Download Medical Foods: An Evidence-Based Approach to Product

Medical Foods: An Evidence‐Based Approach to Product Development
Robert McQuate, Ph.D.
Chief Regulatory Officer & Senior VP of Business Development, GRAS Associates
Cheryl Dicks, M.Sc., RAC
Director of Operations & Senior Regulatory Affairs Project Manager, GRAS Associates
William J. Rowe, BA
President & CEO, Nutrasource
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Objectives of This Session
You will learn:
 Business and market expansion opportunities for food ingredients in the medical foods category
 Regulatory compliance requirements for medical foods
 What part Generally Recognized as Safe (GRAS) status plays for a food ingredient in medical food compliance
 What is the “gray zone” in medical food regulations
 Review of FDA warning letters and the marketing and regulatory pitfalls to avoid
 Overview of the scientific evidence required to support an ingredient as a medical food
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Medical Foods: An Evidence‐Based Approach to Product Development
Cheryl Dicks, M.Sc., RAC
Director of Operations & Senior Regulatory Affairs Project Manager
GRAS Associates
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Medical Foods: An Evidence‐Based Approach to Product Development
Medical food category
• Is a special regulatory category for “food” as regulated by FDA
• Defined under the Orphan Drug Act (21 USC 360ee (b)(3))
• 21 U.S. Code § 360ee (a)(3) authorizes the government to “make grants to and enter into contracts with public and private entities to assist in defraying the costs of developing medical foods for rare diseases or conditions”
• Appropriated $30,000,000 for each of fiscal years 2013 through 2017.
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Medical Foods: Steps to Market
Confirm regulatory status Registration of Manufacturing Facility
Confirm Label
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Market to Physicians
THE FIVE CRITERIA FOR DEFINING MEDICAL FOODS
1. Specially formulated and processed product (as opposed to a naturally occurring foodstuff used in its natural state) for the partial or exclusive feeding of a patient by means of oral intake or enteral feeding by tube
2. Intended for the dietary management of a patient • because of therapeutic or chronic medical needs, has limited or impaired capacity to ingest, digest, absorb, or metabolize ordinary foodstuffs or certain nutrients or
• special medically determined nutrient requirements, the dietary management of which cannot be achieved by the modification of the normal diet alone.
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THE FIVE CRITERIA FOR DEFINING MEDICAL FOODS
3. Provides nutritional support specifically modified for the management of the unique nutrient needs that result from the specific disease or condition, as determined by medical evaluation
4. Intended to be used under medical supervision
5 Intended only for a patient receiving active and ongoing medical supervision wherein the patient requires medical care on a recurring basis for, among other things, instructions on the use of the medical food.
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FDA’s Compliance Program for Medical Foods
Classification of Medical Foods
• Nutritionally complete formulas;
• Nutritionally incomplete formulas, including individual "modular" type/ingredient products that may be mixed with other products before use (e.g., protein, carbohydrate, or fat modulars);
• Formulas for metabolic (genetic) disorders in patients over 12 months of age
• Oral rehydration products
http://www.fda.gov/downloads/Food/GuidanceComplianceRegulatoryInformation/ComplianceEnforcement/ucm073339.pdf
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Medical Foods: An Evidence‐Based Approach to Product Development
Robert McQuate, Ph.D.
Chief Regulatory Officer, Senior VP of Business Development
GRAS Associates
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Regulatory Compliance for Medical Foods: GRAS Considerations for Ingredients in Medical Foods
• From FDA’s Definition of Medical Foods…
• …It is a specifically formulated and processed product (as opposed to a naturally occurring foodstuff used in its natural state)…
• Medical foods comprised of one or more ingredients
• Critical question: What ingredients are permitted in medical foods? – Safe & Suitable Ingredients
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FDA Guidance Document
Safe & Suitable Ingredients
• Approved food additives (21 CFR 172)
• Approved color additives (21 CFR 73 & 74)
• Substances authorized by FDA by prior sanction
• Generally Recognized As Safe (GRAS)
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More on GRAS Ingredients
INGREDIENTS HAVING GRAS STATUS
• FDA GRAS Listings in 21 CFR 182 & 184 • FDA GRAS Inventory of GRAS Notifications Submitted to FDA for Review & Feedback— 594 GRNs on FDA’s Website (as of October 5, 2015)
• Self‐Determined (i.e., Self‐Affirmed or Independent) GRAS Determinations
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FDA GRAS Inventory
• FDA GRAS Notifications Specifying Medical Food Usage – ~ 20 as of October 5, 2015 • Topics Include Dietary Sources of – Carotenoids
– Selenium
– EPA/DHA & Krill Oil
– Fiber
– Sweetener Substitutes
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Selected Examples of GRAS Substances with Medical Food Applications
• GRN 242 Neptune Technologies Krill Oil
• GRN 260 Cypress Systems High Selenium Yeast
• GRN 278 Blue California Rebaudioside A
•
GRN 437 Garuda Intl β‐Glucans from Oat Bran
Prepared by GRAS Associates, LLC
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Self‐Determined GRAS Assessment
Whey‐Derived Protein for Phenylketonurics
• Whey protein treated to remove aromatic amino acids including phenylalanine – PKU
•
Pleasant tasting mixture with more complete amino acid protein composition since can add back tyrosine & L‐tryptophan (which are also removed in processing)
• After documenting removal of phenyalanine with pilot scale production & confirming favorable taste profile, firm pursued self‐
determined GRAS status
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Ingredient for Phenylketonuria
• Reasonable Certainty of No Harm Under Intended Conditions of Use…GRAS Requirement
– Thorough Compositional Characterization
– Validate Food Grade Whey Protein Starting Material
– Rigorous Review of Production Method to Assess Potential for Presence of Toxic Components & Residues
– Determine Estimated Dietary Intake Levels
– Assess Safety of Finished Product from Composite Information – Including Inherent Safety of Whey Protein Starting Material
• Added Safety Feature with Medical Foods – FDA ‐ Required Healthcare Professional Oversight
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Medical Food Category
• Growing speciality product category presents both interesting business opportunities for market expansion • Estimates to be approximately a $1‐1.3 billion market
• U.S. has seen over 100 new medical foods since 2009 (From Business Insights: The Emerging Market For Medical Foods Nutraceuticals World
• Regulatory challenges within the “gray zone” of FDA regulation of medical foods. www.ifosprogram.com
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“gray Zone” in Medical Foods
With medical foods it is important to remember:
• Distinctive nutritional requirements
• Can be Foods intended for persons not able to ingest foods in certain physical forms
• An integral part of the patent's clinical management under medical supervision
• is intended for the "specific dietary management" of a disease or condition
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“gray Zone” in Medical Foods
• August 2013 FDA revises their draft Guidance for Medical Foods
– Draft Guidance for Industry: Frequently Asked Questions About Medical Foods; Second Edition (http://www.fda.gov/Food/GuidanceRegulation/GuidanceDocumentsR
egulatoryInformation/MedicalFoods/ucm054048.htm)
FDA considers the statutory definition of medical foods to narrowly constrain the types of products that fit within this category of food
• Distinguished from “specialty foods”
•
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“gray Zone” in Medical Foods
FDA response letter to GRAS Notifiers
Included a detailed definition of a medical food and states:
“…does not address the question of whether any particular food product that contains (the ingredient name) would be a medical food within the meaning of section 5(b) of the Orphan Drug Act, and thus would be except from the requirements for nutritional labeling, nutrient content claims, and health claims.”
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“gray Zone” in Medical Foods
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FDA Warning Letters
Marketing and Regulatory Pitfalls
In reviewing medical Food warning letters from FDA find a common theme
• Misbranded :
FDA… “is not aware of any distinctive (unique) nutritional requirements for patients with _____, nor aware of evidence that patients with _____ have limited or impaired capacity to ingest, digest, absorb or metabolize and specific nutrient”.
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FDA Warning Letters
Marketing and Regulatory Pitfalls
• “No distinctive nutritional requirement” This covers such therapeutic areas as:
– mild to moderate Alzheimer’s disease (Accera, Inc. Warning Letter, 2013)
– with fibromyalgia, chronic fatigue syndrome, or cardiovascular disease (Bioenergy Corvalen Warning Letter, 2010)
– allergies or asthma (Efficas Warning Letter, 2007)
– Type 2 diabetes, arthritis, psoriasis, eczema, chronic fatigue, and migraine headaches (Metagenics Warning Letter, 2003)
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FDA Warning Letters
Marketing and Regulatory Pitfalls
• Important to be able to demonstrate through good scientific evidence the unique nutrient need that the medical food fulfils for the intended disease or medical condition • The ‘Gold” standard for Human Clinical Trials is Important
– Shell WE, Charuvastra EH, DeWood MA, et al. A doubleblind trial of a singledose naproxen and an amino acid medical food Theramine for the treatment of low back pain. Am J Ther. 2012;19:108–114.
– Shell WE, May LA, Bullias DH, Pavlik SL, Silver DS. Sentra PM (a medical food) and Trazodone in the management of sleep disorders. J Cent Nerv Syst Dis. 2012;4:65–72.
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FDA Warning Letters
Marketing and Regulatory Pitfalls
• Important to be able to demonstrate through good scientific evidence the unique nutrient need that the medical food fulfils for the intended disease or medical condition • The ‘Gold” standard for Human Clinical Trials is Important
– Double blind randomized trial design
– Sufficient number of subjects to support nutrient need
– Appropriate safety endpoint
– Appropriate efficacy endpoints
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FDA Warning Letters
Marketing and Regulatory Pitfalls
Examples of “Gold” standard Clinical Trials that address nutrient deficiency and effect on targeted disease •
•
•
Shell WE, Charuvastra EH, DeWood MA, et al. A doubleblind trial of a singledose naproxen and an amino acid medical food Theramine for the treatment of low back pain. Am J Ther. 2012;19:108–114.
Shell WE, May LA, Bullias DH, Pavlik SL, Silver DS. Sentra PM (a medical food) and Trazodone in the management of sleep disorders. J Cent Nerv Syst Dis. 2012;4:65–72.
Phenyl Free 2: Comparative study of special products “Tetraphen” and “Phenyl‐free” in diet therapy of children with phenylketonuria (http://www.ncbi.nlm.nih.gov/pubmed/9680665) •
Efficas caretm for Asthma ‐Six clinical studies with 228 participants demonstrated the efficacy and/or safety (http://www.efficas.com/Content/HCP/Efficacy/ClinicalStudies.aspx) www.ifosprogram.com
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Marketing Channels for Medical Foods
The regulations do not restrict marketing channels, yet FDA has narrow view to comply with “under medical supervision” Examples:
• Chiropractors
• Physicians
• Pharmacies/ Apothecaries/Compounding Pharmacies (not over the counter‐ by prescription)
• Internet ( with proof of medical supervision/prescription)
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FDA Warning Letters
Marketing and Regulatory Pitfalls
There are several successful medical foods currently on the market
• Designs for Health: Arthoben™, Osetoben™, Aphthamin™
– “medical food formulated for the metabolic management of the underlying processes of recurrent aphthous stomatitis (RAS).”
• Pam Labs, LLC now owned by Nestlé Health Science
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Wrap Up ‐ Synergistic Pathway
Map Out a Synergistic Strategy Which Includes:
Intellectual Property Considerations
Appropriate Clinical Trial Design
Regulatory Plan from Concept to Claim
Product Testing for Characterization and Stability
Bio‐analytical for Biomarker Identification
FDA Communication Plan
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Wrap Up ‐ Synergistic Pathway
Map Out a Synergistic Strategy Which Includes:
How the Ingredient/Formula Meets the Medical Food Definition
Patient Population (slightly sick)
The Indication Related to the Patient Population
The Primary and Secondary End Points Related to the Patient Population and Indication How Your Ingredient/Formula Impacts the End Points
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Questions?
To learn more about the medical foods category, or to obtain regulatory and product development guidance for your next project, contact the Nutrasource and GRAS teams today at [email protected].
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© Nutrasource Diagnostics Inc., GRAS Associates LLC
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