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copyright Whitney Consulting 1

By Chang-Hong Whitney Whitney Consulting Ltd.

CHINA REGULATORY REQUIREMENTS CHINA REGULATORY REQUIREMENTS FOR MEDICAL DEVICESFOR MEDICAL DEVICES

AND IN-VITRO DIAGNOSTIC PRODUCTSAND IN-VITRO DIAGNOSTIC PRODUCTSPrepared for

Round Table - “China Opportunities for U.S. IVD and Device Companies”

Newport Beach, September 22, 2009San Jose, September 23, 2009


Agenda Overview of Key China Regulatory Agencies:

State Food and Drug Administration (SFDA) Administration of Quality Supervision Inspection and

Quarantine (AQSIQ) SFDA Regulations - Medical devices vs. IVD products

Product Registration Process Registration requirements Product Testing Clinical evaluation Dossier documents

Compliance Issues Policies on adverse incident reporting and product recall Labeling and IFU Record keeping

AQSIQ and Reagent Import


I am… Chang-Hong Whitney, President, Whitney Consulting Ltd. China business and regulatory consulting since 1994 Services:

Regulatory – strategy, daily operating issues Product registrations – SFDA, CCC Importation, sourcing, logistics consulting

Offices – Beijing, Boston Presentations at Regulatory Affairs Professional Society (RAPS),

American Academy of Clinical Chemistry (AACC), Florida International Medical Expo (FIME), Asia Pacific Healthcare Forum, Management Roundtable, Medical Device Regulations in Asia Pacific, and other conferences

Columns on “Medical Product Outsourcing” Magazine and “Regulatory Affairs journal”.Chang-Hong Whitney

Whitney Consulting Ltd.Tel: 978-394-2724

Email: [email protected]


Top Regulatory Agencies:

Responsible For Medical Devices, Pharmaceuticals And Health Food ProductsMedical Manufacturers and Products

Responsible for Customs, Import Goods Quality Inspection and Quarantine All Industries and Products

China RoHS Law – “Administration on Control of Pollution by Electronic Information Products”

AQSIQ


State Food and Drug Administration (SFDA)

Medical Device Department

Pharmaceutical Department

Provincial FDA Agencies

Registration Division

Standard Division

Safety Supervision Division

General Division

…. ….

Registration Application Hall

Center for Medical Device Evaluation

• Dept 1: Sourced device• Dept 2: Non-sourced device, implantable• Dept 3: IVD, instrument & reagents• Dept 4: Non-sourced device, other

www.cmde.org.cn

www.sfda.gov.cn


SFDA Regulations for Device and IVD Measures for the Administration of Medical Device Registration

Decree of SFDA No. 16, August 9, 2004

Administrative Regulation on Medical Device User’s Manual, Label and PackagingDecree of SFDA No. 10, July 8, 2004

In-Vitro Diagnosis Reagent Registration and Management Method (Interim)SFDA [2007] #229, April 19, 2007

In-Vitro Diagnosis Reagent Clinical Study Technical GuidanceSFDA [2007] #240, April 28, 2007

In-Vitro Diagnosis Reagent User’s Manual Drafting GuidanceSFDA [2007] #240, April 28, 2007


Classifications vs. Testing, ClinicalClass I, II, III based on product risk

levels: Classifications for general medical

devicesClassifications for IVD reagent

products (many gray areas)

Type Testing: Class II, III products, imported or domestic

In-China Clinical: Now: Class II, III domestic, some

Class III importedFuture: uncertain

IVD reagent’s usage can affect classification:

Tests for proteins, carbohydrate, steroid, enzyme, if for cancer diagnosis and treatment monitoring or genetic disease diagnosis, are Class III.

Drug related or drug metabolism tests, if the drug is anesthetic drug, psychotic drug or other narcotic drugs, are Class III.


Product Registration Process

Type Type TestingTesting

China China ClinicalClinical

DossierDossier submissionsubmission

SFDA EvaluationSFDA Evaluation Center for Medical Device Center for Medical Device

EvaluationEvaluation

RegistrationRegistration CertificateCertificate

Class II, III

Authorized testing center

Chinese industry

standards

Class II, III Domestic

Class II, III IVD

products

Company info

Product validation

Additional Info

Q&A

Additional Testing

Additional Info

8-12 wks 18 wks+2-4 wks 6 wks… wks


Product Testing

Type Testing

Mechanical

Electrical

Chemical

Functional and physical features

IEC, EMC standards

Chemical, biocompatibility

• PerformancePerformance• FunctionsFunctions• SafetySafety

IVD SpecificAccuracy,

RepeatabilityEtc.

Almost all instruments

DisposablesImplantables

IVD instrumentReagent


SFDA Principles on Product ApprovalManufacturer’s Eligibility

-Licenses- QA system certification

In-China Support-Service agent

- Representative

Manufacturer’s Promises-Guarantees

-Authorizations

Product Information-Features and spec

-Safety-Effectiveness

-Home country approval

•Safety and Effectiveness Safety and Effectiveness •Product focusedProduct focused•Manufacturer focusedManufacturer focused


Guideline in China Clinical Evaluations Regulation: In-Vitro Diagnosis Reagent Clinical Study Technical Guidance

SFDA [2007] #240, April 28, 2007 Consent form is needed when collection of samples or research result

will affect patient greatly. Trail site must be authorized and known in the field, provincial level

hospitals preferred. Lower level site is permitted for legitimate reasons.

Participating doctors must be experienced and knowledgeable in the given field or specialty.

Conduct pre-trial trial, for training and practice purpose For products that are new to the Chinese market:

Compare to Gold Standard method/product Two groups of subjects: confirmed positive and unconfirmed Synchronized blind study Double blind study

For products that have predicate products on Chinese market: To demonstrate “equivalency” to the existing product Select the product that has good clinical result, as comparison If results do not match, use Gold Standard method to confirm


IVD China Clinical StudiesClassification Clinical samples:

Class III: Generally: 1000 samples minimum from 3 provincial hospitals PCR tests: 500 samples Tests related to anesthetic, psychotic and other narcotic

drugs: 500 samples Tests with radioactive markers: 500 samples

Class II 200 samples from 2 hospitals

Class I No clinical needed

• Time: vary, ~4-6 months• Cost: vary, RMB800-1200 per sample• Clinical Report:

Trial site agreementProtocol

Reports from each siteSummary report


Registration Dossier1. Certificates: manufacturer, product, agent2. User’s manual 3. Product standard 4. Type testing report 5. Authorization and acceptance of authorized China agentsFor IVD reagent, add -6. General description of product, technology and specifications

Key material research information 7. Key manufacturing process and reaction study information8. Analysis of product features9. Reference value (or range) information10. Stability information (3 batches, real time)11. Clinical report (foreign and in-China)12. Production and self testing records13. Packaging and label design samples


Product Registration Process

Type Type TestingTesting

China China ClinicalClinical

DossierDossier submissionsubmission

SFDA EvaluationSFDA Evaluation Center for Medical Device Center for Medical Device

EvaluationEvaluation

1. Q&A

2. Expert Committee

3. Additional testing

4. Additional clinical

RegistrationRegistration CertificateCertificate


China Regulatory Compliance Regulations:

Administrative Regulation on Medical Device User’s Manual, Label and PackagingDecree of SFDA No. 10, July 8, 2004

Medical Device Adverse Incident Monitoring and Product Re-evaluation Management (interim)SFDA Doc [2008] #766, December 29, 2008

Medical Device Product Recall Management (for public comments) March 18, 2008

IFU and Labels: Product name in English and Chinese must be consistent with those on SFDA

certificate IFU and labels must show China service agent contact info, besides other

required info IVD product labels must be consistent with the ones approved at registration. All documents packaged with product must be in Chinese or have Chinese

translation Record keeping

Sales records by distributors, by hospitals Distributors’ QA system and daily operating documents


Administration of Quality Supervision Inspection and Quarantine (AQSIQ)AQSIQ is a ministry level agency, while SFDA is a bureau level

agency, Responsible for all goods in and out of China

Regulations: “Regulations for the Implementation of the Law of the People's

Republic of China on Import and Export Commodity Inspection”

14 Sept. 2005 Decree No. 447

IVD product importation must also follow “The Inspection and Quarantine Management of Special Material for Entry-Exit”

AQSIQ document No.83, 2005, October 17, 2005

for importation of micro organism, human tissues, biological products, blood and blood products


Importation of Reagent


Reagent import follows import procedure for “biological products”

Importation of Reagent for Clinical or Testing

Importer submits “Application for special goods I/E inspection”.

Health Inspection Dept reviews application, if approves, issues “Health Inspection Form”.

Importer ships in products and applies for inspection by Customs.

Importer

Inspector releases products, conducts follow-up inspection is needed.


China Regulatory Strategy – Product RegistrationPlan earlyThe first’s:

Simple product first (Class I ahead of Class II, ahead of Class III) Commonly used, least risky product first (predicated product

available) Mature product first Equipment first, equipment and reagent separately Communication first

The Must’s: Read and follow regulations Try to understand what regulators are looking for Ask why Be understanding and cooperative Apply logic


New Development on China Healthcare China’s Healthcare ReformUniversal Medical Insurance ProgramMOH issues draft regulation on “Clinical Safe Use

of Medical Devices” on 7/9/09Forbid uses of devices without registration certificate,

quality assurance certificate, expired or invalid products or considered technically obsolete products

Adhere to user’s manual, technical specifications and operating procedures

Record implants in patient recordsHospital equipment department to establish inspection

procedure for routine inspections and evaluation of medical devices.


Positive Future for the Chinese Medical MarketEnormous domestic demand fuels GDP growth - 8.4% growth in

2009 estimated by China Academy of Social Sciences, April 09$5.9 billion economic stimulus package for healthcare,

education and culture$125 billion USD healthcare reformBy Whitney Research (www.whitneyresearch.com):

The average growth of Chinese IVD manufacturers: 22% in 2008.

Multinational companies post best performance in China than rest of the world.

Whitney Research predicts that the Chinese IVD market will grow 25-30% in 2009 and 2010.


Thank You!

Chang-Hong WhitneyWhitney Consulting Ltd.

Email: [email protected]: 978-394-2724

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