Key factors in the choice and development of a cleaning strategy

ABSTRACT

Many aspects need to be considered in setting up a cleaning procedure. This is certainly a multidisciplinary
issue that involves various company areas: from “Regulations” to Engineering, from Quality Control lab to Production department. Contributions of all these areas together can lead to a robust and reproducible cleaning process.
Keywords: Cleaning, COP, cleaning equipment.

INTRODUCTION

Cleaning is an essential practice for any pharmaceutical activity: it is impossible to manufacture drugs in dirty conditions, even if dirt is not evident. Defining differences between a sterilization and a cleaning treatment is important in order to understand in depth the main problems and peculiarities when defining a cleaning strategy. To sterilize means to destroy or inactivate microorganisms:

we know the target and we can define it in terms of a number (UCF/unit) and resistance (D, z). The definition of sterile product/item (PNSU – Probability of Non-Sterile Unit or SAL – Sterility Assurance Level), is probabilistic but is universally accepted. The kinetics of ordinary sterilization processes are well understood and as a result so is the determination of the lethal dose to be administered.

On the other hand, for a cleaning process, the “enemy” is not defined and in any case can vary on a case-by-case basis: residue of previously processed product, diluents, solvents, various chemicals, lubricants, generic dirt, m.o., etc. There is no absolute definition of cleanliness. The kinetics of the  cleaning procedure is unknown. Consequently, also the definition of “cleaning dose” to be provided is undetermined.

In these conditions, even regulatory bodies struggle. Essentially, they allow manufacturers considerable flexibility in establishing their own cleaning specifications. The FDA, for example, does not define methods describing how a cleaning process should be validated. FDA inspectors have to assess the rationale used to set the cleaning limits, making sure that their basis are scientifically justifiable and grounded on adequate knowledge of the materials involved.

PDA Technical Report no. 29 suggests a Cleaning Spectrum, which includes cleaning program development criteria, equipment characteristics, formulation/product characteristics and production/process characteristics (see Table 1).