The 21 CFR guideline for cleaning validation is primarily found in the broader context of contamination control and manufacturing materials within the regulations governing medical device manufacturing. Specifically, while there isn't one single section explicitly titled "cleaning validation," the requirements are derived from sections that emphasize preventing contamination.
Here’s a breakdown of the relevant guidelines:
21 CFR 820.70 (e) Contamination Control:
This section mandates that each manufacturer must:
- Establish and maintain procedures to prevent equipment and product contamination.
- Ensure that substances do not adversely affect product quality.
This foundational requirement necessitates cleaning validation. The goal is to demonstrate, with documented evidence, that your cleaning procedures effectively remove residues of cleaning agents and previous product batches, preventing them from impacting the quality of subsequent batches.
21 CFR 820.70 (h) Manufacturing Material:
This section requires manufacturers to prevent contamination of product and equipment by ensuring that procedures are in place to handle materials properly. The section underscores that manufacturers must have processes to address contamination from any source, including manufacturing materials and equipment.
This section further solidifies the need for cleaning validation, as it covers more than just the finished products. It explicitly mentions the prevention of contamination within manufacturing equipment, which inherently involves cleaning.
Practical Implications for Cleaning Validation:
To adhere to these guidelines, manufacturers should:
- Develop Cleaning Procedures: Design comprehensive, written cleaning procedures for all equipment that comes into contact with products or product materials. These procedures must be detailed enough to allow for consistent cleaning by different operators and must be validated through testing.
- Establish Acceptance Criteria: Determine acceptable levels of residues for cleaning agents and previous products. These acceptance criteria should be scientifically justifiable and based on safety and quality considerations.
- Examples: Parts per million (ppm) for cleaning agent residues, or a specific limit for the next product analyte.
- Conduct Cleaning Validation Studies: Perform tests to verify that the cleaning procedures consistently achieve the established acceptance criteria. The validation must be a documented process.
- Maintain Validation Records: Keep detailed records of the cleaning validation studies, including the procedures used, the results obtained, and the acceptance criteria. Records should be kept and accessible for audit purposes.
- Periodic Review and Revalidation: Conduct periodic reviews of the cleaning procedures and revalidate as necessary, especially when there are changes to the equipment, product formulations, or cleaning agents used.
Summary
While there is no specific section dedicated to "cleaning validation" in 21 CFR Part 820, sections 820.70(e) and (h) clearly establish the need for documented and validated cleaning processes to prevent contamination of equipment and product that could affect product quality. Cleaning validation is essential for manufacturers of medical devices to demonstrate that their processes meet the regulation requirements and that the product is safe for use.
