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Choosing the right testing techniques while still keeping an eye on the bottom line.
With FDA’s Good Manufacturing Practices for dietary supplements effective for nearly a decade now, it’s time to accept that the cost of running a business in this industry has increased considerably from 10 years ago-not only due to rising wages or material costs but also the expense of maintaining a good quality-control system.
FDA’s cGMPs for dietary supplements (21 CFR 111) state that 100% of the ingredients in a product must be verified for identity by an appropriate, “scientifically valid” test method by the manufacturer.
“The DS CGMP rule requires you to conduct at least one appropriate test or examination to verify the identity of any dietary ingredient,” FDA states. “It is up to you to determine the appropriate test(s) or examination(s) necessary to verify the identity of a dietary ingredient. In some cases, a single test or examination may be all that is needed to verify the identity of a dietary ingredient; in other cases, it may be necessary to conduct more than one test or examination.”
According to FDA, tests should include at least one of the following: gross organoleptic analysis, macroscopic analysis, microscopic analysis, chemical analysis, or “other scientifically valid methods.”
Companies are at liberty to decide on a path of quality control and the types of technologies that make the most sense for the business. Fit-for-purpose testing is crucial. Like driving a nail into a piece of wood with a sledgehammer instead of a carpenter’s hammer, not adequately considering which testing technique is fit for purpose can be a waste of time, money, and energy if a different method would be better suited. Below is a quick overview of some of the methods available to industry today.
Over the course of 10 years, technology has changed the way we test samples to be compliant with cGMPs.
Newest on the scene is DNA testing for raw botanicals. DNA testing is gaining more interest from those looking to identify botanical materials to the species level where other techniques have failed. On occasion, other more-established techniques may fail due to poor quality material or lack of marker compounds that make up a fingerprint used for identity. DNA testing compares two short, specific DNA regions against a database of known reference samples and can sometimes “see deeper” than analytical techniques. The newest DNA testing techniques investigate multiple regions of the genome across a wide sampling of target species-including closely related and adulterant species-thereby not only identifying the test sample but also potential adulterants.
Several recent articles highlight cases in which DNA testing may not have been fit for purpose, however. In some of those cases, this was because some formal validation protocols were missing. For instance, in some cases, at the time the articles were written, no studies had been performed by the equipment manufacturer to indicate that the equipment used was suitable for plant DNA testing or anything other than R&D use.
Like any newer technique, DNA testing has some “application bugs,” such as those related to plant part differentiation and, in some cases, herbal products that contain plant metabolites. For instance, DNA testing can only be performed on raw, un-extracted materials (it does not work for extracts or extract powders). Also, DNA testing only shows the genetic barcode or fingerprint of the plant; the data will be the same whether the part tested is the leaf or root of the same plant. DNA testing will tell you if a plant part is the species Echinacea angustifolia, but it will not distinguish the plant’s part.
Despite the technology’s limitations, DNA testing is here to stay. Like all scientific techniques, it isreliable when performed on appropriate material and is a useful technique to add to a strong arsenal of methods for cGMP compliance.
The other new kid on the block is FT-NIR (Fourier transform near infrared spectroscopy). While the technology itself isn’t new, it’s the computing power of today coupled with the technology of yesterday that allows purveyors of this technique to tout this method as one that enables manufacturers to save time and money, while at the same time providing a robust solution to quality needs. Methods are based on chemometric analysis, analyzing chemical-derived data. In today’s FT-NIR testing, the computer does 100% of the work, analyzing the sample against reference standards and giving operators a simple “pass/fail” answer, eliminating operator interpretation.
Other tried-and-tested methods are still valid, such as organoleptic testing, in which olfactory characteristics are combined with taste and visual characteristic testing to positively ID a raw plant. Microscopy is another nearly ancient technique still approved by the FDA in which microscopic anatomic characteristics of the plant material are used to effectively distinguish between disparate and closely related species in whole, cut/sifted, or powdered form. It has been shown that a simple and quick microscopic analysis of a raw botanical sample can reveal the presence of virtually chemically inert adulterants/contaminants, such as sand, dirt, cellulose, and soluble excipients-contaminants that may not be easily detected by alternatively available, more-technical routine analytical procedures such as HPTLC (high-performance thin-layer chromatography), UV/VIS (ultraviolet-visible spectroscopy), or HPLC (high-performance liquid chromatography) testing.
Still, the most popularly used testing technologies for cGMP compliance in laboratories today is HPTLC and HPLC.
HPTLC is the essential and most commonly used analytical tool to efficiently and accurately determine botanical identity and to authenticate other raw materials. It is by far the most globally accepted method for plant identity.
HPLC is one of the most commonly used and accurate analytical technologies employed to identify and quantify specific compounds in a sample. HPLC is the primary tool used to determine purity, compare claims by raw material suppliers, determine degradation of actives, test the shelf life of dietary supplements, and verify a product’s contents to its nutrition label claims.
In some regulatory markets, government bodies are still deciding which testing methods they will officially accept as part of quality control. In the United States, FDA says that as long as a testing technique is “scientifically valid,” it can be used. But, for example, the Therapeutic Goods Administration in Australia does not accept FT-NIR technology for ingredient identification.
Weighing the Costs
When it comes to deciding which testing technologies make the most monetary sense for your company, keep in mind where the cost of testing lies and what the needs of your company are. DNA testing, for instance, is limited to use only on raw materials, not extracts, so this may not be suitable for all needs.
FT-NIR can also save time and money because the educational entrance level for using this testing technology is low. Today’s computing power makes this technique largely automated, with the computer essentially doing 100% of the work. One doesn’t need to be a PhD chemist to run the machine and can hire another laboratory to review and advise on the data. All other testing techniques mentioned above require hiring scientists with a foundation in chemistry or biochemistry to perform. (Of note, some FT-NIR units, while very expensive to purchase, can be used on a pay-per-service basis. Also, some units of this sort are sold with reference libraries that theoretically enable a company to do comparisons on site; however, these references libraries are limited only to the contents of the library that came with the machine, and there is no scientific oversight of the company’s process.)
Organoleptic and microscopy testing are by far the least expensive of testing techniques; however, they require experts with years of experience to perform with confidence. Time-tested equipment like HPTLC and HPLC, coupled with physical tests like organoleptic and microscopy, stand with proud posture as the most reliable and accepted techniques worldwide for cGMP compliance. Of the analytical techniques available today, HPTLC is the least expensive when one takes into account the cost of equipment, materials used, and the analysts needed to perform the analysis.
Return on Investment
Quality testing is undoubtedly expensive, but highly necessary. Without cutting corners, reducing compliance costs is a challenge. How does a company ensure quality control while still turning a profit? Of course, you could distribute this additional expenditure across the board by raising product prices-or, at worst, dip into your profit margin. Another option is to simplify your formulas and cease including ingredients that require advanced lab testing to verify and validate. FDA has made it clear that what is listed in ingredient label must be quantifiable-you must be able to indicate how much of the ingredient is present in your product. In order to measure many of these phytochemicals, new methods must be developed and sometimes require the most expensive of equipment to do so. None of those solutions may be ideal, however.
There are other ways to seek a return on your investment. Do not forget to make customers aware of all of the hard work you have put into your quality system. Advertise this as a part of your quality platform.
Remember that the investment you make in quality control can be leveraged with consumers. Through good marketing, make customers aware that you’re a company that invests in good quality management. In these times, when questions about supplement quality abound, customers will respond to a company whose product quality they can trust.
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