|21 CFR 111.70(e)
||Specifications – identity, purity, strength, composition
|21 CFR 111.103
||Written procedures – quality control operations
|21 CFR 111.553
||Written procedures – product complaint
|21 CFR 111.75(c)
||Specifications met – verify; finished batch
|21 CFR 111.75(a)(2)(ii)(A)
||Component – qualify supplier
|21 CFR 111.205(a)
||Master manufacturing record – each batch
|21 CFR 111.255(b)
||Batch record – complete
|21 CFR 111.453
||Written procedures – holding
|21 CFR 111.75(a)(1)(i)
||Component – verify identity, dietary ingredient
|21 CFR 111.70(b)(2)
||Specifications-component purity, strength, composition
Late last year FDA released inspection observations (483 citations) for FY 2017. The table above shows the top 10 dietary supplement (21 CFR Part 111 cGMP) inspection observations found during inspections in FY17. Significantly, failure to verify the identity of all dietary ingredients has now dropped to 9th place, down from 2nd place in FY 2016. Lack of established specifications for identity, purity, strength, and composition of finished dietary supplements continues to be a problem found at a large number of firms. Failing to establish written procedures for quality control operations moved up to #2. Subpart E observations (for Production and Process Control) together made up nearly 34% of the total observations by FDA inspectors, continuing the trend upward of the past few fiscal years.
FDA has just released inspection observations for FY 2016. Preliminary data (see chart above) show that the total number of inspectional observations for dietary supplement cGMPs rose in FY 2016, having declined for the previous several fiscal years.
The most commonly cited observation in FY 2016 was once again failure to set appropriate specifications for finished dietary supplements, namely 21 CFR Sect. 111.70(e) Specifications – identity, purity, strength, composition.
Classifications for FDA inspections during the first half of FY 2016 (Oct 2015 thru March 2016) were released by FDA a few weeks back. The above chart shows inspection outcomes under CFSAN (which includes foods and dietary supplements). The number of 483s issued in the area of “Food Composition, Standards, Labeling and Economics” continues to decline slightly — just short of 60% of inspections in that area now result in no 483 being issued. Most DS inspections occur in that project area, along with “Foodborne Biological Hazards” (which also applies to regular food facilities.) See more by clicking on the chart.
FDA released new spreadsheets for FY 2015 (10/1/2014 – 9/30/2015) which have now been incorporated into my charts.
The total number of observations found during cGMP inspections at dietary supplement firms has declined from FY 2014 (the peak was in FY 2013). Production and Process Control (Subpart E) citations continue to dominate, consisting of ~30% of the problems found. In FY 2015, finished product specifications for identity, purity, strength, composition (and for limits on contaminants) remained the most frequent item (as it was in FY 2014) but by a greater margin. Identity testing of components, followed by batch record requirements, continue to top the list of inspectors’ favorite inspection findings.
Based on preliminary FY 2015 data released by FDA’s Denver District at the Rocky Mountain Dietary Supplement Forum in Boulder, Colo. last week, Form-483 citations are down overall for dietary supplement firms, and there has been a shift from focusing on identity testing of ingredients (although this is still a very common and important finding) toward observations related to setting specifications for finished products. This trend continues from FY 2014. Data are preliminary because FY 2015 was not yet closed when the data were gathered (closes Sept 30, 2015). I will be publishing complete FY 2015 figures when they become available from FDA’s website. In the meantime, here is a chart based on last week’s data and historical 483 observations from 2009-2014, ordering is based on preliminary FY 2015 frequency.
Note: there are a total of 11 CFR sections listed above (as presented by FDA representatives)