Validation process documentation

The staff has identified a number of open items with respect to the HOP program. Principal areas of concern are the Verification and Validation process, documentation, and administrative controls. Upon satisfactory resolution of those deficiencies, the staff will be able to conclude that the EOP program is acceptable for restart. The resolution of these open items will be addressed in a supplement to the SER. 

Obviously, GMP requirements, especially extensive personnel training, calibration, qualification and validation, enhanced documentation, extensive cleaning and sanitation, and sharpened in-process control must considerably influence process organization and output. All these GMP-related activities are costly and time consuming, and will result in decreased productivity and increased production costs. On the other hand, a quality assurance system contributes to consistent production with a lower number of rejected batches and complaints. 

In contrast to many other validation protocols, the description of the NMKL validation process starts with the protocol of planned validation. This protocol should include, e.g., the needs of the client, available equipment, the chemical form in which the analyte occurs (i.e., in pesticide analysis the residue definition), matrix types, the availability of reference materials and the working range. Consequently, an extra paragraph is dedicated to the requirements for the documentation of validation results, which refers to the rules in Section 5.4.4 of EN 45001 (amended by ISO 17025). 

FieldNotes user verification can be conducted by following the SOP written by Astrix, which can be downloaded from the Astrix Web site. The SOP contains a script that is typed into the computer system. If the printout matches the SOP script, then verification is complete. A record of this must be placed in the facility archive. This verification process takes 1 h or less. For FieldNotes, calculations are not verified at the field site since the manufacturer feels that the software developer and the sponsors have performed adequate validation of these calculations previously. This may, therefore, require a visit to the sponsor or to the manufacturer to confirm that this important step of the validation process has been completed and is adequately documented. By following the Astrix SOP, the user is simply ensuring that the program operates on their system(s). The SOP script must be typed in exactly as written in order to confirm the printout accuracy. QA must ensure that the verification documentation is properly archived. Just as with any other SOP, this SOP must be approved in writing by field site management to comply with GLP. 

For /-Advantage, more extensive field site verification is conducted. A field site notebook is used which verifies every step in the data entry process. Following this procedure, a form is completed and returned to American Agricultural Services, Inc. (AASI), where the form is checked to ensure that verification was properly conducted and documented. This verification takes approximately 2 h to perform. Documentation and verification may require a visit to AASI to confirm that the validation process has been completed and is adequately documented. 

Regardless of the objective, the study director and advisory staff will need to determine the scope of validation prior to use of the method in specimen analyses. Criteria for acceptance of the method or for establishment of laboratory capability should also be established and documented prior to the validation process. 

Parts II, III, and IV cover basic techniques for modeling with objects and advanced techniques for factoring and then recombining models and designs using packages, frameworks, and components. They do not describe a development process the steps to validate and document these models. 

Computer validation establishes documented evidence to show that the computerized system will consistently function and meet its predetermined specification and quality attributes with a high degree of assurance. Some of the parameters tested in the validation process include the following ... 

If it has not been already completed, the first recommended task is to establish/designate a validation team within the company—perhaps one snch team at each of mnltiple sites. If one elects to have a separate team at mnltiple sites, these teams mnst make certain that they carry ont the validation processes consistently across all sites. In larger corporations, this is often accomplished via a central validation committee managing the individnal gronps at the varions sites. For smaller companies a team may consist of only one individual. The goal of the team(s)/committee is to draft comprehensive validation plans and protocols across all the instrnments, systems and processes that reqnire validation. They must then diligently execnte, document and verify each validation procedure. 

All individuals involved with the validation process should be thoroughly acquainted with the following documents, as these can all be very useful ... 

When the validation process is complete document the procedures of the method (also important for auditing and evaluation purposes)... 

Validation Validation was defined in Section 3. It is the process of evaluating a method, an instrument or other piece of equipment, a standard material, etc. to determine whether it is appropriate for the work at hand and whether it will meet all expectations and needs for a given analysis. For example, an analyst may propose that a new gas chromatograph, one that has a new design of electron capture detector, be used for a certain pesticide analysis performed in the laboratory. A validation process would involve testing the new instrument (alongside the unit currently used in the procedure) with standards and samples used in the analysis to validate whether the new unit will perform up to the standards that have been set for the work. If it can be documented that the quality of the overall analysis by the new instrument meets expectations, then it can be brought "online."... 

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... 

When new equipment is purchased or there is a change in the manufacturing site, qualification exercises are performed as part of the validation process. Qualification (installation qualification, operation qualification, and performance qualification) for any equipment or facility is an extreme process which involves testing, verification, and documentation to assure that the particular equipment or facility is per the specification and meets the appropriate standards as defined by vendor and required by manufacturing and engineering personnel [14]. 

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... 

Each validation process should have a documented protocol of the steps to follow and the data to collect during the experimentation. As an example, App. I presents a protocol for the validation of a steam sterilization process. 

For validated processes, the monitoring and control methods and data, the date performed, and, where appropriate, the individual(s) performing the process or the major equipment used shall be documented. 

Validation (policy, documentation, qualifications, approaches to process validation, periodic review of validated systems, cleaning validation, and analytical methods validation)... 

Recommendation on Validation Master Plan, Installation and Operational Qualification, Non-Sterile Process Validation and Cleaning Validation. This document is the basis for Annex 15 to the EC Guide on Good Manufacturing Practices for Medical Products. Figure 4 displays the most commonly used topics to be described in a VMP. 

The results of any risk analysis should be well documented as they become the key input into the qualification and validation process. They are the basis for defining tests in the IQ, OQ, and PQ phases. It is often impossible to say prior to a risk analysis what steps of qualification need to be performed. It depends on the risks and measurements defined during the risk analysis. Equally important, this procedure increases the efficiency of the qualification process. In the past, the decision on which qualification tests to perform was outlined by writing qualification protocols. These usually prompted long and expensive discus-... 

Review and approval process—The plan should address the review and approval process for all protocols and other documentation created as a result of the validation process. This would also include deviations occurring during the implementation of the validation protocols and any failures of data to meet acceptance criteria. 

Revalidation—At some point it may be necessary to revalidate all processes, equipment, and people. Life in the pharmaceutical world is a constantly changing situation. Some changes may be planned while others are not. For example, we may plan to change a mixer in a tank and we may implement the appropriate change control documentation that ensures that the change will be carefully evaluated and tested as to impact upon validated processes. 

Use of clear, precise operating instructions, including the documentation of process performance and verification. A company s system includes the issuance of a master production and control record and the batch production and control record (for each batch). These records document the fact that the company continues to manufacture each batch of product with the validated process of record. 

Retrospective validation has become synonymous with achieving validation by documenting all the historical information (e.g., release data) for existing products and using that data to support the position that the process is under control. It was originally discussed in a public forum by Meyer [16] and Simms [17]. I also refer the reader to articles in the first edition of Pharmaceutical Process Validation [18]. 

This approach to validation is the clearest example of validation being a QA tool. It appears that this approach will rarely be used for validation today, however, because it s very unlikely that any existing product hasn t been subjected to the PV process. The technique may only be justifiable if it is used for the audit of a validated process. With retrospective validation, the generated data already exist, but must be documented in a manner that clearly demonstrates that the existing process is under control. Quality assurance must first outline a plan for the validation effort, however, which would include the following items ... 

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