Finished Product Manufacturing Process Updates

Any change to the manufacturing process should be supported by batch data from at least one batch of the product manufactured using the revised process, in order to ensure that the process leads to a satisfactory product. It is recommended that the batch produced is the largest registered, or if a range is registered, the upper limit of the range should be produced. The aforementioned is especially true for products manufactured by a complex process*. In addition, at least one month of stability data generated from the product using the revised process should be submitted along with the information provided below, however, it should be noted that more data, in line with the change code requirement, may be requested during the assessment.  

*Complex manufacturing processes is intended to cover situations where the actual manufacture of the finished product involves a process which includes one or more processing steps that may give rise to scale-up difficulties. These will be considered on a case by case basis.


Where relevant, if a change is submitted as a type IB variation, it is up to the applicant to provide adequate justification for not considering a manufacturing process as a 'complex' one, in terms of scale-up. However, under the safeguard clause, it should be noted that if the supplied justification is not accepted, it is possible for the competent authority to upgrade the submission to a type II variation during the validation phase
Bulk holding time, i.e. the time between manufacturing and packaging of the tablets. A B.II.b.3.z code would be appropriate, provided a justification is included  outlining that the change does not have a significant impact on quality, safety and efficacy of the product. 

It should be noted that the shelf life of the product commences with the first mixing of an excipient with the active, and that the extended holding time for the bulk tablets would need to be supported by validation data.  The data should demonstrate that the bulk tablets still meet the release specification and that quality is unaffected by the extended hold time.  Extending the holding time of the bulk tablets prior to packaging does not change the registered shelf life of the product. 

wet granulation to dry blend formulation </b>

A change from wet granulation to a dry blend formulation will be considered as a significant change and therefore, this change should be submitted under a type II variation (change code is B.II.b.3.b).