Regulatory Science Unlocks Therapeutic Innovation Worldwide
By Wayne Koberstein, executive editor
Dr. Ling Su looks back on a long career in drug development with big companies like Novartis — and on his past year as board president of the Drug Information Association (DIA). At the same time, he looks forward to his new role on the front line of regulatory science in China, where he is strategic adviser at Sidley Austin’s China life sciences practice and volunteers his expert support to the China Food and Drug Administration (CFDA). I recently spoke with Dr. Su by phone, between his office in Shanghai and my location on the U.S. West Coast, 15 hours apart. Clinical development folks in companies conducting global trials can likely identify with the situation: When communicating halfway around the world, they know it’s best to ignore extraneous factors like time zones and focus only on the essentials of the conversation.
As it happens, a similar principle applies to how the world’s regulatory authorities may build better pathways for global product development in the life sciences industry: Cut away the undergrowth and overgrowth of local barriers, and plot a route that follows the growing scientific consensus on essential criteria for evaluating and regulating new therapies. Authorities who wish to join the leading regulatory peers, attract global trials, and stimulate therapeutic innovation have already taken a turn toward common goals — and are finding ways to do so without sacrificing their cultural imperatives, according to Su.
SCIENCE BEFORE REGULATION
Although governments have long regulated science, the idea that science should take a firmer hand in guiding regulation seems to have dawned late. Scientific principles can replace bureaucratic expediency to optimize data gathering and analysis. Rational and empirically derived methods can exorcise inefficiencies, standardize formats, and integrate varying data needs in global or multiregional trials. National health authorities can take a scientific path toward adopting common protocols and end points where they can and predictable variations where they cannot. Regulatory innovation can unleash medical innovation. It can all happen, says Su, but only if industry and regulators work on it all together, upon the common ground of regulatory science.
The DIA is an important international platform on that ground. Without the global forums maintained by DIA and other organizations such as the American Association of Pharmaceutical Scientists (AAPS) and the U.S. Pharmacopeia (USP), the regulatory science movement might remain a Tower of Babel, forever divided not only by discipline but also by region and nation. The DIA has always brought together regulatory professionals, scientists, and others on both the industry and government sides through its educational meetings and services. But its traditional reach was mainly confined to North America and to drug development. On Su’s watch, the association has grown in parallel to industry and market trends — becoming more global, more connected, and more diversified in scope beyond drugs to biologics, devices, and other medical products. It is now a key mediator of globalization in the regulatory realm, increasingly focused on addressing the built-in barriers to life sciences innovation, inside and among the world’s leading health authorities.
And “leading” does not always mean “big.” Emerging markets and the nations they represent are huge in potential, but still relatively tiny in their regulatory infrastructures. Their global influence thus far outweighs their current status of development. How the fledgling health authorities take shape as they grow, mature, and interact with the outside world will largely determine the outcome of efforts to rationalize medical-product development on a worldwide scale. China, India, and Latin America are the most dramatic examples of rapid regulatory evolution in emerging markets, which is why they have seen a major expansion of DIA activities during Su’s tenure.
“We need to continue to bring the strength of the DIA to the emerging regions,” Su says. “The benefits are twofold: One, we can use what we already do best — be a neutral platform for information and knowledge exchange among regulators, industry, patients, and others in these regions; and two, because those regions are very different from the U.S. and Europe, there is a need for international dialogue that also facilitates the DIA’s growth and development there.”
Widening the DIA’s product focus also makes sense in light of current trends, despite the prominent use of “drug” in the group’s name. Few medical products now exist in pure isolation; biologics, personalized medicines, companion diagnostics, delivery advances, new drug/device combinations — all are evidence of how development and regulation of various product types can overlap. “We are looking to develop activities to extend into the other product areas,” says Su. “But our new efforts have to be consistent with the quality of our traditional programs, and we must work with other organizations where they are doing things better, to collaborate with them in expanding our competent areas.”
OPENING THE GATES TO INNOVATION
The overall broadening of the DIA’s focus mirrors the evolution of regulatory systems, Su explains — and he says both serve the same goal: innovation. Regulatory science incorporates a wider awareness of factors that determine therapeutic response and outcomes. Thus, the science envisions a new framework for evaluating new treatment candidates and one that is applicable in industry, regulation, and medical care. The framework takes into account not only intrinsic factors such as drug metabolism, but also the extrinsic factors — medical practices, disease definitions, standard-of-care, and even regulatory requirements — that affect how the therapy is used and response monitored in development.
“Extrinsic factors become more and more important, but they are much less understood,” Su says. “You look at metabolism, at the enzymes, and the metabolic pathway, and you get data everyone understands. But the larger context of medical practices — how patients use the product, how the disease is defined, and the risk factors in certain populations — are much less understood, and they pose much bigger issues when we look at the data.”
Until recent years, China and other countries clung to the metabolic focus as the EU and the U.S. moved toward a greater inclusion of extrinsic factors. China, Japan, and South Korea decided to investigate potential differences in drug metabolism between their populations and “Caucasians,” while Western authorities encouraged developers to gather more and more extrinsic clinical data. Now, however, the various agencies have converged considerably, according to Su.
“This is a great example of how regulatory science has evolved with the rise of globalization. If you see how the FDA, the EMA (European Medicines Agency), Japan’s MHLW (Ministry of Health, Labor and Welfare), and the CFDA evaluate data from other countries, they have more or less come to a common understanding whether or not the data may be applicable to their respective populations.”
Su takes proclamations by FDA Commissioner Margaret Hamburg and other agency heads as serious evidence of their commitment to giving developers wider latitude in data points and evaluation. More latitude means more flexibility in designing clinical trials for novel products and combinations for a global market. He sees the shift as a basic change in mission and identity. “Regulators need to be not just gatekeepers but gate-openers — to work with the industry and the academic community to promote innovation and to move ahead with the new ways that products will be developed and evaluated.”
INDUSTRY & REGULATORS MUST WALK TOGETHER
Collaboration in regulatory science is taking several forms: among agencies, between agencies and industry, and among companies in the industry. Of course, regulatory science cannot cure all innovation-impeding ills. It cannot, in itself, raise Big Pharma’s poor R&D productivity, pump more money into novel research, ensure reimbursement, or fund the next Genentech. But to the extent that regulatory science eases the regulatory burden for developers, it will remove a widely acknowledged major impediment to innovation.
Still, in Su’s view, it is a burden that neither the agencies nor industry can remove alone. Whether to reform whole systems or avoid hurdles in a particular trial, companies and regulators must share the heavy lifting, he says.
“When a clinical trial is globalized, we have to think about how to deal with the data coming from all the countries involved. It is too late if you wait until the data comes in and then say, ‘oh, there’s a problem in the scientific, GCP, or regulatory area.’ So regulators and companies need to work together, even before the trial starts, for globalization to show its benefit.”
The FDA’s Critical Path Initiative proposed greater regulator/ academia collaboration to develop new solutions, such as the use of biomarkers in clinical trials. In 2010, MIT, the EMEA (European Medicines Evaluation Agency), and other parties convened a project called NEWDIGS (NEW Drug Development ParaDIGmS), working with the FDA and other agencies “to conceptualize and validate new policy frameworks, technologies, and development processes” in “key areas with potential to transform the healthcare innovation system.”
Companies have also banded with each other to improve the R&D process. In 2012, 10 top pharmaceutical companies launched the consortium TransCelerate “to identify and solve common drug development challenges with the end goals of improving the quality of clinical studies and bringing new medicines to patients faster.”
But in spite of such initiatives, Su says something is seriously missing. “I don’t see a lot of projects addressing the overarching issue — industry and the regulatory agencies working together to build a comprehensive model of what drug development should look like.” To some, the current lack of such collaboration is a huge failure, but to experienced optimists like Su, it is a grand opportunity.
SCIENCE, INDUSTRY, & REGULATION — THE VIEW FROM ALL SIDES
Dr. Ling Su brings a scientist’s perspective to the regulatory field. Pharmacoepidemiology was an early interest, and he still teaches related university courses at Fudan University. After earning his B.S. at Shanghai Medical University, he added an M.S. in clinical pharmacy and drug development and a Ph.D. in epidemiology at the University of North Carolina at Chapel Hill. He saw service at The Bureau of Drugs of the Ministry of Health in China and in the FDA’s CDER; then he joined industry, eventually working in regulatory and drug development positions at MSD, Roche, Wyeth, and Novartis. While still at Wyeth, he joined the DIA board and was elected into the volunteer office of president of the DIA board in 2011. His presidency ends in July 2013. His current job at Sidley Austin places him right at the intersection of China’s small but rapidly modernizing regulatory agency and of life sciences companies of all sizes, types, and national origins seeking market entrance to China.
CHINA AS A HARBINGER OF REGULATORY CHANGE
As president of the DIA board, Dr. Ling Su views the entire regulatory world at once. But as his career focuses increasingly on China, where is he now senior advisor to Sidley Austin’s China life sciences practice, he sees the application of regulatory science in its most fundamental mode — guiding a young agency, China Food and Drug Administration (CFDA), through critical steps in its evolution. Su speaks about the unique challenges and wider context of the CFDA’s evolutionary development.
“There is a critical connection between innovation and regulatory science that has characterized the regulatory landscape in China. Regulators here once had the mission of promoting public health; that is, to protect. They could say, ‘yes, a treatment will work,’ but they had no official interest in facilitating introduction of innovative products.
“CFDA is really different from the FDA and other agencies. It started rather late with regulations, so it is under a lot of pressure to cope with domestic issues such as generic drugs and also to deal with innovation. All the major companies that have business in China and a lot of the innovation works through Big Pharma or small start-up companies. They are very active. So the regulators have to deal with both sides, and it is pretty challenging for the agency by itself. The CFDA is very small and understaffed; there are only about 200 people here. Their responsibility also includes food, cosmetics, biologics, pharma, medical devices, and other health products. So in resources, experience, and expertise, it is nowhere near the FDA and EMA (European Medicines Agency). We do see improvements in the CFDA, especially in technical degrees, and it is moving toward more transparency and also toward more science-based review. It will take time for the agency to develop, and we — industry, academia, society, etc. — need to support it. The CFDA still has a long way to go to become a global regulatory agency, but it is taking the right actions.
“China is putting out a lot of effort to promote innovation for its own market. The CFDA has helped innovative companies a lot, guiding them in creating a product-development plan, holding advisory meetings, and so on. It has also started similar meetings and mechanisms to support innovative companies, including foreign companies doing business in China, in developing their products. That’s a good sign, but there are a lot of issues to solve, particularly on the resources side, and also experience. We need to become more competent and proactive.”