Research into process validation in pharmaceutical companies, with specific reference to Roche, South Africa

Abstract

Each manufacturing facility needs to develop, based on scientific rationale, detailed customized programs for validation. This necessity arises from the fact that the guidelines set for the pharmaceutical industry by regulatory authorities are rather broad. It is also not practical to adopt standards for process validation since every strategy must be tailored to the actual circumstances of every manufacturing site. The aim of this research study was therefore to develop validation approaches capable of ensuring that pharmaceutical products are manufactured free from microbiological and decomposition products. Furtheromore, the study has focused on exploring the adequate methods through which the manufacturing/cleaning processes are kept under a state of control, therefore preventing the risk of product contamination (e.g., with cleaning agents) and cross-contamination (e.g., with previously manufactured drug residues) within a given manufacturing group. A cleaning validation program was formulated and implemented in the pharmaceutical manufacturing plant of Roche, South Africa. The approach for validation was proposed afer a risk analysis. The various aspects of validating the cleaning procedures were challenged with regards to selecting the appropriate sampling methods, acceptance criteria and suitable analytical techniques. The cleaning validation approach proposed was exemplified with studies for two sulfonamide drugs formulated in combination with their potentiators, namely Fansidar® and Co-trimoxazole. For Fansidar® tablets an RP-HPLC method was developed and validated in conjunction with a swab sampling method. The validated method was used to assess the level of cleanliness (LOC) of the equipment chain used in the manufacturing process. The results obtained were situated below the calculated LOC values deemed to be safe (4.99 ìg/ cm2 for PYR and 19.14 ìg/ cm2 for SUL). A sufficient LOC was therefore achieved with the designed cleaning procedures. For Co-trimoxazole syrup a capillary electrophoresis MEKC method was developed for assaying swab samples containing active pharmaceutical ingredients, their decomposition products and detergent at trace levels. The method was validated for the following optimum experimental conditions established through method development: 30 mM phosphate electrolyte, pH 7.8, containing 10 mM SDS and an applied voltage of 22 kV. All the components were resolved within 14 minutes. A qualification approach for a steam sterilizer was elaborated and exemplified for the trypticase soy broth. The sterilization process was designed and validated such as to obtain a satisfactory sterility assurance level without physically or chemically altering the media during its sterilization. These validation approaches have set practical examples for the future validation work within the manufacturing facility under examination. Although the validation strategy follows several standard steps, exact prescriptions for validation cannot be offered because of the multitude of variables involved in every process. As long as the strategy for validation is based on logical, systematic approach and all the activities undertaken are based on a scientific rationale the outcome results of the validation will be meaningful. Copyright