..Japan Regulations CR..Sc

8/2/2019 ..Japan Regulations CR..Sc

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REGULATORY REQUIREMENT IN

J APAN AND CHINA 1



REGULATORY AUTHORITY

Japanese Ministry of

Health, Labor, and Welfare

(MHLW)

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3



4



5



The Pharmaceuti- cals and Medical Devices Evaluation

Center (PMDEC), usually known as ´The Center,µ is the actual

decision- maker for approval of new drug applications (NDAs).

The Organization for Pharmaceutical Safety and Research

(OPSR), also known as ´Kikoµ or ´the DOµ (Drug

Organization), is an independent body, related to the

MHLW, that is in charge of discussing drug development

programs with industry.

A merger of these two organizations has been announced in the

past few years, and would result in the creation of an equivalent

to the American FDA.

The three aforementioned organizations are involved in

approval reviews

The regulatory body and ultimate decision-maker is the MHLW .

6



7



8



9



Pharmaceutical regulatory authority of Japan is

the Pharmaceutical and Food Safety Bureau

(PFSB) of the MHLW

10



11



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A REVOLUTION IN J A P AN

The implementation in Japan in 1997 of the GCP guideline

ICH E6

Guideline ICH E5, the ethnicity guideline

13



A REVOLUTION IN J A P AN

The implementation in Japan in 1997 of the GCP

guideline ICH E6, known in Japan as ´the new

GCPµ

y ICH E6 was published in three separate

documents

y

An English translation of the Japanese GCP isavailable

y new written informed consent 14



In 1997 the new GCP regulations allowed the CROs to

take over responsibility of phase 2 and 3

In hospitals involved in phase 2 and 3 clinicaltrials, SMOs now assume the training of

physicians and nurses, setup of clinical trial centers,

staffing with the CRCs, writing of standard operating

procedures (SOPs), and interaction with monitors or

auditors from the regulatory authority

15



THE CONCEPT OF ETHNIC BRIDGING

Guideline ICH E5, the ethnicity guideline

16



A IM OF ICH E5

To reduce duplication of clinical studies by setting up a

process for evaluating the possibility of extrapolating

clinical data from one regulatory area to another.

Successful in reducing the

necessity to reproduce clinical research programs in

Japan for drugs that have already been approved in the

West.

The guideline describes in detail which drugs may be

more easily ´bridgedµ from one area to the other17



Additional information regarding the phar-

macokinetics of the drug in the new populati

on is needed.

design a comparative trial involving bothJapanese and Western

subjects in one protocol.

18



F ACTORS (ICH E5)

ICH E5 defines two types of ethnic factors that

may have an influence on drug development

y

Intrinsic factors are genetic and related to the actualhuman population of the regulatory area.

y Extrinsic factors are related to the culture of the

area.

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20



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NDA REVIEW PROCESSES AND TIMELINES -1-

23

PAC

Additional route, indication,

formulation, doseNMEAdditional spec,

manufacture*

DO

Secretariat

Review

Review Review

Review Report

Report

MHLW Approval ApprovalApproval Approval

Expert Review ReviewReviewReview

1 ± 2 m

1 ± 2 m 0.5 ± 1 m

1 m

1 m

Team Review

PMDA

MHLW

*not conduct clinical trial

9 ± 11 m3 m

NDA

? m



NDA SUBMISSION REQUIREMENTS

24



DIAGRAMMATIC REQUIREMENTS OF THE ORGANIZATION OF

THE ICH CTD

25

Module 2

M 1

Regional

Administrative

Information

M 2.3

Quality

Overall

Summary

M 2.4

Nonclinical

Overview

M 2.5

Clinical

Overview

M 2.6

NonclinicalWritten&Tabul.

Summaries

M 2.7

ClinicalSummary

M 3

Quality

M 4

Nonclinical

Study Reports

M 5

Clinical Study

Report

Not part of the CTD

CTD

M 2.1 CTD ToC

M 2.2 Introduction



26



HISTORY BACKGROUND

In 1998, State Drug Administration established;

± SDA oversees all drug manufacturing, trade, andregistration.

In 2003, the SDA was restructured to becomethe State Food and Drug Administration(SFDA)

In 2003, Newly added functions-Drugs (Including Chinese Crude Drugs, Processed

Slices of TCMs, TCMs, A PIs, Chemicals, Antibiotics,Biochemicals, Radiopharmaceuticals, Vaccines, etc.)

-Medical Devices

-Food, Cosmetics, Health Food 27



Establishment of a single drug regulatoryauthority

It eliminated the conflicting standards

that prevailed among provincialgovernment agencies

Centralized the Chinese healthcare

regulatory system

More transparent.28



SFDA :new regulations follow FDA's model.

SFDA required all pharmaceutical companies in

China to obtain GMP certificates from SFDA by

June 30, 2004 to be licensed to sell their drug

products in China

In 2005, SFDA launched a regulation on drug

research and supervision management aimed at

enforcing GLP to investigative drugs, traditional

Chinese medicine injections and biotechnology

products.

29



China is following and copying U.S. rules.

National regulation is implemented by SFDA and

other state agencies, while local regulation isimplemented by provincial agencies.

30



the SFDA was formerly an autonomous

regulatory agency, it has now been put under the

direct command of the Ministry of Health (MOH)

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US FDA IN CHINA

important development in late 2008

establishment of US FDA offices in China

Open in Beijing, Shanghai, and Guangzhou.

These offices were conceived in response toshortfalls in the FDA·s inspection of overseas

manufacturers.

In particular, in the wake of American

deaths from tainted Chinese heparin, itwas discovered that the heparin·s

Chinese manufacturer had never been

inspected despite having FDA approval.32



A BOUT SFDA

State Food and Drug Administration (SFDA)

founded in 2003, directly led by the State Council

of P. R. China;

Local Agencies: 31 provincial-, 433 municipality-

,1,936 county- level agencies (2,401 total);

Technical Organizations: 16 state-, 122

provincial-, 373 municipality-, 436 county- level

organizations (947 total)

33



SFDA IS :

In charge of administrative supervision and

technical supervision over the research,

production, distribution and use of drugs

and medical devices.

Drugs :

including Chinese crude drugs, prepared slices of

Chinese crude drugs, traditional Chinese

medicine preparations, chemical drug substances

and their preparations, antibiotics, biochemical

drugs, radioactive pharmaceuticals, serum,

vaccines, blood products and diagnostic agents 34



China has established drug regulatory

departments under the unified leadership of the

central government, with vertical management

below the provincial level.

35



By the end of 2007,

2,692 drug regulatory departments in China,

including

y 31 at the provincial level,

y 339 at the municipal (prefecture) level

y 2,321 at the county (county-level city)level (including districts and counties of municipalities directly under the centralgovernment);

36



More than 1,000 drug technical supervision

organizations with 64,000 personnel in China.

Rural areas, drug safety coordinators andinformation specialists had been employed to

ensure drug safety and promote the building of a

drug safety supervision network.

A total of 578,000 stations of rural drug

regulatory network had been established.

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38

State Council

SFDA

Gener

al

Office

Dept. of

Drug

Registra

tion

Dept. of

Drug

Market

Compliance

Dept. of

Drug

Safety

&Inspection

Dept. of

Medical

Devices

Dept. of

Personne

l &

Education

Dept. of

Internati

onal

Cooperation

Dept. of

Policy &

Regulatio

n

Dept. of

Food

Safety

Supervision

Dept. of

Food

Safety

Coordination

Organizational Structure of SFDA



FUNCTION

Develop policies and programs ,supervise theirimplementation; participate in drafting relevantlaws, regulations and normative documents;

Develop good practices ,supervises theirimplemantation

Incharge of hygiene licencing and safetysupervision of health food

Is in charge of administrative and technicalsupervision of drugs and medical devices.

Draw up relevant national standards of drugs and

medical devices, and supervise their implementation Carry out the Adverse Drug Reaction (ADR)

monitoring ,organize the implementation of classification system for prescription drugs andOTC drugs; 39



Charge of formulating regulations of

Traditional Chinese Medicines (TCMs) and

supervise their implementation

Supervise the quality and safety of drugsand medical devices

To organize the investigation and

punishment of illegal activities

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FUNCTIONS«..

To direct relevant local work regarding food

and drug administration, emergency response,

inspection and informationalization;

To draw up and improve qualification systemfor licensed pharmacist, direct and supervise the

registration of licensed pharmacist;

To carry out international exchanges and

cooperation related to food and drug regulation;

To undertake other work assigned by the State

Council and the Ministry of Health.

41



N ATIONAL-LEVEL DRUG TECHNICAL

SUPERVISION ORGANIZATIONS

National institute of the control of pharmaceutical

and biological products (NICPBP)

Chinese pharmacopoeia commission (CPC)

Center for drug evaluation (CDE)

Center for certification of drugs (GMP Inspection)

(CCD)

Center for drug reevaluation (Postmarketing) (CDR)

National committee on the assessment of the

protected traditional Chinese medicinal products(NCA PTCMP)

Center for medical device evaluation (CMDE)

Other centers and associations 42



These organizations, all affiliated to SFDA, take

the responsibility of

y routine testing,

y testing methodology research,

y conservation of breeds of experimental animals,

y standardization research,

y technical evaluation of registration applications and

ADR monitoring.

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