Validation philosophy

Validation Master Plans typically have three main sections. The first section states how the phar-maceutieal or healtheare eompany s own validation philosophy and policy address regulatory GxP requirements. The seeond section defines the scope of validation, identifying which computer system systems require validation. All computer systems whose malfunction could possibly affect... 

The other factors mentioned come into play with the inherent mismatch that occurs when an overall factor must be appUed to correlate the flange-to-flange method. The correlation proposed in the code is based on work by Schultz [8] and was quite good for its day. When combined with modem calculation methods and equations of state, the philosophy is still valid. 

As is well-known in philosophy, certain feminist critics of science and technology, for example, Keller [27] and Harding [28], have argued that the scientihc community has maintained the status quo in its exclusion of women and women s concerns. To the extent that a person believes that the scientihc community has or has not excluded women, and to the extent that a person believes exclusion is unjust, that person may address the question of computer use favoring the status quo and excluding women. Although there are good reasons to think that the scientihc community has not been the disaster that certain feminists think it is [29], any researcher should be well aware of the possibility of exclusion not only for the effect on scientihc validity but also for the moral questions exclusion raises. 

CIBA GEIGY Corporation is presently using models as an aid to data interpretation for risk assessment. Our general philosophy is to use the model as an aid to risk assessment and not as a predictive tool to eliminate definitive studies. Hopefully, environmental fate models will be useful as a predictive tool as they become validated. 

The recent position of the USA is to take into consideration the scientific validity of the tool, and not necessarily the validation process. This is the philosophy adopted within the Tox21 (http //epa.gov/ncct/Tox21/) and ToxCast (http //www. epa.gov/ncct/toxcast/) initiatives. The reason for this is that the validation process takes 10 years or more before a method is officially approved, and this period would seriously limit the possibility to rapidly produce the necessary data needed within few years. Furthermore, the techniques are rapidly changing. 

Our philosophy was instead top-down . We decomposed the molecular TAE (total atomization energy TAEe at the bottom of the well, TAEo at absolute zero) into all components that can reasonably affect it at the kl/mol level. Then we carried out exhaustive benchmark calculations on each component separately for a representative training set of molecules. Finally, for each component separately, we progressively introduced approximations up to the point where reproduction of that particular component started deteriorating to an unacceptable extent. Thus, experimental data entered the picture only at the validation stage, not at the design stage. 

As in the case of DREIDING, the underlying philosophy of UFF does not allow for parameters to be developed for specific molecular systems (e.g. amino, nitro or nitroso). Rather, these are extracted from atomic parameters using a set of combination rales. Several calculations on amino and nitro compounds were performed as part of the validation of UFF58,59. In the following we refer to the structural results and save the discussion of the energetic ones to Section II.D. 

In conclusion, we must concur with both Shakespeare and Haldane. There are more things (a trillion more) in heaven and earth than are dreamt of in our philosophy, and, yes, the universe is not only queerer than we suppose, but queerer than we can suppose. To place the preceding observations in context, there are only about 600 molecular solvents commonly in use in industry today. So the reasons for discussing ionic liquids as designer solvents are valid with a trillion solvents to select from, an optimum solvent for any given reaction will exist. The only problem will be findiug it. Thus, we believe that the future of ionic liquids will. 

An example of the minimum requirement for potency assay of the drug substance and drug product is tabulated in Table 4. Note that the postponement of intermediate precision is aligned with previous discussion that the use of early phase analytical method resides mainly in one laboratory and is used only by a very limited number of analysts. Each individual company s phased method validation procedures and processes will vary, but the overall philosophy is the same. The extent of and expectations from early phase method validation are lower than the requirements in the later stages of development. The validation exercise becomes larger and more detailed and collects a larger body of data to ensure that the method is robust and appropriate for use at the commercial site. 

Once the manufacturing projection questions have been answered, a manufacturing philosophy must be decided on. This includes deciding on documentation requirements, special materials handling, controlled substance security, cleaning validation criteria, and equipment and facility qualification requirements. Now that we know what types of batches are to be manufactured, we can be more detailed in the description of the requirements of the facility. These requirements may be based on internal as well as regulatory requirements. In fact, if a full-scale facility is already in place, this step can be completed fairly easily and quickly. Many of the policies and systems may be transferred directly into the pilot facility. And others may be transferred with only slight modifications. 

Such is the explanation of Graham s law from the viewpoint of corpuscular philosophy from it follows that this law should be valid for a capillary of any width on the condition that the pressure along the capillary is constant. 

The PIC/S recommendations were issued as a draft in 1996. They were finalized in 1999, and are now in force as PIC/S 1/99-2. They were written as instructions for the inspectors with the aim of establishing a common philosophy of the validation topics. When they were proposed to be annexed to the EU GMP guide the discussion and ensuing revision led to a considerable reduction of the content since it was felt that the tutorial tone was not adequate for a regulation. 

Finally, suppose we allow chemical attack and cyclic hydration. As shown in Fig. 26, the prediction is that failure would occur in about 7 h, which is about 14 cycles of hydration combined with 7 h of chemical degradation. Of course, this result can be checked in the laboratory. That is how this philosophy was validated in earlier publications for other combined effects.44 It is also possible to evaluate what happens when one type of degradation (alone) is followed by another one in a sequence and to check to see if reversing the sequence changes the result. 

Objective and Scope. The objective and scope of the SOP need to be carefully thought through and described. A limited objective could be to validate only those computer systems directly related to the production of pharmaceuticals the broadest one would be to validate all computer systems regardless of their application. Usually it is somewhere between the two. The scope will be determined by the company philosophy, organizational structure and the number of divisions, plants or departments involved. The scope should be limited to as small a unit as possible for the initial validation effort in order to achieve at least one successful computer system validation quickly. 

Policies define the general principles and philosophy that are required within an organization. Each company should have written and approved validation policies that communicate the expectations of senior management for the execution of a validation project. 

Validation plans are documents that tailor a company s overall philosophies, intentions, and strategy to establish performance and computer systems or software adequacy. Validation plans state who is responsible for performing development and validation activities, who identifies which systems are subject to validation, who defines the nature and extent of inspection and testing expected for each system, and who outlines the framework to be followed to accomplish the validation. 

The corrective action plan may be contained within a validation plan. The validation plan is a document that describes the company s overall philosophy, intentions, timetable, and approach to be followed for the corrective action compliance program. The approach to be taken may consist of writing procedures, performing verifications, and/or performing qualification activities. Refer to Chapter 19 for information on remediation project. 

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