According to the new guideline maximum allowable hold times, that is the period before the next processing step, should be described for starting materials, intermediate and bulk products and supported by data. This data can be collected during development, during process validation, or as part of a deviation with appropriate testing. The data shall demonstrate that there will be no adverse effect to the quality during the hold time. Hold times should be determined prior to marketing of a product and following any significant changes in processes, equipment or packaging materials.
When designing hold-time studies the critical stages of the manufacturing process are to be highlighted that could have an impact because of their duration or the conditions. As an example the guideline contains a list of the stages to be considered for the manufacture of oral solid dosage forms.
Furthermore, the contents of a test protocol are presented as well as the requirements on the containers in which the material under test is to be stored. At this point it is mentioned that the corresponding containers should have head space in proportion to the intermediate or bulk product stored in the analogue container. The data can be gathered by means of one or more batch(es).
Finally, the document contains an exemplary overview of the hold times of the different intermediate steps such as granules and blends. Interim storage of the dosage form in bulk containers should generally not exceed six months.
Comments on the guideline can be submitted until April 2013. The draft of the WHO guideline as well as the template for comments can be found in the members area of the ECA Website.