OUTSTANDING QUALITY AND REGULATORY TEAMS
When a company develops a product that represents uncharted territory for a regulatory agency, a standard approach is often to sit back and wait for the agency to muddle through it. But that's not what the regulatory team at Ethicon Inc. (Somerville, NJ), a Johnson & Johnson company, decided to do. Instead, it took an approach that resulted, in one case, in less data needing to be reviewed and a fast approval time.
The challenge was to get its antibacterial sutures, Vicryl Plus and Monocryl Plus, approved by the European Union, which had never reviewed such a product before. The sutures are covered with an antibacterial coating called triclosan, which the EU regulates as a drug. That meant the sutures would have to be reviewed as a combination product. Not only did Ethicon lack experience with European reviews of combination products, but the process was further hindered because European authorities have much less experience reviewing combination products than FDA does.
“The novelty of it was an issue in Europe,” says Jennifer Paine, manager of regulatory affairs at Ethicon. “The process is not as clear-cut in Europe as it is in the United States. You have to go to a different competent authority to have the drug portion reviewed, and there is less consistency from competent authority to competent authority. Whereas in the United States, one group deals with it all.”
The stage was set for a slow and hesitant process. The notified body that Ethicon uses for European device reviews, BSI, reviewed the device portion of the application. The drug agency of The Netherlands, the Medicines Evaluation Board (MEB), was selected to review the drug portion.
Sergio Gadaleta and Jennifer Paine.
“The drug authority was looking for all of the traditional components of a drug review, and we didn't understand that they were planning to give it that level of review,” says Sergio Gadaleta, PhD, Ethicon's worldwide director of regulatory affairs. “The drug review is supposed to evaluate ‘the safety, quality, and usefulness of the drug by analogy.'” Because the EU had already approved triclosan many years ago, the company thought a complete drug review wasn't necessary. But the EU wanted to know why certain data weren't provided. “There were two issues: They were used to seeing more data for drugs, and because they were from The Netherlands, there was a language [barrier] and it was hard to understand exactly what they were asking,” Gadaleta says.
But good communication practices made the process easier. When MEB started asking questions about the device portion of the application, Ethicon's team challenged BSI to assert its jurisdiction over the device portion. This decreased the number of questions from the drug authority.
The team decided to press for a more efficient review for Monocryl Plus when filing its application after Vicryl Plus was approved. “We thought the difference between Monocryl Plus and Vicryl Plus was the amount of triclosan and the way the triclosan was deposited onto the suture. Because of that, we did not see the need for a full drug review,” says Gadaleta. BSI disagreed, so the Ethicon team developed a strategy.
“The safety, quality, and usefulness of Vicryl Plus had already been reviewed, so we argued that MEB should only need to review the things that had changed” from Vicryl Plus to Monocryl Plus, Gadaleta says. “We thought they should review the properties unique to the higher amount of triclosan and the quality aspect of how the triclosan was put on the suture.”
The argument was cohesive and sufficient for both BSI and MEB. It enabled Monocryl Plus to be reviewed in eight months, as opposed to the 18 it took for Vicryl Plus.
Of help was that throughout the process, the regulatory team had Ethicon's technical people meet with BSI and MEB to educate them about the product, its clinical studies, and its manufacturing process. “We are very lucky to have a strong technical team,” says Paine. “They made our job easier because we could leverage their expertise. They helped us better understand the interaction between the drug and the package, and the drug and the suture.”
Another decision by the team helped shorten the time frame before the launch of Vicryl Plus. Manufacturing was to be based in two locations, one in the United States and one in the EU. Each was to supply customers in its own region. Because Vicryl Plus received FDA approval long before it got EU approval, the U.S. manufacturing site was ready far earlier than its EU counterpart. So rather than wait for the EU site to be completed before filing the manufacturing and validation data with BSI, the Ethicon team decided to use data from the U.S. site. Then, immediately after approval was granted, Ethicon filed a change notification to transfer the manufacturing process to the EU site, which by then was ready. (Five change approvals were needed. BSI agreed that it, in conjunction with a pharmaceutical consultant, not MEB, should review four of them). This strategy enabled the product to be launched in Europe about nine months sooner than planned.
Ethicon's corporate culture played a role in the success of the projects, Gadaleta and Paine agree. “It's a combination of things, from corporate leadership to department leadership to being closely involved with the R&D, marketing, clinical, and operations teams,” says Gadaleta. “We all work toward one goal, and we all address everyone's requirements.”
“The culture here really encourages people to be innovative in how they approach everything,” Paine explains. “It allows you to suggest things that might not be considered elsewhere.”
For example, Gadaleta says, on the Monocryl Plus project, “other RA groups might have said, ‘This is what it is, and we'll see how it goes.'” Ethicon, he says, is not like that. “We are encouraged to think about different ways to get things done. We ask, what is the spirit of the regulation, and does it allow for things to be done in a different way? We try to understand what the health authorities are looking for, and once we do, we look for ways that are efficient and effective as well as compliant.”
But that is not always easy. “Health authorities always have some form of bureaucracy that is used to doing things a certain way,” he says. “But in the end, the health authorities share our goal: to get safe and effective products on the market in a manner that is efficient.”
The Ethicon Team
- Sergio Gadaleta, worldwide director, regulatory affairs
- Jennifer Paine, manager, regulatory affairs
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