Aim: Study of Regulatory Framework and Drug Product

Approval Process in China

Formation: 1950 (predecessor organization) ,2018 (latest re-organization)

Headquarters: 26-Yuan, Xuanwumen Avenue West, Xicheng District, Beijing
The National Medical Products Administration (NMPA) (Chinese: 国家药品监督管理
局 ) (formerly the China Food and Drug Administration, or CFDA) was
founded on the basis of the former State Food and Drug Administration
(SFDA),In March 2013, the former regulatory body was rebranded and
restructured as the China Food and Drug Administration, elevating it to a
ministerial-level agency, In 2018 the name was changed to 'National Medical
Products Administration' and merged into the newly-created State
Administration for Market Regulation.
 Objectives:
1) To study the market value of Chinese pharmaceutical industry.
2) To compile data required for the pharmaceutical regulatory requirements for
product registration in China.

 Drug Regulatory Reform

 NMPA organizations:

1) Department of Comprehensive Affairs, Planning, and Finance Affairs

2) Department of Policies and Regulations
3) Department of Drug Registration
4) Department of Drug Regulation
5) Department of Medical Device Registration
6) Department of Medical Device Regulation
7) Department of Cosmetics Regulation
8) Department of Science, Technology and International Cooperation (Office of
Hong Kong, Macao and Taiwan Affairs)
9) Department of Human Resource.
 Regulatory authorities relating to Drug Administration:
 National Institutes for Food and Drug Control (NIFDC): Verify the drug
specification and test the samples
 Centre for Food and Drug Inspection (CFDI): Inspect the manufacturing
Facility of the drug
 Central for Drug Evaluation (CDE): Conducts Drug evaluation
 Centre for Drug Re-evaluation (CDR)

 Recent activities:
1. In June 2017 NMPA joint ICH as 8th regulatory member.
2. CFDA renamed as National Medical Product Administration on 1st Sep 2018.
3. Administered by the State Administration for Market Regulation (SAMR).

 Site overview-

 The NMPA regulations given on-

1) Drugs
2) Medical device
3) Cosmetics

 The NMPA website is available in two languages Chinese and English.

 Main Responsibilities of the National Medical Products Administration.

(1) To supervise the safety of drugs (including traditional Chinese medicines

(TCMs) and ethno-medicines, the same below), medical devices and cosmetics; to
draw up regulatory, policy plans, organize the drafting of laws and regulations.
(2) To undertake standards management for drugs, medical devices and cosmetics;
to organize the formulation and publication of the Chinese Pharmacopoeia and
other drug and medical device standards, organize the drafting of cosmetic
standards.
(3) To regulate the registration of drugs, medical devices and cosmetics
(4) To undertake quality management for drugs, medical devices and cosmetics; to
develop Good Laboratory Practices (GLP) and Good Clinical Practices (GCP) and
supervise the implementation to develop Good Manufacturing Practices (GMP)
(5) To undertake post-market risk management for drugs, medical devices and
cosmetics
(6) To undertake management of qualifications for licensed pharmacists
(7) To organize and guide the supervision and inspection of drugs, medical devices
and cosmetics
(8) To engage in international exchange and cooperation in the regulation of drugs,
medical devices and cosmetics, and participate in developing relevant international
regulatory rules and standards.
(9) To guide the work of drug regulatory departments of all provinces, autonomous
regions, and municipalities directly under the Central Government.
(10) To complete other tasks assigned by the CPC Central Committee and the State
Council.
 Centre for Drug Re-evaluation (CDR)
Drug Classification System:
China new classification system for Chemical drug (2016)

Monitoring
Classification Definition/Scope
Period
Class 1 API& their formulation which have clinical
Innovative new drug which have never value and contains compound with new 5 years
marketed within or outside china. structure and Pharmacological effects.
1. Drug substance or preparation which
contain optical isomers of known
active ingredients by using splitting or
synthesis new method. 1. 3 years
Class 2
2. New drug preparation using new 2. 4 years
Improved new drug which have never
dosage form. 3. 4 years
marketed within or outside china.
3. New Compound preparation known 4. 3 years
active ingredients.
4. New preparation of known active
ingredients with new indication.
Class 3
Domestic Drug which imitate innovative Drug substance /Preparation have same API
drug that have not been marketed with in dosage form,strength,indication,usage same 0 Years
china but have been marketed outside as innovative drug
china.
Class 4
Domestic Drug which imitate Drug substance /Preparation have same API
Innovative drug that have been marketed dosage form,strength,indication,usage same 0 Years
within china. as innovative drug

Class 5 1. Innovative drug that have been apply

Imported drug which have been outside china.
0 Years
marketed outside china, apply in china 2. Non-Innovative drug that have been
domestic marketed approval. apply outside china.
 China eCTD Requirements – Center for Drug Evaluation (CDE)
Guidelines-

The NMPA (National Medical Products Administration) has given China’s draft
eCTD guidelines after attending the ICH (International Conference on
Harmonization) in June 2017. It is time for any company seeking approval in the
Chinese market for their goods to plan to take advantage of this regulatory change.
 A single eCTD business process goes through a number of steps –
Understanding each of these steps for prepare for eCTD in China.

 Insights from China’s Draft eCTD Information

1. eCTD Approach: Module 2 to Module 5 will adhere to the ICH eCTD format
specifications.
2. Non-Chinese eCTD submitters is that documents must be provided in Chinese
with English versions as reference. eCTD leaf titles also must be in Chinese.
3. The first sequence will be 0000, which, for the new US 3.3 regional DTD,
deviates from the US requirement of 000
4. China intends to include an eCTD validation link to its official CDE website,
which will be free of charge but in Chinese.
5. Current CDE validation requirements require only information about
errors and warnings and prompt information. Validation is yet to be
resolved for Chinese documents.
 Specific Registration Requirements in China as per NMPA / CDE for
eCTD

1. Blank BMR, KSM control validation, repeat validation on existing

pharmacopoeial specifications
2. Providing justification of starting materials in accordance with ICH, KSM
vendor details with GMP compliant certificate, Quality indicative methods
in KSM specification, and Characterization of KSM, Audit and
compliance report of vendor.
3. Provide manufacturing process with at least 3 chemical conversations,
executed process validation protocols and reports.
4. For Drug Registration Certificate specifications and ChP compliance:
microbial studies in release specification, complete analytical method
validation report and justification of specifications.
5. Structural elucidation of working standard including raw data.
6. Raw data of each stability time interval, microbial test in stability
specification, Stability influencing factor study (CP 2015, 9001), invoice
and photographs of the reference standards

 eCTD Format for China -

 Process for Import drug SFDA Registration
 Step I: Application for approval for Clinical study (clinical trial or bio-
efficacy study)

It usually takes10- 12 months for approval of clinical studies.

Step II: Clinical Studies
 Procedures for IND/NDA Approval
60 working days for the approval timelines of IND, 150wds for NDA
- Phase 1 trial is allowed in China to enable China joining global simultaneous
Development
- Review based registration test and inspection
- One CTA approval is valid for Phase I, II and III trials
- CHANGE MANAGEMENT based on risk assessment
- A linked review and approval regime (similar to US DMF) for API, excipients
and packaging materials with DP application together

Medical device

 Definition-

Any instrument, apparatus, appliance, material, or other article whether used alone
or in combination, including the software necessary for its proper application. It
does not achieve its principal action in or on the human body by means of
pharmacology, immunology or metabolism, but which may be assisted in its
function by such means; the use of which is to achieve the following intended
objective-

1. Diagnosis, prevention, monitoring, treatment or alleviation of disease;

2. Diagnosis, monitoring, treatment, alleviation of or compensation for an injury or
handicap conditions;

3. Investigation, replacement or modification for anatomy or a physiological

process;

4. Control of conception.
 Following regulatory bodies in the Chinese government are responsible for
medical device registration in China:
 The China Food & Drug Administration (CFDA)- Is responsible for
medical devices, drugs, and healthcare services.
The organization is headquartered in Beijing, with offices in each province.
 The Center for Medical Device Evaluation (CMDE) - Is responsible for
conducting the dossier review during the medical device registration process.
 The General Administration of Quality Supervision, Inspection, and
Quarantine (AQSIQ)- Conducts mandatory safety registration, certification,
and inspection for certain devices.

Classification of medical devices-

 Class I: low risk devices for which safety and effectiveness can be ensured
through routine administration
 Class II: Medium risk devices for which further control is required to ensure
safety and effectiveness
 Class III: High risk devices which are implanted into the human body, used for
life support, requiring strict control with respect to safety and effectiveness.

Cosmetics-

 In China, cosmetic products are health-related products, so Chinese government

asks all cosmetic industries to register their cosmetic products before they wish
to market their cosmetic products.

In China, the Ministry of Health (MOH) and State Food and Drug
Administration (SFDA) classify cosmetic products into 2 categories, i.e.,
'ordinary cosmetics' and 'special cosmetics.
 Special cosmetics are products containing biological ingredients, such as, hair
dye, sun block, deodorant and slimming products.
 Ordinary cosmetics are items such as lipsticks, nail care and perfume.

 Conclusion:
The current provisions for drug registration have added many new items, such as
regulation on the qualification of drug registration applicants, the classification of
drug into various categories, the regulatory requirements for NCE registration, etc.
Consequently, the provisions are more reasonable and suitable for China’s entry
into the WTO, and further guarantee that safe and effective drugs are available to
the Chinese people.

 Reference-

1. http://www.nmpa.gov.cn/WS04/CL2042/
2. http://sfdachina.com/
3. https://www.celegence.com/china-ectd-requirements/
4. China Releases Draft eCTD Submission Information (sarjen.com)
5. Looking toward eCTD in China: What You Need to Know | Calyx