Why is Pharma Cleaning Validation Important?

Cleaning validation is the procedure followed to ensure that a cleaning process has successfully removed the chemical and the microbial residues of the active, inactive or detergent ingredients of the product manufactured. A product can be manufactured in single equipment or even multiple equipment. Is Cleaning Validation as important as it sounds? What will happen if Cleaning Validation is not carried out? Let us understand about the process first.

Principle behind Cleaning Validation

The logic behind cleaning validation is simple. Look at the image below and select the utensil which you would like to cook with. If you have chosen Utensil B, by now you would have understood the importance of Cleaning Validation in Pharmaceutical Industry. It is just time to dig deeper into the scientific reason behind the importance of this procedure.

The objective of any manufacturing process would be to avoid cross-contamination at all times. This case is even more serious in the case of Pharmaceutical Manufacturing since the end products deal directly with the lives of people and animals. The products can be contaminated by various types of substances such as contaminants associated with microbes, previously manufactured products which includes both the excipients and the active ingredients, cleaning agent residues, airborne substances such as dust, and so on. To avoid these, there are several cleaning procedures but they vary in use and efficiency. Validation and approval of these methods provide documented evidence that an approved cleaning procedure will provide clean equipment, suitable for its intended use.

Thus, the objective and the idea behind cleaning validation is to prove that the equipment is consistently cleaned of product residues to an acceptable level, to prevent possible contamination and cross-contamination. It should be considered vital in multi-product facilities specifically.

Applicability of Cleaning Validation

Cleaning validation is primarily applicable to cleaning of process manufacturing equipment in the pharmaceutical industry. The focus of cleaning validation is those cleaned surfaces that, if inadequately cleaned, could potentially contaminate the product subsequently manufactured in that same equipment. This primarily covers product contact surfaces in the cleaned equipment—these are the surfaces that directly contact the next product.

This includes the interior surfaces of vessels, agitators, piping, hoses, pumps, and other items that directly contact the manufactured product, and thus can directly transfer residues to the next product. There are some applications where indirect residue transfer may occur. Some examples of indirect transfer are clear. The reflux condenser in the organic synthesis of an active ingredient may not directly contact the next manufactured product; however, the refluxing solvent does contact the condenser surfaces and could potentially carry residues from the condenser surfaces to the solvent containing the active ingredient.

A more controversial example of indirect transfer involves the interior surfaces of a lyophilizer (or freeze dryer). The possibility exists that residues left on shelves (for example) could potentially transfer by an airborne route from the shelves to the manufactured product. Such a transfer has not been demonstrated in real-life cases. However, because the products manufactured in a lyophilizer are usually parenteral products, some companies have been asked by regulatory authorities to validate the cleaning of lyophilizers, while others have chosen to pursue cleaning validation for other reasons.

Other types of cleaning cannot be validated because of the frequency of performing the identical cleaning procedure (SOP). For example, for clinical trial materials or drugs made infrequently (every year or two), it is doubtful that the same cleaning SOP would be used three successive times to obtain three PQ runs. In such cases, the cleaning process cannot be validated; however, it is still necessary to determine that the equipment is suitably cleaned for the manufacture of the next product. This calls for cleaning verification, and involves performing tests similar to those done for the three PQ runs in cleaning validation, except that the tests are performed for every cleaning event.

Still, other types of cleaning do not require either validation or verification. For example, cleaning of the outsides of tanks and the cleaning of walls and floors is required under GMPs. There should be SOPs defining those cleaning processes. However, those processes are not critical, and therefore do not require validation.

The applicability of cleaning validation should be written into a facility’s Cleaning Validation Master Plan to define clear situations which require validation but to permit professional judgment in cases which may require considered reflection.