Our Approach to Cleaning Consulting

 

Clean6Sigma, LLC has adapted ICH Q9's Risk Assessment elements for developing thorough, comprehensive Cleaning Validation Master Plans and Protocols based on Risk Assessments.

 

Hazard Identification

 

Clean6Sigma, LLC doesn't just "round up the usual suspects" (API, Cleaning Agent and Micro / Endotoxin) - instead Clean6Sigma, LLC ensures that all potential hazards are identified and mitigated to provide the highest degree of patient safety by starting with a Hazard Identification to look for ALL potential hazards presented; chemical and microbiological hazards, the hazards presented by equipment and its design, and any potential hazards from failures in cleaning SOPs.

 

Science-based Limits for Hazards

 

Clean6Sigma, LLC has been a strong advocate for changing the current approach to setting Cleaning Validation Limits. The 20+ year old approaches of setting Cleaning Validation limits have been shown to be wildly inaccurate from a patient safety standpoint and have caused operational issues for years. An ADE / PDE (Acceptable / Permitted Daily Exposure) that is derived by a Qualified Toxicologist should be used to calculate Maximum Safe Carryover values (MSCs). We have retained highly qualified Toxicologists who can quickly deliver ADEs for your projects.

 

Risk-based Method Selection and Development

 

Clean6Sigma, LLC believes that the choice of methods should be science and risk based. The goal should be to use the simplest technique that is appropriate and can be justified. Based on the Risk Assessment. We are experts in developing and validating Total Organic Carbon (TOC) analysis and in qualifying Visual Inspection as an analytical method, both of which are suitable and easily justified for low to medium risk situations.

 

Cleaning Process Development

 

Cleaning processes should not be adopted randomly or chosen based on past use. Cleaning processes should be developed to reduce the risk of cross contamination and to provide appropriate cleaning agents for the corresponding conditions. Cleaning processes that have been optimized through the selection of the most appropriate cleaning agents and cleaning parameters can offer the greatest ability to reduce process residues to the lowest risk levels in the shortest time.

 

 

Design of Experiments (DoE)

 

DoE is a cost effective approach to determine the effects and interactions of cleaning process parameters and determine the optimal settings. From the DoE, a "Cleaning Design Space" can be defined providing an area of flexibility in cleaning. Once a "Cleaning Design Space" has been established, new products can be evaluated against the cleaning design space to determine whether any additional cleaning studies are necessary. DoEs can also be used to justify product or equipment grouping strategies.

 

Master Planning and Risk Assessment

 

Risk-based Masterplanning flows naturally from the Hazard Identification and Risk Analysis steps to Protocol Development. In this way the appropriate level of effort, formality and documentation is applied to each situation commensurate with the level of risk. After all hazards have been identified a Risk Analysis is performed to determine the level of Risk presented so that a Master Plan can be developed that covers all Risks with an appropriate level of effort and documentation. 

 

Risk Evaluation

 

Safe Levels derived from ADEs/PDEs should not be used specifically as Cleaning Limits: they should only be used for the assessment of Risk. Cleaning data collected can be used to determine the Process Capability (Cpk, Ppk) of the Cleaning Process using the MSCs as the specification. The Cpks/Ppks derived are a direct measurement of the degree of exposure and consequently can be used to evaluate Risk. Finally, in line with the FDA's 2011 Guidance of Process Validation, we believe limits should be based on process derived data. Data on Cleaning Processes should be collected and limits should be statistically derived from the data using Statistical Process Control techniques.

 

Risk Control - Statistical Process Control

 

Risk-based continued monitoring of cleaning process parameters and sampling of critical cleaning quality attributes is based on the data collected during cleaning process development and qualification runs. Data that has been collected in the risk evaluation or risk control stages can then have SPC limits calculated from these data. These SPC limits are then used for monitoring cleaning processes and in place of the MSSR limits used for the risk analysis in risk evaluation