We have discussed How to Sampling in Cleaning Validation in the Pharma and Cleaning Standard Operating Procedure in Pharma now we move further to Cleaning Procedure Tools (Matrices) and we have also updated the Cleaning Procedure Flowchart for better understanding to our valued visitors. You can read previous articles Sampling in Cleaning Validation as well as other Pharma knowledgeable articles name Cleaning Standard Operating Procedure in Pharmaceuticals.
Now we move to our main topic.
Cleaning Procedure Tools (Matrices)
Tables, schemas, and matrices are the main tools used during the preparation of cleaning validation protocol and procedure, especially for multi-product areas and equipment. This will help cleaning procedure developers to determine the worst-case and to calculate by the most efficient method the limit of contamination.
Equipment Parts Schema
The Equipment Parts Drawing is helpful in illustrating the different critical parts of the equipment that are in direct contact with the product, the parts area, the location of hard-to-clean areas or “trap spots”, and the location of swabs. It contains the name of the equipment, the identification number (tag number), the location of the equipment, the name of each item, the area of the item, the swab factor, and the products to be manufactured on the machine.
Products Type Matrix
A table should be established that groups the different active products according to their biological activity, physical characteristics and toxicity. This type of grouping provides an overview of the manufacturing area of the products and the equipment to be used. Products that have the same characteristics may require dedicated equipment or installation. A matrix of product types helps you choose the appropriate cleaning procedures for each product group.
Based on this information, similar products should be gathered into one group
Equipment Parts Schema
Multi-Product Equipment Contamination Acceptance Criteria Matrix
Where equipment is used for multi-products manufacturing, it is useful to establish a matrix listing the contamination acceptance limits of products compared to the worst-case. This matrix gives a quick overview of the maximum contaminant carryover per product (contaminant followed by contaminated). A, B, C, D, and E are the different products manufactured using the same equipment. The contaminant limit for each product expressed in µg / cm2 is determined during the active product carryover acceptance criteria determination exercise. Values are reported properly in the matrix. For example, after manufacturing product D (contaminant), the equipment is cleaned according to the cleaning procedure then sampled (by swabs).
Samples after analysis give the result of 18 µg / cm2 as the total residue of active product D (contaminant) in all product contact parts of the equipment. If the next product to be manufactured is B, the allowable limit of contamination figured in the matrix for this case (D followed by B) is 25 µg / cm2. Consequently, the equipment will be declared “clean” and labeled accordingly. Cleaning validation matrices should be reviewed and revalidated following any change of cleaning elements e.g., modification of cleaning procedure, use of new equipment, and equipment modification could result in a surface change of product contact parts, changes in regulatory requirements, the introduction of a new product, etc.
Now better understanding we analyze next figure
Contamination Acceptance Criteria Matrix
Cleaning Procedure Flowchart
This flowchart summarizes the main steps of a cleaning procedure validation.
You can see it starts from cleaning products identification and further all steps are mentioned clearly.
It is virtually impossible to prove that production equipment is 100% “clean”. However, it is possible to demonstrate that the remaining active product traces, scattered around the equipment parts, are within an acceptable limit and that we are able to detect and quantify these trace levels. Cleanliness validation provides a means of demonstrating that contamination levels have been reduced below contamination acceptance limits.
The cleaning validation program should include a rational monitoring program to maintain a validated state. The cleaning validation activity should cover active residue identification, selection of active residue detection method, selection of sampling method, the establishment of residue acceptance criteria, method validation, recovery studies, and the identification of the parts of the equipment in direct contact with the product.
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