Documentation validation protocols

Written procedures stressing documentation, validation protocols, change control, and procedural deviations must be in place. 

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). 

Validation protocol Document describing the specific item to be validated, the specific validation protocol to be carried out and acceptable results, as per acceptance criteria... 

Partial or complete re-validation is another precedented approach to method transfer. Those variables described in method validation guidance documents (ICH Q2B, 1996 USP, 2012c) that are likely to be impacted by method transfer, should be assessed and documented (transfer or validation protocol). Agut et al. (2011) indicated that, in the changing industry model with the increased outsourcing of R and D activities (alliances, outsourcing, etc.), method re-validation may constitute, in some cases, an efficient approach when the transfer is performed from the Analytical Development Laboratory of an external partner who does not share exactly the same environment (validation standards, analytical culture or traditions , equipment, etc.). ... 

Transfer waivers should be assessed and documented (transfer or validation protocol). 

The scope generally defines the purpose of the IQ protocol. It should describe what component/software will be installed and what will be validated/evaluated during installation. The scope should also provide a basic outline as to implementation tasks, and define the overall documentation, validation and installer s qualification requirements. 

Ensure that all deviations from the validation protocol are investigated and documented... 

The validation method for neutralizing the antimicrobial properties of a product must meet two criteria — neutralizer efficacy and neutralizer toxicity. The validation study documents that the neutralization method applied is effective in inhibiting the antimicrobial properties of the product (neutralizer efficacy) without impairing the recovery of viable microorganisms (neutralizer toxicity). Validation protocol may meet these two criteria by comparing recovery results for three treatment groups. 

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... 

The VMP should be a summary document and should therefore be brief, concise, and clear. It should not repeat information documented elsewhere but should refer to existing documents such as policy documents, standard operating procedures (SOPs), and validation protocols/reports. The documentation format is illustrated in the VMP. 

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... 

A validation protocol is a document that describes the item to be qualified, the tests and checks to be performed, as well as the results that are expected to be obtained. It is a file in which the records, results, and evaluation of a completed validation program are assembled. It may also contain proposals for the improvement of processes and/or equipment [1]. Validation protocols are important in ensuring that documented evidence is taken which demonstrates that an equipment item, a system, a process, or a method consistently performs at a specified level... 

Validation protocols are required to describe the objective, methodology, and acceptance criteria for installation, operational, and performance qualifications. They are written to ensure test methods, and acceptance criteria are reviewed and approved before qualification of protocols. In practical terms, there are several stages for the production of protocols. First, an acceptable format needs to be agreed. No universal format exists for protocols, but to some extent, the type of equipment, the size of the project, and the personal preferences will dictate the protocol style. However, some norms have been established. Like other controlled documents, protocols are assigned unique reference numbers and revision numbers. They are titled and numbered on every page and have a particular place for approval signatures. Other common elements in protocols tend to be brief descriptions of the item being qualified and a clear statement of responsibilities. 

A validation protocol is necessary to define the specific items and activities that will constitute any validation study. It is advisable for companies to draw up a VMP indicating the overall validation strategy for either the product range or equipment type or the entire site. The protocol must be prepared before initiation of the study and must either include or refer to the documentation required to provide information about a specific process, the parameters involved in that specific process, the personnel responsibilities, and the acceptance criteria. 

A validation report is a written document that cross-references the validation protocol, summarizes the results obtained, describes any deviations observed, and draws the necessary conclusions, including recommending changes required to correct deficiencies for the qualification and validation performed [5]. In this report it is required to present both the results and conclusions and the secure approval of the study. The report should include a summary of the procedures used to clean, sample, and test as well as the physical and analytical test results or references for the same. The conclusions regarding the acceptability of the results should also be included. Other information would be the status of the procedures being validated, any recommendations based on the results, or any relevant information obtained during the study. These include, re validation practices (if applicable), the approved conclusions, and any deviations of the protocol that might have occurred. In cases where it is unlikely that further batches of the product will be manufactured for a period... 

Validation Team A well-defined validation team with a well-written description of responsibilities is required and assures the adequate realization of the validation tasks. A validation team should be composed by different responsibilities responsible-of-validation team, team leader, archive manager, test coordinator, quality assurance member, tester, and witness. The responsible-for-validation team elaborates and approves the VMP, protocols, and reports. The team leader should be responsible for the computer system validation and utilization. An archive manager is responsible for the management of all computer system validation documents. The test coordinator is responsible for the computer system test and coordinates the elaboration and operation of tests for evaluating the performance of the computer system. A quality assurance member is required to periodically inspect and train the personnel and review all the validation documents. The tester is responsible for the execution of the tests required to perform the validation protocol. The witness is responsible for observing and reviewing the operations of the tester. 

In the present chapter, the pharmaceutical industry validation system has been reviewed. To have an appropriate validation system it is first required to define which equipment, facilities, and processes will be validated, when they will be validated, and by whom this must be performed. This definition is based on a risk assessment priority and is written in a specific document, the so-called MVP. In order to generate an adequate validation report, all the validation activities should be described in the validation protocols, SOPs, and specific procedures. 

The validation protocol and report may also include the product stability data or a summary and documentation concerning cleaning and analytical validation. 

Let us examine what a protocol should accomplish. During an inspection of a given product or process, FDA will more times than not conduct a review of the process validation protocol. As mentioned earlier, the process entails everything used to manufacture the transdermal—procedures, personnel, methods, documents, and so on. Given the fact that the protocol will likely fall under FDA scrutiny at some point and that other documents used to complete the validation may as well, it should be easy to understand that the process validation protocol should be used to reference as many of these other supporting documents as possible. 

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. 

Once the prerequisites are in place, it is time to set about validating the cleaning process. The primary documentation associated with this event is the validation protocol. 

The PV of a new facility [21] must be documented in such a way to ensure that the facility s design and the operations within it are fully covered. An outline of such activities is listed in Table 4. For example, the validation of a new facility makes it necessary to document the equipment performance under relevant conditions. All process (or facility) equipment will undergo IQ testing to make sure that each piece of equipment operates as it was designed to do. The technologist will determine how the equipment s performance will vary without the influence of the process material (OQ). This information will form the basis for the remainder of the validation report. From a QA viewpoint, it should also be noted that this information might be useful if it is compared against the parameter measurements under load conditions. Since this information is more properly included in the performance qualification (as process optimization), however, it should not become a part of the validation protocol... 

On the other hand, if the process must be validated in an existing facility, existing IQ and OQ information may be adequate. In this case, the validation protocol might merely refer to the data rather than require its regeneration, especially when a credible calibration/audit program had been performed for the facility and equipment after the initial IQ and OQ were performed. This part of the validation work thus might merely be referenced in the validation document. 

---