With Regulatory Agencies Comparing Notes, Companies Need Coordinated Registration Approach

An increased emphasis on global drug development and safety concerns has prompted regulatory agencies to develop more synergistic relationships that facilitate information sharing. As such, pharmaceutical and biologic companies planning to market their products in multiple countries need to develop registration strategies that account for this new level of regulatory cooperation.

“As 2010 begins, the industry is at a crossroads regarding registration,” according to Anne Tomalin, president, i3 CanReg. “Whereas in the past companies might have wanted to keep one country’s market approval application independent from their applications for that same product in another country, today they are less likely to succeed by taking a jurisdiction-by-jurisdiction approach because those countries are talking to each other about the applications,” she said.

The recent safety focus on drug products has given regulatory agencies a “nice platform” on which to build new processes for sharing information, Tomalin remarked, noting that regulators now attend summit meetings on a routine basis and convene at the International Conference of Drug Regulatory Agencies.

i3 CanReg’s analysis of six regulatory agencies – in Canada, the United States, the European Union, Australia, Switzerland and Singapore – found that as these agencies explore opportunities to communicate, they are developing confidentiality agreements and Memorandum of Understanding (MOU) through which they can discuss and share information about market authorization submissions. For example, the United States has confidentiality agreements with 17 countries.

Countries discuss issues, provide feedback

Although these agreements do not allow proprietary information to be exchanged and prohibit the sharing of trade secrets, they do allow peer-to-peer contact and discourse among nations’ regulators. Indeed, specific “clusters” have been formed between the Food and Drug Administration (FDA) and the European Medicines Agency (EMEA) to deal with oncology, pediatrics, pharmacogenomics, orphan drugs, advanced therapies and vaccines, according to Tracy Tsuetaki, president of i3 Research.

“At cluster meetings, regulators discuss the issues they are grappling with in a given month,” he said. Because the countries they represent have individual requirements or differing perspectives – e.g., the FDA emphasizes placebo-controlled trials and the EMEA looks for more active-controlled trials – regulators may evaluate the same set of data and come up with different decisions, he indicated.

However, the frequency and scope of the communication among regulators allows them to discuss how to interpret a potential carcinogenicity signal, handle missing data or contextualize rare adverse reactions. “Even if regulators reach a different decision about a registration application, their discussions may help to influence that decision or shape postmarket requirements or risk minimization efforts,” Tomalin asserted.

Sponsors must accept, prepare for cross-communication

Although sponsors are not invited to or even informed of the discussions among regulators, they need to be aware that the meetings are happening and work toward integrating their registration approach. “In the current climate, issues raised with one agency can easily migrate to another agency,” she said. “Companies should not be afraid of this scenario, but they should start preparing for it in a positive, cohesive manner.”

One way of laying the groundwork for integration is taking advantage of joint advice meetings offered by various regulatory agencies, according to Tomalin. “It’s a little puzzling why more companies do not take advantage of these joint advice meetings, because, for example, if a company meets with U.S. and EMEA authorities and reaches agreement on a certain clinical testing approach, the company has a very solid path for registration,” she said. Tsuetaki agreed, adding that as available venture capital for clinical research shrinks, “these meetings can go a long way toward using R&D resources wisely.”

In addition to participating in integrated pre-meetings when available, companies – especially those moving into such new markets as Brazil, China, India and Russia – need to pay close attention to any specific requirements these countries have in place. “The days of developing a drug for one market are over,” Tsuetaki said.

Of course, this is not necessarily an easy task. Even though the International Conference on Harmonisation (ICH) has made tremendous progress in harmonizing many requirements in the United States, Europe and Japan, those efforts are ongoing and cannot account for every policy variation. “From a regulatory perspective, harmonization is not homogenization,” Tomalin noted. Further, she said, companies must keep track of which countries accept bridged applications from another country.

“A relatively large pharma company may sell 60 products across 120 countries. Different formulations likely will be sold, differing indications and dosages may be used and safety data likely will vary from country to country, particularly with legacy products,” she explained. “That’s a lot to monitor and control when companies are striving to deal with issues in a uniform manner.”

Plotting a course with i3 CanReg

To help companies navigate the world’s registration requirements, i3 CanReg – one of the largest regulatory consulting firms in the world, which was acquired by i3 Research at the end of 2009 – offers companies more than 100 consultants and staff who can provide intelligence, guidance and practical assistance to medical products companies, some of which may not have the infrastructure to take on such a complex endeavor.

According to Tomalin, i3 CanReg can help companies, which may have expertise in several, but not all jurisdictions, make sense of the requirements for registration. First, i3 CanReg can address the data package, including the clinical development plan that will be needed to obtain registration in the jurisdictions in which the company is interested. “This may involve looking at competitive packages, researching guidelines or analyzing how decisions may have varied in the past,” Tomalin said. “This step takes significant resources and expertise that many small or mid-size companies simply don’t have.”

Further, i3 CanReg consultants can help companies move to the next phase by interfacing with the agency or agencies representing the countries where the company would like to market its product. “We can help companies understand what issues will be red flags to certain nations and keep the lines of communication with the regulators – who already are talking to each other – open,” she remarked. “We will help sponsors uncover specific country requirements and determine from the agency whether taking a specific path is likely to end in market authorization.”

Finally, companies can utilize i3 CanReg to help them submit their dossiers. “We can put all of the data into a high-quality application for companies and then address whether it qualifies for priority or fast-track treatment or special data exclusivity protection,” Tomalin said. “And, after the product is approved we will look at lifecycle management to determine how the product can be improved continuously to meet market needs, no matter where that market resides.”

With the regulatory environment changing on a daily basis, “i3 is dedicated to keeping up with the landscape and helping sponsors to develop innovative ways of conducting their development activities,” Tsuetaki said. Bottom line, Tomalin concluded, “Working with i3 ensures that companies will achieve approval for their products in any country in the world in the least amount of time, with a maximized lifecycle over time.”

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