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:

2

Why clinical study?

Health-claim regulations in China

Basics of good clinical practice

Procedures of clinical study

Outline:

3

Why clinical study?

Health-claim regulations in China

Basics of good clinical practice

Procedures of clinical study

6

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?

7

Dietary

Supplement

Companies

Ingredient

Companies

Legal & Regulatory

Requirements

Marketing Purpose

Legal & Regulatory

Requirements

Conscious Consumers

Clinical Study

Outline:

6

Why clinical study?

Health-claim regulations in China

Basics of good clinical practice

Procedures of clinical study

9

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)

10

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

?

11

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

12

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:

11

Why clinical study?

Health-claim regulations in China

Basics of good clinical practice

Procedures of clinical study

14

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

15

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:

14

Why clinical study?

Health-claim regulations in China

Basics of good clinical practice

Procedures of clinical study

17

Investigator

Data management &

Biostatistics

LogisticsProtocol

Volunteer recruitment

Ethics committee

approval

Clinical Study

Lab analysis

Monitoring

Elements of Clinical Study

Any Plug & Play solution?

18

CRO: Plug & Play Solution

Most of food and/or ingredient companies

lack the capability to operate clinical study

19

• 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

20

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

21

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

22

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

23

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

24

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

25

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

26

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

27

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….

28

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!!!

29

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☺

30

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!

31

Contact:

Dingqiang Li Ph.D.

dingqiang.li@mxns.com

Cell: +86-18989133124

Tel: +86-21-64967600 ext. 1107

Let us know what you think about the session you

attended here:

https://www.surveymonkey.com/r/L5TPHX9

Feedback Form