After reading our previous article about Sampling in Cleaning Validation in the Pharmaceutical now we move to another step of cleaning validation named Cleaning Standard Operating Procedure in Pharma. In this article, we try to cover all the essentials about the Objective, responsibilities, and other information.
The standard cleaning operation procedure should include the following essential points:
The objective of Cleaning Standard Operating Procedure
The purpose of the study is to validate the analytical method for the determination of traces of API content in Swab & Rinse samples and to establish documented evidence and provide the procedure for the same.
Describe the range of applications for the SOP, equipment, and products. The scope should assess the acceptability of an analytical method for the determination of traces of API content in swab and rinse samples by HPLC. This protocol should define the procedure, documentation, references, acceptance criteria, and evaluated results for the determination of traces of API content in Swab & Rinse samples by HPLC.
Identification of who is responsible for carrying out cleaning operations.
Description of the cleaning method to be used, including the cleaning agent; concentration of detergents, surfactants, and disinfecting agents used during the cleaning procedure; the temperature of the wash and rinse water or another solvent (s); flow rate and/or pressure at which wash and rinse solvents are delivered; volume or quantity of water or other solvents used to wash and rinse equipment; diagrams describing the location of difficult to clean areas and “trap points”: inspection and/or testing regimen to assess cleanliness and dryness; and labeling the status of equipment and facilities to ensure cleanliness for all staff.
Additional concerns to be considered in the cleaning SOP include the following: When the preparation of a cleaning solution is done locally, it must be against a procedure that includes manufacturer’s instructions, lot numbering, and expiration date. Operator training records must be displayed for each cleaning procedure. When implementing an automated and validated cleaning procedure, which produces a validated impression of the critical stages of the processing, a triple check of the critical stages should be performed.
The validation review or revalidation status should be reassessed based on any changes in the operating situation, equipment replacement, cleaning procedure changes, regulatory requirements, or adverse market feedback related to the validation of Cleaning. Revalidation must be done at least once a year. The use of non-specific test methods may be allowed for revalidation exercises as long as the limits set can be related to a specific result in the initial validation or can be justified by some other means. Methods such as conductivity of drain water and TOC analysis can be used.
The analytical method used to determine the residual amount of active should be validated. A proper performance qualification protocol and report should be appropriately established and approved prior to starting the cleaning procedure. This demonstrates that the laboratory equipment and techniques are capable of evaluating with precision, according to written and validated analytical methods, the small amount of residual contaminant (s) (active or others).
A simulation exercise using the active product and the same material sur face of production equipment would be suitable for the validation of the analytical method. Serial dilutions of active standard preparations could be used along with a placebo preparation containing the additives and excipients. These preparations would be suitable for simulating contamination during this exercise. Prior to the collection of samples from the cleaned equipment, it is important to prove the effectiveness of the swabbing method and the swab materials to be used.
Cleaning Analytical Method Validation
The following sections should be included:
Acceptance Criteria Describe the method followed to determine the acceptance criteria. The major and critical acceptance criteria to be mentioned are as follows: active product recovery percentage and active residual (contaminant) µg per cm2 , or µg of active residual (contaminant) per maximum daily dose units of next product.
Description of analytical methods used: standard preparation, sample preparation, analytical equipment used, analytical parameters, equipment parameter, sample volume, materials used, and the determination of the following values (which are specific to the analytical method and are relative for each active product):
- Limit of Detection
- Limit of Quantitation (LoQ)
- Linearity (where appropriate, linearity of detector response for standard solution over a range of concentrations)
- Recovery percentage
- Absence of interference between swab materials and active product
- Absence of interference between solvent and active product
Residual Limit of active (contaminant) A in mg / cm2 of cleaned equipment or the concentration of active (contaminant) A carried over to unit dose of product B (contaminated) is calculated.