Risk management is a reasonable method to achieve good decision-making, which runs through the whole quality system management, GMP put forward the concept of quality risk management, clear enterprises in the whole cycle of drug production risk assessment. Then, risk management tools are also required for cleaning verification at the source of production, and below the scientifically set allowable residue level, the removal of production product residues or cleaning agent residues from equipment based on risk management methods is an integral part of cleaning verification.

First of all, Amy shares the following flow chart of cleaning verification. Risk management runs through cleaning process design, cleaning process evaluation and continuous cleaning confirmation.

A summary of examples of QRM applications in cleaning validation is listed below:

The following risk assessments can also be used during the cleaning verification lifecycle:

Initial Cleaning Validation Assessment: This phase of validation assessment helps determine the scope and extent of validation activities from a risk perspective.

(1) Analytical methods: supplies (such as containers, cotton swabs), specificity (specificity), supplies (such as containers, cotton swabs), specificity (specificity), stability, range, sensitivity, activity degradation, confirmation of unknown peaks;

(2) Cleaner: ADE / PDE grade, cleaning effect, flushability, detectability;

(3) Cleaning cycle development: number of runs

(4) Cleaning procedures: TACT characteristics, repeatability (e. g., automated, semi-automated, manual), level of training, level of detail (e. g., manual cleaning);

(5) Clean execution: determine the number of runs;

(6) Holding time: dirty (e. g., influence on cleanliness), clean (e. g., cleaning method, storage time)

(7) Production equipment: equipment and process product contact sites, equipment complexity (e. g., components, circuits, shapes), cumulative problems, groupings (e. g., products, equipment);

(8) Production process: cleanliness after pollution, repeatability of process steps, pollution load/batch change

(9) Residues: ADE/PDE levels of process residues (e. g., APIs, excipients, degradants, process aids, lubricants), cleanliness, detectability;

(10) Safe cleaning limits: the calculation and rationality of cleaning limits, the basic principles of selecting cleaning limit methods, the calculation and certification of HEBEL safety limits;

(11) Sampling method: indirect sampling, direct sampling and visual inspection;

(12) Sampling recovery rate: recoverability (detergents, active ingredients and microorganisms), materials, recovery rate.

Risk Assessment for New Product Introduction: Introducing a new product into the plant requires a deep understanding of the new hazards that may be implied. The assessment should take into account the following factors:

(1) Historical knowledge of current processes

(2) Process and equipment similarity

(3) Cleaning methods used

(4) Use cleaner

(5) Excipients/formulations in equivalent or condition

If the new product to be introduced does not represent a new poor condition chemical or cleaning active substance, the existing cleaning process can be considered sufficient. Complete a comprehensive risk assessment to evaluate any changes to the existing control plan, including updating the reasonableness report on the HBEL, sampling and all other elements of the cleaning plan. Conversely, if the new product introduces new chemicals or active substances that exceed the capabilities of the current cleaning process, a comprehensive evaluation of the cleaning plan is required.

l Continuous Monitoring Maintenance Risk Assessment: Evaluate the level, type and frequency of testing during the continuous monitoring of the verified cleaning process through an initial risk assessment assessment. The scope of the risk assessment should be determined early in the process as part of the Validation Master Plan (VMP), with periodic verification of the cleaning process.