Challenges with Running Clinical Research in China

The prospects of medical product commercialization in China are massive, as many biopharmaceutical enterprises are rushing to enter that market. However, the lacking clinical research infrastructure in China is causing challenges not only for ex-Chinese biopharmaceutical enterprises, but, also Chinese companies. Peter Schiemann, PhD, Partner at Widler & Schiemann Ltd., is currently on the ground in China, and conveys his perspectives on the regulatory infrastructure and challenges that sponsors are facing in China.   Moe Alsumidae: Can you describe some of the biggest GCP challenges currently happening in China?   Peter Schiemann: The problem we have in China is that all of the research sites are hospitals so you will never have any general practitioner practices; the result is that patients in clinical trials are treated in the same fashion as they are treated when they are regular patients, and patient records are amended regularly. So when a patient is seen, and study staff note things down in medical records, these records can change over the time without an audit trail. When a patient is hospitalized for five days and are treated, the records made on the first day might have been erased and replaced by other records. That is a problem for clinical trials because site staff practice the same policy with the source. Hospitals are also very overcrowded, so a physician in a regular hospital sees about 400 patients a day. You can imagine that doctors do not have much time to take care of patients, so the same accounts for clinical studies.   Another challenge is that many clinical trial staff have not yet fully understood what GCP is about. A monitor just recently, after a database lock, went back to the site and changed the data in the source to make it look more "pretty" and thought she was doing the hospital a favor. She did not recognize that making changes in the data and source after a database lock is falsification and is not what companies and regulators want to see.   MA. How are the differences in GCP interpretation affecting biopharmaceutical enterprises running clinical trials in China?   PS: Large US companies, and any non-Chinese companies, are suffering from these issues because it is a requirement that if you want to sell a drug in China, you have to include Chinese patients in your trial and generate results from Chinese patients as well. The same accounts for medical devices. Additionally, Chinese companies who have very innovative compounds, also suffer from this environment because they, too, have to include Chinese patients in order to market medical products in China. Hence, these companies are trying to do as little research as possible in China and are running studies in places like Europe, United States, Australia, and South America. Other Chinese sponsors do not really understand that GCP’s purpose is to uncover errors. GCP accepts that there will be data outliers, because this is the nature of science, however, Chinese sponsors are having a hard time understanding that.    The way of thinking in China is a little different and we need a small revolution in the thinking process, but I believe change is coming because the CFDA is engaging in dialogue with the industry, and are working with the US FDA as well as the EMA.   MA: What is the Chinese FDA (CFDA) doing to address those issues?   PS: The Chinese government has launched an initiative 10 years ago to improve the healthcare system in China. One aspect is the development of new drugs. They want to be more competitive in not only importing drugs and having their own generics, but they also want to develop new innovative compounds.   Some years ago the Chinese government has taken a bold step where they have launched a program called 2020. So, by 2020 they want to have a clean environment where clinical studies can take place and where international standards are adhered to, but they are still a long way from achieving that. The Chinese government paves the way by making the right provisions with the regulations. On the other hand, sometimes they are shooting themselves in the foot; for example, by law, hospitals are not allowed to keep different records for patients enrolled in clinical trials, whereas in the past, hospitals kept different records for clinical trials. Even though the government and CFDA are trying their best to support an environment to foster GCP, the thinking process and the recognition of what GCP actually is, is not there yet. One possible reason is that, the CFDA’s focus was on GMP and not so much on the GCP area because they had many factories in China of which a high number were closed because of poor drug production conditions. That was the CFDA’s main focus and now they are shifting their focus also on clinical studies. But again, I think it would take at least a couple of years until that understanding has sunk in.   MA: How do you expect the CFDA to change to bring gold standard quality to clinical trials in China?   PS: The CFDA is on the right track towards establishing gold standard quality in clinical trials. The CFDA is listening to others, they are accepting advice from the outside, and they are very closely working with other regulators from other countries such as the US FDA and EMA. They are building their own regulations; when you read the regulations you see similar content as you would in Europe or the US. The regulations look less sophisticated at first but when you read it, the basic requirements for quality management are all there. The CFDA has established their regulatory infrastructure; the CFDA’s commitment should now be focused on getting adequately staffed because the CFDA is heavily understaffed. They hardly have inspectors that have a good understanding of GCP, hence, that gap needs to be filled.    ExL's 7th Annual Clinical Quality Oversight Forum, takes place October 17-19 in Philadelphia.