Cleaning Evaluation Documentation and Instruction-Records for Cleaning Activities
Introduction
This guidance addresses recommendations for developing and documenting the rationale to support the product contact equipment cleaning program and to justify the validation strategy. This documentation may be described as a Cleaning Evaluation Report.
The cleaning program requires that cleaning is conducted and the cleaning activities documented following written instruction-records, or SOPs with attached checklists.
All cleaning practices requiring validation should first be evaluated and the results of the evaluation documented and approved. Every aspect of the cleaning practice should be reviewed including all materials and methods involved.
Cleaning instruction-records or SOPs with attached checklists, should include all relevant cleaning parameters and confirmation that significant steps have been completed.
Recommendations and Rationale
Cleaning Evaluation Documentation
In order to appropriately document the development of the cleaning requirements for a material and/or equipment train, it is recommended that a cleaning evaluation report be prepared. This may be a single report or several reports; there is no requirement for a document to be titled, “Cleaning Evaluation Report’. This may be fulfilled by documenting the evaluation within a separate report, the site cleaning validation master plan, validation project plan or validation protocol as appropriate for the site.
The evaluation may be equipment-centric or process-centric and may include or reference relevant information.
Examples of what may be described in a cleaning evaluation report could include:
- If a grouping strategy will be used, document that the design of equipment, and/or the characteristics of the products are sufficiently similar to scientifically justify the grouping rationale.
- If the cleaning evaluation is to address more than one active ingredient or API step, then justification for the scope should be included as well as the rationale for the selection of worst case materials if the process is to be validated.
- Consideration of removal requirements for microbiological organisms and cleaning agents (if used), including any non-active containing drug product materials such as granulating or film-coating solutions. A documented and approved risk assessment should be performed to determine if microbial acceptability limits are required for cleaning validation of non-sterile product contact equipment and considerations.
Any documentation used to describe and justify the cleaning validation approach should be subject to site change control procedures and be reviewed and approved by the site Quality Authority and Production Authority.
Use of Quality Risk Management
Risk assessment tools may be useful in documenting the rationale supporting the cleaning program. For example, determining the residues that should be looked for:
Probability of the residue/cleaning agent being a contaminant Based on solubility in cleaning agents and amount present
Severity of impact Based on toxicity / minimum therapeutic dose
Cleaning Instruction-Records
Equipment Cleaning Instruction-Records should be written in a detailed stepwise format for manual cleaning methods and in a defined sequential operation for automated cleaning systems.
Completion of each significant cleaning cycle should be recorded either manually (initial, date, and time) or using a validated computerized system.
Such instruction-records should include or reference, at least, the following parameters, where applicable:
- Cleaning and sanitizing agents, including concentration, amount to be used and contact time;
- Quality of water or other solvents used;
- Requirements for equipment disassembly and re-assembly;
- Temperature and pressure parameters;
- Flow rates or times of known volumes for wash solutions and rinses;
- Identification of defined recycle and transfer piping pathways for cleaning;
- Start and end times of each critical cleaning cycle or step;
- Volume or weight of rinse;
- Number of rinses;
- Frequency of cleaning (e.g., Campaign length or after each batch);;
- Tools and/or utensils employed;
- Agitation, recirculation, and/or reflux;
- Draining and drying;
- Identification and inspection of dead-legs;
- Method for indicating equipment cleaning status;
- Method for protecting clean equipment from contamination;
- Maximum time intervals for between use and cleaning; and
- Verification of critical cleaning steps and supporting data (e.g., UV, pH, visual inspection).
Cleaning Solutions that are prepared and stored should be prepared following written instructions-records and labeled to indicate, at least, the following information:
- Signature or initials of person preparing the solution;
- Concentration of solution at time of preparation;