Framework for the determination of yield limits In pharmaceutical operations

Abstract

The manufacturing production of active pharmaceutical ingredients often involve a series of processing stages in which yield limits are prescribed to ensure that the target yield has been achieved for a batch and that the workers may proceed to the next batch of materials. Such yield limits is comprised of a maximum value for yields above 100% and a minimum value for yields of lower than 100%. These yield limits for each of the processing steps are conventionally prescribed based on accumulated experiences with production after an extended period of time. This paper is based on an internship project at a major pharmaceutical firm in Singapore, and it discusses the sources of yield losses and the reasons behind yield excursions which have not been well documented within the production facility. In doing so, the paper attempts to provide insights into the possible explanations for the current maximum and minimum yield limits application. Furthermore, using the yield limit values as applied for certain products, a preliminary framework is developed to provide a set of recommendations for the adjustment of conventional yield limit values to suit similar processing stages for the manufacturing of a novel drug product. This framework should prove to be useful in meeting the uncertainties inherent in the production of new products and in making initial recommendations for yield limits since there is usually limited experience from drug developments and clinical manufacture.