Basics of Cleaning Validation

Cleaning of pharmaceutical instruments after a product has been manufactured is critical to ensure that the subsequent products to be manufactured are not contaminated. The removal of the residues of the previous products from manufacturing equipment is known as cleaning. If the whole process of cleaning has been documented, it is referred to as cleaning method validation.

Cleaning validation is proof that the cleaning process is effective to removed all residues of the product that was manufactured, cleaning agents those were used during the cleaning process and prevents micro-organisms from developing. This process is done as a requirement of regulatory authorities.

Manufacturing companies should not do it for the sole reason of satisfying the regulatory authorities but they should put it in mind that it is required to ensure that the patients are safe.

What is required for a cleaning validation process?

Protocol

First, you must create a protocol. When preparing a protocol, some of the factors that should be considered are the quality of the water, the detergent to be used, the rinsing period and the system's size. The protocol should contain the objective of the whole process, the scope of the protocol, responsibilities of the departments, the procedure of cleaning, acceptance criteria and cleaning method validation report.

Personnel

The people conducting the process should be trained before they start the process of cleaning method validation. They must have knowledge of cleaning procedure, standard operating procedure and validation protocol.

Determine the Parts of the Equipment’s to Clean

There are some parts of the equipment that come into contact with the product during manufacturing. This places should be labeled contact parts while those that do not come into contact with the product are labeled non-contact parts. When cleaning, contact parts of the equipment should be cleaned properly. A lot of care should be taken for cleaning the of the place those are difficult to clean. However, for non-contacts take care that these residues during cleaning do not move to these places. Consideration should still be given to the design of the equipment as this influences how it will be cleaned and the time it takes to clean.

Determine the Detergent Used

A good detergent should be easily removed during the cleaning process by rinsing. Detergents which have residues that are hard to remove usually are discouraged. There before choosing any cleanser, a manufacturer must know its composition. The manufacturer should also define the limits of the detergent residue that are acceptable.

Prevent Microorganisms

It’s also a requirement that the validation process does not support the growth of microbes. In determining if the validation process has supported microbial growth, the storage of the equipment before cleaning and after cleaning is often considered to decide whether they support microbial growth. Make sure that after cleaning the equipment is dry. Store it in a dry place. This is important as any other sterilization procedure that might be applied to the equipment will more likely achieve the required standard.

Sampling

Samples are needed to determine the level of residues present in the equipment. There are two types of sampling used in the validation process. Rinse sampling and direct sampling. Direct sampling is used to collect samples for areas that are hard to clean. With rinse sampling, you can get a sample of a place that is inaccessible or for a large surface area. Using the two methods is highly recommended.

Calculating the Acceptance Criteria

A cleaning process is determined before the process begins. An appropriate method is determined by creating a matrix of the product's attributes, and the equipment is used. The method chosen should be sensitive enough to detect any residuals on the equipment. The accepted method should also detect an acceptable limit of the contaminants and residues.

A proper cleaning method validation will enhance the process of the company’s equipment cleaning and will free the company from facing legal actions for not performing it. Therefore every company where a pharmaceuticals or whatsoever industries it operates in must always observe this process.

Frequently Asked Questions (FAQs) for Cleaning Validation

Q1. What is Cleaning Validation?

Answer: Cleaning validation is a documented evidence that a cleaning process consistently removes product residents and contaminants from equipment surfaces and ensures no cross contamination in future batches.

Q2. Why is Cleaning Validation necessary?

Answer: Cleaning validation is essential to:

• Prevent cross contamination
• Ensure product safety
• Meeting GMP and regulatory requirement and
• Maintaining product quality

Q3. What types of residues must be evaluated during cleaning validation?

Answer: Cleaning validation helps to evaluate:

• Product residues
• Cleaning agent residues
• Microbial contamination and endotoxins

Q4. What are Acceptance Criteria in Cleaning Validation?

Answer: Acceptance criteria in cleaning validation is predetermined based on maximum allowable carryover (MACO), toxicological data, 10 ppm or visually clean standard and analytical detection limits.

Q5. How is MACO calculated?

Answer: MACO is calculated using therapeutic dose, toxicity data (LD50), NOEL/PDE values, safety factors batch size and equipment success area using following formula.

MACO = (NOEL x MBS)/ (SF x TDD)
Where,
MBS – Maximum Batch Size
SF – Safety Factor (1000 for oral drugs)
TDD – Total Daily Dose of Next Product

Q6. What is the difference between cleaning verification and cleaning validation?

Answer: Cleaning verification is performed each time when cleaning is done.
Cleaning validation is performed once and then cleaning is monitored regularly.

Q7. How many cleaning validation runs are required?

Answer: Generally, three consecutive batches are validated for successful cleaning cycles per equipment per product.

Q8. Which sampling methods are used for cleaning validation?

Answer: Swab sampling yield form hard to clean areas on the equipment.
Rinse sampling is useful for equipment surface areas those are hard to access and clean in place systems.

Q9. What analytical methods are used in cleaning validation?

Answer: HPLC, TOC, UV Vis spectroscopy, microbial limit test and endotoxin test are the analytical methods used in cleaning validation. These analytical methods must be validated for their specificity, sensitivity and accuracy.

Q10. When is revalidation required?

Answer: Cleaning process must be revalidated when a new product or equipment is introduced. Process must be validated if there is any change in manufacturing conditions or regulatory findings or product failure.

Get ready to use editable Validation Protocols in MS-Word FormatView List

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