Nutrition Related Nutrition Related Regulatory Issues Regulatory Issues Kathleen Ellwood, Ph.D. Director, Division of Nutrition Programs and Labeling Office of Nutritional Products, Labeling, and Dietary Supplements
Dec 20, 2015
Nutrition Related Regulatory Nutrition Related Regulatory IssuesIssues
Nutrition Related Regulatory Nutrition Related Regulatory IssuesIssues
Kathleen Ellwood, Ph.D.Director, Division of Nutrition Programs
and LabelingOffice of Nutritional Products, Labeling,
and Dietary Supplements
Topics To Be CoveredTopics To Be Covered
• Fortification Policy• Biotechnology Labeling Guidance• Health Claims
Fortification PolicyFortification Policy
• Established in 1980• A uniform set of principles as a model for the
rational addition of nutrients to foods• Lists the 20 vitamins/minerals and ptn for which
there were established U.S. RDAs in 1980; appropriate fortification levels based on a nutrient density
Fortification Policy – con’t.Fortification Policy – con’t.
Addition of nutrients to foods can:• be an effective way to maintain and improve
overall nutritional quality of the food supply• create nutrient imbalances in the food supply• contribute to deceptive or misleading claims for
certain foods
Fortification Policy – con’t.Fortification Policy – con’t.
FDA does not consider it appropriate to fortify:• fresh produce;• meat, poultry, or fish;• sugars; or• “snack foods such as candies or carbonated
beverages.”
Biotechnology LabelingGuidance
Biotechnology LabelingGuidance
Voluntary Labeling
Indicating Whether Foods Have or Have Not Been Developed Using Bioengineering
Labeling of Bioengineered Foods
Labeling of Bioengineered Foods
• Food must be labeled when there is a significant change in the food: • nutritional;
• compositional;
• change in conditions of use; or
• when an allergenic component has been introduced in a food where it does not naturally occur.
FDA Actions FDA Actions
Held three public meetings in 1999
Conducted focus group studies
Developed draft guidance in
January, 2001
Biotechnology Draft GuidanceBiotechnology Draft Guidance
• Does not require special labeling of all bioengineered foods based on production method
• Restates agency’s policy regarding when special labeling is required for bioengineered foods
• On web at: http://www.cfsan.fda.gov/~dms/biolabgu.html
What It Takes To Get A Health Claim
Evidence-Based Ranking SystemEvidence-Based Ranking System
The review of the evidence for SSA health claims and qualified health claims is the same review.
Reviewing the Evidence 1999 and 2003
Reviewing the Evidence 1999 and 2003
Define substance/disease relationship
Identify relevant studies Classify studies Rate studies for quality Rate for strength of body of
evidence: quantity, consistency, relevance
Report “rank”
Substance/Disease RelationshipSubstance/Disease Relationship
Causal relationship between a substance and a disease or health related condition for the general U.S. population or subpopulation:
• Substance – food or food component
• Disease – damage to an organ, structure or system of the body such that it does not function properly (e.g. CHD), or a state of health leading to dysfunctioning (e.g. hypertension)
SSA and Qualified Health ClaimsSSA and Qualified Health Claims
Health Related Condition:• A condition so equivalent to the disease as to be
indistinguishable from the disease (e.g. hypertension), or
• A validated modifiable risk factor for disease (e.g. LDL cholesterol)
56 Fed Reg 2478 at 2481, Jan 6, 1993.
Relationships Between Diet and Disease
Or Health Related Conditions
Relationships Between Diet and Disease
Or Health Related Conditions
ValidatedModifiable
Risk Factors
Disease/Health Related
Condition
DiseaseSymptomsand Signs
Drugs21 USC 321 (g)(1)(B)
Health Claim21 USC 343(r)(5)(D)
Substance
Diseases and Validated Modifiable Risk FactorsDiseases and Validated Modifiable Risk Factors
CHD Total/LDL cholesterol
Cancer Colorectal/polyps
Diabetes Blood sugar levels
Osteoporosis Bone mineral density
Dementia Mild cognitive impairment
Identify Relevant StudiesIdentify Relevant Studies
• Studies involving healthy humans
• Studies that measure validated, modifiable risk factors
• Studies that measure reduced risk of disease or health related condition
Classify StudiesClassify Studies
• Intervention studies – “ Gold standard” -- Measured modifiable risk factor, i.e. LDL-
cholesterol soy protein and CHDwalnuts and CHD
-- Measured incidence of onset of diseaseomega-3 fatty acid and CHD fiber-containing grain products, fruit and
vegetables and cancer
Classify Studies – con’t.Classify Studies – con’t.
• Observational studies – less reliable-- measurement of substance-- confounders of disease (other nutrients)
• Prospective cohort
• Case-control
• Cross-sectional – least reliable
Rate Studies for QualityRate Studies for Quality
• Study design
• Data collection
• Inclusion and exclusion of study subjects
• Statistical methods/analysis
+ (good)
(moderate)
(poor)
Rate for Strength of the EvidenceRate for Strength of the Evidence
• Type of studies
• Quality
• Quantity of studies and sample size
• Consistency of findings
• Relevance to general population or target subgroup
Report “Rank”Report “Rank”
Significant Scientific Agreement
Strong, high quality, relevant and consistent body of evidence. Conclusions not likely to be reversed with new data (1999 and 2003)
High Level of Comfort = A
Report “Rank”Report “Rank”
Qualified Health Claims
• Moderate/good level of comfort (B)
• Low level of comfort (C)
• Extremely low level of comfort (D)
Qualifying LanguageQualifying Language
Intended to qualify the level of credible scientific evidence for a substance-disease (risk-reduction) relationship in the general population.
But Not Intended To Qualify The…• Extrapolation of treatment/mitigation data (drugs) to
risk reduction (nutrients).• Lack of a validated, modifiable risk factor which
serves as the link between a substance and disease risk reduction.
• Fact that evidence on disease risk reduction is only observed in animals.
Selenium and CancerSelenium and Cancer
Selenium and CancerIntervention Studies
Selenium and CancerIntervention Studies
• Clark et al., 1996 (Nutritional Prevention of Cancer Trial) – U.S. No effect on the primary end-point (non-melanoma skin cancer), reduced risk of total, prostate, lung and colorectal cancer
• Duffield-Lillico et al., 2002;• Reid et al., 2002 – post-hoc analysis, 7.9 yr follow-up,
reduced risk of total and prostate cancer; no longer with lung and colorectal; especially for males with low plasma selenium levels
• Yu et al., 1991 – reduced rate of liver cancer in malnourished Chinese
• Blot et al., 1993 (Linxian Trial) – lower stomach cancer mortality in malnourished Chinese
Selenium and CancerIntervention Studies – con’t.
Selenium and CancerIntervention Studies – con’t.
Multi-nutrient supplement provided - Not able to evaluate the effect of Selenium per se• Blot et al., 1993, 1995 - China
• Li et al., 1993 - China
• Prasad et al., 1995 - India
• Bonelli et al., 1998 - Italy
Selenium and CancerObservational StudiesSelenium and CancerObservational Studies
36 Studies
16 prospective cohort studies,
3 retrospective case-control studies,
17 ecological and cross-sectional
½ supported an association for total cancers½ did not support an association for total cancers
Observational studies showed the greatest benefit with prostate cancer and no association of Se intake and
breast cancer.
Qualified Health ClaimQualified Health Claim
• Nutritional Prevention of Cancer Trial, showed a benefit in males with low plasma selenium levels with post-hoc analysis; only study applicable to U.S. population
• Yu et al., 1991, China, indicated Se per se decreased liver cancer
• Blot et al., 1993, 1995, China, Se containing multi-nutrient decreased stomach cancer
FDA determined evidence to be limited and not conclusive.
What’s Needed?What’s Needed?
• Well controlled clinical trials
• Substance well defined
• Well defined and measured surrogate endpoints that demonstrate risk reduction
• If validated endpoints lacking, then trials need to be of long enough duration to measure incidence of disease
Food Labeling InformationFood Labeling Information
www.cfsan.fda.gov/label.html