Magazine Article | December 7, 2011

China's Pharmacovigilance System: The Hunger For Safety Insights

Source: Life Science Leader

By Sara Gambrill, contributing editor

China’s importance as a pharmaceutical market is well-known. It has the world’s largest population of more than 1.3 billion and edged out Japan last year to become the world’s second-largest economy as well as Asia’s largest. In 2009, IMS Health ranked China as the world’s fifth-largest pharmaceutical market, with a market size of about $31.7B, and expects it to be ranked the second-largest pharmaceutical market by 2015, usurping Japan’s ranking.

Driving the growth of China’s pharmaceutical market, in part, is the government’s $125B healthcare reform initiative, which has resulted in 90% of China’s population being covered by health insurance as well as better access to healthcare services and affordable drugs by the country’s rural population. In addition, a growing middle class with exposure to Western habits, such as fast food, driving, and smoking, have contributed to an increasing incidence of obesity, various cancers, and diabetes in China.

With nearly 1/5 of the world’s population, China’s potential contribution to global medical safety is gigantic. Johnson & Johnson — through its pharmaceuticals division, Janssen — is working with regional and national health authorities in China to help support strong pharmacovigilance in China and globally.

“China has a tremendously proactive, forward-looking desire to offer the best safety science. When an opportunity comes to apply a new technique or a new scientific methodology, I’ve seen openness and an excitement about what this knowledge could do for patients. This is the dynamic I have observed in our interactions with the Chinese health authorities,” said Amrit Ray, M.D., MBA, chief safety officer at Janssen.

China’s Drug Safety Surveillance Program
China has a relatively short history of drug safety surveillance — compared with the United States, many European countries, and Japan — but, just as its economy is growing at a rapid clip, so, too, is its system for watching over drug safety. The core of China’s rapidly developing drug safety surveillance program is its National Center for Adverse Drug Reaction (ADR) Monitoring.

Originally a project initiated with support from China’s Ministry of Health in 1988, the National Center was formally established the following year. Ten years after its initiation, the National Center joined the World Health Organization’s Collaborating Center for International Drug Monitoring (Uppsala Monitoring Centre). In 1999, the center joined China’s competent authority for drug regulation, the State Food and Drug Administration (SFDA), reporting both to it and to 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 SFDA 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 the National Center’s first 11 years, it received only 4,700 reports. But, in 2002 alone, the number of reports was nearly triple that, and, in 2005, the number of reports grew another tenfold to 173,000. In 2010, the National Center for ADR Monitoring received 692,904 reports of adverse reaction cases, 8.4% more than in the year before, according to SFDA. Of these, 109,991 were reports of new or severe adverse reactions, an increase of 16.2% over 2009. Most ADR cases, 84.7%, were reported by medical institutions; 12.7% were reported by pharma companies; and 2.5% were reported by individuals.

Training Forum on International Pharmacovigilance Standards and Practices
Though the surge in the number of ADR/ADE reports indicate an increased awareness of and participation in reporting, the Chinese health authorities continue to strive to improve pharmacovigilance in the country. For this reason, Janssen has collaborated closely with the Chinese health authorities to develop the “Training Forum on International Pharmacovigilance Standards and Practices,” a training workshop held in China every year for the past five years, during which Janssen shares its best practices in pharmacovigilance with Chinese health authorities.

“There’s a hunger not only for information on safety but also to go from information to insight. This is what effective safety and pharmacovigilance is all about, making the jump from noise and a plethora of information to insight and meaning that enable effective communication and risk management,” said Ray. “We’ve spent a lot of our time and energy on developing best practices in pharmacovigilance to move patient safety forward globally, including in China. Proactive pharmacovigilance discriminates between noise and signal with a methodology, a process, and an appropriate application of information technology.”

One of the recent initiatives that SFDA’s office in Beijing has undertaken is an intensive safety monitoring program. The Beijing office of the SFDA has developed a close collaboration with a number of Beijing hospitals, establishing pharmacovigilance centers with trained and certified safety specialists who monitor, collate and report safety data. Collectively, more than 2 million patients are seen at these hospitals every year. With these safety specialists, and associated systems and processes, hospitals can closely monitor adverse events to allow for the early detection of potential safety signals, actively manage high risk medicines, and generate hospital safety surveillance reports submitted on a regular basis to the Beijing office of the SFDA as an integral part of their safety surveillance activities.

This year’s workshop in October offered a two-day training session for approximately 200 government and hospital attendees who participated. Also in attendance were safety leaders in China, including representatives from the Beijing office of the SFDA, SFDA’s main office, and the National Center for Adverse Drug Reaction Monitoring. Fifteen Janssen colleagues from local and global pharmacovigilance departments also attended.

“In the past several years, Janssen has made significant contributions to China’s pharmacovigilance enterprise, supporting safety education and pharmacovigilance knowledge sharing,” said Dr. Xiaoxi Du, director, National Center for ADR Monitoring.

The agenda for the workshop is shaped through dialogue between Janssen and the health authorities in China. Both parties work to develop a training that encompasses what will be helpful to Chinese health authorities and also reflects the trends Janssen sees in pharmacovigilance globally. Janssen shared best practices on how a biopharmaceutical company sets up and runs a global pharmacovigilance system, how it codes and categorizes all the data that come from adverse events, the techniques and methodologies it uses to review those events in the process of signal detection, and how it conducts proactive surveillance.

“The safety specialists are on the ground, near the patient,” said Ray. “They need to know what to look for. When the information comes, they need to know how to categorize it, interpret it, and record it in a standardized way from one hospital to another hospital, or from one country to another, to enable cross-analysis. That’s why we support international coding standards, which were the focus of this particular training program.”

Janssen is well suited to the task of collaborating on a training workshop for the health authorities in China because its global safety organization has safety officers at the local and national levels in China, as well as the Asia-Pacific regional and global levels, that afford the company insights for proactive pharmacovigilance. The company has a relatively long history in China, as Janssen was the earliest joint-venture pharmaceutical company there — established in 1985 — and its safety officers have a good grasp of the issues and challenges on the ground. These on-the-ground officers worked closely with their Janssen colleagues globally to develop the workshop.

“What is interesting for global pharmaceutical companies is trying to get a perspective on whether there is a safety signal. You have to have an understanding of what are the characteristics in each area of the world and in each patient. You have to know your patient, which can be challenging at a distance, and that is why we are committed to a presence on the ground, with colleagues who speak the language of the patient,” Ray said. “Other insights can come when you start looking globally and ask, how does the experience in China compare with the experience in a European country or in the United States and can we learn something for patients from the totality of the experience that we could not learn from partial experience from one country alone? The best science is aimed at trying to take as thoughtful and intelligent a perspective on safety surveillance as possible.”

The Future of Global Safety Is Collaboration
The training workshop exemplifies just one type of collaboration Janssen participates in with China to help support enhanced pharmacovigilance. In addition, a number of Janssen safety scientists have authored academic papers in pharmacovigilance that have been published in the National Center for ADR Monitoring’s academic journal, called the Chinese Journal of Pharmacovigilance. “This is something we’ve made a conscious decision to do because we would like our best thinking to be openly available,” Ray said. Janssen safety representatives also gave the keynote address at the 2011 Annual China Drug Safety and Public Policy Summit in Shanghai.

China’s proliferation of new conferences a few years ago, covering topics related to the biopharmaceutical industry, exemplifies the country’s collaborative spirit. These conferences meet annually now and attract key opinion leaders within China from Big Pharma, representatives from the Chinese health authorities, as well as key opinion leaders from the West, both as attendees and presenters. The conferences demonstrate China’s great willingness to exchange ideas and information about the industry.

In 2011, an important milestone in global safety involved China’s collaboration. The National Center of ADR Monitoring at SFDA and Uppsala Monitoring Centre signed an agreement to enhance data exchange from China’s ADR database and Vigibase, WHO’s global database of more than 6 million ADR reports. The two-year project is called “Standardization Study and Applications of Adverse Drug Reaction Monitoring Cooperation Agreement.” The project consists of various subprojects, including establishment of a data exchange platform, Chinese-English translation standards, and improvement of the Drug Dictionary specifically for China.

“I think there are some very interesting changes that we’re seeing in China. There is a recognition that safety is really about collaboration. The goal is to support strong, scientifically robust pharmacovigilance in China. It’s ultimately the patient, both in China and globally, who will benefit. We recognize that we have a shared commitment with the health authorities in that we both serve patients,” Ray said. “The future of safety is about collaboration, and we are committed to that. No one group can do it alone.”