REGULATORY REQUIREMENT IN JAPAN AND CHINA

REGULATORY AUTHORITY
Japanese

Ministry of Health, Labor, and Welfare (MHLW)

The Pharmaceuti- cals and Medical Devices Evaluation Center (PMDEC), usually known as The Center, is the actual decision- maker for approval of new drug applications (NDAs). The Organization for Pharmaceutical Safety and Research (OPSR), also known as Kiko or the DO (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 organiza- tions has been announced in the past few years, and would result in the creation of an equivalent to the American FDA. The three aforementioned approval reviews organizations are involved in
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The regulatory body and ultimate decision-maker is the MHLW.

Pharmaceutical regulatory authority of Japan is the Pharmaceutical and Food Safety Bureau (PFSB) of the MHLW

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A REVOLUTION IN JAPAN
The implementation in Japan in 1997 of the GCP guide- line ICH E6

Guideline ICH E5, the ethnicity guideline

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A REVOLUTION IN JAPAN

The implementation in Japan in 1997 of the GCP guide- line ICH E6, known in Japan as the new GCP
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ICH E6 was published in three separate documents An English translation of the Japanese GCP is available new written informed consent
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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 clinical trials, 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

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THE CONCEPT OF ETHNIC BRIDGING

Guideline ICH E5, the ethnicity guideline

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AIM 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 bridged from one area to the other
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Additional information regarding the pharmacokinetics of the drug in the new populati on is needed. design a comparative trial involving both Japanese and Western subjects in one protocol.

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FACTORS (ICH E5)

ICH E5 defines two types of ethnic factors that may have an influence on drug development
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Intrinsic factors are genetic and related to the actual human population of the regulatory area. Extrinsic factors are related to the culture of the area.

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NDA REVIEW PROCESSES AND TIMELINES -1NDA NME Additional route, indication, formulation, dose Additional spec, manufacture* 9 11 m Secretariat Review Review Review

3m Team Review ?m Expert Review Review

PMDA
12m DO Review 12m PAC MHLW Review 1m Approval Approval Approval Approval
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MHLW
Review Report 0.5 1 m Report 1m

*not conduct clinical trial

NDA SUBMISSION REQUIREMENTS

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DIAGRAMMATIC REQUIREMENTS OF THE ORGANIZATION OF THE ICH CTD

M1 Regional Administrative Information M 2.1 CTD ToC M 2.2 Introduction M 2.4 Nonclinical Overview M 2.6 Nonclinical Written&Tabul. Summaries M4 Nonclinical Study Reports M 2.5 Clinical Overview M 2.7 Clinical Summary

Not part of the CTD

Module 2
M 2.3 Quality Overall Summary

CTD

M3 Quality

M5 Clinical Study Report

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HISTORY BACKGROUND

In 1998, State Drug Administration established;

SDA oversees all drug manufacturing, trade, and registration.

In 2003, the SDA was restructured to become the State Food and Drug Administration(SFDA) In 2003, Newly added functions
-Drugs (Including Chinese Crude Drugs, Processed Slices of TCMs, TCMs, APIs, Chemicals, Antibiotics, Biochemicals, Radiopharmaceuticals, Vaccines, etc.) -Medical Devices -Food, Cosmetics, Health Food

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 Establishment

of a single drug regulatory

authority
It

eliminated the conflicting standards that prevailed among provincial government agencies the Chinese healthcare regulatory system More transparent.
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Centralized

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.
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China is following and copying U.S. rules. National regulation is implemented by SFDA and other state agencies, while local regulation is implemented by provincial agencies.

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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 to shortfalls in the FDAs inspection of overseas manufacturers. In particular, in the wake of American deaths from tainted Chinese heparin, it was discovered that the heparins Chinese manufacturer had never been inspected despite having FDA approval.

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ABOUT 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)
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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

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China has established drug regulatory departments under the unified leadership of the central government, with vertical management below the provincial level.

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By the end of 2007, 2,692 drug regulatory departments in China, including

y y y

31 at the provincial level, 339 at the municipal (prefecture) level 2,321 at the county (county-level city) level (including districts and counties of municipalities directly under the central government);
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More than 1,000 drug technical supervision organizations with 64,000 personnel in China. Rural areas, drug safety coordinators and information 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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Organizational Structure of SFDA State Council SFDA

Gener al Office

Dept. of Policy & Regulatio n

Dept. of Food Safety Coordinati on

Dept. of Food Safety Supervisio n

Dept. of Drug Registra tion

Dept. of Medical Devices

Dept. of Drug Safety &Inspec tion

Dept. of Drug Market Complia nce

Dept. of Personne l& Educatio n

Dept. of Internati onal Cooperati on

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FUNCTION

Develop policies and programs ,supervise their implementation; participate in drafting relevant laws, regulations and normative documents; Develop good practices ,supervises their implemantation Incharge of hygiene licencing and safety supervision of health food Is in charge of administrative and technical supervision 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 and OTC drugs;

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Charge of formulating regulations of Traditional Chinese Medicines (TCMs) and supervise their implementation Supervise the quality and safety of drugs and 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 system for 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.

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NATIONAL-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 (NCAPTCMP) Center for medical device evaluation (CMDE) Other centers and associations

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These organizations, all affiliated to SFDA, take the responsibility of

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routine testing, testing methodology research, conservation of breeds of experimental animals, standardization research, technical evaluation of registration applications and ADR monitoring.

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Thank you for your attention!

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