China's Drug Regulation Revolution: An interview With Dr. Ling Su

Ling Su, PhD, RAPS China Advisory Committee member, provides insights into drug administration reform and calls for top-level design ideas and long-term solutions.

Since the 1980s, in conjunction with the transition from a planned to a market-oriented economy, the contemporary Chinese drug administration system has experienced much improvement. The developed countries spent more than 100 years building their mature drug administration system, and although China has been playing catch-up for the past few decades, it is introducing new regulations and reorganizing the administration department of the China Food and Drug Administration (CFDA). With the August 2015 publication of the Opinions of the State Council on the Reform of the Review and Approval System for Drugs and Medical Devices, CFDA began a new reform initiative.

Dr. Su has worked at both the Chinese regulatory agency and the US Food and Drug Administration (FDA), and served in R&D managerial positions at a number of large, multinational pharmaceutical companies. He was the first person from Asia elected to serve as the president of Drug Information Association (DIA). He is a visiting professor at several universities and also serves on editorial boards of well-known medical journals. During his 20 year career, Dr. Su has witnessed the improvement of China's drug administration system. In his view, China's current reform calls for clear, top-level design ideas and long-term solutions.

"China should emulate the US in approach rather than specific methods because of national differences."

RAPS: Since you have worked at both CFDA and FDA's CDER, you are familiar with drug regulation in the two countries. What's the biggest difference between the Chinese and US regulatory systems? What characterizes each system, respectively? Where can China learn from the US regulatory system?

Dr. Su: US laws, regulations and state systems are different from those in China. The laws of the United States are enacted by Congress. FDA is part of the executive branch of the US government, which has a strong ability to request and obtain resources needed to implement laws. For example, Congress enacted a law to regulate tobacco products; however, FDA did not promulgate specific regulations until resources and funds were allocated by Congress. The situation in China is completely different. The difference of China and US state system, determines the difference of China and US regulators' role in developing and executing regulation.

There are disparities in resources and staff between FDA and CFDA. Since the Pure Food and Drug Act of 1906, FDA has amassed manpower and resources. In contrast, CDFA does not have equivalent funding. So, if we want to learn from FDA's approach, we'll find many areas that are not applicable or feasible. Yet, we can learn from FDA, as long as we take our differences into account.

For example, thousands of people work for FDA. Where can CFDA find so many professionals? Even though its salaries are not as competitive as those in industry, FDA attracts talented people from pharmaceutical companies who value the experience of working for the agency. But in China, the flow is reversed: from CFDA to industry. As another example, FDA seldom uses a tactical approach, such as a special inspection, to solve a problem. A more common practice is to do research and promulgate a regulation or guideline, which can solve the problem fundamentally. This is worth emulating.

Another point is we are doing many "horizontal" comparisons, e.g., comparing China and the US in the same year, say 2015, and discovering we are not on a par with FDA. This makes us frustrated. However, we should do the comparison vertically: what has the US done from 2010 to 2015? Maybe what we are facing now is the same problem they had in 2010. So what key adjustments have they made since that time? Are they applicable for China? This is more helpful and constructive.

"Chinese regulatory professionals should be much more than messengers."

RAPS: How do regulatory professionals differ in the two administration systems, CFDA and FDA?

Dr. Su: As I said more than 10 years ago, regulatory professionals cannot be satisfied to be just messengers who transmit information between parties. They should have a deep knowledge of the R&D process, the regulatory problem involved and the product characteristics. Senior RA managers need a deep understanding of regulatory strategy, know the correct actions to take and the reasoning behind them, and how to communicate effectively. This is the biggest difference between the two countries. However, the situation is much better now, especially in multinational companies operating in China. Because of their frequent communication with headquarters and involvement in the global development, Chinese regulatory professionals have gradually learned what to do and can justify their point of view. In addition, some domestic R&D enterprises are also doing well, although there's no precedent when developing new drugs, so they can only slowly grope their way within the regulations.

"Drug safety management challenges include how to improve the system and guide public opinion."

RAPS: What are the main challenges for China's drug safety management?

Dr. Su: China is currently facing a manifold challenge in drug safety management.

First, China's postmarket administration system for drugs is weak in spite of our improved social system. Although the government has established the National Centre for Drug Reevaluation and ADR Monitoring, a big gap remains when compared with international levels of monitoring and analysis, including using advanced technology for signal detection and analysis.

Second, many doctors haven't done a good enough job providing medical guidance for patients. Based on the research experience abroad, one of the main reasons for adverse drug reactions are medication errors and irrational use of drug. Pharmaceutical research and development and regulatory approval may not be the problem; instead, problems occur while using the drug. There is a lot of room for improvement.

Third, China hasn't established an ADR reporting system that clearly spells out industry's responsibility. In developed nations, pharmaceutical companies have heavy responsibilities related to the safety of their drug products, including setting up a well-organized reporting and evaluation system. The company and its officers may face criminal punishment if the system fails. By working together, drug manufacturers, doctors and patients and regulators can ensure drug safety by reporting and analyzing ADR information. The three parties can openly discuss safety issues. Considering China's short drug administration history, vast population and imbalanced development across different regions, further discussion is needed to determine how to monitor postmarket drug safety more efficiently and what kind of national regulatory system to build.

Another big problem is fraud, e.g., manufacturing that does not comply with standard specifications or approved SOPs, clinical trial data fraud, counterfeit or substandard drugs, etc. This problem is complex, involving many factors such as economics and social culture, and cannot be completely solved by CFDA alone.

Finally, there is public opinion, which affects the whole social environment. It's important to offer proper guidance to public opinion from an impartial and fair point of view. For example, if a drug safety issue is caused by ADRs (rather than fraud), it should not be exaggerated because the ADRS is probably inevitable.

"Drug administration reform calls for clear, top-level design ideas and long-term solutions."

RAPS: The Opinions of the State Council on the Reform of the Review and Approval System for Drugs and Medical Devices was published in August 2015. How will it impact drug registration? What are the challenges and opportunities for regulatory professionals?

Dr. Su: These are all good things. Compared with the moderate drug administration of the last few years, it's revolutionary to see what we are doing and what's to come. I think China's drug regulation revolution requires what I call the 4Ps:

• Political determination and wisdom
• Professional knowledge
• Personal experience
• Public understanding

 Now that we've seen the determination at the high government level, what's needed is to translate this strategy into specific tactics, for example, management of filing for bioequivalence studies, acceleration of clinical trials, establishment of an "easy in and strict out" review strategy. A particular focus should be how to join the old and new systems. These complex problems require a lot of wisdom. Then, what can the industry do to help? We may not be able to find the best answer to all questions, but we will make incremental progress, and the process will be more reasonable. While I think this is the general trend, ups and downs will be inevitable. Some regulations may be too strict or lenient which make the industry uncomfortable. Industry may be left wondering what to do, especially regarding long-term projects, such as R&D, which are impossible to adjust continually to align with regulatory changes.

I hope this reform will focus on two points:

One is the need for real top-level strategy. In this reform, we've seen the government's determination. They've made changes in many aspects, but haven't presented a clear, objective and scientific principle to guide regulatory authorities. It will be much better if there's a clear framework.

The second is to put permanent systems in place to fight against fraud, nonstandard and incomplete dossiers, which could guarantee the effects of our long-term regulation. In addition, though China is reforming its review and approval systems for drugs, we still need a system to ensure quality, safety and effectiveness of drug clinical trials.

Overall, our reform needs continued leadership, science-based drug regulation and improved efficiency. It is equally important to determine and explain how to implement the law. It will surely be a long process. Facing the changes, regulatory professionals need to be more flexible, more strategic and more aware. When formulating a work plan, they need to be able to adapt to regulatory changes, reduce regulatory changes' impacts to the products and ensure quality.

"Achieving science-based regulatory approach and strengthening transnational communication regarding best practices."

RAPS: China has always been a high-generic drugs country, but with increasing globalization, many Chinese returned students choose to do R&D for new drugs back in China. China has established major projects for new drug development and domestic new drugs are increasing. Facing the above changes, do you think China's drug regulatory approach needs to adjust accordingly?

Dr. Su: Many aspects of this reform showcase CFDA's encouragement of new drugs and change in regulatory approach. The trend to be more scientific is undoubtedly reasonable. Regulations should be based on science, and now CFDA takes that into consideration.

The launch of more R&D projects for new drugs will drive two requirements:

Scientific and Technical Knowledge on Both Sides

Based on the premise of scientific regulation, regulators need strong skills to communicate with sponsors and researchers at an academic and scientific level, and promulgate timely and effective regulations. Regulatory reviewers must be qualified to communicate with researchers on technical topics, which means they require the same knowledge and education as research scientists. On the sponsor side, regulatory professionals also need to understand scientific issues and not rely on researchers to communicate with the reviewers. All of this is necessary to ease the transition to scientific regulation.

Cooperation with Regulatory Agencies in Developed Countries

These regulatory agencies may have encountered the same problems as China or may even have solved them. We don't need to repeat the process. In fact, CFDA is already starting to cooperate with international regulators. But further efforts are needed to communicate with ICH or other organizations about new drugs or even share information or exchange review reports. The US, Japan and the EU have such a tripartite agreement now. Even so, there is a lot of work to do to keep information or intellectual property confidential, and it is necessary to enhance communication, information sharing and cooperation in this area. Thus, we can improve our review capability with the help of others.

About Dr. Ling Su

Dr. Ling Su is strategic advisor, life sciences for Sidley Austin LLP where he advises clients on medical product development and regulatory and clinical strategies. He has more than 25 years of industry and government experience in both the US and Asia. His career includes working in the Bureau of Drugs of the Ministry of Health in China, the predecessor of today's CFDA, and in CDER, US FDA and in various R&D and management positions at Merck, Roche, Wyeth/Pfizer and Novartis. He is a Professor in Shenyang Pharmaceutical University, a Research Fellow at the Research Center of National Drug Policy and Ecosystem of China Pharmaceutical University and in the Yeehong Business School of Shenyang Pharmaceutical University. He was elected the President of Drug Information Association (DIA) in 2012-2013.

Dr. Su received his bachelor's degree in pharmacology from Shanghai Medical University and master's degree in clinical pharmacy and PhD degree in epidemiology from University of North Carolina at Chapel Hill.

Note: This interview was translated by Cherry Fu, RA Specialist, CF PharmTech, Inc.

Cite as: "China's Drug Regulation Revolution. Regulatory Focus Interviews Dr. Ling Su." Regulatory Focus. May 2016. Regulatory Affairs Professionals Society.