china update: what's new with cfda - brandwood...

BRANDWOODBIOMEDICALsecuring your compliancewww.brandwoodbiomedical.com

China Update: What's New with CFDA

Steven Wen

Director China Operations and Senior

Consultant

20 years experience in Chinese Medical

Device and IVD regulatory affairs

Previous Senior RA roles in for

Medtronic, GE Healthcare, Bausch &

Lomb and devices start-up


BRANDWOOD:BIOMEDICALsecuring your compliance

Medical Devices and IVDs

Global Perspective

Highly Engaged

Highly Networked


Agenda

Revision to Decree 650 - draft

Order 25 - GCP implementation

Second wave of clinical exemption list - draft

Prioritized device evaluation pathway - draft

Update of innovative pathway – draft

China ROHS 2.0


Revision to Decree 650 - Draft - Affecting articles 34, 56, 63, 64, 68, 73,76

Purpose

• to assure Large Medical Equipment is available and fully utilized across China

• Avoid unnecessary waste, duplication, unnecessary competition between hospitals.

Large Medical Equipment

• High cost and complex capital equipment

• Will be listed in a CFDA catalog

Requirements:

• Hospitals will need permission from provincial Administration of Public Health ( APH ) to purchase “Large Medical Equipment.

• Fines apply for breaches

Questions:

• When will CFDA publish the Catalog?

• What is the timeframe and cost to apply for the purchase permission?


v

GCP – Good Clinical Practice

Pre-Study preparation

Responsibilities of Ethic

committee

Protection of patient rights and benefits

Management of device in trial

Responsibilities of Investigator

institute

Documentation management

Responsibilities of Sponsor

Study protocol design

Study reports and records

GCP – Order 25(effective Jun 1 2016, replaced Order 5)


Order 5 Order 25 - GCP

Article 6

1) The device shall have verified product registration standard or

applicable national standard or industry standard,

2) The device shall have self-test report

3) The device shall have local type testing report issued by test

lab which is accredited by CFDA together with the State

Quality and Technology Supervision Administration ( within

half year ), and the conclusion of report is pass

Article 7 Before clinical study, the sponsor shall complete the pre-

clinical study of investigational devices, including the product

design (structure and composition, working principle and

mechanism, intended use, applicable technical requirements) and

quality inspection, animal study and risk analysis report, etc, and

the results shall support the clinical study. The quality inspection

results shall include self-test report and local type testing report for

registration issued by a qualified test lab within one year.

Article 6

4) For any implantable device to be used on human body for the

first time, it should have animal study report.

Article 27 For any new devices which have not been approved to

market in China or other countries, its safety and effectiveness

have not been validated clinically, a feasibility study with small

sample size should be conducted prior to designing the pivot

clinical study protocol. After the primary safety is confirmed, the

sample size of pivot clinical study shall be determined according

to statistical requirements

Critical changes in GCP Vs Order 5:Pre-Study Preparation




Article 6

• Device must have China or industry

product standard

• Do in house testing

• Obtain Type Test Report within 6

months of study commencement

Article 7

• Do preclinical studies and testing

• Obtain Type Test Report within one year of

Study commencement.

• First human use devices must have animal

study report.

Article 27 New devices with no prior china or

international approval must have:

• Pilot clinical study

• Statistically valid pivotal study



Article 12 The study protocol of Class III implantable devices

which had never been used before or devices produced

according to traditional Chinese medicine theory shall be filed at

CFDA’s medical device technical evaluation center ( CMDE )

prior to conducting the study.

Article 11 Clinical study shall be approved by ethic committee of

clinical institute. The studies of devices listed in the <High Risk

Class III Device Directory > shall be approved by CFDA.

Article 12 Before the clinical study, the sponsor shall file the

protocol at its local provincial level CFDA. The sponsor’s local

CFDA accepting the protocol filing shall notify the local CFDA and

Public Health department of the clinical institute

none

Article 8 Before clinical study, the sponsor shall prepare

adequate investigational devices. The production of

investigational sample devices shall conform to relevant

requirements in applicable quality management system





Article 12

• New-to-China Class III devices (and Traditional Chinese Medicine Devices) required CFDA review of Study protocol

Article 11

• All studies require Ethics Approval

• Class III Devices in CFDA High Risk Catalog require CFDA approval of Protocol

Article 12

• Protocol must be filed with local CFDA (who will audit the study)

No requirement

Article 8

• investigational devices shall be produced under relevant quality management system



No requirement

Article 29 The multi- center clinical study ( three or above )shall

be carried out simultaneously by a number of investigators in

different institutes by following the same protocol. The protocol’s

design and implementation shall meet below requirements:

• The protocol shall be drafted by sponsor then discussed and

finalized by all investigators from clinical institutes together

with sponsor, and the investigator from the leading institute

will be acting as the coordinating investigator.

• The coordinating investigator is in charge of the coordination

among clinical institutes during the process of clinical study,

and organizing the investigator meetings in the early, middle,

late stage of clinical study, and be responsible for the

implementation of the whole study together with the sponsor;

• In principle, all clinical institutes shall carry out and complete

clinical study at the same time;

Critical changes in GCP Vs Order 5:Protocol design



No Requirement

Article 29

• Multi Centre Study required (Minimum 3

Centres)

• Common Protocol

• All sites conduct study at same time

• Must be one coordinating investigator who is

responsible for implementation along with the

sponsor




None

Article 29 - Continued

• The sample size and distribution ratio of each clinical

institute, and the justification of meeting statistics analysis

requirements;

• Sponsor and clinical institute’s training plan and training

record requirement for study

• Establishing the procedure to transmit, manage, audit and

query clinical data, and clearly requesting the study data and

relevant documents from all clinical institutes shall be

managed and analyzed centrally by the leading institute;

• After the multi- center clinical study is completed, the

investigator of each clinical institute shall submit a brief study

outcome summary, along with the case report forms （CRF

）which have been verified upon appropriate procedure, to

the coordinating investigator to consolidate and issue the

study summary report.





No requirement

Article 29 - Continued

• Study Sample size and distribution ratio

between sites justified statistically

• Sponsor and site training plans and records

• Data managed and analyzed centrally by the

leading institute;


Critical changes in GCP Vs Order 5Ethics Review and Document Management


NoneChapter 5

Article 30 ~ 37 Detailed Ethics Review Requirements

Article 27

The clinical study documents shall be properly kept and managed. The clinical institute shall keep such documents for 5 yeas after the study is completed, and the sponsor shall keep such documents for 10 years after the last manufactured device had been put into use

Article 91

The clinical institute shall keep the clinical study documents for 10 years after the study is completed. The sponsor shall keep the clinical study documents until the devices are not used in market any more.


Critical changes in GCP Vs Order 5:Ethics and Records Requirements


No Requirement

Chapter 5

Article 30 ~ 37

Detailed Ethics Review Requirements

Article 27

• Site Document Retention for 5 years after the study is completed

• Sponsor Document Retention for 10 years after the last manufactured device used.

Article 91

• Site Document Retention for 10 years after the study is completed.

• Sponsor Document Retention until the devices are no longer used in the market


3 Paths for Submitting Clinical Evidence

In Class II & III exemption list

Justify that device matches description

in exemption list

Comparison to a substantially

equivalent device

Not in exemption list but Sufficient Clinical

evidence compared to predicate

device

Clinical Evaluation Report with detailed

comparison to substantially

equivalent predicate device

Not in exemption list, Insufficient clinical

evidence compared to predicate

device

In-China Clinical Trial


Exemption list of clinical study

Wave Class II devices Class III devices Effective date

Wave 1

488 79 Oct 1, 2014

Wave 2 ( Draft ) 259 93TBD ( draft released

on May 20, 2016 )


Prioritized Device evaluation pathway – DraftEligibility Criteria (Meet Any One)

State R&D Priority Area

Clinical Priority Area

• Rare Disease

• Cancer

• Paediatrics

• Geriatrics

• Unmet clinical need

• Urgent clinical need with no equivalent device approved in China

Others to be determined by CFDA


File request with CFDAregistration submission

CFDA judgment in 5 working days

CFDA monthly review

State R&D Priority

Area

Clinical Priority

Area

Prioritized Device evaluation pathway – DraftApplication Process


Innovator Devices Fast Track

Single Contact Person to Manage Review

Advance Feedback from Test Centre

Classification category is decided in parallel with technical review

Special Review Team appointed by Office of Innovative Devices

Priority ProcessingChina Patent

+ Design Controls

and DHF


Comparison: Innovative and Priority Pathways

•

Innovative pathway Prioritized pathway

Conditions• Patent registration in China

• Innovative technology with clinical

advantage

• State level R & D project

• Clinical urgency

• No equivalent device in China

• Clinical advantage

Request procedure Prior to registration submission With registration submission

CFDA Decision > 40 working days• State level R & D – 5 working days

• Clinical Priority – monthly review

CFDA pre-consultation Yes No

CFDA Prioritized review Yes Yes


Current status of innovative pathway March 2014 – July 2016

•

Local device,

63, 94%

Import device,

4, 6%


China ROHS 2.0 - Background

Promulgated by multiple government departments jointly

Replaced China ROHS 1.0 published in 2006.

China’s Ministry of Information & Industry ( MII );

National Development and Reform Commission ( NDRC);

Ministry of Science & Technology ( MST);

Ministry of Finance ( MOF);

Ministry of Environment Protection ( MEP );

Ministry of Commerce ( MOC ),

General Administration of Customs ( GAC)

General Administration of Quality Supervision, Inspection and Quarantine ( AQSIQ)


China ROHS 2.0 - Definitions

Restriction of Hazardous Substances in Electrical & Electronic Products

ROHS

Equipment and ancillary products which operate on electric current or electromagnetic field, or to generate, transmit or measure electric current or electromagnetic field, with rated working voltage under 1,500V DC or 1,000V AC.

Equipment for electricity production, transmission or distribution are excepted.

Electrical & Electronic Products

Lead and its compounds (Pb)

Mercury and its compounds (Hg)

Cadmium and its compounds (Cd)

Chromium VI and its compounds (Cr 6+)

Poly-brominated Biphenyl (PBBs)

Poly-brominated diphenyl ethers (PBDEs)

Others to be announced later

Hazardous substance


China ROHS 2.0 – Content Limit

A product list for mandatory compliance will be published shortly. The hazardous substance in enlisted product must be lower than below limits:

Hazardous substance Content limit ( %)

Pb 0.1

Cd 0.01

Hg 0.1

Cr6+ 0.1

PBBs 0.1

PBDEs 0.1


China RoHs 2.0 – Labeling requirements

Hazardous substances are below the limit (or absent).

Hazardous substance contents above the limits

The number represents the years that the product can be safely used


China ROHS 2.0 – Labeling requirements

In case of orange logo, the user’s manual needs to include a table as below to indicate the name and hazardous substance contained in each part.

Parts Hazardous substance contents ( “O” or “X” in each cell)Pb Hg Cd Cr6+ PBBs PBDEs

Part 1 O O O O O XPart 2 X O O O O XPart 3 O X O O O O

…

O: Content of hazardous substance in any homogenous materials of this part is below the limit set by GB/T 26572-2011

X: Content of this hazardous substance in at least one of the homogenous materials of this part exceeds the limit set by GB/T 26572-2011 (the supplier shall explain the technical reasons of “X” here)


China RoHs 2.0 – Relevant standards

Content Limit

GB/T 26572-2011

Requirements of concentration limits for

certain restricted substances in electrical and

electronic products

Labeling Requirements

SJ/T 11364-2014 Marking for the restriction of the use of hazardous substance in electrical and electronic

product

Testing Method

GB/T 26125-2011 Electrical and electronic products—

Determination of six regulated substances (lead,

mercury, cadmium, hexavalent chromium, poly-brominated biphenyls, poly-brominated diphenyl ethers

GB/T 29783-2013 Determination of

chromium(VI) in electrical and electronic products –

Atomic fluorescence spectrometry


Comparison to China RoHs 1.0

China RoHs 2.0 China RoHs 1.0

Scope Electrical & Electronic products Electronic Information Products

Mandatory

compliance listYes No

Inspection product list No Yes

Labeling requirement Logo + table Logo + table


Comparison to EU RoHs requirements

China RoHs 2.0 EU RoHs

Content limitProduct in mandatory compliance list must be lower than the limit

All products must be lower than limit

Exemption provision

No Yes

Compliance evidence

• Design and manufacturing control documents

• Labeling information ( Logo + content table in user manual )

• Design and manufacturing control document


Actions for suppliers

Suppliers of Electrical & Electronic products shall collect the hazardous substance content information from upstream suppliers of parts.

Products produced after July 1, 2016 must bear the green or orange ROHS logo, and include a hazardous substance content table in user manual for orange logo.

Once the mandatory compliance list is published (the date is unknown by now), suppliers of enlisted products shall take measures to reduce the hazardous substance down to the limit then change to green logo, if necessary.


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