View
2
Download
0
Category
Preview:
Citation preview
DISCUSSION GROUP 4 REPORT
ISAPP 2015
GEORGETOWN UNIVERSITY
What is the future of probiotics in USA? Regulatory challenges.
Group members 1. Dan Merenstein, Georgetown University Medical Center
2. Mary Ellen Sanders, ISAPP
3. Pat Hibberd, Massachusetts General Hospital, Boston
4. Andi Shane, Emory
5. Richard Oberhelman, Tulane
6. Girish Deshpande, Nepean Hospital Sydney
7. Peter Marks, FDA CBER
8. Chris Elkins, FDA CFSAN
9. Jennifer Patro, FDA CFSAN
10. Linda Duffy, NIH-NCCIH
11. Martin Hahn, Hogan Lovells
12. Sarah Roller, Kelley Drye & Warren LLP
13. Diane Hoffmann, Univ Maryland
14. Tina Tan (rapporteur) - Georgetown University
15. Greg Leyer, UAS
16. David Keller, Ganeden Biotech
17. Maeve Murphy, General Mills Inc
18. Solange Henoud, Lallemand Health Solutions Inc
19. Thomas Tompkins, Lallemand Health Solutions Inc.
20. Berenice Ocampo Guevata, Mead Johnson Nutrition
21. Seema Mody, DSM
22. Danielle de Montigny, BioK+
23. Wafaa Ayad, Church & Dwight
Chairs
Clinical experts
Regulators
Lawyers
Industry experts
Research funding
Group photo
Objective
Improve current regulatory approach to human research on oral probiotics in the USA
Focus:
Human research
Oral
USA (next year – EU)
Probiotics (not prebiotics)
Key challenges
INDs required when not appropriate
Foods and supplements
When IND is appropriate
Impossible unless manufacturer cooperates
Limits investigator-initiated research
Difficult to obtain IND for foods
Phase 1 safety studies on well-studied probiotics
Everyone agrees that the goal is appropriate oversight commensurate with risk to human subjects.
Bureaucratic interference that prevents needed research or wastes money on unneeded safety studies benefits no one.
Consequences
Studies going outside the USA
Companies being advised to use CROs instead of academic PIs
Guidance's are not law
Companies advised not to seek federal funding
Probiotic research hindered
Scientists having to be vague about endpoints to prevent undue oversight
CBER, CDER and CFSAN
FDA issued a final guidance September 2013 that requires essentially all human research conducted on foods to be conducted as an investigational new drug (IND)
Exception is studies on taste, aroma, nutritive value and approved health claims
FDA re-opened comments through April 7, 2014
65 comments received
FDA response still pending
FDA-Center for Biologics (CBER) Request for Comment
https://www.federalregister.gov/articles/2015/03/31/2015-07273/early-clinical-trials-with-live-biotherapeutic-products-chemistry-manufacturing-and-control
Issued March 31, 2015. Comments due May 29, 2015
CBER action
CBER is proposing that a product label can serve as CMC info for an IND for commercial probiotics
This will facilitate investigator-initiated INDs
Comments (due May 29) – ISAPP will comment; you should, too
This does not address the issues of food research, unnecessary INDs or safety studies
87% of hospital formularies
surveyed carry at least one probiotic
Is research on food/supplement (not device, marketed drug, etc)1
Does research use healthy or at risk members of the general population ?2
Is research on endpoints that are (a) structure/function or (b) reduction of risk
of disease?3
Does PI or study sponsor indicate that research is part of a drug development
pathway?
YES
YES
YES
CBER
YES
NO
NO
NO
CFSAN
Is study on a commercially available probiotic?
Does local IRB consider it safe for the proposed
population?
YES NO. Safety is not
adequately demonstrat
ed for intended
use
FULL DISCUSSION NEEDED WITH CBER; LIKELY PHASE 1
STUDY NEEDED
PRODUCT LABEL SERVES AS CMC, WAIVER OR ABBREVIATED IND.
CAN PROCEED TO EFFICACY STUDIES
NO
Is probiotic adequately characterized to strain level (gene sequencing) AND is
probiotic quality adequate?4
NO
YES
YES
Is probiotic of a well-studied species with
history of safe or documented safety (e.g.,
GRAS, QPS list?) YES
NO
ISAPP 2015: Proposed decision tree for human research on probiotics
NO
Footnotes 1. Clarify what is meant by food/supplement (currently marketed, or food format or declared by PI to be food/supplement) 2. Need to discuss general population (include IBS, healthy people on antibiotics, others that would not be vulnerable subjects for probiotic
studies) 3. Since structure/function and reduction of risk of disease endpoints can be both drug and food, CFSAN would be appropriate oversight agency if
study PI/sponsor declares the research to be on a food/supplement 4. Approach to characterization can be developed and applied to probiotic research
Recommendations
New framework that considers vulnerability of study population and safety data
Subject Vulnerability
Low High
Strength of safety data (history of
use or research)
Strong safety info
CFSAN IRB enough
CBER IND discussion Full CMC not required
Unstudied safety
CBER IND Discussion
IND Phase 1 safety study
Suggested approach
Recommendations
New framework that considers vulnerability of study population and safety data
If provide one of the following, safety study not necessary for generally healthy population study
GRAS notice, or
New Dietary Ingredient Notification (NDIN)
Key points
Lawyers: substance category dictated by intent of vendor, not study endpoints
CBER has experience with streamlined IND process
Recognized value of better inter-agency communication (CBER and CFSAN)
2013 guidance on IND requirements has not been revised – we hope FDA will revise
Don’t forget possible food categories with more potential for claims Foods for special dietary use
Medical foods
Recommended