Table of contents


How to categorize changes?

Changes fall into one of five levels. Levels 1, 2, and 3 changes are expected to have a possible impact to a drug manufacturer; level 3 changes are anticipated to have highest impact and levels 2 and 1 progressively less (see figure 1). Level 0 changes are those for which it is highly unlikely that the change would have an impact on the drug manufacturer. To categorize a change (0, 1, 2, or 3), one should have a group of individuals who represent internal subject matter expertise and a strong understanding of bioprocessing (see page 11). This group should holistically assess the proposed change to estimate the complexity of drug manufacturer’s change qualification effort. Because “complexity” is not a quantifiable term, the team should then estimate the time needed by a typical drug manufacturer to qualify the change. This estimate of time is then used as the means by which a change level is derived (see table 2). When the supplier team is uncertain, it is recommended to discuss the proposed change with one or more drug manufacturers to gain help in understanding relative complexity and hence qualification time associated with a change. The fifth level of change, “emergency,” is a change that normally would be described as level 1, 2, or 3. However, due to unusual circumstances, the change must be managed in an expedited manner.

What do we mean by non-notifiable change?

‘Non-notifiable is a change that has no anticipated impact to either patient safety of drug product quality. This change has been reviewed by the supplier change management team and determined not to have an anticipated impact as defined. This review is documented and stored in a document control system’.

What is the role of the N2 supplier in change notification?

N2 suppliers are to notify their direct N1 customers at a minimum. The N2 suppliers should also notify the end user if it is known the end user uses the product or the end user requests notifications (even if they are not selling the products directly). The N2 suppliers should take into the account the same timelines listed in this guide. N2 suppliers may also need to interact directly with the end users in sharing the data package and supporting questions the end users may have when evaluating the change.

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