China's vaccine regulatory system passed WHO reassessment, announced on July 4th, 2014.
In April of 2014, WHO conducted re-assessement of the China FDA vaccine regulatory functions, and found that it has met or exceeded all WHO criteria for functioning at international standards of excellence.
This evaluation is a follow-up to an initial successful evaluation three years prior. WHO conducted the initial assessment of the national vaccine regulatory framework on December 13-17, 2010. This review encompassed indicators for the overall regulatory framework, marketing authorization and licensing, post-marketing surveillance (including adverse events surveillance), lot release, laboratory access, inspections of manufacturing sites and supply chain, and authorization and surveillance of clinical trials.
The first Chinese manufacturer received WHO prequalification for Japanese encephalitis vaccine in October 2013.
Clinical Trial Data Requirements
Clinical trial requirements are outlined in Chapter 3 of CFDA Order No. 28 ("Provisions for Drug Registration"). This is available here.
For Clinical Trial Approval, investigators submit an application to the CFDA. During a preliminary review, which lasts 5 days, the dossier format and content is verified. The Center of Drug Evaluation (CDE) will subsequently conduct a technical evaluation of the submission which takes an estimated 90 days (80 days for fast track approval or special review-studies involving innovative new drugs, HIV drugs, malignant neoplastics or orphan drugs with significant clinical superiority, and drugs for diseases without existing effective treatment). If the CDE requests supplementary data, it should be provided within 4 months (8 months for fast track or special review). After the CDE has issued its recommendation, it takes an estimated 30 days for the CFDA to issue Clinical Trial Approval.
For investigational drugs that are classified as biological products, the investigator must submit product samples to the National Institute for Food and Drug Control (NIFDC) for full quality control testing. The timeline for this is 60 days and 90 days for vaccines and drugs under special control.
Clinical Trial Import Authorization
Import authorization is outlined in Chapter VI Section 1 of CFDA Order No. 28 ("Provisions for Drug Registration"). To apply to import a drug, the drug must already have drug marketing authorization in the producing country. For drugs that have not yet received marketing authorization abroad, the CFDA may approve importation after conducting an assessment of safety, efficacy, and clinical needs. The sponsor should submit the Application Form for Drug Registration with relevant dossiers, samples, and documents to the CFDA.
Clinical Trial Estimated Timeline
Estimated timelines differ for ordinary and fast track approval. CFDA has a flow chart of timelines available here.
Clinical Trial Costs
In-Country Manufacturing Requirements
Good Manufacturing Practice (GMP) provisions in China cover quality management, organization and personnel, premises and facilities, equipment, materials and products, qualification and validation, documentation management, production management, quality control and quality assurance, contract manufacture and analysis, product distribution and recalls, and self inspections. The GMP for Drugs decree is available here.
According to Baker & McKenzie LLP's clinical trial guide, China requires that sponsors have insurance to cover any clinical trial related injuries. Global insurance that covers the study in China is sufficient.
According to Baker & McKenzie LLP's clinical trial guide, sponsors are required to cover the cost of treatment for trial subjects who sustain injuries as a result of the trial.
Product Registration Data Requirements
Product registration is outlined in Chapter II ("Application for Drug Registration") of CFDA Order No. 28 ("Provisions for Drug Registration"). Applications from domestic sponsors are considered new drugs or generic drugs applications, while applications from foreign sponsors are considered import drug applications. The sponsor should submit clinical trial data and cited literature (with Chinese translations if foreign literature) in the dossier.
Precedent (Clinical Trials Approved/Denied in Last 2 Years)
55 clinical trials approved from July 2012 to July 2014.
Product Registration Estimated Timeline
According to timelines listed in Chater XII ("Timeline") of CFDA Order No. 28 ("Provisions for Drug Registration"), sample testing takes an estimated 30 days, and sample testing and verification takes 60 days. For a controlled drug or vaccine, sample testing takes 60 days, and sample testing and specifications verification takes 90 days. For technical review, a new drug application for product takes 150 days (120 days if special review). For a change in dosage of a marketed or generic drug, review should take 160 days.
Post Registration Labeling Requirements
Labelling requirements are outlined in Chapter 14 of CFDA Order No. 28 ("Drug Registration Specifications and Insert Sheet"). This is available here.
Post Registration Pharmacovigilance Requirements
Pharmacovigilance regulation is outlined in "Measures for the Reporting and Monitoring of Adverse Drug Reactions (2011)" (unavailable), which went into effect July 1st, 2011.
The National Center for Adverse Drug Reaction (ADR) Monitoring is part of the WHO’s Collaborating Center for International Drug Monitoring (Uppsala Monitoring Centre), and reports to both the WHO and the Ministry of Health. The National Center for ADR Monitoring has five divisions and a network of 32 provincial centers for ADR monitoring. These provincial centers are affiliated with local CFDA offices in various provinces, autonomous regions, and municipal governments.
Pharmaceutical companies, hospitals, pharmacies, and drug distributors report ADRs and adverse drug events (ADEs) to regional centers, which then report all new and all serious ADRs and ADEs to the National Center within three days. Other ADR/ADE reports can be sent quarterly. Individuals can file reports with either the regional or National Center.
In 2013, 1.3 million adverse events were reported, 78.4% from hospital and 19.6% from distributors and 1.4% from manufacturers.
Good Manufacture Practice for Drugs (Ministry of Health Decree No. 79) contains two relevant articles on ADR reporting:
-Article 269. System of ADR reporting and mornitoring should be established, with special department and full-time staff.
-Article 270. Manufacturer should collect ADR actively, record in detail, survey, analysis and evaluate, take actions in time to manage the potential risk and report to authority agency according to the requirements.
In June 2010, Ministry of Health and CFDA co-issued a National Guideline on Surveillance of Suspected Adverse Events Following Immunization (unavailable), which specifies requirements for AEFI surveillance reports, data analysis and application, and ADR procedures.
May 19, 2015.