by Roseline Tio, Dhika Prameswari, and Qadly Ameen (SEA Process Validation, Pilot Scale, and CQV SME)

Cleaning validation is a critical component of any GMP compliance procedure in a regulated medication manufacturing plant. Cleaning validation in the pharmaceutical business has been one of the most dynamic and discussed topics as the industry shifts toward risk and science-based validation.

The definition of Cleaning Validation is the collection and evaluation of cleaning data, from the cleaning process design stage to routine repeatable cleaning during commercial production, to provide documented assurance that the cleaning procedures are effective in reliably, reproducibly, and consistently reducing the levels of all contaminants, including previous product residues, cleaning agent residues, and microbial contaminants, to levels below acceptable safety limits.

The lifecycle approach of Cleaning Validation considers the cleaning validation as a continuous process having the following three phases:

Phase 1: Process Design – Design and Development of the Process by Quality of Design

It entails designing, developing, and implementing a cleaning validation procedure to remove process residues. Create equipment-specific cleaning techniques for product-contact surfaces. This should also include methods for cleaning the associated manufacturing area, equipment cleaning area, and locations supporting the manufacturing and cleaning processes.

• Create methods for cleaning between batches of the same product, as well as for cleaning during product changes.
• Evaluate the effectiveness of environmental measures in preventing cross-contamination, such as the sufficiency of dust control systems.
• Select a cleaning agent(s) and create cleaning cycles.
• Develop the cleaning process and optimize the cleaning cycle to create scientific knowledge and data to define the cleaning process for routine manufacturing.
• Identification of hard-to-clean areas
• Establishing Acceptable limits (Equipment surface area data, dosage values, safety factors)
• Develop product-specific analytical procedures for residues or use non-specific analytical methods where necessary.
• Cleaning process parameters
• Lab testing methods
• Conduct swab recovery investigations on all materials of construction (MOC) used in product-contact equipment parts.
• Toxicity of residues and the development of analytical methods with adequate sensitivity levels.
• Create a worst-case matrix of items that can be aggregated for cleaning validation.

Phase 2: Process Qualification – Validation of Cleaning Process

As per the guidelines, “Guidance for Industry – Process Validation: General principles and practices, 2011 by FDA” Stage 2, the process qualification stage has two elements:

• Design of a facility and qualification of the equipment and utilities: Equipment that is considered for cleaning validation and CIP systems that are used during cleaning of the equipment and the laboratory instruments shall be ensured for completion of the qualification activity (Installation Qualification, Operation Qualification & Performance Qualification).
• Process Performance Qualification: Process performance qualification involves developing the cleaning validation protocol including acceptance criteria for the residue limits based on the scientifically justified. The cleaning validation is performed under cGMP conditions with the purpose of demonstrating controls over the cleaning process conducted during the routine cleaning operations. Cleaning validation is performing under routing commercial manufacturing conditions by the trained operators for the commercial purpose.

Completion of a validation study should have a minimum of three runs of one product to another change over cleaning, after completion of a single run an interim report shall be approved by stating, that the cleaning procedure is as per the approved procedure, the swab and rinse results are meeting the acceptance criteria, conclusion of the single run. A complete validation report shall be prepared after the completion of successful three runs and the validation report is necessary to present the results and conclusion and approval of the cleaning validation study.

Phase 3: Continued Process Verification – Improvement of Process by Trending the Outputs

Providing continuous assurance that the Cleaning Validation stays under a condition of control for the duration of commercial activities during the product life is the aim of Phase 3. During regular manufacturing operations, the important cleaning process parameters are monitored at this point. It entails evaluating the overall effect on a regular basis of the individual modifications that are implemented based on assessments of those individual changes. During this phase, the CAPAs that have been implemented are also periodically evaluated. A potent instrument for successfully implementing Continued Process Verification is the application of Statistical Process Control (SPC) techniques, such as Control Charts for tracking the essential control parameters.

As part of Stage 3 activities, instances that call for cleaning unclean equipment again, modifications to the verified procedure, and other non-conformances are examined and assessed. Unless the product is discontinued, stage 3 never comes to an end.

Adopting a lifecycle approach in cleaning validation promotes the integration of new technologies and fosters continuous improvement through an ever-deepening understanding of processes, with no finish line in the quest for excellence. PharmEng Technology is the ideal partner for cleaning validation due to our team’s unparalleled expertise in pharmaceutical compliance, comprehensive support from initial assessment to ongoing maintenance, and steadfast commitment to quality, integrity, and professionalism. With PharmEng Technology, clients can trust their process validation needs are in capable hands, ensuring fully validated, compliant, and optimized systems for long-term success.

For more information, please explore our website at www.pharmeng.com or reach out to us today via email at info.asia@pharmeng.com. Discover how PharmEng Technology can enhance your pharmaceutical initiatives with comprehensive process validation solutions.

Reference:
1. US FDA Guidance for Industry – Process Validation: General Principles and Practices-January 2011.

About PharmEng Technology

PharmEng Technology is a global consulting firm specializing in pharmaceutical engineering, regulatory affairs, and compliance. With a commitment to quality and innovation, PharmEng Technology provides comprehensive solutions to meet the evolving needs of the pharmaceutical and biotechnology industries.

Contact Information

PharmEng Technology
Email: info.asia@pharmeng.com