Validation process Performance Qualification protocols

IQ Installation Qualification protocol OQ Operational Qualification protocol PQ Performance Qualification protocol PV Process Validation protocol PM Preventive Maintenance procedure... 

Enhanced turn-over package Installation qualification protocols Operational qualification protocols Change control initiation Cycle development Performance qualification protocol Process validation protocols Validation final reports Validation package Certificate for use in manufacturing Required protocols and procedures for dry production Required protocols and procedures for liquid and semisolid products... 

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). 

Instrument qualification or validation refers to the process of demonstrating an instrument s suitability for its intended use. The first step is to write protocols to cover the four main qualification elements design qualification, installation qualification, operational qualification, and performance qualification. Another qualification element, re-qualification, can be written as a separate protocol or included as part of the PQ protocol. These protocols must be performed in sequence. If the protocol meets its acceptance criteria, then the next protocol in the sequence can be executed. 

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 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-... 

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... 

In all large and complex systems developed by contract developers, it is normally the practice to perform an SAT. The SAT is the set of activities comprising the system installation, start-up, operational testing, and user orientation performed by the software supplier/integrator in the operational environment. For the purposes of this book, the operational testing performed as part of the SAT is also known as the OQ2. If the SAT is conducted according to approved protocols, test results are properly documented, and test results reviewed and approved by the user and QA, it may not be necessary to repeat the installation and operational qualifications. This provides cost savings and can streamline the validation process. Refer to Sidebar 10-2. 

An important part of any validation protocol for NIR or other instrumental methods is the process of instrument qualification. In any GMP/GLP facility, instrument performance must be validated. This instrument performance validation, also called instrument qualification, involves three phases [9] installation qualification (IQ), operational qualification (OQ), and performance qualification (PQ). 

Systems specifications provide all the information needed for the technical implementation of the system. This includes hardware, networking connections, and backup requirements as well as all information needed to install, operate, and qualify the performance of the system. It generally includes all of the qualification protocol documents (installation, operation, and performance qualifications) created during the validation process. 

Documented evidence is achieved by preparing written validation protocols prior to doing the work, and writing final reports at the completion of the work. Information must be in writing, otherwise it does not exist, according to the FDA. The process equipment used should undergo installation qualification (IQ) and operational qualification (OQ) to establish confidence that the equipment was installed to specification and purpose and is capable of operating within established limits required by the process. Performance characteristics which may be measured could be uniformity of speed for a mixer or the temperature and pressure of an autoclave, for example. 

The engineering firm will be responsible for identifying key supplier documents required for validation (IQ and OQ) and also specifications and ranges for equipment. The validation services will develop protocols for executing each component (IQ and OQ). Performance qualifications are performed after completion of OQ. The engineer or contractor will typically not be involved in PQ. Our experience has been that the producer will perform PQ on the new process. 

Performance qualification (testing)—That portion of the overall validation program that deals specifically with the evaluation (validation) of the process. It includes the protocol development, data acquisition, report preparation, and the requisite approvals. In the distant past this activity was considered process validation, but over the years the industry has come to realize that validation encompasses a broader spectrum of activities and continued use of the word process is limiting. 

It must be proven that a device will be suitable for the intended function in the preparation process by appropriate validation or qualification, see Sect. 34.15. Qualification and validation must be planned, described and documented. Responsibilities must be clear before the vaUdation process starts. Tests, calibrations, inspections and acceptance criteria must be laid down in a pre-approved qualification protocol. Raw and processed data, test results and ccmclusions must be documented. The result is the qualification or vahdation report, including test results and conclusirais. Qualification effort are highly dependent on the criticality of the equipment and the direct or indirect effect (impact) of the device on the quality of the preparation process and product. When purchasing a new device it is often possible to ask the supplier (by quality agreement) to qualify the equipment. This involves, usually, the Installation Qualification (IQ) and the Operational Qualification (OQ), sometimes also parts of the Performance qualification (PQ), although usually the user of the equipment has to take the responsibility for the execution of the PQ (see Sect. 34.10). 

Qualification Verification. Again, the process validation protocol should reference all items that support the validation the procedures, personnel, methods, and equipment. This section therefore lists and summarizes the various installation, operational, and performance/process qualifications completed for the equipment used in the process validation. These qualifications should list each by equipment name and number and qualification and type. A typical verification section is illustrated below. 

The PQ is the phase in which either a technical system is tested over a long period of time (e.g., water system), or a complex technical system is tested overall (connected filling line). For many systems OQ is the last phase performed during qualification. If there are only a few performance tests needed, it might be more practical to include them during OQ or process validation. Combining OQ and PQ decreases the number of documents (less documentation work in the future) and cuts approval time and effort. Again, the procedure for PQ is the same as for IQ and OQ ([develop PQ protocols, approve PQ protocols (by the quality assurance, production, and technical departments), perform PQ, work out the PQ report, and approve the PQ report (by the quality assurance, production, and technical departments)]. The documentation and test description are identical to those in the OQ phase. 

The principles of planning, organizing and performing process validation are similar to those for qualification. It should be done in accordance with process validation protocols, data should be collected and reviewed against predetermined acceptance criteria, and reflected in process validation reports. 

The master plan is finalized during detail engineering. The protocols prepared (IQ s, OQ s and PQ s) and the validation files started during construction. The IQ s (Installation Qualifications) are performable as construction is completing and can be completed by the constructor under supervision. The OQ s (Operational Qualifications) can be performed during the earlier parts of start-up as verification of mechanical completion. The PQ s (Process Qualifications) are performed as start-up completes and continue through the operating life of the plant. For maximum schedule... 

The Validation protocol should clearly describe the procedure to be followed for performing validation. The protocol should include at feast the objectives of validation and qualification study, site of the study, the responsible personnel, description of equipment to be used (including calibration before and after validation). SOPs to be followed, standards and criteria for the relevant products and processes, the type of validation, and time/frequency should be stipulated. The processes and/br parameters to be validated (e.g., mixing times, drying temperatures, particle size, drying times, physical characteristics, content uniformity etc.) should be clearly identified. 

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