Clean qualification

Rules for the welded fabrication of pressure vessels cover welding processes, manufacturer s record keeping on welding procedures, welder qualification, cleaning, fit-up alignment tolerances, and repair of weld defects. Procedures for postweld heat treatment are detailed. Checking the procedures and welders and radiographic and ultrasonic examination of welded joints are covered. 

The qualification just stated should also preferentially be performed on prepacked columns to ensure that the column fulfills the users own specifications. Furthermore, it is good practice to run the qualification periodically and after cleaning and stand still. 

Quality systems require that facilities and equipment should be appropriate to the activities undertaken. Surfaces that are easy to clean and maintain in hygienic condition are a requirement in many situations. For example, cloth-backed chairs would not be acceptable in a laboratory that handled potentially biohazardous materials. Equipment should be checked at installation to demonstrate that it can perform its desired function. This is frequently done using an Installation Qualification, Operational Qualification and Performance Qualification (IQ /OQ/PQ) commissioning process. Routine maintenance and calibration programmes are then required to ensure that equipment continues to deliver the specified performance. 

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. 

Berg, T., Humphreys, P., Phillips, B. and Scherz, B., Recommendations on Validation Master Plan, Installation and Operational Qualification, Non-Sterile Process Validation, Cleaning Validation , PIC Publication PH 1/96. 

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. 

Validation of automated systems must demonstrate a lack of contamination or interference that might result from automated transfer, cleaning, or solution preparations procedures. Equivalency between the results generated from the manual method and the data generated from the automated system should be demonstrated. Since sensitivity to automated dissolution testing may be formulation related, qualification and validation of automated dissolution equipment needs to be established on a product-by-product basis (8,13) (see also Chapter 12 for a more detailed description of automation issues). 

Instrument e.g., cooling system, capillary types and lengths possible, type of detectors, instrument sensitivity, software and integration functions, maintenance status of instrument and qualification status, definition of instrument cleaning procedures... 

Design qualification auditing the design of a facility (or element of a facility, such as a clean room) to ensure that it is compliant with the specifications laid down and that it is therefore capable of meeting GMP requirements. 

The lyophilizers are cleaned using a validated clean-in-place (CIP) cycle using hot WFI. After the cleaning process, a validated sterilization cycle is mn. The qualification of the steam sterilization cycle was performed during the operation qualification (OQ) of the lyophilizer. 

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... 

Scale-up ensuring that installation qualification, operational qualification, performance qualification (IQ/OQ/PQ) activities are properly conducted These include cleaning validation, process validation, sterilization validation, and so forth, according to established corporate procedures. 

Finally, during the qualification of the facility, all systems are tested, calibrated, and cleaned. The mechanical and service infrastructure must be qualified. The operational qualification will involve practice runs. All documentation must be finalized. This includes standard operating procedures, batch records, and equipment logs. 

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. 

As part of the planning part of the project, an evaluation of the cleaning requirements for both the equipment and the facility must be done. An overall plan must be outlined for the evaluation of the success of the team. This success may be measured by the results of the equipment and facility qualification. What criteria will we use to qualify our construction and installation The answer to this question will allow us to tailor our activities so that we can remain focused on the task at hand. 

D Equipment Installation and qualification of equipment and cleaning methods... 

Facility design is critical. Likewise, individual utilities require qualification. The most important of these are heating, ventilation, and air conditioning (HVAC), water (including clean steam), and compressed gases. 

The establishment stage includes verification, qualification, and individual validation, including process validation, computer validation, method validation, and cleaning validation. These establishment stage steps shall satisfy the principal requirements in Table 6. 

In practical terms, the verification, qualification, analytical validation, cleaning validation, and process validation need to satisfy certain requirements. 

The protocol must include the clarified purpose of each item, such as design verification and installation qualification. For example, the purpose of cleaning validation is to avoid any contamination. 

Installation qualification Operational qualification Cleaning validation Ranging studies PLC qualification Process validation... 

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

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