Qualification documentation manufactured

If one or more of the following data are not supplied by the manufacturer, it is recommended to measure and to include them in the qualification document of the plants ... 

Standard components Document manufacturer/supplier details Installation qualification verifies installation and connections Record model, version, and serial number of preassembled hardware Can use hardware data sheet or other specification Challenge hardware during SW OQ/PQ as necessary... 

Installation qualification— Documentation that the equipment was manufactured and installed in accordance with the intended design. This is essentially an audit of the installation against the equipment specifications and facility drawings. 

The validation life cycle is basically split into six main qualification phases as shown in Table 9.2 and all under the control of the Validation Master Plan (VMP). It must be clearly demonstrated that the QA function of the pharmaceutical manufacturer is endorsing the implemented system. In its simplest form, this will require the QA representative to authorize the documentation produced to support validation (e.g., VMP, Source Code Review, qualification documentation, reports, etc.). Table 9.2 shows the linkage between project activities and the qualification process, which is under the control of the VMP. 

Defined maintenance procedures should include model or manufacturer specifics and a list of parts to be inspected, cleaned, lubricated, replaced, and/or calibrated. The replacement part numbers, cleaning solutions and lubricants, and calibration standards, along with the manufacturer s maintenance procedures to be followed, should be specified. Documentation is easily managed by creating a one-page checklist of instructions or performance parameters that can be checked off as each task is completed. Any issues or comments can be captured directly on the checklist. Provisions for failure or out-of-tolerance notification need to be clearly defined, as the equipment cannot be put back into service until the performance has been verified by conducting a performance qualification. 

An organized document filing system must be maintained. This could be a paper file, an electronic document file, or a mixture of both. The equipment inventory system contains key information on the components of each system, their performance criteria and maintenance and calibration status. All documents including installation and performance documentation, as with other documents necessary to demonstrate the quality of the data, include SOPs for the qualification procedures, calibration, maintenance, personnel training, etc. If the manufacturer s operating, service, or maintenance manuals are used or cited in the operating procedures, copies of these manuals should be maintained. To facilitate retrieval, documentation should be stored in a central location and be indexed for easy retrieval. 

The following documents of the manufacturer can be used as part of this qualification Description and instruction manual, installation drawings and - instructions, test and take over-certificates, and soft ware documentation. It is recommended to list and specify all necessary documents and their format in the purchase order, as this reduces time and effort for the buyer as well for the seller. 

The degree of lot-to-lot reproducibility you require from a column is ultimately a function of the needs of a particular assay, which makes it impossible to state definite limits that will be appropriate in every case. Whatever the level of variation, it is important that it be documented. As new lots of media are brought into use over the course of years, their performance vs. the established reference should be included in a master database begun with the original qualification testing. Among other factors, this will allow you to track the column manufacturer s performance over time and possibly detect trends that could affect your assay performance — before a problem occurs. 

Installation Qualification (IQ) This provides documented verification that the equipment or systems, as installed or modified, comply with the approved design and that all the manufacturer s recommendations have been duly considered. 

Automated qualification software is yet another area of CDS development that has been affected by regulatory compliance. When you look at today s CDS solutions, it is typical to see the system providing direct digital control of the instrumentation. Many CDS manufacturers offer software tools that are capable of automating the installation qualification (IQ) and operational qualification (OQ) process. In addition, some manufacturers also offer software that can automate the performance qualification (PQ) for the various forms of instrumentation that it is capable of controlling. These automated software tools are not only time savers for the laboratory, but they also help to properly document the system qualification effort. 

This statement suggests that provided the manufacturer has performed and adequately documented the functions mentioned in the Analytical Instrument Qualification chapter no further qualification activities that are specific to the software is required by the user of the instrument. 

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 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... 

Installation Qualification After equipment selection, it is necessary to assure that the equipment is installed well. The IQ document describes and validates the procedure of the equipment installation. It establishes confidence that the process equipment and ancillary systems are capable of consistently operating within established limits and tolerances [10]. The equipment manufacturer and pharmaceutical company must agree and check the IQ, which must be approved by the pharmaceutical company at the end. This document certifies that equipment was installed as specified by the manufacturer and the purchaser. 

Operational Qualification The OQ document certifies that the equipment works as desired and defined by the manufacturer and the purchaser. An example is the acquisition of a new high-shear mixer/granulator where the paddle is put on rotation with a real calibrated rotation speed tester and, if the value obtained meets the specifications, the mixer paddle rotation passes the OQ test. If not, additional requalification must be performed. All the test results must be introduced and verified in the OQ report that is approved by the company at the end. The OQ document must describe several tests and related specifications to perform on the equipment in order to evaluate if it is working well, and the test to be performed must be described and approved by the manufacturer and the purchaser. Therefore, tests must be performed on the equipment, and for each one a description and signature of who performed and verified the test are required. Usually the tests are performed by the manufacturer and verified by the purchaser. These tests usually consist of evaluating if the mechanical and electric components of the equipment are working as desired. 

The categories listed above require qualification and validation documentation. It is advisable that process automation and companion computer-integrated manufacturing operations not be initiated until sufficient prospective and concurrent validation studies have been completed. 

Having chosen the analytical instrument or system, Installation Qualification, IQ, should be carried out to ensure that the equipment works the way the vendor or manufacturer specifies it should. IQ should be performed in accordance with a written test protocol with acceptance criteria with certification from the installation engineer, who is suitably qualified. Full written records of all testing carried out should be maintained as well as ensuring that adequate documentation and manuals have been supplied. The latter should include any Health Safety information from vendor or manufacturer. 

Once the manufacturing projection questions have been answered, a manufacturing philosophy must be decided on. This includes deciding on documentation requirements, special materials handling, controlled substance security, cleaning validation criteria, and equipment and facility qualification requirements. Now that we know what types of batches are to be manufactured, we can be more detailed in the description of the requirements of the facility. These requirements may be based on internal as well as regulatory requirements. In fact, if a full-scale facility is already in place, this step can be completed fairly easily and quickly. Many of the policies and systems may be transferred directly into the pilot facility. And others may be transferred with only slight modifications. 

Now I would like to turn to some of the issues of operations within the manufacturing process itself and speak to certain process controls that are expected. In a chemical synthesis sequence, as I mentioned above, intermediates will need to be fully characterized. That characterization will then lead to a set of specifications for the intermediate, that is, its level of purity, its form, etc. Test procedures that demonstrate that the intermediate meets specifications must be established. Some intermediates are deemed to be more important than others and are given specific designation, such as pivotal, key, and final intermediates. In those cases, it is necessary to demonstrate that the specific and appropriate structure is obtained from the chemical reaction and that the yield of the intermediate is documented and meets the expected yield to demonstrate process reproducibility and control. Purity of the substance is to be appropriately documented. And, finally, in reactions which produce pivotal, key, and final intermediates, side products or undesirable impurities are identified and their concentrations measured and reduced by appropriate purification procedures so that the intermediate meets in-process specifications. Thus, those important intermediates become focuses of the process to demonstrate that the process is "under control" and functioning in a reproducible and expected manner. All of these activities ultimately are designed to lead to the production of the actual active ingredient which is referred to then as a "bulk pharmaceutical agent." That final product will need to be completely characterized which then will document that it meets a set of specifications ("Final Product Specifications") for qualification as suitable for pharmaceutical use. 

Process demonstration formerly called process qualification, represents the actual studies or trials conducted to show that all systems, subsystems, or unit operations of a manufacturing process perform as intended that all critical process parameters operate within their assigned control limits and that such studies and trials, which form the basis of process capability design and testing, are verifiable and certifiable through appropriate documentation. 

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