How to Train and Qualify Personnel on Manual Cleaning Processes

Human variability is a significant concern when manual cleaning processes are used to clean equipment. Each time personnel perform manual cleaning, parameters such as the scrub technique and the pressure used to scrub can vary. Even the most detailed written procedure can be interpreted differently by personnel, which may lead to drift from the validated cleaning process and the critical cleaning parameters. Robust training and qualification are paramount to mitigate the inherent variability in manual cleaning processes (operator to operator, operator day to day). In this memo, we will discuss the expectations for how personnel should be trained and qualified for manual cleaning processes. 

While training and qualification are often used interchangeably, they are distinct. Training refers to the learning of a concept, i.e., read and understand or classroom training of an SOP [3]. This is contrasted with qualification, which requires documented demonstration of a person’s ability to competently execute the described activity or procedural requirements [3]. For manual cleaning processes, qualification is completed by the personnel performing the validated manual cleaning process under the supervision of a qualified witness. After cleaning, the equipment is visually inspected and analyzed for previous process residues (swab and or rinse) to ensure the results fall within pre-determined acceptance criteria, confirming the cleaning has been effective.

Training for manual cleaning should cover, at a minimum, the cleaning procedure, cleaning boundaries, hard-to-clean locations, disassembly and reassembly of the equipment, cleaning tools, and the correct use of the cleaning agent (e.g., concentration, volume to use, how to apply, etc.) [2]. This information is vital for personnel to understand, as cleaning details can differ between products or equipment types. For example, a reactor is not disassembled the same way a rapid mixer granulator (RMG) is, nor do they have the same hard-to-clean locations.

The first step of training should be a “read and understand” of each procedure the individual will be responsible for performing, followed by a quiz on the material to ensure comprehension. It is typically expected that personnel score at least 80% on the quiz. All training should be documented in the personnel’s training record, including the date of training, the subject matter covered, and the score achieved on the quiz. Fully trained personnel should know and understand the cleaning process, including how to disassemble and reassemble the equipment, where the cleaning boundary starts and ends, where the hard-to-clean locations are, what the critical cleaning parameters are, which tools are required for cleaning, and how to prepare cleaning agents.

After completion of training, qualification on each cleaning procedure should be done under a pre-approved qualification process, where all qualification steps and activities are documented. The completed qualification documentation should be kept in the personnel’s training records [1]. During qualification, personnel should first observe an experienced, qualified trainer perform the cleaning process to familiarize the trainee with the technique, the specific challenges they may encounter, and allow the trainee to ask questions. The trainee will then perform the cleaning process in triplicate on soiled equipment under supervision, with the qualified trainer providing any necessary guidance and corrections.

If the trainee is expected to clean multiple types of equipment, the cleaning procedures may be grouped for the purposes of qualification. For example, if the trainee is undergoing qualification to clean silos, reactors, and binder solution tanks, the trainee can perform triplicate cleaning runs on one equipment type (e.g., reactors) and perform single confirmatory qualification cleaning on the other equipment types (i.e., one cleaning on a silo, and one cleaning on a binder solution tank). If cleaning procedures across equipment types are grouped, written justification should be provided.

The effectiveness of the trainee’s cleaning should be verified through visual inspection and analytical analysis (swab or rinse sampling). The results from these samples should fall within cleaning acceptance criteria. Should cleaning results fail to meet acceptance criteria, or the qualified trainer does not feel the trainee is competent due to repeated interventions during cleaning, the trainee must repeat the qualification. If a trainee fails the repeated qualification, they should be assigned duties other than manual cleaning.

Evaluation of training effectiveness plays a crucial role in preventing drift in the validated cleaning process and reducing variability between personnel [1]. Regular evaluations and on-going monitoring provide insight on the ability of personnel to perform the process as written, the effectiveness of the qualification, and the adequacy of the procedure to instruct personnel. Re-training and re-qualification should be performed on a risk-based frequency, supported by factors such as the number of deviations and periodic monitoring data. The best practice frequency for evaluation of training effectiveness for manual cleaning processes is on at least an annual basis and should not only be event-based.

Evaluations can be done through written exams, audits, on-the-job demonstrations, or a combination of all three.  Evaluations should focus on the personnel's understanding of the cleaning procedures and ability to execute them correctly.  Regular assessments help identify if there are gaps in knowledge or the procedure and allows for targeted retraining or revision of the cleaning procedure.

Manual cleaning is inherently variable: no personnel can perform a task the same way every time. To mitigate this risk, personnel must be fully trained on the cleaning procedures and qualified through a documented demonstration to consistently execute the cleaning process and meet established cleaning acceptance limits. Training, qualification, and re-evaluation provide some of the strongest risk mitigation of human variability and helps to minimize cleaning failures.

References:

1.     International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). (2016). ICH Q7: Good manufacturing practice guidance for active pharmaceutical ingredients.

2.     International Society for Pharmaceutical Engineering (ISPE). (2020). Guide: Cleaning validation lifecycle - Applications, methods, and controls. ISPE.

3.     Parenteral Drug Association (PDA). (2012). PDA technical report no. 29: Points to consider for cleaning validation. PDA.

4.     U.S. Food and Drug Administration (FDA). (2024). 21 CFR Part 211: Current good manufacturing practice for finished pharmaceuticals. U.S. Department of Health and Human Services.

Contributors: Jenna Carlson, Tim Cirbo, Alec Fufidio, Joanna Joseph, Helen Stranahan, and Harrison Sweeney