Equipment cleaning validation

Neal, C. Equipment cleaning validations for transdermals. J Val Tech (Nov. 1997). 

Equipment List of equipment used, validation of the equipment, validated methods for cleaning, and procedures for contamination control... 

The cleaning validation is required to demonstrate that, after cleaning, the equipment and surfaces are essentially free from product residues and traces of cleaning agents to prevent cross-contamination. 

Equipment cleaning Visual inspection Machine operator Cleaning validation officer Equipment usage/ cleaning log book Production supervisor... 

Attachment No. 2200.10(C) EQUIPMENT CLEANING PROCEDURE VALIDATION REPORT... 

Attachment No. 2200.20(C) Equipment Cleaning Procedure Validation Report... 

Five discrete cleaning validation protocols related to aseptic manufacturing equipments, solution preparation tanks, mobile tanks, filtration assemblies, freeze dryers, and vial filling machine parts are provided in Section Val. 2200. 

In order to avoid cross-contamination, another concern with respect to equipment is the cleaning process, which must comprise cleaning SOPs to ensure adequate cleanliness. Cleaning validation must be performed based on risk assessment and worst-case scenarios. 

Usually the most difficult aspect of cleaning validation is in determining how to evaluate the efficacy of the cleaning method. Equipment should be sufficiently clean so that the incidental carryover in the first batch after cleaning presents an acceptable risk to excipient quality and performance. Once this determination has been made, it is possible to calculate the maximum amount of residue carried over into the excipient batch. Then a calculation can be made as to how much residue can be left on the equipment surface, assuming the residue is uniform throughout the equipment. 

Once the cleaning validation has been completed, equipment can be cleaned in a routine manner. This involves records to show that the cleaning followed the proscribed instructions. Also there should be an evaluation of the efficacy of cleaning which can involve documentation of a visual inspection. 

Once the manufacturing projection questions have been answered, a manufacturing philosophy must be decided on. This includes deciding on documentation requirements, special materials handling, controlled substance security, cleaning validation criteria, and equipment and facility qualification requirements. Now that we know what types of batches are to be manufactured, we can be more detailed in the description of the requirements of the facility. These requirements may be based on internal as well as regulatory requirements. In fact, if a full-scale facility is already in place, this step can be completed fairly easily and quickly. Many of the policies and systems may be transferred directly into the pilot facility. And others may be transferred with only slight modifications. 

Let us now examine the role of trials in a CGMP environment. Cleaning validation will be the model used to illustrate the need for trials. In accordance with subpart D of 21 CFR, Section 211.67, equipment used in manufacturing trans-... 

Cleaning validation protocols should describe the equipment to be cleaned, procedures, materials, acceptance criteria, parameters to be monitored and controlled, and the analytical methods to be employed for testing. Validation of cleaning procedures should reflect equipment to be used for key and final intermediates and APIs. The selection of cleaning procedures to be employed should be based on material solubility and cleaning difficulty. The calculation of residue limits should consider the potency, toxicity, and stability of critical materials. 

Another factor that helps define the cleaning strategy is recognizing the type of cleaning situation we are faced with relative to what is going to be manufactured next in the equipment. I like to tell people that you ve got to learn to look downstream in cleaning validation in order to determine what you might contaminate and thus determine the element of risk. Some situations are simply more risky than others and we must be able to study and deal with risk. We must be able to accept a certain level of risk because it is always with us and unfortunately cannot be driven down to absolute zero. 

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