Pharmacy Courses

Hold Time Study Guidelines for Pharmaceutical Industry


In some cases, the intermediate may be stored, and if necessary, transported in a suitable container before further processing. It may also be subject to confirmatory testing prior to further processing to confirm that quality attributes have not changed and therefore any additional testing details should be provided.

As per EMA,

Hold time validation for the storage of intermediate product is a GMP matter and normally need not be presented routinely in the application for a marketing authorization. However, some specific types of products (e.g. sterile products, biological products) may require presentation of data relevant to the type of product and this should be taken into consideration depending on the characteristics of that particular product.

As per 21 CFR 211.111,

Hold time limits for the completion of each phase of production shall be established to assure the quality of the drug product (when appropriate). Deviation from established time limits may be acceptable if such deviation does not compromise the quality of the drug product. Such deviation shall be justified and documented.

As per WHO Annex 4,

Hold time can be considered as the established time period for which materials (dispensed raw materials, intermediates and bulk dosage form awaiting final packaging) may be held under specified conditions and will remain within the defined specifications

As an 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.

Where relevant, the maximum holding times of the bulk product or, alternatively, the maximum batch manufacturing time from start of product manufacture to completion of packaging into the final primary container for marketing should be stated, appropriately justified and supported by data in relevant parts of the dossier (e.g. challenging the maximum hold time in process validation studies or providing dedicated stability studies for the bulk storage).

Read also: 


  • EMA guideline on manufacture of the finished dosage form
  • 21 CFR 211.111
  • WHO Technical Report Series No. 992, 2015

Tags in: hold tume study guidelines in pharmaceutical industry, hold time study guidelines usfda, eu, ema, pics, who, 21 cfr 211.

Previous Post Next Post