28/29 September 2021
After the World Health Organisation (WHO) had released the second draft of the guideline for the design of hold-time studies in March already, it now released the final version as part of the Technical Report Series 992 (TRS 992, Annex 4).
The GMP regulations require that raw materials, packaging materials, intermediate, bulk and finished products need to be stored under suitable conditions. This also includes the definition of maximum hold-times for intermediate and bulk products prior to their further processing. The definition of these times should be justified on the basis of scientific data. This guideline aims at reflecting aspects that may be important in the design of hold-time studies. Active substances and biological products are explicitly excluded. According to WHO, hold-time studies can be part of the development or also be carried out during the later Scale-Ups. In any case they should be confirmed during product validation, though.
With coated tablets as an example the guideline demonstrates at what points in the manufacturing process samples can be taken and examined for durability. The number of batches to be examined is supposed to be risk-based. The times, according to which the listed intermediates could be sampled and examined are also mentioned exemplary. Whereas the original draft comprised propositions with regard to combined hold times - meaning the impact of hold times of various intermediates among one another - they are not part of the final guideline any more.