The Intricacies of Cleaning Validation

GMP Trends has seen multiple observations related to cleaning validation cited by the U.S. FDA in the last six months. Issues 1085, 1084, 1081,1077, and 1075 all featured FDA observations related to cleaning validation. We asked guest contributor and GMP Trends Subscriber Karim Panjwani for his insights. 

cleaning validation

Karim Panjwani brings 16 yrs of experience in the pharmaceutical industry in the area of Quality Assurance. He is a seasoned professional with expertise in Quality Management System, Risk Assessment, Investigations, and Validations.

Companies are cited for the following commonly seen errors that were not considered during the cleaning validation studies. These are examples and not exhaustive lists that should be considered while establishing the cleaning procedures.

  • Identification of hard to clean products/ products which are likely to leave stains
  • Identification of hard to clean and hard to reach areas
  • The volume of water, rinsing time, the pressure of spray jet, temperature
  • The concentration of cleaning agent
  • Scrubbing time and instruction for intermittent verification
  • Consideration of person to person variability in manual cleaning operations

The cleaning process documents need to be controlled and securely maintained- similar to a batch manufacturing process for a pharmaceutical product. We have seen firms cited for not controlling documentation forms related to cleaning. 

Issue 1075 of the GMP Trends bi-monthly report brings forth an important 483 observation: 

Written procedures for the cleaning and maintenance fail to include assignment of responsibility, maintenance and cleaning schedules, description in sufficient detail of methods, equipment and materials used, description in sufficient detail of the methods of disassembly and reassembling equipment as necessary to assure proper cleaning and maintenance.

Cleaning instructions play a vital role in a successful cleaning validation program. Adequate and step by step written instruction makes things easy for the person responsible for cleaning operations. In addition, such instructions reduce the potential for person-to-person variability during cleaning operations, are easy to follow without missing any critical steps, and allow contemporaneous documentation. 

We must link the equipment cleaning procedure with the area cleaning process for stepwise instructions and chronology of steps to ensure that clean equipment are not again getting contaminated while cleaning the area. The stepwise instructions and cleaning workbook should include but are not limited to the following points:

  • Step by Step instructions to remove the previous product materials and tailing from area and its recording
  • Steps of disassembling the equipment and its recording
  • Equipment cleaning steps with details such as rinsing with water, amount of water, time of water spraying, spray pressure, temperature of water, concentration and amount of cleaning agent required to be used, scrubbing time, final rinsing volume and time, assembling steps, equipment drying, visual verification of equipment after drying before declaring equipment as cleaned, and recording provisions of each step with time and parameters.
  • Provisions to add comments in case technician observes anything abnormal or important. Such documentation can be used to further improve the procedure as part of a continuous improvement process. 

While developing the equipment cleaning procedures, it is imperative to consider microbial aspects where equipment is used for sterile processing or non-sterile processing where the products may support microbial growth.

For additional information pertaining to cleaning validations and equipment cleaning, refer to FDA’s GUIDE TO INSPECTIONS VALIDATION OF CLEANING PROCESSES, FDA Presentation: Facilities and Equipment: cGMP Requirements and FDA Guidance Questions and Answers on Current Good Manufacturing Practices – Equipment.

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