Flawed Specifications & FDA Inspections
Ensuring the quality and safety of products begins with the raw materials used in their manufacture. However, developing and maintaining appropriate raw material specifications often presents significant challenges; the same goes for any critical in-process components or materials as well as finished products. Specifications are critical as they define the quality, purity, composition, strength, and contamination limits of the materials, impacting the final product’s efficacy and safety. Unfortunately, common issues frequently arise in this area leading to many regulatory and compliance problems exemplified by Form 483s and Warning Letters. So what should your Quality Unit look out for?
1. Inconsistency in material quality – suppliers may provide incoming materials that vary in composition from batch to batch, making it difficult to maintain a uniform ingredient or product standard if too tight of specifications are set, especially if one or more manufacturers are in the mix. Exacerbating this is the use of a method that hasn’t been qualified or validated by a suitable laboratory. With respect to botanical ingredients especially, this inconsistency can stem from numerous factors, including differences in sourcing, harvesting, and processing methods. Not having adequate specifications with justifiable or suitable ranges or limits developed for ingredients from qualified suppliers will guarantee your operation to receive a violation upon inspection – regardless of whatever GMP Certificate might hang on the wall!
2. Use of non-qualified or not scientifically valid analytical methods – laboratories, whether in-house or contracted out, that fail to adequately qualify a method with qualified reference standards for testing a given sample i.e. validating the method on its own equipment and personnel, can result in significant variability to contend with. Often labs run tests “as is” hoping the result lines up and if it does, nothing more to do. Worse, just accepting results from a Certificate of Analysis that doesn’t have any trace back to a scientifically validated method is one way to guarantee a violation. Testing into compliance is a big No No, and failure to investigate a failed result will certainly land you in violation territory. Have you audited your lab yet?
3. Unqualified Reduced Testing Schemes & Finished Product Testing Exemptions – just deciding one day to not test a product for one or more particular components or blindly writing language into your procedures to allow for less or no testing at all, without adequate data on hand will guarantee you a violation. And even once you do have adequate data for either your raw materials or finished products to justify less testing, failing to update the specification for that or investigating a given failure should one occur (and they frequently do), will certainly tie up your Quality Unit with lots of operational waste and delays. Do you know how to properly implement optimized testing strategies?
4. The Methods are not Fit-for-Purpose – if you think testing everything by FTIR for identity confirmation is the way to go because it is fast and cheap, think again. Upon inspection, if certain methods being used are not appropriate for the test article or “fit for purpose”, welcome to having another violation! And if we are talking about an ingredient of issue, this will likely ensnare one or more products it is contained in – and Yahtzee, more violations! Methods have utility in the certain applications, and sometimes with combinations thereof, provided they are qualified appropriately; not having this understanding or qualified staff to know the basic tenets of testing and quality control is going to result in some additional headaches.
5. Not testing for known adulterants or contaminants – If the raw materials or finished product are prone to adulteration or if the process is likely to have something in it that isn’t supposed to be, you better have some additional assays integrated into your specification for common or known adulterants and contaminants; failure to do so will get you a violation. If you are not sure if your raw materials used in your product have any contaminants starting out, then first speak with your laboratory to confirm – they will often have the first look at investigation such issues before it becomes mainstream. And if they do, make sure that is written in to your specification accordingly and that you have adequate procedures in place to handle a sample failure event.
6. Difference between an Analytical Method vs. Analytical Technique – An Analytical Technique is the instrumentation or type of analysis/detection that is used to conduct the test or assay. An Analytical Method, is the procedure that encompasses the respective analytical technique(s), and is the specific set of steps across two main parts, a) the sample preparation and b) the sample analysis. HPLC, LCMS, GC, FTIR, etc. are all analytical techniques – these are not “methods” so don’t put that on your specification in lieu of an actual compendia method or method reference number that can be reviewed upon request. If you present such a specification with this mixed up to to the FDA, welcome to having one more violations!
Addressing these issues requires a comprehensive and proactive approach to writing and updating specifications by qualified quality staff. By tackling these common issues head-on, brand owners and manufacturers alike can better ensure the quality and safety of their dietary supplement products, ultimately protecting consumer health and maintaining regulatory compliance.