Dietary Supplements: Legal and Quality Issues - A Primer for Healthcare Practitioners
worked for pharmaceuticals
now on natural products
wrote a book with Pizzorno on FDA's missing the boat on GMPs
works w/ Cancer Treatment Centers of America
July launch of supp formulary committee in a hospital
he will offer guidelines for product selection
GMP = great mounds of paperwork
regulating agencies: FDA, FTC (regs advertising), USDA, EPA, US Customs, ATF
FDA regs: biologics, cosmetics, drugs, foods except meat/poutry, med devices, vet products, supps
Supps since 1994 (DSHEA)
SUPPLEMENT DEFINED by DSHEA
PRODUCT INGESTED IN PILL, CAPSULE, POWDER, TABLET OR LIQUID FORM, (NO SL, OTIC, TOPICALS, ETC), intended to supplement the diet
a vit, mineral, herb or bot, aa, dietary substance for incr dietary intake, concentrate, metabolite, constituent extract or combo of any ingredient described above
FDA regs labeling
label = display on container
labeling = written or graphic matter on any container, wrapper of accompanying info
label must contain:
1999 statement of identity on PDP, supp facts box (1999), proprietary blend provision
can't say: "more", "high", "antioxidant" etc
can't recommend using in combo with a drug (CoQ10 w/ statins)
health claims: can describe relation btw substance and dz or condition
structure/fx claims: descbe relat btw substance and effect on body
must be "truthful and not misleading"
mislabeled = inaccurate
misbranded = error of omission
adulterated = risk of illness/injury
unapproved new drug = unapproved health claims
cholestin = red yeast rice
Shalala vs Pharmanex 1998
gras = generally recognized as safe, a claim that is not well regulated
companies can say that anything in diet is gras
(at what dose for how long in what pop?)
if an ingredient is gras you can put it in food
botanical drug = use in dx, cure, mitigation, tx or prevention of dz in humans
introduced in 2000
incl veg, tea, topical, injx
400 INDs submitted since 2000 (investigational new drugs) only 1 approved per M
approved: antiviral green tea based vaginal cream
final rule for cGMPs published in 2007 when expected in 1995
why the gap?
during that time only enforcement in the most egregious circumstances
blames it on "FDA malfeasance"
Peter Barton Hutt ex general counsel for FDA
said-->Kessler ordered FDA not to enforce new law,
he wanted supps to "run wild" so congress would repeal law
who is Kessler need more about him
result of delay: variability in quality, recalls, tx failures, subpotent prods,
failed research, cred of supps undermined, people are confused,
contamination-->future health issues???
NDI = new dietary ingredient, incl no hx use, chem alteration, evidence of safety
wasn't marketed before 1994 DSHEA
NDIs require 75 day pre-market notification to FDA
ex: DMSA (dimercaptosuccinic acid) smacked down for chelation, was sold as supp before 1994 (start in 89?) which predates IND for DMSA, now is prescription only, last Nov FDA said it's an unapproved new drug but FDA produced evidence that it was in a radiological kit in the 1980's that predated supp use so now scrip only
CGMPS = current good manufacturing process
"Quality is neven an accident, it is always the result of high intention, sincere effort, intelligent direction and skillful execution, it represents the wise choice of many alternatives."
many different GMP labels
2003 proposed FDA cgmp rule came out
831 pages, response to 400 Q's, modeled after infant formula cgmps
some say final is diluted and "deeply flaxed version" of 2003 proposal:
adulteration included loss of identity, purity, quality, strength, composition
final rule doesn't require potency or contaminant testing
16 sections: general, personnel, physical plant, equipment, production, quality, pkging and labeling, master record, batch production record, lab op, manufacturing ops, pkg & labelin ops, distrib, returns, complaints, records
companies with over 500 employees up to standard by 2008, smaller later, under 20 next june
FDA Quality = meets specs for id, potency, purity, composition, allowable levels of contaminants
all components must have specifications:
dietary ingredients are components, must have at least one spec for identification
(optional: potency, purity, composition, allowable contaminants)
specs defined by company not FDA
FDA didn't set limits for microbes
FDA focus: flexibility, minimal impact on economy (pro-business slant)
"fox is guarding the henhouse"
FDA on purity:
"that portion or percentage that represents the intended ingredient"
Calif prop 65 sets limits for carcinogens or reproductive toxins
USP defines purity in terms of a % (ppm, ppb, etc)
state of CA took different angle, defines 400 chems with absolute limit
above which there must be labeling to warn: carcinogen or reproductive toxin
Imports are supposed to comply with cgmps
"when pigs fly"
no requirement for independent testing
quality depends on company integrity
invoice gives product specs
5 ELEMENTS OF QUALITY per Mike
DESIGN = evidence based formula in appropriate dose
AUTHENTICITY = ingredients verified
POTENCY = verfied using validated methods
PURITY = proven free of bio & chem contam
VALIDATION = safe and efficacious for intended use
"industry in general doesn't do a good enough job validating their input"
supply chain is fractured
25% of supps subpotent, contaminated, or both
1400 prods, 250 manufacturers
78% of milk thistle products failed based on 3 tests: lead, disintegration, silymarins
consumerlab not testing for aflatoxin, solvents, pesticides, microbes
saw palmetto 19% subpotent
chondroitin 46% subpotent
ginseng 36%, 8/22 had pesticides, lead, subpotent
CoQ10 3% subpotent (17% of label claim), volatile price history, when price high more subbing
St JW 33%
Vit E 27%
B vits 7%
one company had huge lead spike dt silicon dioxide mined in "hot spot"
green tea 43%
heavy metals less than 10ppm means what??
method 231 in US pharmacopoea: cheapest test
nonspecific colorometric test measuring presence of heavy metals at ppm
from 1918 or something like that?
doesn't tell what metal is there, expresses everything as lead
better technology is available, you can tell what metals are in there
ask HOW they test for heavy metals
Why product failures? contamination?
incr imports from China, water shortages, less envir control, irrig w/ indust wastewater
1998 China has most hep ca mort
Chloramphenicol in food, toxic amounts in honey dt bee farming use toxin instead of smoke-->
(aplastic anemia)--> Eur bans chinese food in 2003, temporary
EMA = economically motivated adulteration "spiking"
CRN = council for responsible nutrition
intentional reliance on outdated or nonspecific testing methods
few if any consequences for violations
GMPs alone don't defence against ema because cos make own specs
"dyes, colored sawdust, and even crayons are used to imitate far more expensive extracts from fruits, berries, etc"
milk thistle loaded with acetone, aflatoxin at 2x fda limits
"paper never refuses ink" you can't trust
curcumin contam w/solvent 10x limit
hirsutella sinensis: 30x limit melamine!! dt milk powder from China, otherwise fine
WHAT CAN I DO
ask to see specs
ask to see analytical results for product and lot
don't accept skip-lot testing
rushed through end of presentation
I missed the sign in for this presentation and learned that the contact in that case is NOT sheryl it is skateschinoy at ncnm dot edu...