Regulatory updates on China, Jan. 1-15, 2019

Dr. C. Benson Kuo and his team is documenting the evolving regulatory landscape in China! For general information on Education Initiatives, click hereHighlight posted on January 17th, 2019

Clinical Trials 
PAREXEL Cooperates with Lilly to Develop China’s Clinical Research Workforce

Parexel and Lilly established a partnership to launch a clinical research learning and development program in China. The aim of the program is to bring high-value training opportunities to China’s clinical trial sites and investigators, enhancing the execution of local clinical trials and driving innovation in China’s biopharmaceutical industry.

Recently, the Chinese government released a series of policies for clinical research to encourage innovation in drug development, that have resulted in a sharp increase in the number of clinical trials in China. According to China’s clinical trial registration platform, 1,258 drug clinical trials were first registered in China in 2017, an increase of 62.66 percent compared to 2016. This increase in clinical research demands has brought opportunities and challenges to the clinical research capacity and resources in China.

China’s CMDE Launches Voluntary Device Master File Process

China’s Center for Medical Device Evaluation (CMDE), part of the National Medical Products Administration (NMPA), is responsible for conducting dossier reviews during the medical device registration process. CMDE plans to launch a registration system of master files for medical devices. A Medical Device Master File (MAF) is a submission to NMPA used in support of premarket submissions to provide confidential detailed information about establishments, processes, or articles used in the manufacturing, processing, packaging, and storing of one or more medical devices. The MAF allows each company to submit confidential data to NMPA without disclosing to anyone outside NMPA. A MAF is a submission of information to the NMPA by the Medical Device Master File holder. CMDE hopes that the quality of medical devices review can be improved further through this registration system, build a more scientific and efficient review system, and protect trade secrets.

China’s Lawmakers Get Tough on Vaccine Industry

On December 23, 2018, China lawmakers considered approval of the first draft of the law aimed at tightening control of the vaccine industry. The draft vaccine management law, which was released by the State Administration for Market Regulation in November, had been approved by the State Council. The lawmakers are now soliciting public opinion on the draft legislation and claim this is the “strictest” ever regulation on vaccines. The draft vaccine management law not only applies to domestically produced vaccines but also imported ones. The draft law consolidates existing rules on industry including their research, development, approval, production, distribution, and use. It removes the restrictions on pediatric clinical trials and emphasizes the importance of maintaining ethical and quality standards in clinical trials.

The drug authorities will supervise the entire production chain of vaccines and inspect vaccine production sites to ensure manufacturers digitally record data related to production and inspection, and to certify the authenticity, integrity, and traceability of the data. Approval procedures and inspections must cover every batch of vaccines before they enter the market. The draft law also outlines the increased penalties for production, distribution, and sales of counterfeit vaccines, adding the followings:

  • Increases the minimum penalties for manufacturing and selling counterfeit vaccines, and may ban for life from conducting business in the pharmaceutical industry;
  • Rewards reporting illegal manufacturing, distribution, and sales of counterfeit vaccines.

Dietary Supplement
National Medical Products Administration: New Program Launched in China for False Advertising and Promotion on Dietary Supplement

On January 8, 2019, 13 departments in China, including the State Administration for Market Regulation, held a joint televised conference to rectify the dietary supplement market management. Recently, the dietary supplement market exposed a series of problems such as false propaganda, illegal advertising and promotion, consumer fraud and counterfeiting, which seriously infringed on the legitimate rights and interests of consumers and disrupted market order. The program helps the agency to evaluate whether dietary supplement advertising and promotion are truthful while establishing long-term supervision mechanisms to crack down on illegal fraud and counterfeiting activities.

Pricing and Procurement
China’s Junshi Prices Homegrown anti-PD-1 at Great Discount

Shanghai Junshi Biosciences Co. Ltd. has won China’s first approval for a homegrown anti-PD-1 treatment, an emerging cancer therapy that boosts the immune system to help the body to target and kill tumors. The drug is trademarked as Tuoyi (Toripalimab) and is designed to treat skin cancer melanoma. The National Medical Products Administration under priority review conditionally approved Tuoyi (Toripalimab) on 17 December 2018, about nine months after the company filed its new drug approval application.

Tuoyi (Toripalimab) has a lower price compared to Keytruda (pembrolizumab) from Merck & Co. Inc, which has been approved in China and has the same mechanism. On 7 January 2019, Junshi set Tuoyi’s price at RMB7, 200 ($1,050.91) per 240 mg. On a per-milligram basis, the price of Tuoyi is 16% of Keytruda.

54 Innovative Medical Device Listed through the Fast Approval Track in China

In December 2018, China’s National Medical Products Administration (NMPA) issued “Special Review Procedure for Innovative Medical Devices” in order to implement a system of fast approval track for innovative medical devices. To date, 197 products have entered the fast approval track for innovative medical devices and 54 products have been approved, including 22 implantable medical devices, 9 diagnostic devices, and 13 in vitro diagnostic reagents. The review time through the fast track pathway has been shortened by an average of 80 days. The system of fast track approval dramatically reduces the time for innovative medical devices to the market.

Digital Reporting and Monitoring System Upgraded and Rectified on Controlled Drug Substances

To protect the legal manufacture, importation, possession, use, distribution, and trade of controlled drug substances, while at the same time protecting the public health, an upgraded Digital Reporting and Monitoring System has been implemented in China. According to China legislation, the following four categories of drugs are defined with high potential for abuse:

  • Narcotic drugs
  • Psychoactive drugs
  • Medicinal Toxic drugs
  • Radiopharmaceuticals

The upgraded reporting and monitoring system requires all firms involved in manufacture and trade of controlled drug substances to submit the detailed information of their APIs and excipients per label, strength, and batch in 7 days of their production and distribution.

The qualifications of firms and their data integrity revealed by the submitted digital information on controlled drug substances will be routinely supervised and inspected by provisional medical products administrative departments.

China’s Oncology Drugs Market is Expected to Expand at 13.5% CAGR

China’s oncology drug market has expanded rapidly in recent years. Revenue of oncology drugs in China grew from 83.4 billion RMB in 2013 to 139.4 billion RMB in 2017, showing a compound annual growth rate (CAGR) of 13.7%. Among all types of cancers, lung cancer, liver cancer, stomach cancer, colorectal cancer, and breast cancer are the top cancer types in China by incidence rate, accounting for more than 50% of the annual incidence.

According to the “China Monoclonal Antibody Market by Targets (PD-1, CD20, HER2, VEGF, EGFR, TNF-a) Research Report, 2018-2055”, the market is expected to grow further to 262.1 billion RMB in 2022 at a CAGR of 13.5% from 2017, and to 654.1 billion RMB in 2030 at a CAGR of 12.1% from 2022. While in 2017, the majority of the top 10 oncology drugs globally are either molecularly targeted drugs or immuno-oncology drugs, only three of these molecularly-targeted drugs were approved in China in 2018, the remaining seven are chemotherapy drugs. This difference indicates China is at the early stage of a paradigm shift to molecularly targeted drugs and immuno-oncology drugs. Monoclonal antibodies (MAbs), including fusion proteins, only accounted for 5.4% of China’s biologics market in 2017, while globally the figure was 43.2%, representing a sizable market potential. In addition to monotherapies, PD-1/L1 inhibitors have shown significant potential in combined therapies. The market size of PD-1 and PD-L1 inhibitors together is estimated to grow to 37.4 billion RMB in 2022, representing a CAGR of 534.4% from 2018 to 2022. In December 2018, the State Drug Administration announced approval of the first domestically produced PD-1 monoclonal antibody injection, developed by Shanghai Junshi Biosciences Co.

New 2019 Standards for Medical Devices in China

China’s National Medical Products Administration (NMPA) pays close attention to the standards of medical devices and improves the standards of medical device quality systems continuously in accordance with “the four most strictly” requirements. Some of the issues are interpreted as follows:

  • Strengthen the development of the quality system for medical devices;
  • Accelerate and revise the medical device standards to ensure their quality system is adequate to provide high-quality components or safe and effective finished medical devices;
  • Improve the management of the standardization committee for medical devices;
  • Promote the harmonization of the regulatory requirements for medical devices and encourage collaborations with other groups of regulators around the world, especially in the International Medical Device Regulators Forum (IMDRF).

Clinical Trials
CDE Accepts the Larotrectinib IND Application

Loxo Oncology’s broad-spectrum anticancer drug Vitrakvi® (larotrectinib), has filed a clinical trial Investigational New Drug (IND) application in China, which was accepted by the Center for Drug Evaluation (CDE) on 14 January 2019. This anticancer drug Vitrakvi® (larotrectinib) was approved by the accelerated process and breakthrough therapy by the U.S. Food and Drug Administration (FDA) in Nov 2018, as the first oral TRK inhibitor for the treatment of solid tumors that test positive for NTRK genes.

Vitrakvi is indicated for the treatment of adult and pediatric patients with solid tumors that have a neurotrophic receptor tyrosine kinase (NTRK) gene fusion without a known acquired resistance mutation are metastatic or where surgical resection is likely to result in severe morbidity and have no satisfactory alternative treatments or that has progressed following treatment.

This CDE approval is a significant step in the development of cancer drugs that treat tumors based on their tumor genetics rather than their site of origin. Larotrectinib’s clinical application and acceptance in China is another major step in the global registration of the drug.

Loxo Oncology was recently acquired by Lilly for $8 billion.

Pricing and Procurement
Dalian, the First City Released Detailed Requirement for Centralized Drug Procurement

A government pilot program, named as “4+7 cities” quantity purchases, has been implemented and became one of the most concerning issues in the pharmaceuticals industry in China. Under this new government program designed to garner lower drug prices, drug manufacturers were invited to bid contracts to supply 31 drugs to public medical institutions in the eleven cities. As a result, 25 drugs and related pharmaceutical manufacturers have been selected to supply drugs to 11 major Chinese cities from the Joint Procurement Office (JPO).

Dalian, as one of the eleven cities, is the first to release detailed requirements for implementation of related pharmaceutical procurement, including permission for the drugs to enter hospitals, health insurance payment, drug payment settlement, and clinical use.