Market Entry and Regulation - Vitafoods Asia€¦ · •Study Design •PI/Site Searching...
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Market Entry and Regulation
Transcript of Market Entry and Regulation - Vitafoods Asia€¦ · •Study Design •PI/Site Searching...
Market Entry and Regulation
Demonstrating health improvements and building
convincing health-claim dossiers through nutritional
clinical trials
Speaker:
Dingqiang Li, Clinical Research Project Manager, Mérieux NutriSciences (China)
Nutritional Clinical Study:
A New Challenge to Traditional Industry
Dingqiang Li Ph.D.
09/11/2018 Singapore
Outline:
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Why clinical study?
Health-claim regulations in China
Basics of good clinical practice
Procedures of clinical study
Outline:
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Why clinical study?
Health-claim regulations in China
Basics of good clinical practice
Procedures of clinical study
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Health BenefitsOptimized Product
2 complementary objectives to ensurebusiness success
Delivery efficiency
Clinical Study: Who? & Why?
Bioavailability
Other benefits?
Satisfactory DRI
Shelf life
Sensory attribute
Clinical Study: Who? & Why?
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Dietary
Supplement
Companies
Ingredient
Companies
Legal & Regulatory
Requirements
Marketing Purpose
Legal & Regulatory
Requirements
Conscious Consumers
Clinical Study
Outline:
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Why clinical study?
Health-claim regulations in China
Basics of good clinical practice
Procedures of clinical study
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Some Basic Facts
Designated logo for B2C
health foods:
“Blue Hat”
Two routes to get “Blue Hat”:
✓ Filing
✓ Registration
✓ Privilege of “Blue Hat”: claim health
functions
✓ 27 health functions in total
✓ Guideline: “Health Food Testing and
Evaluation Technical Specification”
(2003 Edition)
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Two Routes to “Blue Hat”
Filing
▪ Applicable Products:
✓ Vitamines
✓ Minerals
▪ Dossier submitted:
✓ Raw materials
✓ Manufacturing process
✓ Safety & quality
▪ Validity period: permanent
Registration
▪ Products claiming health functions
▪ Mandatory evaluation for function claims
▪ 27 functions in “Health Food Testing and Evaluation Technical Specification” (2003 Edition)
▪ Validity period: 5 years
Radical change since June 7th 2018
?
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New Trends
Cross border e-Commerce:
✓ No health claim!!!
✓ B2C mode, online transaction, cross border logistics
✓ Bonded import:
stocking in bonded warehouse orders from consumers sending
products from bonded warehouse
✓ Direct purchase import:
orders from consumers sending products from overseas
Remarks:
Temporarily supervised as personal behavior
Necessary quarantine
Regulation is still in perfecting phase
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New Trends
Symbi
ontsComme
nsals
“ Clinical study”
“Business success”
Just my two cents:
to do the right thing!
The future:
✓ Much stricter
policy in China
✓ Good money
drives out bad
What is happening?
① “Blue hat” is NOT ultimate goal anymore
② Major companies are still doing clinical studies
③ To get good result and to publish scientific paper
④ Numerious ways to let consumers being aware of
the solid evidence
Outline:
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Why clinical study?
Health-claim regulations in China
Basics of good clinical practice
Procedures of clinical study
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ICH: International Council for Harmonisation of Technical
Requirements for Pharmaceuticals for Human Use
GCP: Good Clinical Practice, an international quality standard that is
provided by ICH for clinical trials involving human subjects
✓ Declaration of Helsinki, 1964: basic principles, informed consent
✓ In different countries, governments transpose ICH-GCP into
various regulations
✓ Other related documents:
• Nuremberg Code, 1948
• Belmont Report, 1979
• International Ethical Guidelines for Biomedical Research, 1982
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Essentials of GCP
✓ Ethics: Protect the rights and safety of the subjects
✓ Science: Ensure clinical trial complies certain specification and the
result is reliable
Ethics Committee: a body responsible for ensuring experimentation
and human research are carried out in an ethical manner in
accordance with national and international law
✓ Variations in different countries: IRB, REB, REC, etc.
✓ Documents to be reviewed
• Protocol, informed consent form
• Investigator’s resume, sponsor’s qualification material
• Documents pertaining to product’s safety and regulation compliance
Outline:
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Why clinical study?
Health-claim regulations in China
Basics of good clinical practice
Procedures of clinical study
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Investigator
Data management &
Biostatistics
LogisticsProtocol
Volunteer recruitment
Ethics committee
approval
Clinical Study
Lab analysis
Monitoring
Elements of Clinical Study
Any Plug & Play solution?
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CRO: Plug & Play Solution
Most of food and/or ingredient companies
lack the capability to operate clinical study
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• Study Preparation
• Study Design
• PI/Site Searching
• Protocol Development
• Database & eCRF Building
• EC Submission & Approval
• Site Initiation Visit
• Recruitment
• Study is rolling
• Monitoring
• Source Document Verification
• Biostatistics
• Study Report
PI: principle investigator
eCRF: electronic case report form
EC: ethics committee
ICF: informed consent form
CRA: clinical research assistant
CRC: clinical research coordinator
SIV: site initiation visit
SDV: source document verification
DBL: database lock
SAP: statistical analysis plan
AE: adverse event
Overview
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At The Very Beginning
For food industry, clinical study is luxury, not life necessities
✓ Confidence and motivation are vital
✓ Money is decisive
The cost of clinical study
✓ It is not flat rate.
✓ Influenced by various factors:
type of study, sample size, site location, ending points, lab testing
methods, etc.
Feasibility Evaluation
✓ The rationales behind your clinical study
✓ Financial capability
✓ Timeline (plan 1-2 years in advance for new product launch)
✓ The measurement of beneficial effects of nutritional products?
Tips:
Consult CRO focusing on
nutritional clinical study
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PI/Site Searching
Synopsis Discussion
✓ Major ending points (goals & methods)
✓ Study design:
randomized; controlled; number of arms (?); number of sites (?)
double blind, single blind, open (?)
parallel, cross-over (?)
✓ Inclusion/Exclusion Criteria
PI/Site Searching
✓ Investigator who is familiar with clinical study and GCP
✓ Balance between reputation and interests
✓ Investigator’s resource
✓ Site location
✓ Capability of hospital laboratory
Multi-satisfaction?
Sign contract with CRO
officially
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Protocol & Database Development
Drafting full protocol
✓ CRO will input more resource from this time point
✓ Protocol will be reviewed by sponsor and PI
Developing database and eCRF
✓ Who: data management team
✓ When: near the end of protocol discussion
Material preparation for EC review
✓ Parallel with protocol development
Multi-agreement?
Now ethics committee
submission
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Ethics Committee Review
Types of EC in China’s hospital:
✓ Drug/device registration (strict)
✓ Phase IV or IIS (relatively easy)
Core materials must be approved by EC
✓ Protocol
✓ Informed consent form
✓ Recruiting advertisement
✓ Volunteer insurance (if applicable)
Other materials could be reviewed by EC
✓ Investigator’s resume
✓ Sponsor’s business license
✓ Case report form (if ready)
✓ Safety materials of study product
✓ Amendment (if applicable)
✓ Educational materials (if applicable)
✓ Investigator’s brochure
✓ Research fund
Tips:
The requirement of each
hospital may be different
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Ethics Committee Review
e.g. full nutrition meal replace (new formulation)
✓ Protocol
✓ Informed consent form
✓ Recruiting advertisement
✓ Safety materials
• formulation information & nutrients DRI
• GMP & HACCP certificates of manufacturing plant
• testing reports from CNAS certified laboratory
nutrients; micro; heavy metal; packaging contaminant migration, etc.
✓ Investigator’s resume
✓ Sponsor’s business license
✓ CRO’s business license
Caution!
Version number of documents
Timely file amendment
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Site Initiation Visit
Kick-Off Meeting
✓ Purpose: to rehearsal the protocol with everyone who will involve in the study
✓ Who: PI, nurse, PM, CRA, CRC, sponsor delegate, administration staff of hospital
✓ Where: each site
✓ When: after study product is ready, before subject enrollment.
Content of SIV
✓ Check-in form
✓ Introduction of each party
✓ Thoroughly review the protocol in details
✓ Discuss the potential adverse event and solution
✓ Lab analysis and logistics
✓ Make sure PI has all the necessary documents
✓ Assign everyone’s duty in the study
Tips:
Assign multiple personnel
to each duty
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CRA & Monitoring Plan
Functions of CRA
✓ To ensure the quality of clinical study
✓ To facilitate the study progress
✓ To keep documents updated if applicable
✓ The goal is NOT to supervise investigator
Monitoring Plan
✓ Should be prepared prior to SIV
✓ Each study has its specific monitoring plan
✓ The guideline for all sites:
how to monitor
what to monitor
✓ The frequency of monitoring is higher at the early stage of recruitment
✓ Then, monitoring could be done once a month or twice a month
Tips:
Important means to keep the
integrity and consistency of
data
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The First Screening
The First Screening
✓ CHAOS……especially when recruiting health volunteer
✓ CRC, CRA & PM should be at the site
to ensure compliance with protocol, GCP and regional regulations, etc.
✓ The workflow will be smooth after then
Why?
Limited medical resources;
Large number of outpatients:
Conflict with working schedule;
Difficult to travel in large metro
city;
Unfamiliar with study procedure;
Other unexpected reasons….
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Source Document Verification
Why SDV?
✓ Confirming the authenticity of the subject
the subject does exist
the subject does meet the I/E criteria
✓ Confirming the authenticity of research data.
How?
✓ Everything about subject should be recorded on case report form (CRF)
✓ In paper version, every modification should be signed and dated by PI
✓ In eCRF, every action is trackable (preferred)
Remarks:
If it is not written down, then it didn't happen
Source documents and CRF should be completed at the same time
No Procrastination!
Caution!
No document. No Activity!!!
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Database Lock & Analysis
Final Steps
✓ Issuing queries (CRA) & resolving queries (investigator)
✓ All queries are resolved and SDV is done, it is time to lock database.
✓ Statistical analysis
• A detailed Statistical Analysis Plan (SAP) outlining the complete
technical aspects of the analyses will be written
• Usually the sponsor will have its own statistician as consultant
Happy Ending? Hopefully☺
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10 Tips for A Successful Study
1. Choose a good service provider
2. Good project management team
3. Follow protocol all the time
4. GCP compliance
5. Volunteer management
6. Documents management
7. Data management
8. Good communication
9. Quality of monitoring
10. Choose a proper principle investigator
Happy Ending!
Thank you!
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Contact:
Dingqiang Li Ph.D.
Cell: +86-18989133124
Tel: +86-21-64967600 ext. 1107
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