessment of the documentation, premises, equipment, utilities and materials. It should also cover verification of data and documentation such as results, batch records, compliance with SOP and information submitted on the manufacturing method, equipment and aspects including (but not limited to) validation of the manufacturing process, validation of utilities and support systems, and validation of equipment. 

Another approach towards human glyco-sylation is followed by the utilization of a humanized mouse cell line, a human/ mouse heterohybridoma presented by Dr. Volker Sandig from ProBioGen. I have known Volker for a couple of years, since when I invented a real-time PGR test kit for the detection of mycoplasma contamination in pharmaceutical products. Using an internal standard we developed this method for rapid in-process (IPG) control for production of biopharmaceuticals and ProBioGen was one of the partners participating in the validation of the system as they wanted to use it for rapid quality analysis of their designer cell lines. As we have learned from previous examples, the development of mammahan super-producer cells from CHO (or also from the mouse myeloma cell line, NSO) starter cell... 

Process water—The water used in BPC production is usually deionized water through the early process stages. If the product is isolated from a water solution in its last step, then a compendial grade of water, purified water or WFI may be utilized depending upon subsequent steps in dosage manufacture and the final use of the product. Cleaning of equipment can be performed with city water, provided the last rinse of the equipment is with the same water utilized in the process step. The validation of water systems has been well documented in the literature (15,16). 

Generate and maintain an inventory of all systems utilized by the organization, categorizing them as regulated and nonregulated systems. Identify prospective validation or retrospective evaluation needs for each system and record the current validation status. 

For systems with regulatory impact, a numerical exercise is then conducted to prioritize the validation activities. This prioritization considers all of the following system criticality, industry distribution of the software, regulatory experience, and the vulnerability at downtime. The numerical rating facilitates prioritization of validation efforts utilizing limited resources. The numerical priority ranking of each system with regulatory impact can then be compared with other systems to identify the order in which to address the various activities. 

Our analysis is based on solution of the quantum Liouville equation in occupation space. We use a combination of time-dependent and time-independent analytical approaches to gain qualitative insight into the effect of a dissipative environment on the information content of 8(E), complemented by numerical solution to go beyond the range of validity of the analytical theory. Most of the results of Section VC1 are based on a perturbative analytical approach formulated in the energy domain. Section VC2 utilizes a combination of analytical perturbative and numerical nonperturbative time-domain methods, based on propagation of the system density matrix. Details of our formalism are provided in Refs. 47 and 48 and are not reproduced here. 

The d-d spectra of copper(II) compounds have provided a fruitful field for practitioners of the AOM. A wealth of structural data is available, and a rich variety of coordination geometries has been revealed. If we can make allowance for the dependence of the AOM parameters on the intemuclear distance, we are provided with excellent opportunities to test the validity of AOM parameters over a range of related systems. However, the progress of such studies over the years has illustrated the fact that a simple model may be very successful in explaining a limited amount of dubious experimental data as more crystal structures appear and as better spectroscopic data become available, the simple model may require considerable refurbishment, perhaps to the extent that it loses some of its appeal and utility. 

The long-range term has been satisfactorily described by the Debye-Huckel formula and is retained. The short-range contribution is modeled by utilizing the concept of local compositions in a manner similar to Renon and Prausnitz (20) but with additional assumptions appropriate for electrolyte systems. Preliminary results suggest the validity of the model since good fits to experimental data have been obtained for a wide range of binary and ternary systems with only binary parameters. 

Facilities and Equipment System This includes (1) buildings and facilities along with maintenance (2) equipment IQ, QQ, calibration, maintenance, cleaning, and validation of cleaning processes and (3) utilities such as HVAC, compressed gases, steam, and water systems. 

However, the most severe criticism of the CIEEL hypothesis relates to the chemiexcita-tion efficiency experimentally obtained for the standard CIEEL systems, diphenoyl peroxide (4) and 1,2-dioxetanone (2) . In a study on the electron transfer catalyzed decomposition of l,4-dimethoxy-9,10-diphenylanthracence peroxide (21), Catalan and Wilson obtained very low chemiexcitation quantum yields with various commonly utilized activators (4>s =2 10 EmoH ) and reinvestigated the CL of diphenoyl peroxide (4), determining quantum yields in the same order of magnitude (4>s = (2 1)10 Emol ) as those obtained by 21 (Table 1). We have more recently determined the quantum yields in the rubrene-catalyzed decomposition of dimethyl-1,2-dioxetanone (9) and also found a much lower value than the one initially reported (Table 1) °. Since the diphenoyl peroxide and the 1,2-dioxetanone systems are the two prototype CIEEL systems, the validity of this hypothesis itself might be questioned due to its low efficiency in excited-state formation. ... 

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