Validation of an Automated Parts Washer

Validation of an Automated Parts Washer

Author: Antonio Ortiz, STERIS Life Sciences

This content has been reviewed and endorsed by the ISPE Sterile Products Processing Committee.

Introduction

Automated parts washers are used in pharmaceutical manufacturing facilities for cleaning various materials and equipment parts used in the manufacturing process. Cleaning equipment parts in automated washers is preferred to manual cleaning processes as automation reduces variability, resulting in an easier cleaning process validation. Automatic washing cycles ensure that critical process parameters, such as the temperature, mechanical cleaning action, cleaning agent concentration, and cycle times are consistent from cycle to cycle.

The goal of this concept paper is to provide recommendations for a standardized and science-based approach for equipment qualification of the automated parts washer and process qualification for the automatic cleaning process performed by the washer. For the qualification of an automatic washer cleaning process, there are two elements to consider for the process qualification: equipment qualification (IQ/OQ) and cleaning process qualification (PQ). However, a validation lifecycle approach is recommended to develop a thorough understanding of the equipment and process by investing more time on the process design phase, prior to the process qualification phase. Continued monitoring of the process after qualification promotes continuous improvement and optimization of the cleaning cycle1, 2.

Lifecycle Approach to Cleaning Validation for an Automated Washer

The lifecycle approach to validation is recommended as mentioned in the 2011 US Food and Drug Administration (US FDA) guidance document, “Process Validation: General Principles and Practices”, where it states that “the lifecycle concept links product and process development, qualification of the commercial manufacturing process, and maintenance of the process in a state of control during routine commercial production”2. In summary, using the lifecycle approach, the validation is divided into three stages:

The lifecycle approach to validation promotes more focus on the process design stage (Stage 1) and ensures quality is built into the process – in contrast with traditional approaches that rely on testing to ensure process is effective. Decisions for equipment selection and process design should be based on the principles of Quality by Design that require all decisions be made utilizing a risk-based approach3. Risk analysis tools are deployed to understand how critical process parameters (CPP) affect the critical quality attributes (CQA) of the cleaning process. The goal of the lifecycle approach is to invest the most time in Stage 1 to develop a thorough understanding of the equipment design and the cleaning process. The time invested during Stage 1 provides confidence when going into the process qualification stage (Stage 2 of the lifecycle), ensuring a successful validation. 

During Stage 1, the automated parts washer is specified (URS/FS/DS) and qualified (FAT/SAT/IQ/OQ) and the cleaning cycle is developed in preparation for performance qualification (PQ). A team approach encompassing production, engineering, quality, quality control (QC) lab, research and development, and the washer and cleaning agent(s)’ manufacturers is suggested when designing or selecting an automated parts washer. The team approach helps to understand how process parameters specified affect the different quality attributes that the process is intended to control. The integrated team enables a thorough understanding of the manufacturing process and equipment parts (materials of construction and cleanability aspects) as well as the soil to be cleaned (chemical properties and condition of the soil on surfaces), which is essential for the correct design or selection of a washer.

Under the guidance of the washer manufacturer and prior to delivery, the factory assessment test (FAT) allows end users to verify that the parts washer functions as intended4. The FAT provides an opportunity for any malfunctions or out of specifications for equipment design to be detected at the manufacturer’s site, where quicker repairs or modifications can be performed. A well-planned FAT can include the execution of coverage testing as well as the execution of an actual cleaning cycle, with soiled parts, to test the performance of the washer. An optimized FAT can reduce the amount of work required for equipment qualification once the washer is installed at the user’s site.

When developing the cleaning cycle, it is recommended to conduct multiple trials, varying process parameters, to understand and optimize the process. Before receipt of the washer, trials can be easily performed in the lab using material-representative coupons of the surfaces to be cleaned. For example, the coupons can be soiled with a master soil and a set of cleaning experiments can be designed and executed by varying detergent concentration, temperature, contact times and mechanical action needed. A master soil is a surrogate residue and can be either a representative process residue or worst-case process residue, depending on the selection criteria. The worst-case soil can vary based on the equipment train or cleaning method used. A worst-case residue is generally selected based on a risk-based approach5. This scientifically based process design method will provide justification for the preliminary selection of CPPs, while reducing the amount of time and resources needed to develop the cleaning cycle once the washer is installed.

The main deliverable for Stage 1 is the automated washer cleaning SOP. Prior to equipment and process qualification during Stage 2, the process parameters to study and optimize include the following:

• Design and placement of spray devices ensuring complete coverage of all parts within the washer.
• Loading configuration of the parts within the washer ensuring spray coverage efficiency
• Dirty hold times – the maximum amount of time parts may be dirty prior to cleaning
• Temperature of rinse water and cleaning solutions
• Concentration of cleaning agents
• Time for rinse and wash cycles
• Clean hold times and storage/handling requirements for clean parts

Once all these critical aspects of the process design phase are established, the cleaning SOP can be created, where all CPPs of the cleaning process are clearly documented and standardized.

Stage 2, or the process qualification stage, essentially confirms that the cleaning SOP developed is effective, robust, and reproducible for cleaning the loaded equipment parts in the automated washer. During Stage 2, the cleaning validation protocol is developed and approved. The protocol shall cover the validation strategy, including washer load configuration, cleaning cycle steps, CPPs, sampling methods and rationale, reference to validated analytical methods, and acceptance criteria for cleanliness (i.e., limits for residual drug, conductivity, TOC, visual, etc.). Once the PQ has been executed, a final report is written, which summarizes the results of all testing performed and clearly indicates that the process has been validated. The protocol may also include critical attributes of the process that may require continued monitoring during routine operation that would give assurance of the validated state of the process.

Stage 3, or the continued process verification stage, consists of preventive maintenance activities, periodic reviews of generated data, and continued monitoring of the cleaning process that helps maintain a state of control when conducting cleaning cycles at the commercial scale. Proper maintenance of the equipment is fundamental to the consistent performance of the system. Preventative maintenance procedures, based on the washer manufacturer’s recommendation and the user’s experience with the equipment, should include periodic inspections of critical equipment components to facilitate immediate repairs or replacement. A periodic review of cleaning process-related documentation should be included in Stage 3 activities. The review should include analysis of process parameter data as well as analysis of any quality test results (i.e., conductivity, TOC, swabs) produced throughout the review period. Additionally, a review of any change controls, investigations, corrective and preventive Actions (CAPAs), or other quality system activities6 should be performed to confirm whether any changes to the system have been made to the process that warrant revalidation. Using risk analysis tools, the continued process verification stage should indicate opportunities for cleaning cycle optimization, process improvement, and/or revalidation requirements.

As stated above, it is recommended to invest as much time as possible during cleaning process development to gain a comprehensive understanding of the automated washer equipment characteristics as well as the developed cleaning cycle. The obtained knowledge is particularly valuable when conducting root cause analysis in cases when either the equipment or the cleaning process fails. A well-executed and documented development phase will provide the information necessary to deal with unanticipated failure modes. Lab studies may be performed as part of root cause analysis to simulate or attempt to recreate out-of-specification (OOS) conditions. Root cause analysis should prompt a review of prior risk assessments performed to indicate whether new process controls are needed and to identify opportunities for process optimization and improvement.

Table 1 provides important points to consider for qualification of an automated parts washer and summarizes some common failures that may occur during qualification.

Conclusion

The qualification of a cleaning cycle using an automated parts washer consists of equipment design and qualification as well as cleaning process design and qualification activities. Recent validation regulations and guidelines recommend completing validation activities utilizing the lifecycle approach. The lifecycle approach to validation encourages more focus be placed on the development of robust processes and continued monitoring of such validated processes. This ensures a process remains under control through its entire lifecycle. By investing more time during development, a thorough understanding of the washer equipment components and cleaning cycle is obtained. Risk assessment tools are employed to prioritize process design activities to develop the proper critical controls needed to ensure critical quality attributes for cleaning are met. After process qualification, continued verification of process parameters and quality attributes ensure early detection of process drifting that may warrant re-design and/or revalidation of the cleaning process. A thorough understanding of the process and how the equipment functions is fundamental during root cause analysis when any out of specification results are obtained. Since not all failure modes can be anticipated during process development, proper root cause analysis, driven by systematic risk assessment, will advance continuous process improvement.

Acronyms

• CAPA – Corrective and Preventive Actions
• CPP – Critical Process Parameter
• CQA – Critical Quality Attribute
• DS – Design Specification
• FAT – Factory Acceptance Test
• FS – Functional Specification
• IQ – Installation Qualification
• OQ – Operational Qualification
• P&ID – Process and Instrument Diagram
• PLC – Programmable Logic Controller
• PQ – Performance Qualification
• SAT – Site Acceptance Test
• SOP – Standard Operating Procedure
• TOC – Total Organic Carbon
• URS – User Requirement Specification

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