China's State Food and Drug Administration Discusses Drug Applications

Xie: Can you provide me with a brief overview of SFDA application and approval of foreign drugs?

SFDA: Drug registration applications include applications for new drugs, generic drugs, imported drugs and their supplementary applications as well as re-registration applications. To apply for an import drug registration, the applicant shall fill out the Application Form for Drug Registration, submit relevant dossiers and samples, provide relevant approval documents, and submit the application to the State Food and Drug Administration.

Xie: What is the standard application procedure for an imported drug?

SFDA: Application for an imported drug refers to the registration application for drugs manufactured abroad to be marketed within the territory of the People's Republic of China. A drug being applied for importation shall have already obtained the drug marketing authorization in the producing country or region where the overseas pharmaceutical manufacturer is located; those that have not yet obtained marketing authorization in the producing country or region, may still be approved for importation by the State Food and Drug Administration if they can confirm safety and efficacy through clinical trials.

Xie: What is the application for a generic drug?

SFDA: The generic drug shall have the identical active ingredients, route of administration, dosage form, strength, and therapeutic effects as a registered drug. When a drug has been produced by more than one manufacturer, the selection of registered drugs for comparative study shall be in accordance with relevant technical guidelines.

Xie: Who should file an application for an imported drug registration?

SFDA: An overseas applicant applies for an imported drug registration, which shall be done by its branch in China or an entrusted agency within the territory of People's Republic of China. The people who handle the application for drug registration must have professional knowledge and be familiar with the laws and regulations on, and the technical requirements for, drug registration.

Xie: What is required to provide in the application?

SFDA: The applicant shall provide sufficient and reliable research data to prove the safety, efficacy, and quality of the drug, and be liable for the authenticity of all the dossiers submitted. The cited literature of the dossier of drug registration shall indicate the title of works or the name, volume number, issue, and page of the journal. Where the cited references are not published, an author's permission shall be provided. For foreign literatures, Chinese translation shall be provided as required.

Xie: What are the application and approval procedures for a foreign drug?

SFDA: The approval procedures can be divided into the approval of clinical trial and approval of imported drug application.

For Approval of clinical trials, four steps are involved

a. Application submission and review by SFDA (timeline: 30 days). It is important to submit the application in the format that SFDA requires. Once the application is received, SFDA will check the dossier content and format and send notification of quality test and specifications verification conducted by National Institute for the Control of Pharmaceutical and Biological Products (NICPBP) (timeline: 85 days).

b. Technical Evaluation by the Center of Drug Evaluation (timeline: 90 days)

c. Final Decision by SFDA (timeline: 30 days)

d. If approved, Notification of Clinical trial protocol and the list of investigators to SFDA

For the approval of an imported drug application, three steps are involved:

a. Submission of clinical trial results and other amended or supplemental data by applicant

b. Technical evaluation by the Center of Drug Evaluation (timeline: 150 days)

c. Final Decision by SFDA (timeline: 30 days)

The timeline for drug registration in the Provisions refers to the maximum time for acceptance, review and approval of drug registration. The time for the suspension of the review and approval prescribed in laws and regulations or for the applicant to supplement data is not included.

Xie: What are the difficulties involved in handling the application and approval of a foreign drug in China?

SFDA: The First difficulty involves the lack of familiarity with the laws and regulations in China. The success of handling an application of import drugs registration depends on the person or agent's familiarity of the laws and regulations on drug registration in China. The applicant should realize the difference between laws and regulations of drug registration in China and other countries in order to well prepare the applications according to the laws and regulations in China.

Xie: Can you tell me what is involved in the preparation of an application?

SFDA: The dossier for drug registration application shall be submitted at one time. No other technical materials should be added by the applicant after a drug registration application is accepted, with the exception of applications for special review and approval, new findings regarding drug safety, or supplementary materials that are requested. Also, It is required that all the materials including dossier and references in a language other than Chinese be translated in Chinese. The accurate translation is also a key factor in the approval of an application.

Xie: What types of applications and indications for foreign drug approval are encouraged?

SFDA: The State encourages the research and development of new drugs and adopts the special review and approval with respect to innovative drugs, new drugs for serious and life-threatening diseases, and to address unmet medical needs and drugs. An application for new drugs refers to an application for registration of drugs that have not been marketed within the territory of People's Republic of China.

a. Active ingredients extracted from plants, animals, and minerals, etc. and their preparations not yet marketed in China

b. Chemical drug substances and their preparations and biological products not yet approved for marketing in China or abroad

c. New drugs for the treatment of diseases such as AIDS, malignant tumors, and rare diseases, etc. with significant clinical advantage

d. New drugs for the treatment of diseases, for which effective therapeutic methods are not available.

Xie: Drugs with what technology platforms are simpler to receive approval in China?

SFDA: The SFDA encourages applications with new and advanced technologies and products with new technologies that have demonstrated efficacy, safety, and clinical needs.

a. Advanced technology and industrialization in pharmaceutical preparations

b. Advanced technology and industrialization in natural medicine and traditional Chinese medicine (TCM)

c. Advanced technology in bio/pharmaceutical research & development and industrialization

d. Advanced technology in small-molecule drug research & development and industrialization.

Xie: Are there common issues that arise in the application and approval of a foreign drug, and how can one overcome them?

SFDA: The most common issue in an application of an imported drug registration is preparation of the application. This heavily depends on the familiarity of laws and regulations on drug registration in China. Due to the differences of laws and regulations in different countries, the applicant must realize the requirements of application submission are different, and the applicant must meet all the requirements listed in the regulation. To overcome this issue, the applicant should

1. Get familiar with the laws and regulations for drug registration in China

2. Prepare the dossier and related materials according to the regulations

3. Keep good communications open with your agents in China as well the SFDA to get updates of changes in laws and regulations.

Xie: How does SFDA work with the Chinese Pharmacopoeia Commission?

SFDA: The Chinese Pharmacopoeia Commission is directly affiliated with SFDA and is responsible for

a. Compiling the Pharmacopoeia of The People's Republic of China

b. Establishing the state drug standard, packing material standard, equipment, and pharmaceutical excipients standard

c. Conducting state drug standard in testing phase in order to finalize the drug standard of China

d. Providing training and consulting for the state drug standard

e. Establishing standard information systems for state drug standard, participating in international exchanges and collaboration of drug standard

f. Publishing the journal of State Drug Standards and other drug-standard-related publications

g. Any additional tasks assigned by SFDA.

U.S. manufactures can find information about the Chinese Pharmacopoeia from the SFDA website or Chinese Pharmacopoeia Commission at www.chp.org.cn (only Chinese version is currently available).

Xie: How does SFDA work with the newly created International Pharmaceutical Excipients Council (IPEC) in China?

SFDA: IPEC-China was established in 2008 as a nonprofit organization. IPEC-China members are from pharmaceutical excipient manufacturers, users, and distributors. IPEC-China can assist with the SFDA and Chinese Pharmacopoeia Commission to improve safety of excipient application and guarantee public safety.

Xie: Where should manufacturers submit an application for review? To whom at SFDA and to what address should applications be submitted?

SFDA: Reception Center

State Food and Drug Administration

Address: A38, Beilishi Road, Beijing 100810, P.R. China

Office Hour: 8:30–11:30am / 13:00 –16:00

Tel: 010—68315572

Fax: 010—88330265

e-mail: slzx@sfda.gov.cn

Xie: Can applications be submitted electronically, and if so, is there a templated form?

SFDA: Applicantants must use the software provided by SFDA to file an application. Both electronic files and hard copy must be submitted to The Reception Center at SFDA.

Xie: Do submissions need to be in Chinese?

SFDA: Yes, All submissions need to be in Chinese.

Xie: Is there a website where manufacturers outside of China can get contact information as well as more general information about SFDA and its drug approval/marketing process?

SFDA: Yes, the website of Reception Center (to download application, submit applications, and check the status of an application): http://www.sfda.gov.cn/WS01/CL0399/.

Xie: Is there any literature available that advises foreign manufacturers on the processes and procedures involved in submitting drug applications? Where/how can people obtain this literature?

SFDA: Literature is available at the website of the Reception Center: http://www.sfda.gov.cn/WS01/CL0147/. You can also check SFDA Order No. 28 (Provisions of Drug Registration) http://eng.sfda.gov.cn/cmsweb/webportal/W45649039/A64028429.html.

Xie: What is SFDA's working relationship with the US FDA, which now has offices in Beijing, Shanghai, and Guangzhou?

SFDA: SFDA is an important strategic partner of the USA. Both parties reached a consensus in 2007 on further expanding the exchange and cooperation between the food and drug regulatory departments of the two countries, hoping to conduct in-depth communication in the application of new technologies, guidelines of supervision, future strategic planning, and other aspects. Both parties are cooperating in the fields of pharmaceutical and biological products, and US FDA provides assistance in technical support and capacity building.

*This is the first in an ongoing series of interviews to be conducted by Advanced Pharmaceuticals, LLC, an international business engaged in technology transfer to China, licensing of drugs to China, and obtaining SFDA approvals for drugs and devices in China. This interview was translated by Ji Xie and Feng Li and edited by John R. Choate, all of Advanced Pharmaceuticals.