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.
Where hold time study data give the assurance the maximum allowable hold times for bulk and in-process drug products. Generally, one lot can be used for validating hold times if any inconsistency results were observed then another two lots can be used for this study.
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.
Although there are no specific regulations or guidance documents on bulk product hold times, GMP dictates that hold times should be validated to ensure that in-process and bulk product can be held, pending the next processing step, without any adverse effect to the quality of the material. Hold time study provides the re-assurance of the quality at each in-process stages.
A written protocol, procedure or programme should be followed, which includes, for example, the activities to be performed, test parameters and acceptance criteria appropriate to the material or product under test.
The protocol and report should generally include the following:
- a title;
- reference number;
- version;
- date;
- objective;
- scope;
- responsibility;
- procedure;
- description of the material or product;
- sample quantities;
- sampling method and criteria;
- acceptance limits;
- frequency of sampling;
- sampling locations;
- pooling of samples;
- storage conditions;
- type of container;
- methods of analysis;
- results;
- conclusion & recommendation;
- signatures; and dates.
For certain products, microbiological aspects should also be considered and included where appropriate. All testing of bulk intermediates and product should be performed using validated stability-indicating methods.
Read also:
