GMP Test Methods: Whats Appropriate?

Valid. Validated. Depending on who you are, those two words can have very different meanings.

“Validated" to most chemists in the field means a method that has undergone and passed scrutiny via a body such as AOAC. Though the dietary supplement GMP (good manufacturing practice) regulations do not require the usage of such methods, firms may choose to use them if available for particular materials.

The regulations state that a “scientifically valid method" must be used in order to verify (another word potentially subject to a variety of interpretations) the identity of a component or dietary ingredient prior to its usage in a dietary supplement, as well as determine whether specifications are met. Verify means, in layman’s terms, confirming that what showed up at the facility’s receiving dock in the drum, carton, box, etc. is what it says it is/should be (and in some cases, not a known adulterant).

“Scientifically valid methods," according to the regulations, means using any one (or more, if necessary) of a variety of potential analytical means to achieve that confirmation: sensorial (which is called “gross organoleptic analysis" in the regs, and includes taste, smell, etc.), macroscopically, microscopically, or by any number of a means of chemistry, such as a plethora of chromatography (HPTLC, HPLC, UHPLC, flash, etc.), Infrared (FTIR, NIR, etc.), NMR, and DNA, among many others. The regulations also list “other scientifically valid methods" as an option. What the regulations do not do in the preamble or elsewhere is define exactly what is meant by “scientifically valid method." What they do state within the preamble is this:

“We decline to define ‘test,’ ‘scientifically valid analytical method’ or ‘scientifically valid method’ in this final rule. As the comments recognized, the analytical methods for components are evolving. A regulatory definition for ‘test,’ ‘scientifically valid analytical method’ or ‘scientifically valid method’ could become obsolete if we based it on specific sources such as INA, AHP or USP that may or may not themselves stay current or that may be modified in a manner that did not enjoy widespread support.

“…it is the responsibility of quality control personnel to approve the use of those scientifically valid tests that will ensure a product’s identity, purity, strength and composition."

What the vast majority of businesses owners therefore want is for QC to determine the single, most inexpensive test method in order to get this verification or confirmation. Sight/smell/touch/taste are, relatively speaking, cheap. Chemistry is expensive. The less expensive the method(s) used, the less the product will cost consumers and/or the better the margin for the brand owner.

So, Which Method(s) Do I Use?

Method and technology usage will depend on a variety of factors including equipment needed/available, training, costs, timeframe, etc. There is no one size fits all methodology for testing. Selection of methods will also depend on the established specifications.

Orthogonal methods are something QC departments and business owners should consider, which are methods that work differently enough from one another, but individually can provide a reliability factor, at some amount greater than 50-percent accuracy. When used in conjunction, these methods may be enough to provide a reasonable amount of data to verify identity (or other specifications).

As an example, an IR scan of a variety of verified, different batches of burdock root powder will provide the lab with a library of data that, when compiled, could serve as the “reference standard" for future materials to be “graded" against. If the peaks match up from a new suppliers’ offering, the reliability of the method to show the new material is burdock root powder can be considered high.

In the case of a colorimetric method, it may only provide 60-percent reliability – which on its own isn’t enough to be considered suitable to verify identity. Two other orthogonal methods looking for the same elements may provide an additional 60 percent each. Running all three, if successful, the results can be about a 90-percent reliability of confirmation—which by most standards is enough to satisfy the requirements for verification.

Running experiments using other technologies that provide the necessary qualitative or quantitative results can be used to develop this reliability data. As an example, aloe vera can be characterized and identified completely via NMR. If, for example, a colorimetric method existed that analyzed for acemannan (the primary identifying constituent in aloe vera) and other compounds found in the plant was tested for qualitative results at the same time the samples were run via NMR, one could reasonable say the reliability data would be established.

There are of course other validated, botanical reference standards available from a variety of reputable sources – including United States Pharmacopeia, Botanical Liaisons and American Herbal Pharmacopoeia, all of which can be used to comply with the testing requirements (though this is most often in the case of a business with an in-house lab). In addition, there are several contract labs in the industry that have extensive expertise in the area of botanical analysis, such as Alkemist Labs or ChromaDex, including offering botanical reference materials. All to say it’s not as if the ability to do the hard work is impossible. It just may cost additional time and money.

In the case of many of the smaller businesses operated by, in particular, herbalists or those with extensive training and knowledge of herbs from a sensorial or organoleptic perspective—creating data to demonstrate a person’s ability to differentiate and verify identity may be somewhat tedious, but not impossible. And certainly would not be as expensive as purchasing a $100,000 machine, hiring qualified lab personnel to run it, and all of the necessary chemicals etc., to boot.

It’s not as easy as the one test approach—but, depending on the tests needed, it may (or may not be) less expensive and/or time consuming. And, depending on the technology/methodology needed to do a one-shot confirmation, it may be cost prohibitive to many firms to consider doing in-house (or via third-party contract lab), especially smaller ones (NMR machines cost somewhere around $1 million or so). So, looking for other ways to be in compliance and reduce costs is more or less a constant consideration; regardless of size, every business wants to save money.

Devon Powell was formerly the chief operations officer at the American Herbal Products Association and executive director at the International Aloe Science Council. He is currently a consultant to the dietary supplement industry, assisting manufacturers and brand marketers with regulatory initiatives including GMP compliance, QA, QC, auditing, and related elements. He can be reached at [email protected].