James Cai, AstraZeneca's VP, Healthcare Policy Research, sat down with PharmAsia News' Shanghai bureau during the China Trials 2008 conference in November to discuss the burgeoning CRO landscape in China and how multinational companies can work with local CROs to improve the clinical trial infrastructure there.

PharmAsia News: You mentioned in a previous speech that the time for new drugs to reach the China market is usually three to five years behind Europe, the U.S. and other countries. And yet you mentioned that AstraZeneca can get new drugs approved in China 12 months after getting approvals in the U.S. and Europe when you leverage global studies in China for local registration. Can you talk about how that works?

James Cai: The first reason is that multinational companies' headquarters are located in other countries; therefore they usually initiate drug development abroad. Another important reason is that for most of the drugs you must finish clinical trials in China, and after that you can file or apply for the new drug marketing authorizations and get approval according to China's regulations.

You must get approval from [China's State FDA] if you want to conduct clinical trials in China. The problem is that it takes much more time to get approval in China than other countries. Generally speaking, it takes about one to three months to get approval in the U.S., Europe and in neighboring countries of China [to begin trials]. It will still take at least eight to nine months in China, even after China amends relative regulations to shorten the period.

Also, recently China's SFDA announced it would issue fast-track procedures for drug registration to further shorten the approval time. But we have not seen any successful examples of this yet. In conclusion, China is slower than any other country to get approval for clinical trials.

[Editor's note: China's State FDA announced it would launch a new fast-track mechanism by year-end called the special approval procedure for drug registration to accelerate drug registration, SFDA Center for Drug Evaluation Official Yi Feng, told China Trials 2008 attendees in Shanghai Nov. 10 (Also see "China Will Issue New Fast-Track Procedure For Drug Registration – CDE Official " - Scrip, 19 November, 2008.).]

From our experience, we spent lots of time waiting for approval. The time actually was spent on review of the application by SFDA and [the Center for Drug Evaluation], which is about one to two weeks in most cases. The rest of the eight to 12 months were wasted on queuing.

China doesn't have enough resources to deal with so many cases. For example, CDE only has 100 to 120 staff members, but they need to review over 10,000 cases a year in China, according to a presentation from a CDE official. I think we need to find a solution to help regulators to strengthen its resources.

My suggestion is to raise the fee for services, which could make SFDA and CDE hire more reviewers and investigators. It also can filter out some unnecessary repeat applications to reduce the number of applications.

Another suggestion is that possibly SFDA and CDE could temporarily recruit staff from the institutes, international organizations and even pharmaceutical companies to help them.

This is a problem of capacity, and another problem is the capability. It is difficult for China reviewers and investigators to review new drugs, especially when they face drugs that haven't been approved by the U.S. and Europe. My suggestion is for China regulators to be open minded to follow some of the successful experience of China's Banking and Financial Securities Commissions, and to invite international experts to work for SFDA on a short-term bases, maybe one to two years.

By doing this, China investigators can share and gain experience and skills. It could be a very efficient way to level up the capability rapidly.

Third, maybe SFDA could allow some experts from institutes to do some post-doctorate practice in SFDA as internships.

There is another very serious problem here. Is it really necessary to repeat some clinical trials in China for drugs that have already been scientifically demonstrated to be safe? Of course, from the safety respect, it is more clear if you do clinical trials in a local population. But some cases have already been demonstrated by science. … Therefore, we should pay more attention to post-marketing surveillance. Because it is still a very small sample if you do clinical trials with 10,000 patients compared with the sample number when the drug is marketed.

To conduct clinical trials successfully for your drugs in China, I suggest that sponsors consider the needs of China when they set up their global R&D strategies. It must be a solid strategy that can be understood throughout the company. It is an organizational know-how and knowledge and not individual know-how and knowledge.

Second, find the right experienced talent to keep good communication with the regulators during the drug review process. It takes time and effort to train your staff.

Third, you must execute your core strategy with a certain level of flexibility with environmental changes. Because China is an emerging market, the environment changes quickly.

PharmAsia News: Do you think that China will play a more important role in global clinical trials such that China becomes a more attractive spot to conduct multi-center trials?

Cai: The answer to this question is very obvious in that China's role and contribution is becoming more and more important. For example, China contributed 13 percent of subjects for Phase III global trials in which China participated with AstraZeneca in 2007. It happened in only three years. In 2004, the share was less than one percent.

PharmAsia News: What kind of CROs are you looking for and what kinds of services are you outsourcing to CROs in China?

Cai: In my opinion, we can deliver any phase work to CROs. It depends if the service provided by CROs could bring you some extra value. It is not a simple delivery service. First, we want our CRO to become an integrated partner who can develop a strategy and provide some coaching and consultations on developing a strategy in China. Second, it should specialize in certain fields. In China, for example, [the CRO] should have some expertise in regulatory strategy and execution. The third is getting quality data quickly. The cost of conducting trials in China is about 50 percent compared to the U.S., 30 percent compared to Japan. The service price for a China CRO is much less than a U.S. or a Japan one. If CROs can improve quality and can provide more help in regulatory speed, even if the charge increases 60 to 70 percent, China's CROs will become more competitive.

PharmAsia News: Could you tell us the difference between local CROs and global CROs?

Cai: Each of them has their own strengths. Local CROs have a better understanding of the situation and environment in China, while global CROs have the advantage of global exposure and being multidisciplinary.

Global CROs first have to show their extra value from higher charges is what they need to be concerned about. But for now, we don't see significant value from them. Specifically, they must execute their global quality and know-how expertise in the local environment, that's where their value is.

Second, global CROs should take a leadership role to establish the standard for the CRO industry. I believe global CROs have more roles to play in this field.

For local CROs the problem may be how to internationalize. They need to make efforts to reach international quality [standards]. If they can use their local knowledge and do the things that CROs are doing in developed countries, and at the same time be cost effective, they will be more competitive and attractive.

As of now, I haven't seen such an integrated partner in China. From my personal observation, in most of the local CROs, the people who run the company don't have a good understanding of drug development. Therefore, it is hard for them to reach multinational companies' requirements. Global CROs charge a global price but sponsors have not received global services yet.

PharmAsia News: How do you work with CROs? Do you use their standard operating procedures or do you train them by your SOPs?

Cai: We have tried both ways. For most cases, we ask them to follow our requirements and standards. For projects we also use the SOPs from CROs. I think it is not a problem. I may be the first person who used CROs in China for multinational companies in 1996, when I was with Pfizer. I was working on Viagra and Trovan .

The challenge is finding a team with passion and know-how to work with you. I have two or three long-term integrated partners who know what we need and we know how they work, so I don't need to educate and coordinate with them all the time.

I wish local CROs had more patience and willingness to build a better infrastructure. For global CROs, you have to lower your standards to harmonize with China's environment. Quintiles and Covance are doing well in China.

Lastly, the experienced talent that intends to develop in the industry should not be restricted to multinational companies. You must have courage to go to the local CRO companies, especially when there are so many opportunities in China. It is beautiful to have this entrepreneurial spirit [coupled] with corporate discipline. By doing this, CROs may welcome a step-change in the future.

Meanwhile, multinational companies should take the responsibility and effort to accept and train more young and inexperienced talents. From that I believe we will be able to build a science-driven pharma community for patients who are waiting for more and better cutting-edge medical alternatives.

- Jialing Dai (j.dai@elsevier.com)

[Editor's note: PharmAsia News will host a webinar Dec. 16 for pharmaceutical and medical device firms entitled "The Chinese Regulatory Outlook - A Changing World for Drug and Device Companies." For more information, please click here.]

AstraZeneca Healthcare Policy Research VP James Cai On Building A CRO Community In China: An Interview With PharmAsia News

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