July/August 2011 Update 21FDLI

Generic Drug Approval Process in ChinaBy Steven J. Rizzi and Max Lin

tively follow innovations developed in the West. It is thus not surprising that China currently has about 3,500 drug compa-nies, most focused on generic drug manufacturing. In 2010, the State Food and Drug Administration of the People’s Republic of China (SFDA) approved 886 domestic drug registration applications, 651 of which were for generic drugs (73 percent). This article provides an overview of the regulatory framework for SFDA’s generic drug approval process.

As an initial matter, it is important to understand the basic differences between the prescription drug regulatory schemes in China and the United States. In the United States,

The domestic prescription drug market in China is grow-ing rapidly. China is expected to become the world’s third largest prescription drug market in 2011, and the

Chinese pharmaceutical market may double by 2013.1 This growth is likely to continue for some time considering that China accounts for 20 percent of the world’s population, but only 1.5 percent of the global drug market. And because a large portion of the Chinese population is not covered by basic health insurance, low cost generic drugs will account for the major-ity of the growth of China’s prescription drug market. Chinese manufacturers are also known for their ability to cost-effec-

Steven J. Rizzi is a partner at Foley & Lardner in New York, NY.

Max Lin is a China associate with Foley & Lardner LLP.

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22 w w w . f d l i . o r gUpdate July/August 2011

China Issue

a “branded drug” typically refers to a patent-protected, brand-name drug marketed under a proprietary name or trademark as opposed to its chemi-cal name. A generic drug is a copy of a branded drug that is approved by the Food and Drug Administration (FDA) for sale and use based on the safety and ef-ficacy data developed by the branded drug manufacturer. Until recently, China’s regulatory scheme did not incorporate the concepts of “branded” v. “generic” drugs. In 2007, SFDA promulgated the Amended Regulation on the Administration of Drug Registration (Amended Regula-tion), which governs the approval and registration processes applicable to drugs in China. The Amended Regulation uses the concepts of “new” drug and “generic” drug. A new drug is one that has not been previously marketed in China, whereas a generic drug is one that has an existing national drug standard, and was previ-ously approved to be marketed by SFDA.

Bioequivalence Testing The Amended Regulation specifies

that the generic drug shall have the same active component, route of administra-tion, dosage form, strength and thera-peutic effect as the existing, approved drug. To the extent possible, bioequiva-lence testing is an important aspect of the SFDA approval process for generic drug applications. For example, the Annex to the Amended Regulation provides that for oral solid preparations of chemi-cal drugs, bioequivalence testing shall normally be conducted on 18-24 cases. Bioequivalence tests include human tests to determine if there is any statistical difference in absorption and absorption speed of the active component between the same or different dosage forms of the same drugs under the same test condi-tions, by using the methodology of a

bioavailability study with pharmacoki-netic parameters.

Clinical TrialsA generic drug application, or so-called

“abbreviated application,” may omit pre-clinical and clinical test data on the basis that the drug is already on the market and its effectiveness and safety under-stood. The key aspects of the examina-tion and approval process focus on the quality of the manufacturing process and conformity with the existing national drug standard. In certain circumstances, clinical trials are required for safety reasons. According to the Annex to the Amended Regulation, for generic drugs based on traditional Chinese medicine (TCM), or natural drug injections, clini-cal trials on no less than 100 pairs of cases are required. For generic chemical drugs where the quality is controlled by defined processes and standards, clinical trials on 18-24 cases are typically required. For biosimilars, Annex III to the Amended Regulation, which applies specifically to the registration of biological drugs, provides that biosimilars applications are subject to full-phase III clinical trials.

Application ProcedureGeneric drug applications must be filed

by the drug manufacturer in the provin-cial FDA (PFDA) where the applicant is located. The PFDA serves as the receiving office for the generic application and de-termines whether the application dossier is in proper order. If the requirements are met, the PFDA provides notification of acceptance of the drug registration application. If the requirements are not met, the applicant is provided with an explanation of the reasons for rejection, and the opportunity to reapply. Within five days of acceptance of the applica-tion, the PFDA will conduct an on-site

inspection of the production site, as well as the original drug research data, and take samples of three consecutive batches to send to the Drug Control Institute for inspection. The sample products are required to be manufactured in a facil-ity with Good Manufacturing Practice (GMP) certification.

After completing examination of the application dossier, the PFDA will submit the dossier along with its examination recommendation, verification report and results of its inspection of the produc-tion site to the SFDA Center for Drug Evaluation (CDE) within 30 days. CDE will organize pharmaceutical, medical and other technical staff to examine the verification recommendation and the application dossier, and may request that the applicant provide supplemental information if necessary. At the same time, the Drug Control Institute tests the sample products and provides its sample test report to CDE, the PFDA and the applicant. CDE prepares a general examination recommendation based on the technical examination recommenda-tion, production site inspection informa-tion and sample test report, and then submits to SFDA along with related data. SFDA then makes its approval decision based on the general recommendation and issues a Drug Approval Number (if no clinical trials are needed), or a Clini-cal Trial Approval (if clinical trials are needed). Upon completion of clinical trials, the applicant must then submit the clinical trials data to SFDA for issuance of a Drug Approval Number. For drugs that do not meet safety requirements, the Amended Regulation grants SFDA authority to suspend acceptance or ap-proval of the generic drug application.

FDLI

1. IMS Health Report (http://www.chinadaily.com.cn/business/2010-03/17/content_9603154.html)

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July/August 2011 Update 23FDLI

China Issue

Applicant completes Drug Registration Form; submits production application dossier and application for inspection of production site to the PFDA.

SFDA makes approval decision based on the general recommendation.

Issue Drug Approval Number (within 10 days).

Clinical Trial Approval (within 10 days).

Applicant submits clinical trial report to CDE.

CDE conducts technical exam-ination of clinical trial report.

SFDA makes approval decision based on the technical exam-ination recommendation (30 days).

Issue Drug Approval Number (within 10 days).

Notification of approval opinion (within 10 days).

After completing the examination of the application dossier, PFDA submits application dossier, its examination recommendation, verification report and conclusions from its inspection of production site to CDE. (30 days)

CDE arranges for pharmaceutical, medical and other technical staff to examine the verification recommendation and the application dossier (160 days), and may request that applicant provide supplemental information if necessary.

CDE concludes a general examination recommendation based on the technical examination recommendation, inspection report of production site, and sample test report, and submits to SFDA along with related data.

PFDA conducts formal examination; if accepted, within five days PFDA conducts on-site inspection of production site and drug research data, and takes sample drugs from three consecutive batches.

The Drug Control Institute tests the sample product and sends the sample test report to CDE, PFDA and applicant. (30 days)

Generic Application Approval Flow Chart & Timeline

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