7.1 Finished Product Verification, Storage, and Handling

This page will address various regulatory issues related to this section of the GMP Institute framework.  Click below to view the issues that are relevant to you.

How often must manufacturers examine finished product reserve samples? Can FDA investigators visually examine a manufacturer's reserve samples?

How often must manufacturers examine finished product reserve samples? Can FDA investigators visually examine a manufacturer's reserve samples?

Reference: 
21 CFR 211.170(b), Reserve Samples; 
211.192, Production record review; 
211.160, General requirements [Subpart I, Laboratory Controls]

The CGMP regulations, at section 211.170, require that at least annually manufacturers visually examine reserve samples from representative lots of each drug product manufactured, unless such examination would affect the integrity of the samples. This section also requires firms to use acceptable statistical procedures in selecting the samples. (Note that the regulation exempts medical gases, radioactive drug products, and radioactive drug kits from the reserve sample retention requirement; therefore, the examination provision would, of course, not apply to those products.)

Per section 211.160, firms must have written procedures for those reserve sample examinations.

Although section 211.170 specifies at least annual visual examination, firms may themselves determine that for certain products, and under some circumstances, a more frequent interval may be warranted. The regulation gives manufacturers considerable leeway in this regard. For example, as part of complaint or failure investigations performed in accordance with section 211.192 (that requires a thorough investigation of any unexplained discrepancy or failure of a batch to meet specifications), a firm may, in addition to conducting an immediate examination of the reserves, conclude that reserve samples for one or more products, or particular lots of one or more products, merit more frequent visual examination for a given period of time. 

During inspections, investigators should not on a surveillance basis routinely examine a manufacturer's reserve samples. However, on a for cause basis, such as when investigating product contamination or mix-ups, it may be appropriate for investigators to open and examine a manufacturer's reserve samples. In those situations, if the manufacturer produces evidence that such examination would affect the integrity of its remaining reserve samples, an attempt should be made to examine samples of the suspect products taken from other sources, such as commercial inventories.

Contact for further information: Barry Rothman, HFD-325, 301-594-0098, e-mail: rothmanb@cder.fda.gov