Validation process reporting

The validation process is subject to the following design specifications, user and performance requirements, preparation of a master plan/validation protocol (installation qualification, operational qualification, and performance qualification), execution of the protocol, preparation of a summary report, and on-going validation (and revalidation if changes are made). 

GLP regulations require QA personnel to inspect/audit each study conducted, but the extent to which QA personnel are involved in software development and the val-idation/verification process varies from company to company. In some companies, there is little or no QA involvement in these processes, whereas in others QA personnel are involved. QA personnel can provide assistance in the area of vendor audits for purchased software or can conduct inspections of in-house software development to ensure that internal procedures are being followed. QA personnel, who conduct in-process inspections and review the resulting data and validation report for accuracy, could provide inspection support during the validation and verification process. During system development and validation, properly trained QA personnel can provide the regulatory advice needed to ensure that the system will meet government standards. QA personnel become more familiar with the system(s) that will be used when they are involved early in the validation process. 

A number of computer software packages are available to the analyst to assist in the planning and execution of both method development and validation experiments. The attraction of these systems is that they can automate the validation process from planning the experiment to test execution to the presentation of the data in a final report form. 

Reviewing and approving validation reports. The validation process is a program that provides a high degree of assurance that a process will consistently produce a result meeting predetermined acceptance criteria. 

In many companies, the scale-up process may include or overlap with the validation process. In any case, demonstration of the process in the production environment at full scale, using the materials, equipment, procedures, and personnel established in production, is required. Often, multidisciplinary teams are arranged to manage the scale-up, and the overall roles and responsibilities for those involved with the product may change. Typically, extensive documentation, including protocols and reports, is involved, as... 

Based on the validation requirements, samples are collected at different stages and submitted for analysis per the validation protocol. The data are finally compiled in the form of a validation report. A systematic validation protocol and validation report are the backbone of the validation process. Table 12 gives key components of any validation activity [16]. These protocols and reports should be verified and approved by the relevant functions. 

Scope of Validation Processes Validation Master Plan Validation Protocols and Reports... 

A VMP should be divided into chapters covering different subjects. First, an introduction should state the manufacture s validation policy, general description of the scope of those validation activities covered by the VMP, and their objectives, derivation, location, and schedule. Then, it must declare all validation activities and their organizational structure in terms of personnel responsibility for the VMP, validation protocols, validation work, report and document preparation projects, approval of the same validation protocols, reports in all stages of validation processes, and the training needs in support of validation. Other requirements of the VMP are cross references to other documents and to specific characteristics of the processes that are critical for yielding a quality product. Next, all validation activities comprised in the VMP should be summarized and compiled in a matrix format. Such a matrix should provide an overview and contain all items covered by the VMP that... 

It may be that the method as developed has no particular client in mind. Now the method validation process is to discover and report the values of... 

As discussed, the manufacture of suspensions presents additional problems, particularly in the area of uniformity. The development data should address the key compounding and filling steps that ensure uniformity. The protocol should provide for the key in-process and finished product tests, along with their specifications. For oral solutions, bioequivalency studies may not always be needed. However, oral suspensions, with the possible exception of some of the over-the-counter antacids, usually require a bioequivalency or clinical study to demonstrate their effectiveness. Comparison of product batches with the biobatch is an important part of the validation process. Make sure there are properly written protocol and process validation reports and, if appropriate, data for comparing full-scale batches with biobatch available during FDA inspection. 

As noted, excipient manufacture should take place using qualified equipment and a validated process. Generally excipient equipment has been in place for many years so that classical methods of qualification, which is done as new equipment is commissioned, are inapplicable. To retrospectively qualify the installation, operation, and performance of equipment, it is suggested to rely on historical records. For installation and operation qualification, a protocol is prepared that illustrates how maintenance and production records will be used to support the hypothesis that the equipment was installed properly and is operating as intended. Then the protocol is executed by reviewing the maintenance and production records for the supporting data. Finally a report is prepared that includes the data from the records, which support the conclusion that the installation and operation of the equipment conforms to protocol requirements. It is suggested that maintenance and production records for a minimum of one year but preferably five years be reviewed. 

The most accepted validation method is prospective. This validation approach relies on completion of the validation before commercial production begins and requires the manufacture of at least three consecutive batches during protocol execution. The batches are evaluated for conformance to the protocol requirements a report is prepared and approved. Then the lots are released for sale and production commences using the validated process. For excipient manufacture, where the material has been produced for quite some time, this approach is usually inappropriate. 

Audit Report. A report of an independent audit of the computer validation process by an internal auditor (i.e. Quality Assurance) should be included with the summary report to management. The audit should compare the SOP and the initial parts of the protocol (what the system should do) with the test plan results (what the system actually does) and the summary report conclusions. 

In the course of data validation, data qualifiers are attached to the data. Data qualifiers are the alphabetic symbols that indentify an undetected compound or a deviation from acceptance criteria. Data qualifiers are also called data flags. The findings of data validation are detailed in a data validation report, which documents the validation process and explains the reasons for attaching the qualifiers to the data. Laboratories also use data qualifiers for indicating deviations from laboratory acceptance criteria. These qualifiers are replaced with the validation qualifiers in the course of data validation. Qualifiers are rarely used in data review. 

Developing the validation protocol is a crucial step in the validation process. It is the culmination of the regulatory and technical accomplishments to this point in the development of the method. The protocol must define which validation parameters are needed and the specific experiments necessary to demonstrate the validity of the analytical method. The protocol must contain all of the acceptance criteria for each of the relevant validation parameters. Additionally, the protocol must define the number of replicates, the reporting format, and the number of significant figures. In short, the validation protocol instructs the analyst on how to validate the analytical method. 

Formal documentation of the method-transfer results as addenda to the original validation report would further substantiate the overall validation process. Thus, each new laboratory setting would either confirm the original method validation, or indicate a possible need for method modification with revalidation. 

The validation report should be a living document that reflects the dynamic validation process. Therefore, it should be updated using addenda to report method transfer results, ongoing system suitability and any revalidation efforts. 

The CRS s VMP (or corporate policy) should state during the validation process that a system will be managed under the firm s change control policy or system. For example, the subject system will be considered to be under change control upon the acceptance of the OQ summary report by the quality unit. Consider when the system in question will actually begin to be used to support GXP production. 

The Validation Report for a system must not be approved until all the relevant documents defined within its Validation Plan have been approved. Approval of the Validation Report marks the completion of the validation process. The Validation Report must, therefore, include a clear statement confirming whether or not all computer systems are validated and fit for purpose. 

The validation process begins in method development in that the documentation reporting the validation data must include a record of the method development process, giving details of the conditions explored and the rationale of the progression of the process. The validation proper consists of a series of tests for which there are acceptance criteria which vary depending on the type of assay being carried out. Literal definitions of the parameters for which tests must be carried out are discussed elsewhere in this book but are repeated here as a reminder. 

Quantitative methods are assays that result in meaningful numeric measurements for a characteristic of a product. Quantitative methods are used in assessing whether final product meets specifications. They are also used to measure product quality (or quantity) in various stages of manufactuiing and the results are often used in quality control charts. Validation is an objective process used to determine whether a quantitative method is performing as expected and is appropriate for its intended use. This chapter provides the motivation behind validation, some terms and definitions used in validation, a consolidated statistically sound approach to validation, along with appropriate statistical analysis, and reporting of validation results. A hypothetical but realistic example is presented and is used to illustrate the validation process. 

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