CLEANING VALIDATION - ORIGIN

Cleaning validation is a program which demonstrates that the used cleaning procedures are adequate to eliminate/ control potential cross contamination.

The Resin story: 

The awareness on cross contamination was came in light in 1988 due to recall of a finished drug product Cholestyramine Resin USP due to inadequate cleaning procedures.

Reason for recall:

The bulk pharmaceutical chemical used to produce the product had become contaminated with low levels of intermediates and degradants from the production of agriculture pesticides.

The main reason for cross contamination is Solvent recovery storage drums were used twice without proper cleaning. Drums that had been used to store recovered solvents from a pesticide production process were later used to store recovered solvents used for the resin manufacturing process.

The firm did not have adequate controls over these solvent drums and did not have validated cleaning procedures for the drums.

This event which increased the FDA awareness over cleaning validation and potential cross contamination due to inadequate procedures.

FDA Expectation: 

1.FDA expects firms to have written procedures detailing the cleaning processes used for various piece of equipment.

If firm have one cleaning process for cleaning between different batches of same product and use a different process for cleaning between product changes, we expect the written procedures to address these different scenario. 

2.FDA expects firm to have written general procedures on how cleaning processes will be validated.

3.FDA expects the general validation procedures to address who is responsible for performing and approving the validation study , the acceptance criteria and when re-validation will be required.

4.FDA expects firm to prepare specific written validation protocols in advance for studies to be performed on each manufacturing system or piece of equipment which should address such issue as sampling procedures, and analytical methods to be used including the sensitivity of those methods.

5.FDA expects firm to conduct the validation studies in accordance with the protocols and to document the result of studies.

6.FDA expects a final validation report which is approved by management and which states whether or not the cleaning process is valid. The data should supports a conclusion that residues have been reduced to an acceptable level.

So as part of cleaning validation firm should focus on following.

Acceptance criteria

Levels of cleaning

Control of the cleaning process

Bracketing and worst case rating

Determination of Amount of residue