U.S. Food and Drug Administration, Center for Drug Evaluation and Research Small Business and Industry Assistance (CDER SBIA).
As our society becomes more global, it has become increasingly clear that the U.S. Food and Drug Administration needs to take a more collaborative approach to our drug approval process. Today, drugs that are approved by the FDA to be marketed in the United States are developed both in and out of the United States.
|Of the 46,391 participants in the clinical trials that supported the 48 novel drugs approved by the FDA in 2019, 60% of the participants were located outside the U.S., showing the international nature of drug development. While many clinical trials have an international component, the |
marketing authorization, including the application and review process, varies from country to country. What also varies is what information is made available to researchers, industry and the public about the scientific basis for each drug approval. Regulatory agencies in different countries are governed by different applicable laws and have their own transparency standards.
To realize the benefits and opportunities provided by a more transparent drug approval process, we must first identify, and address, some of the challenges facing the global drug development community. The FDA is committed to improving collaboration efforts with drug-approving regulatory agencies in other countries, and to increasing transparency related to the scientific basis for drug approval decisions. The FDA is working on multiple fronts to support these efforts and apply best practices.
In 2018, the Center for Drug Evaluation and Research (CDER) at the FDA implemented the Clinical Data Summary Pilot Program, a voluntary pilot program designed to evaluate whether disclosing certain information included within clinical study reports (CSRs) following approval of a new drug application improves public access to drug approval information. When a drug is approved, the FDA releases certain information that the agency used when reviewing the new drug application, including summaries written by our medical reviewers that capture their assessment of the data, the approved labeling or other requirements, and other important, relevant data supporting safe and effective use. This information is included in our drug approvals database, Drugs@FDA. These summaries provide important context on the basis for our approval decisions, but they are packaged in a format that can sometimes make it difficult for external audiences to extract and understand the detailed clinical evidence that supported the FDA’s approval decisions.
The pilot aimed to test a new process for selecting, redacting and posting on the FDA’s public website summaries of information that the agency uses in making marketing approval decisions. The overarching goal of the pilot was to assess the feasibility of improving access to summary clinical trial information about approved drug products for the drug research and development community, medical researchers and the public. With this pilot, we aimed to respond to stakeholders’ requests for greater transparency in the drug approval process and more access to usable information and evaluate whether disclosing certain information improved public access to drug approval information.
After receiving useful internal and external knowledge and feedback as part of the pilot program, we have decided to conclude the pilot. In the interest of increasing transparency in the drug approval process, the agency has learned many best practices through the pilot that we intend to apply to future efforts. For example, we found that there are significant inefficiencies in having multi-regional disclosure requirements relating to often identical clinical data summaries. These inefficiencies multiply the transactional, administrative and redaction (because there are differing regional disclosure standards) costs, whether the costs are incurred by industry or a regional regulatory authority. These costs create barriers to programs to disclose clinical trial information which might be reduced if a centralized or regional approach could be achieved.
Through the CSR pilot, we also identified a potential approach that could facilitate a harmonized system for disclosing study reports. The general framework of this approach includes the following principles:
International Library: A centralized international library, managed by an independent organization, where information is made available to the public rather than each regulatory authority having its own system. MedDRA.org is an example of a successful model of international harmonization through use of an independent organization.
On-Demand: An on-demand system, where sponsors would automatically publish a limited number of documents in the international library, such as the summaries of clinical information and an index of study reports, should be considered. The public could request study reports of interest, and the sponsor would then prepare the report, protocol and statistical plan and add it to the library.
Standardized: Anonymization and disclosure standards would be established to satisfy the requirements of the participating regional regulatory authorities. Our ongoing, independent efforts to establish anonymization
standards and best practices (e.g., PhUSE) will continue.
Voluntary: A sponsor could have the choice of committing to use the international library system to disclose study reports, protocols and statistical plans for all marketing applications or to follow the requirements of each region where they apply for authorization to market products.
While increasing international harmonization efforts to share clinical study reports is a long-term goal, in the short term we are assessing how the lessons learned during the pilot can be applied in our modernization efforts. For example, CDER’s Office of New Drugs, in consultation with relevant stakeholders, may consider whether posting of certain portions of the clinical summary data would improve transparency and enhance our integrated review activities.
As the pilot concludes, our harmonization and transparency efforts will continue. The FDA continues to invest in our work with our international partners. This work brings together regulatory authorities and pharmaceutical industry to discuss scientific and technical aspects of drug development.
We plan to keep stakeholders informed of any future projects in these areas, as appropriate, and we sincerely thank those who took the time to comment on and participate in the pilot. We will continue to look for ways to improve harmonization and transparency in the drug approval process as we move forward with our modernization efforts.
The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products. The Small Business and Industry Assistance program in the Center for Drug Evaluation and Research (CDER SBIA) provides guidance and information to regulated domestic and international small pharmaceutical business and industry through its website, email notifications, and workshops.