Hold time studies General guidance

Manufacturers should ensure that the products that they manufacture are safe, effective and of the quality required for their intended use. Systems should be in place to ensure that pharmaceutical products are produced according to validated processes and to defined procedures. Manufacturing processes should be shown to be capable of consistently manufacturing pharmaceutical products that are of the required quality and that comply with their specifications. 

Good manufacturing practices (GMP) require that arrangements should be made to ensure that the dispensed raw materials and packaging materials, intermediate products, bulk and finished products are stored under appropriate conditions. Storage arrangements should not have deleterious effects on the subsequent processing, stability, safety, efficacy or quality of starting materials, intermediate products and bulk products prior to final packing. Maximum acceptable holding periods should therefore be established to ensure that intermediates and bulk product can be held, pending the next processing step, without producing results outside the acceptance criteria for the quality of the material. Normally, intermediate and bulk products should not be stored beyond the established hold time.

These guidelines focus primarily on aspects that should be considered in the design of the hold-time studies during the manufacture of non-sterile solid dosage 

forms. Many of the principles described here also apply to other dosage forms such as liquids, creams and ointments. These guidelines do not cover aspects for

hold times in cleaning validation, or the manufacturing of active pharmaceutical ingredients (APIs) or biologicals.

These guidelines are intended as a basic guide for use by manufacturers of pharmaceuticals and by GMP inspectors. This document is not intended to prescribe a process for establishing hold times, but reflects aspects that should be considered in the design of the hold-time study. Manufacturers should gather scientific and justifiable data to demonstrate that the dispensed raw materials and packaging materials, intermediate and bulk products:

– remain of appropriate quality before processing to the next stage;

– meet the acceptance criteria.

The finished product should meet the release specifications.

The choice of maximum holding period should be supported by relevant data. Studies may extend beyond the chosen maximum but it is not necessary to extend testing to determine the extreme limits at which failure occurs.