WHO publishes final Guideline for Hold-Time Studies

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The World Health Organization (WHO) has released guideline for the design of hold-time studies as part of the final version of Technical Report Series 992 (TRS 992, Annex 4). The guidance covers liquids, creams, ointments and non-sterile dosage forms.  It does not cover aspects for hold times in cleaning validation, or the manufacturing of active pharmaceutical ingredients (APIs) or biologicals. The guideline is a good tool when determining where to specify a hold time study.

For example, for oral tablets that are coated, the following stages 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 blend;
  • 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.

The guideline recommends that a risk-based approach be used to determine the appropriate number of batches to study. Head space considerations when oxidation can cause degradation must be studied from a worst case perspective.  Both physical and microbiological (where appropriate) characteristics should be considered.

Download the guideline here.