This is a guidance document that comes under Chemistry manufacturing and controls section of USFDA. During formulation development, initially, development process is carried out in small batch sizes generally in the multiples of 10X i.e., small scale or lab scale. The batch size is then increased to multiples of 100X i.e., medium scale or pilot scale. In production scale or large scale, manufacturing is carried out in large numbers usually multiples of 1000X depending upon the requirement. This increase in batch sizes is termed as scale up. Sometimes, batch sizes need to be reduced depending upon the market requirements. This is termed as Scaled down. Quantities of active ingredients, excipients, equipments, formulation parameters differ from lab scale to manufacturing scale. Submission of all this data including excipients, their purpose and quantities to FDA is required for marketing approval by the agency. A need may arise to change the excipient or composition of excipients, batch size, manufacturing site, equipment on due course depending upon the market requirements. These needs are classified as components and composition, site changes, changes in batch size (scale up/scale down) levels under this guidance to avoid resubmission whenever a change has been taken place.

A level 1 change is the one assumed to be that such change will not have any significant effect on product's performance or quality. FDA has given the limits upto which an excipient can be changed. For example, quantity of filler can be used more or less 5 percent of the proposed amount during submission. A level 2 change is assumed to have significant change on quality on product quality and it depends on therapeutic range, solubility and permeability of drug. Change in the technical grade of an excipient comes under this category. A level 3 change also will have significant impact on product's quality and performance and those changes must be done according to the guideline. Guidelines are given for the site change, manufacturing equipment changes, process changes. In summary, SUPAC guideline is a regulatory relaxation to industries that avoids resubmission of data for every small change. Changes can be made subject to the guidelines given in the document.

Reference:

1) http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformati...
/Guidances/ucm070636.pdf accessed on 12/3/11.

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