Hold time study in Pharmaceutical Manufacturing


Hold time study in Pharmaceutical Manufacturing

During pharmaceutical manufacturing sometimes in-process materials need to be hold more than usual.

Hold time

Hold time is a time period in which materials (dispensing raw materials, intermediate and bulk dosage form awaiting final packing) may be held specified condition and will remain within predefined specification.

Hold time study

Hold time studies establish the time limit for holding the materials at different stages of production. It ensure that the quality of product does not produce results outside the acceptance criteria during the hold time. The design of study should reflect the holding time at each stage.

Hold time study also define as it is the validation of hold time period of in-process materials.

World Health Organization recommended the hold time study during different stage of pharmaceuticals manufacturing, their sampling and testing intervals.

So hold time study has more importance during pharmaceuticals manufacturing.

According to WHO TRS 992 “Annex 4 General guidance on hold time Studies” for oral tablets that are coated, the following stage may be considered-

Binder preparation to granulation – consider the granulate

Wet granulation to drying – consider the dried granulate


  • Dried granules to lubrication /blending – consider the lubricated blends
  • Blend to compression
  • Compression to coating – consider the tablet cores
  • Coating solution to preparation – consider the coating solution
  • Coating to packing- Consider the bulk coated tablets
  • Coating to packing in bulk
  • Packing of bulk to finished packed dosage form


For the hold time analysis manufacturer should be prepare a flowchart. Hold time study sample should be taken same container closure system (same material of construction of hold time sample container and production area container).

The hold time study sample should be stored in similar environment condition as the quarantine of production stage. A head space in the container should be left in the same ratio as it is done in routine practice in the production. Hold time study sample should be taken at specified time intervals.

Sampling intervals for Hold Time Study  

  1. Binder and coating solutions hold time – Maximum testing period 8 hours having interval 2, 5 & 8 hours.
  1. Granules, core tablets etc. are hold for days, so the maximum testing may be 60, 90 days having sampling intervals 15, 30 45, 60 and 90 days.

hold-time-stageHold time study protocol should be written before exercise. In this protocol should be mention all parameters of hold time study eg. type of container, storage condition, volume of sample, frequency of sampling, method of  analysis, acceptance criteria of analysis and other required information.