China Update: What's New with CFDA - Brandwood...
Transcript of China Update: What's New with CFDA - Brandwood...
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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
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Medical Devices and IVDs
Global Perspective
Highly Engaged
Highly Networked
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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
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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?
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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)
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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
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Critical changes in GCP Vs Order 5:Pre-Study Preparation
Order 5 Order 25 - GCP
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
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Order 5 Order 25 - GCP
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
Critical changes in GCP Vs Order 5:Pre-Study Preparation
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Critical changes in GCP Vs Order 5:Pre-Study Preparation
Order 5 Order 25 - GCP
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
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Order 5 Order 25 - GCP
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
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Order 5 Order 25 - GCP
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
Critical changes in GCP Vs Order 5:Protocol design
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Order 5 Order 25 - GCP
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.
Critical changes in GCP Vs Order 5:Protocol design
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Critical changes in GCP Vs Order 5:Pre-Study Preparation
Order 5 Order 25 - GCP
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;
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Critical changes in GCP Vs Order 5Ethics Review and Document Management
Order 5 Order 25 - GCP
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.
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Critical changes in GCP Vs Order 5:Ethics and Records Requirements
Order 5 Order 25 - GCP
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
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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
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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 )
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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
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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
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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
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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
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Current status of innovative pathway March 2014 – July 2016
•
Local device,
63, 94%
Import device,
4, 6%
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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)
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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
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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
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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
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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)
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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
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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
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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
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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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