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QUALITY ASSURANCE

The Difference Between Quality Control and Quality

Assurance Using an Example of Pomegranate Extract
Rick Liva, ND, RPh

Disclosure: Dr Liva has been involved in dietary-supplements manufacturing since 1985 and is the president, CEO, and director of
Quality Control and Quality Assurance at Vital Nutrients, a company certified by the Natural Products Association for current Good
Manufacturing Practices.

n this column, I will distinguish 3 things: first, the distinctive

definitions of quality control (QC) and quality assurance (QA);
second, what these terms mean to clinicians; and third, how
these terms can be applied to a product such as pomegranate
extract. As is the case for any supplement/remedy, by making sure
a manufacturer follows some basic quality standards, the clinician
can avoid purchasing low-quality products.
I learned about the reported issues with pomegranate
extract by conducting testing (the QC portion of this article) on
various ingredients available in the marketplace. Pomegranate
extract is emerging as a useful clinical tool for the prevention and
treatment of health issues such as oxidative stress1specifically,
it has been shown to exert significant antiatherogenic, antioxidant, antihypertensive, and antiinflammatory effects2and we
will likely be seeing more products containing it.

QC/QA Definitions and FDAs Use of GMPs

The terms quality control and quality assurance are often

used interchangeably to refer to ways of ensuring the quality of a
product. In actuality, they have different meanings. Below, I have
listed several ways to define both, giving the reader a broad
scope of how to reconcile and think about them.
For this to make sense, there first has to be a general consensus on the word quality. Within the industry, quality means that
the dietary supplement under consideration consistently (ie,
batch to batch) meets the established specifications for identity,
purity, strength, composition, limits on contaminants, and shelf
life. It also means that it has been manufactured, packaged,
labeled, and held under conditions to prevent adulteration.
To this end, quality control means a systematic procedure for
ensuring the quality of a dietary supplement (eg, running tests
such as thin-layer chromatography, high-performance liquid
chromatography, or gas chromatography/mass spectrometry to
determine specific amounts of product constituents and/or contaminants). Thus, QC is a companys control over product quality and involves testing, reviews, and (occasionally) simulations
and mathematical provings. The end result of QC is the answer
as to whether each batch does or does not meet the set product
specifications, as mentioned above, for identity, purity, strength,
composition, limits on contaminants, and shelf life.

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Integrative Medicine Vol. 8, No. 3 Jun/Jul 2009

Quality assurance, on the other hand, refers to the processes

used to create a product. Examples include process checklists
(eg, performance logs) and project audits. Basically, it is the
standard by which a company administers its quality measures
(versus tests for an individual product), often based on regulations such as the US Food and Drug Administration (FDA) current Good Manufacturing Practices (cGMPs). It involves internal
or external audits to ensure compliance with those standards
thus, QA can be ascertained and/or performed by a manager,
third-party reviewer, or even a client.
Simply put, QC is conducting testing and performing
procedures to ensure that established quality specifications for
raw material and finished products are met. QA is the strict regulation of all of the processes used to create the final product.
An important point to remember with all of this is that you
can have QA while doing very little QC testing. That is to say, a
dietary supplements manufacturer can have established raw
material and finished product specifications (a part of GMPs)
and have all its quality assurance processes in place, but some or
all of its products still may not meet standards of acceptable
quality controlproducts may be low potency, contaminated,
not last out their shelf life, etc. The FDA cGMPs do not mandate
that a manufacturer has to establish high-quality specifications,
just that it has to have specifications, even if low quality.
This is why I write these columns, so clinicians can understand this important fact. It is also why the recent FDA cGMPs
can be used as a cover by disreputable companies to hide behind
if, in fact, they have established low-quality specifications.*
Comprehensive QC testing is the key to producing quality natural products because it covers all the bases for high quality (identity, strength, and a full spectrum of contaminants).
QC and QA as Seen in Pomegranate Extract

Pomegranate juice (PJ) has recently become popular in the

United States. It has more potent antioxidant properties than
other common fruit juices due to its high content of polyphenols.
Research has been published on the ability of pomegranate
polyphenols to be antiproliferative, proapoptotic, antiangiogenic, and capable of inhibiting NF-Kappa Beta activity.3
The most abundant polyphenols in PJ are ellagitannins
(ETs), which are not absorbed intact into the blood stream but,
instead, are hydrolyzed to ellagic acid and then released into the
*If you find it surprising that the FDAs cGMPs leave open the possibility of inadequate
testing and poor-quality products, please read 2 articles in IMCJs Oct-Nov 2007 issue:
New FDA cGMPs for Supplements: Smoke or Substance? by Rick Liva, ND, RPh (IMCJ
6.5:28-32); and FDAs Natural Product cGMPsA Missed Opportunity by Joe Pizzorno,
ND, with Michael D. Levin (IMCJ 6.5:8-10).

LivaQuality Assurance

blood.3 Ellagitannins are also metabolized by gut flora into urolithins, which are conjugated in the liver and then circulated in
the blood. These ET metabolites reach many of the target organs
where the effects of pomegranate ellagitannins, such as those
noted above, are seen.3
PJs ellagitannins are part of a family of minor tannins that
include punicalin and gallagic acid. However, at this time, 2 of these
ETs have been found to be unique to pomegranate: punicalagin A &
B. Punicalagins have been reported to be responsible for more than
half of the juices potent antioxidant activity.3 They are most abundant in the fruit husk as opposed to the juicy seeds.3
It is by pressing the whole fruit during processing that ellagitannins are extracted into PJ in significant quantities, reaching levels of >2 g/L of juice. PJ also contains other polyphenols such as
anthocyanins (cyanidin, delphinidin, and pelargonidin glycosides)
and flavonols (quercetin, kaempferol, and luteolin glycosides).3
A significant amount of the published animal and human
research has been done using the POM Wonderful brand of juice
or the POM Wonderful powdered extract. Why is this significant? It makes sense to me that, since a vast amount of research
has been done on this particular juice/extract, any other juices or
powdered extracts should have a chemical constituent profile
that mimics POMs as closely as possible.
I have had the ellagic acid, ellagic acid hexoside, punicalagin, and anthocyanin content of POM juice analyzed by an
independent lab at least twice. In addition, I had other brands
pomegranate products analyzed, including several pomegranatehusk extracts, a concentrated juice product, a freeze-dried,
whole-fruit powder, a spray-dried juice powder, and a raw-husk
product. I found that no product even came close to the punicalagin, ellagic acid, ellagic acid hexoside, and anthocyanin content of 8 oz of the POM juice. In fact, no pomegranate extract
that claimed 40% punicalagins actually tested out at that level;
they were all subpotent.
Lastly, and considerably more blatant in their attempt to
deceive, some pomegranate extracts that claim 40% ellagic acid
are spiked with the acid to reach that claimwhich is actually
not surprising since ellagic acid in naturally occurring pomegranate extract is 2% to 4% on average. Unfortunately, a full discussion of the analytical results are beyond the scope of this
article, but I am happy to speak with whomever may want more
information on these results.
I mentioned all of the above information because it is relevant to the QC portion of developing a clinically efficacious
product. With comprehensive testing (the bones of QC) on the
starting raw materials, a supplements manufacturer can develop
an understanding of the chemical constituents that have proven
medical benefit and generally fashion a product that, in the end,
will have a high degree of efficacy. Without comprehensive testing, however, this is a gamble. As seen above, if a manufacturer
doesnt knowor at least doesnt matchhow much ellagic
acid and punicalagin is in the researched pomegranate juice, how
can it create a product that is equally as effective?
As for the clinician, you need to know if the product you buy
matches the specifications of the product that has been
researched. It doesnt do anyone any good to buy a pomegranate

LivaQuality Assurance

extract to be used for clinical benefit if the product being sold

doesnt have the same amount of necessary constituents as the
researched product. Thats what is called borrowed science (and
not an equitable borrowing at that).
Beyond whether there is medical benefit to the specified
amount of nutrients included in a supplement, the clinician also
needs to know if a product actually meets label claim for these
amounts (which the ones mentioned above did not). So there is a
double whammy. On the latter, consider what I mentioned before
about the deficiencies of FDAs cGMPs: current dietary supplement laws allow for a manufacturer to set specifications for its own
quality. Unfortunately, some or many manufacturers of dietary
supplements will set a low quality specification for their raw
materials. Hence, it is up to you, the clinician, to find out if that is
the case. Ask your vendors what type of comprehensive testing
they are routinely performing on their raw materials and finished
products. Routine comprehensive testing is the most important
key to building high quality into a dietary supplement.
So in this example of pomegranate, QC testing is necessary
to verify that the product being sold matches, to some degree,
the specifications of the product that has been researched and,
also, that the label claim is met. QA is in play throughout because
it is the strict regulation of all the processes used to create the
final product.
Obtain Objective Evidence of Quality Testing and
Then Evaluate the Results

The road to ensuring high quality is successfully traveled

when clinicians ask for and obtain valid evidence (test results) of
a products identity (authenticity), purity (maximum freedom
from contamination), and shelf-life strength. Then, once you
have the test results in hand, they must be evaluated for scientific validity.
To this end, a number of years ago, I developed and wrote a
questionnaire entitled The Manufacturer Quality Assurance
Self-Audit Form, which was published in the Aug-Sept 2006
issue (IMCJ 5.4:41-44) and has since been available since on the
IMCJ website. The form is intended to give clinicians a basis
upon which to question manufacturers and/or suppliers about
their QC and QA practices.
After these several years of use and feedback, I have now
renamed the form and developed a more simplified questionnaire (only 20 questions) that clinicians can use as a productquality testing and verification/certification tool. We have included it in this issue on the pages following this article, and it is also
available on the website, www.imjournal.com. On the menu bar,
click on Resources & Content. The second listing on the dropdown menu is Quality Assurance. On the corresponding web
page, you will see The IMCJ Supplement Quality Audit Form.
Take the Time to Verify Quality; Use the Tool

This new questionnaire is considerably shorter than the

original and focuses primarily on asking for the test data used to
ensure quality. I ask you please, for the sake of your patients
health and safety, to send this form to each of your natural products suppliers and/or manufacturers and see what comes back.

Integrative Medicine Vol. 8, No. 3 Jun/Jul 2009

49

Resources to Help Evaluate QC and QA Data

From Suppliers and/or Manufacturers

The academic experience of most clinicians does not educate

them on the details of how to ensure quality in dietary supplements. Knowing about and using outside resources is a
critical tool in helping you gain some knowledge in this
arena. Think of it as part of your continuing education. The
following resources are available should you choose to use
them (some are consultants who charge for their time and
some may be able to briefly help you for no remuneration).
Blaze Science Industries LLC: Technical expertise in scientifically valid testing of dietary supplements. 4547 West
171st St, Lawndale, CA 90260. Phone: 310.920.4517.
Contact: Jana Hildreth, CEO and Technical Director.
E-mail: janah@socal.rr.com. Website: www.bsillc.org.
EAS Consulting Group LLC: Consultants specializing in
FDA regulatory matters. 1940 Duke Street, Suite 200,
Alexandria, VA 22314. Phone: 877.327.9808. Contact:
Edward A. Steele, President. E-mail: esteele@easconsultinggroup.com. Website: www.easconsultinggroup.com.
Flora Research Laboratories: Resource for evaluation
of scientific validity of lab methods used to test dietary
supplements. 1000 SE M Street, Unit B, Grants Pass,
OR 97526. Phone: 541.472.0980. Contact: James NealKababick, MS , Director, Past Chairman of the
Association of Analytical Communities International
Dietary Supplement Methods Validation Committee.
E-mail: jimk@floraresearch.com. Website: www.floraresearch.com.
The Natural Products Association Dietary Supplement
GMP Certification Program: 1773 T Street, NW,
Washington, DC 20009. Phone: 202.223.0101. Contact:
Vicki Whitsitt, Science and QA Assurance Manager.
E-mail: vwhitsitt@NaturalProductsAssoc.org. Website:
www.naturalproductsassoc.org.
QSD Consulting: A dietary supplement GMP consultant
and auditor. 430 Main St, Benton, PA 17814. Phone:
570.925.2880. Contact: Cindy Beehner, Owner.
E-mail:cindybqsd@netzero.net. (No website.)
QSI: Quality Systems Implementation: A dietary supplement GMP consultant and auditor. Midvale, UT. Phone:
801.838.9603. Contact: Warren Majerus, MS, Owner.
E-mail: majerus@mindspring.com. Website: http://
dsgmpdocs.us.
Tampa Bay Analytical Research Inc. Resource for evaluation of scientific validity of lab methods used to test
dietary supplements. 10810 72nd St, Unit #206, Largo, FL
33777. Phone: 727.544.8481. Contact: Mark Roman, PhD,
Owner, Past Chairman of AOAC International Dietary
Supplement Methods Validation Committee. E-mail:
mroman@tampabayanalytical.com. Website: www.tampabayanalytical.com

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It directs them to answer a series of questions but also asks for

documentation that helps provide verification that they are, in
fact, doing what they claim to be doing. The questionnaire asks
for proof as well as yes-or-no answers. It is easy to answer yes to a
question on a form; it is more difficult to provide proof.
I also include a new guidance document that may help you
evaluate the responses you receive back (see Compliance Guide
for The IMCJ Supplement Quality Audit Form on page 51, after
the questionnaire). Finally, I include a sidebar on this page listing
resources in case you need further clarification and education.

Rick Liva, ND, RPh, graduated from Temple University School of Pharmacy in
1975 and National College of Naturopathic Medicine in 1982. He is the managing physician at the Connecticut Center for Health, located in Middletown and
West Hartford. Dr Liva is a founding member of the American Association of
Naturopathic Physicians and past president of the Connecticut Society of
Naturopathic Physicians.
References
1. Kishore RK, Sudhakar D, Parthasarathy PR. Embryo protective effect of pomegranate
(Punica granatum L.) fruit extract in adriamycin-induced oxidative stress. Indian J Biochem
Biophys. 2009;46(1):106-111.
2. Basu A, Penugonda K. Pomegranate juice: a heart-healthy fruit juice. Nutr Rev.
2009;67(1):49-56.
3. Heber D. Multitargeted therapy of cancer by ellagitannins. Cancer Lett.
2008;269(2):262268.

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