In the past, cleaning or cleaning validation problems were often pointed out by the authorities. A simple and standard cleaning approach can be used in the pharmaceutical industry in absence of specific know-how in order to initiate a reflection about cleaning.

Insufficient or inadequate cleaning can have various consequences. From a health point of view, an absence of good cleaning can lead to contaminated drugs with a risk for patients, but also for the workers within the pharmaceutical company due to a lack of correct protection. The ecological problems can be summarized in pollution risks. The regulatory issues are linked with warnings from agencies up to possible authorization withdrawn. Economic problems start with a diminution of production and stock shortage which imply increased internal costs and financial loss. In addition, image problems for a company exist when patients must return medications to the pharmacy as in the case of batch recall. Agencies can increase inspections due to a lack in confidence, and financial institutions could rate a company as a higher risk due to profit diminutionand poor predictability of the potential benefits.

A clean product, surface, apparatus, fluid, or gasis one “with an acceptable and predefined level ofcontamination.”⁹ Contamination is defined as “thepresence of contaminant” and contaminant means “a solid, liquid,biological, or gaseous matter, a microorganism, or any combination of these likelyto alter inany way the health or safety of workers, patients, productor process.”⁹ Cleaning and cleaning validation are continuous processesfrom the beginning of development until full production and included periodicrevalidations. EU GMP annex 15¹ stresses that “Facilities, systems andprocesses, including cleaning, should be periodically evaluated to confirm thatthey remain valid. Where no significant changes have been made to the validatedstatus, a review with evidence that facilities, systems, equipment and processesmeetthe prescribed requirements fulfils the need for revalidation.”

One main problem is when a first batch of a new product must be manufactured, for example, for the first clinical trials. According to EC 20/2001 guidelines, clinical trial material needs to be produced under GMP conditions, and typically pilot plants are multi-product facilities. It is obvious that “Non-dedicated equipment should be cleaned according to validated cleaning procedures between production of different pharmaceutical products to prevent cross-contamination.” ¹¹As a general concept, until the validation of the cleaning procedure has beencompleted, the product contact equipment should be dedicated.⁸ A highly potentor allergenic product emphasizes those problems.

The aim of this article is to bring some idea about a general concept to approach cleaning and cleaning validation for a new compound.