Validation specificity

Here, it can bee seen that system modules are not directly matched to process structures defined in the Supply Chain Planning Matrix. Also, the asymmetry between market facing parts of procurement and sales are not intuitive. However, APS extend the perspective on business applications extending the classical tasks of ERP and transactional systems to a management and planning level. With APS implemented in multiple industries and validated specifically in the process industry (Schaub/Zeier 2003) or also for Small and Medium Enterprises (SME) (Friedrich 2000), importance will further grow. 

For a liquid or semi-solid pharmaceutical dosage form, it is crucial to include a preservative in the formulation. Commonly used preservatives in these systems include sodium benzoate, EDTA, sorbic acid, and parabens. A generic HPLC method is also recommended for the preservatives used in liquid formulations for routine monitoring to ensure the stability of the preservative itself and it must be validated specific to its use with the dosage form. (See chapters on Sample Preparation and Method Development.)... 

While this is in principle a valid approach to collagenase inhibitor design, there is some question as to whether or not the assumptions on which this model is based are valid. Specifically, there are several reasons for challenging the assumption that collagenases prefer substrate conformations that mimic those found in collagen. First, an examination of a model of collagen... 

No method should be used without validation. The major part of the work of validation might have been done elsewhere at an earlier time, but even then, the analyst should be satisfied that the method as used in his or her laboratory is within the validation specifications. This will be discussed below. ISO/IEC 17025 encourages the use of methods published in international, regional, or national standards and implies that if these methods are used without deviation, then the validation requirements have been satisfied. What does need to be validated are nonstandard methods, methods designed and developed by individual laboratories, standard methods used outside their scope, and amplifications and modifications of standard methods. 

Sample Analysis Appropriate validated specific and sensitive analytical procedure should be used to analyze the samples and to determine the drug concentration and the amount of drug released. 

Although there are only a limited number of methods that have been validated specifically for soft drinks, there are around 80 validated methods available for the analysis of fruit juices, most of which would work equally well for soft drinks. These methods are published in the International Fruit Juice Union (IFU) handbook of analytical procedures, which offers the best reference collection of methods for the analysis of fruit juices in the world, with new methods added on a regular basis (Anon, 2004a). The IFU s collection of analytical methods covers most of the main procedures required to assess the quality and authenticity of fruit juices and nectars. The methods are hsted on the IFU s website (http //www.ifu-fruitjuice.com) at the time of writing they cannot be purchased directly from there, but they can be obtained from the Swiss Fruit Union, Zug, and details of how to do this are given on the website. It is possible that at some time the methods will be made available directly from the website. 

It is recommended that the protocol be divided into three major sections Section I, which discusses the background and validation methodology Section II, which contains areas in which data collected during validation can be documented and Section III, a section for the various attachments that will be involved. It should be understood that the contents of these sections may reside in validation-specific SOPs. Even if appropriate SOPs have been created, however, there is no assurance that the statements will be reflected in the execution of the validation. Contents of each of these three sections are discussed in the following sections of this chapter. 

Prior to performing a formal validation, the analytical chemist should have performed some prevalidation during method development. The expectation is that a well-developed HPLC method should subsequently be validated with no major surprises or failures. Prior to validation, specificity and some degree of robustness should be demonstrated. In addition, some form of system suitability criteria will have been established. System suitability evaluates the capability of an HPLC system to perform a specific procedure on a given day. It is a quality check to ensure that the system functions as expected and that the generated data will be reliable. Only if the system passes this test should the analyst proceed to perform the specific analysis. System suitability can be based on resolution of two specified components, relative standard deviation, tailing factor, limit of quantitation or detection, expected retention times, number of theoretical plates, or a reference check. 

Software tools supporting the functionality of applications should also be validated. Specific validation is not required because validation is inferred by validating the correct operation of the application itself. Examples include operating systems (GAMP Category 1 Software) that should be validated as GAMP Category 1 software. 

Pharmacovigilance systems capture, store, process, maintain, classify, and report adverse event data. Any snch systems generating reports for regnlatory authorities (e.g., expedited reports, periodic safety updates) and the interfaces into them from a variety of sources, should be validated. Specific considerations when validating these systems are ... 

The validation was performed according to the Roche Computerized System Validation Policy and Guidelines. This comprised the definition of a Validation Plan, the performance of the planned activities, and the creation of a Validation Report. In addition, the project was accompanied by external consultants providing knowhow regarding the validation-specific aspects of the development, including the management and auditing of the software developer. The scope of the validation activities was defined by GMP Analysis (also known as a GMP Assessment). The system... 

Since achieving specificity is often the most difficult aspect of developing an assay, establishing specificity is inextricably involved in the method development process. Therefore when it comes to validation, it should be simply a case of demonstrating specificity. It may be the case that when more thorough checks are made as in the validation specificity tests, the method is not as specific as was first thought. 

To ensure that the results of an assay are valid, specific criteria for interpretation of the results have evolved with experience with the tests over time among many laboratories. Both positive and negative (solvent) control values should reasonably be within the normal historical data for the laboratory. Tester strains must be identified and have a characteristic number of spontaneous revertants per plate for the vehicle controls. A minimum of three noncytotoxic concentrations needs to be evaluated. 

To ensure that the results of an assay are valid, specific criteria have been determined. The mutation frequency of the positive control group should be twice that of the solvent control group. The solvent controls should have a spontaneous mutation frequency between 20 and 100 per 10 surviving cells. In addition, the plating efficiency of the solvent controls must be >0%. 

The number of papers addressing method validation specifically has also been growing. Ciurczak addressed the overall problem for all types of spectroscopic methods in the industry [28]. He points out that ICH and FDA guidelines favor separation methods and do not address qualitative and quantitative methods based on spectroscopy. Conzen [29] addressed NIR... 

The validation process is outlined from writing user requirements specification to testing and validating specific analysis using estimation methods. This is followed with brief examples of validation approaches for some commonly encountered software, such as S-Plus , SAS , WinNonlin , and NONMEM . 

Alert and action levels for each parameter in each area or critical utility will be established based on the results from validation testing, compendia requirements, and cGMPs. Area or room limits will be based on the environmental data collected during the validation of the aseptic filling process validation. Specific action plans will be developed for addressing excursions beyond alert and action limits for each area or utility. 

During prestudy validation, specificity and selectivity are confirmed. Selectivity may be expressed as acceptable recovery, applying the same principles as for the assessment of accuracy (see below). Acceptance criteria should be predefined. Acceptance criteria for selectivity and specificity typically do not exist for in-study validation. If potential interference may become a problem caused by the matrix from persons with the disease, specificity and selectivity should be confirmed by repeating suitable experiments once those disease-state matrices become available. 

QTS software validation specifications lack details such as the hardware platforms the software should run on (model number, CPU [central processing unit], RAM [random access memory], hard drive size, free hard drive space, etc.), the software operating system, software database specifications (such as number of records accommodated, number of fields, whether those fields are character or numeric or date or alphabetical fields), the number of concurrent users allowed, the development platform used to write the application, network information, report contents and other information needed to perform testing properly. 

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