Integrator Advisor Speaks: Levin Looks at the Definition of "Quality" in the FDA's cGMP
Written by John Weeks
Integrator Adviser Levin on Dietary Supplements and the FDA's cGMPs: What Defines "Quality?" - a Second Look
Summary: Integrator adviser Michael Levin continues with his analysis and commentary on the current Good Manufacturing Practices (cGMPs) finally published by the US Food and Drug Administration. In this take, Levin looks at how the industry and the FDA have defined "quality" and finds out they are not aligned. What does this mean for practitioners and consumers? Levin brings it all home for ginger lovers with his analysis of a July 2007 action on imported ginger by a California regulatory agency. He credits the American Herbal Products Association (AHPA) for it's response to the FDA and offers a forecast.
Columnist Michael Levin
The current Good Manufacturing Practices (cGMPs) of dietary supplements published recently by the US Food and Drug Administration continues to generate analysis and controversy regarding its ultimate impact. The American Herbal Products Association, for example, petitioned the FDA to amend the rule. This is the third in a series of columns by Integrator advisory board member Michael Levin. Levin is an industry consultant who has served as an executive for both Big Pharma and dietary supplement firms.
Levin's initial column on the cGMPs took a first look at the quality issue. His
second column analyzed the likely impact of the regulations on the
natural products industry.
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The FDA’s New Dietary Supplement GMPs: What Is
"Quality" - Take 2
- Michael D. Levin, Health Business Strategies
The dietary supplement industry has defined “quality” in
several ways. Perhaps the most consumer-relevant definitions revolve around
these three attributes:
authenticity - the ingredients are exactly what is claimed on the label)
potency - the
amounts specified on the label are exactly the amounts contained in the
product) and
pure - the product is contaminant-free.
So, a product is “high
quality” if it’s authentic, potent, and pure, right?
Wrong. FDA disagrees.
In fact, in their Final Rule, FDA has defined “purity” in
such a way that a dietary supplement can be “100% pure” and “contaminated” at
the same time. Huh?
Rather than define “purity” in terms of an absence of
contaminants, FDA, on page 199, defines “purity” thusly:
“(Purity) refers to that portion or percentage of a
dietary supplement that represents the intended product”.
Under this definition, it is, therefore, quite legal to
claim and advertise calcium carbonate tablets as “100% Pure Calcium Citrate”,
when, in fact, the product contains heavy metals (e.g., lead) in amounts that violate California Proposition 65's strict limits for carcinogens and
reproductive toxins. (Prop 65 requires a warning on product labeling if the
product contains hazardous ingredients in amounts identified by the State of
California to cause cancer or reproductive toxicity. For a brief overview,
visit this site.)
In their
intent to provide the industry with flexibility and avoid burdensome quality
mandates, the cGMPs simply do not assure “superior quality”.
Side-bar for Ginger lovers
On July 29th, California
Department of Public Health (CDPH) – not the FDA - issued a warning to consumers not to eat fresh
ginger imported from China because some batches contained residues of aldicarb
sulfoxide, an illegal pesticide found in products sold through Albertsons and
Save-Mart stores. Says the CDPH:
"Symptoms of aldicarb poisoning in humans are likely to
occur within the first hour following exposure. Ingestion of foods contaminated
with aldicarb at low levels can cause flu-like symptoms (nausea, headache, blurred
vision) which disappear quickly, usually within 5 or 6 hours. However, at
higher levels, ingestion of aldicarb contaminated food can also cause
dizziness, salivation, excessive sweating, vomiting, diarrhea, muscle stiffness
and twitching, and difficulty in breathing."
Individuals who may have consumed this product and have
any of the above symptoms should contact their health care provider
immediately.
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That a cGMP-compliant “100% Pure” dietary supplement can
be a carcinogen or cause birth defects may seem odd, but it is a logical legal
approach that is consistent with other food regulations. In 2005, for example,
100% Pure Florida Orange Juice produced by Orchid Island Juice Company was
recalled due to salmonella contamination. It was pure. But it was not free from
salmonella contamination.
Bottom Line: “Pure” does not mean freedom from
contamination.
So, what then, is “quality”? FDA defines quality (page
34) as meaning:
“ ... that the dietary supplement consistently meets the established
specifications for identity, purity [as defined above], strength and
composition and has been manufactured, packaged, labeled and held under
conditions to prevent adulteration under section 402(a)(1), (a)(2), (a)(3) and
(a)(4) of the Federal Food Drug and Cosmetic Act.”
Under the new cGMPs, the manufacturer must define
specifications for:
“ ... identity, purity, strength, composition and for limits on
those types of contamination that may adulterate or that may lead to
adulteration of the finished batch of the dietary supplement” (page 774).
Manufacturers, therefore, have the flexibility to define
quality by the specifications they choose for their products. Analytical testing
is expensive. Some companies may choose to “specify” extensive testing on all
incoming raw materials, looking for solvent residues, pesticide residues, etc.
Many won’t. Many will rely upon the suppliers Certificate of Analysis. Just as
Pharma relied upon the Certificate of Analysis that accompanied the Chinese
glycerin which contained the economic adulterant, diethylene glycol, (aka
“DEG”, sourced from Iran) which FDA reports in 2006 caused more than 40 deaths
in Panama. As a result, FDA commented that the Certificates of Analysis were
fraudulent and issued guidance to Pharma to test for the presence of DEG in
glycerin on incoming batches of glycerin.
The Good News:
There is excellent work being done by certain
organizations like AHPA who have already petitioned FDA to amend the final rule.
Yes, this is the same DEG recently reported in imported
toothpaste.
At a recent presentation, I urged industry to define
their specifications as if the future of the industry depends on it. Because,
it does.
The Good News: There are some great, high minded
companies, committed to quality leadership. Where cost-effective test methods
exist to assure authenticity, potency and maximum freedom from contamination
exist, they use them, consistently. They embrace their responsibility as
“guardians at the gate” to ensure that their health promoting products contain
exactly what they should and don’t contain what they shouldn’t. They know, as
Pharma was told by FDA, that Certificates of Analysis can’t always be trusted.
And there is excellent work being done by certain
organizations who have already petitioned FDA to amend the final rule,
requesting, (AHPA, for example) that suppliers of dietary ingredients (the
active ingredients in the supplements themselves) NOT be excluded from this
final rule (yes, ingredient suppliers are exempted from this rule!)
Forecast: Competition in the industry will increasingly
be done on the battlefield of quality. As this matures, consumers will become
more educated and empowered to make more informed choices. Prices for “high
quality” supplements will increase. FDA forecasted price inflation resulting
from the cGMPs– I agree.
In the meantime, consumers will purchase “100% Pure”
supplements, cGMP-compliant as well as third-party “certified”, that may still
violate California Prop 65 limits. And the higher quality, more extensively
tested and more expensive product, may languish on the shelves because
consumers just cannot discern the quality difference between the two. In their
intent to provide the industry with flexibility and avoid burdensome quality
mandates, the cGMPs simply do not assure “superior quality”.