Validation deliverables

Laboratory instruments are classified into different categories according to their complexity to enable a scalable validation approach. The expected validation deliverables and documentation requirements for each class of laboratory instrument can be defined in the validation guide for the laboratory. 

The audit is a critical step in the validation of LIMS as it allows the pharmaceutical manufacturer to evaluate key testing and validation deliverables from the supplier. The pharmaceutical manufacturer is accountable to the regulatory authorities for any deficiencies in the chosen Supplier/integrator s capability. The pharmaceutical manufacturer is expected to bridge any gap in standards by assigning his or her own staff and employing consultants to assist the supplier in the validation of LIMS. 

Typically, the validation evidence for a SCADA system is created and approved through system development. Large systems are often formed of smaller subsystems and integrated during development and start-up efforts. Care should be taken to avoid using checklists as a substimte for validation deliverables or quality assurance reviews checklists simply indicate the presence or absence of required validation products. 

FIGURE 34.3 Project Phases with Validation Deliverables. 

The Validation Master Plan (VMP) or site plan will usually detail the deliverables to be produced from the validation. At the end of the validation exercise, it is important to check for the completion of this list. If there have been any changes of requirement during the project, and a deliverable is no longer required, it is essential that this be documented. The absence of such a note could lead to criticism from a regulator that the validation deliverables are incomplete. 

Give advice on validation deliverables (plans and protocols). 

From the guiding standards we can extract validation deliverables as follows ... 

The system wide validation deliverables from SAE ARP4754A (Appendix A) can be extracted into Table 9.7. 

The purpose of an analytical method is the deliverance of a qualitative and/or quantitative result with an acceptable uncertainty level. Therefore, theoretically, validation boils down to measuring uncertainty . In practice, method validation is done by evaluating a series of method performance characteristics, such as precision, trueness, selectivity/specificity, linearity, operating range, recovery, LOD, limit of quantification (LOQ), sensitivity, ruggedness/robustness, and applicability. Calibration and traceability have been mentioned also as performance characteristics of a method [2, 4]. To these performance parameters, MU can be added, although MU is a key indicator for both fitness for purpose of a method and constant reliability of analytical results achieved in a laboratory (IQC). MU is a comprehensive parameter covering all sources of error and thus more than method validation alone. 

The activities in the planning phase are commenced after a business need to implement an instrument in the laboratory has been identified. Planning-phase activities include concisely documenting the user requirements and functional requirements of the instrument. Once established, the requirements are then used to evaluate the instrument candidates available from suppliers. A validation plan with deliverables that are commensurate with the class of the instrument being implemented should be developed during the planning phase. 

Validation Plan A validation plan is prepared to highlight the activities and deliverables required in the implementation of the laboratory instrument. The details of the validation plan should be scaled according to the complexity of the system, its intended use, and the impact on the business. A generic validation plan can be used for similar types of laboratory instruments with similar applications. For example, one validation plan can be prepared for the FIPLC. A validation plan typically includes the following sections ... 

Validation Approach and Deliverables Outhne the required documents, qualification testing, and reports to be included in the validation project. The deliverables should be based upon the complexity and the risk associated with the intended use of the system. The dehverables will highlight the acceptance criteria to demonstrate that the system has met the requirements for its intended use. 

The established methodology for computer system validation enables identification and control of each life-cycle phase and its associated document deliverables. It is also recognized that throughout the validation life cycle there is a level of dependency on the methods, services, and resources of the computer system supplier. 

A Validation Report and Validation Pile are ihe main deliverable... 

Another key objective of the URS is to identify the document deliverables to support the validation program and the responsibilities for provision and management of this documentation during the project. 

The tender package documentation needs to provide all the elements necessary to define the project, and typically includes the project validation plan, a detailed scope of work, the URS, the documentation deliverables, and the associated commercial documentation. 

A formal agreement that references all relevant tender documents and clearly identifies responsibilities and document deliverables should be prepared by the pharmaceutical manufacturer. The purchase order should include the final agreement and identify any associated contractual documentation. A copy of the signed final agreement and purchase order should be retained in the pharmaceutical manufacturer s validation file, together with evaluation records applicable... 

It is an FDA requirement that regulated organizations ensure that all computer systems performing functions under FDA predicate regulations conform to the requirements contained in Chapter 3. In the FDA regulation context, computer systems validation is an element of the SLC. The scope includes all the practices and tools necessary to manage the development and maintenance of the deliverable system. 

Perform and document a traceability analysis between the requirements specification deliverable and system specification deliverable Specify Part 11 technical controls Prepare and approve system specification deliverable Revisit the risk analysis and the criticality and complexity assessments based on the system specification deliverable Review validation plan based on the system specification deliverable Approved validation plan... 

Typically, managers, their peers, end-users, and those responsible for delivering the system, approve validation plans. Quality assurance may also sign the document. The validation project plan and the requirements specification deliverable, together define the technical and regulatory requirements applicable for a project. 

The deliverables that are important in order to demonstrate that software has been validated include1 ... 

At the end of the assessment, the Deliverables Matrices detail the documentation that may be required for each level of validation. 

The selection of deliverables for each validation level may differ from those indicated in the Deliverables Matrices depending on the project documentation deliverables policies used by each regulated company. 

Proceed to the Deliverables Matrices that follow and select the matrix that is applicable for the Validation Level that has been determined. This will enable the documentation requirements to be determined. Then proceed to the page after the Deliverable Matrices and enter the documents required for the computer system. 

The following three matrices detail the deliverables for each level of validation. There is one matrix per validation level. 

The testing carried out in the development environment is not sufficient to verily the integrity and performance of the system. The application software must also be tested under actual conditions of intended use in the target or production environment. If the application is to be supplied by a third party in accordance with the end-user s requirements specification deliverable, it should be possible to carry out a completely prospective validation, as would be the case for a system developed in house, providing the requirement for validation is identified at the beginning. As with all systems, the responsibility for validation lies with the system s owner. 

The computer system needs a comprehensive PQ test designed to determine the degree of accuracy with which the system conforms to the requirements specification deliverable. The computer system PQ should not be confused with the process PQ and the product qualification as described in the FDA Guideline on Principles of Process Validation. The PQ occurs under operational conditions but not as part of the actual operational process. The specific test cases include ... 

Once the protocols have been completed, the test results and data need to be formally evaluated. The written evaluation needs to be presented clearly, in a manner that can be readily understood. The report should also address any nonconformances or deviations to the validation plan encountered during the qualification and their resolutions. The format of the report should be similar to the structure of the associated protocols. The qualification testing should be linked with the acceptance criteria in the relevant specification deliverable, so that the PQ will link with the requirements specification deliverable the OQ will link with the company system specification deliverable and the IQ will link with the technical design specification deliverable. 

As with most project plans, it is important for the VMP to include a definition of personnel roles and responsibilities. Numerous documents may need to come together to validate a system (e.g., specifications, SOPs, protocols), and team members must agree upon who will be responsible for specific deliverables, as well as approve the final documentation. 

In order to determine whether all VMP requirements have been met, the CRS VMP should require what will be referred to as a master validation summary report (MVS). The MVS should discuss each deliverable required by the... 

VMP for its successful execution. Reference the location of each deliverable and provide the detail necessary for retrieval at a later date (e.g., SOP and protocol numbers). Identify any conditions surrounding the use of the system. Were some features of the system found to be unsatisfactory for use Clearly state what aspects of the CRS are not approved for use until they are re-engineered and tested and what formal controls are in place to enforce this (SOPs, security programming, etc.). Design the VMP so that approval of the MVS document is the end point that releases the CRS for GMP use by appropriately trained users. This end point is called system acceptance and signals the transition to the validation maintenance phase of the system life cycle. 

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