In February the FDA released a guidance document proposing a standardized format for submitting clinical and nonclinical data to the agency. The FDA maintains that by following this protocol early in the product development cycle medical device and pharmaceutical companies can reduce bottlenecks and speed up the approval process.
Once finalized and approved, the FDA hopes the “Guidance for Industry Providing Regulatory Submissions in Electronic Format—Standardized Study Data” will improve its efficiency at processing new applications, 510(k)s, and pre-marketing approval applications.
The FDA is taking its lead from manufacturers and suppliers that adopt lean techniques to be as efficient and cost-effective as possible. The need for standardization is driven by the immense volume of submissions and supporting documents the agency receives every year. Not only will a standard data format benefit the FDA’s internal operations, it will speed up review and decision-making by its regulators, leading to an overall improved end result for manufacturers.
The guidance outlines the FDA’s cases for submitting study data in a standardized electronic format. This applies to submissions of clinical and nonclinical study data within investigational new drug applications, new drug applications, abbreviated new drug applications, investigational device exemptions, biologics license applications, premarketing notifications (510(k)s), and premarketing approval applications, including original submissions, amendments, and supplements.
“For devices evaluated in a 510(k), studies may compare the products to a predicate device,” states the guidance. “Applicants typically submit study reports, which describe the study protocol, the data collected, the analyses performed, the results of those analyses, and the conclusions of the study. Also accompanying the study reports are the case report forms (CRFs) and the study data as case report tabulations (CRTs) and analysis datasets.”
CRFs are used by the clinical investigator to document the collected data. The CRTs are aggregate (data from multiple subjects grouped together) listings of all the data collected on the case report forms. CRFs and CRTs allow the agency to perform independent analyses of the study data.
Existing federal regulations allow the voluntary submission of electronic records, including study data, in lieu of paper records (21 CFR part 11). For many years, FDA centers have requested that clinical study data be submitted electronically because paper CRTs are widely recognized as being highly inefficient to support analysis and review. The data in paper CRTs are not machine-readable and therefore cannot be easily analyzed using modern analytic software.
“Although submission of clinical study data in electronic format has become relatively routine at some centers, these data are often not standardized,” says the FDA. “Standardizing study data makes the data more useful. Data that are standardized are easier to understand, analyze, review, and synthesize in an integrated manner in a single study or multiple studies, thereby enabling more effective regulatory decisions.”
Six categories of “general submission considerations” are listed in Section III:
- Planning and providing standardized study data
- Controlled terminologies
- Standardization of previously collected nonstandard data
- Data validation
- Exceptions to standardized study data submissions
- Meetings with the FDA
The draft guidance also discusses the importance of three types of interoperability:
- Technical interoperabilitydescribes the lowest level of interoperability whereby two different systems or organizations exchange data so that the data are useful. The focus of technical interoperability is on the conveyance of data, not on its meaning.
- Semantic interoperabilitydescribes the ability of information shared by systems to be understood so that nonnumeric data can be processed by the receiving system. Semantic interoperability is a multi-level concept with the degree of semantic interoperability dependent on the level of agreement on data content terminology and other factors.
- Process interoperabilityis an emerging concept that has been identified as a requirement for successful system implementation into actual work settings. Simply put, it involves the ability of a system to provide the right data to the right entity at the right point in a business process. In a regulatory setting, an example of process interoperability is the ability to quickly and automatically identify and provide all the necessary information to produce an expedited adverse event report in a clinical trial upon the occurrence of a serious and unexpected adverse event.
“In summary,” states the guidance, “the goal of standardizing study data is to make the data more useful and to support semantically interoperable data exchange between submitters and the FDA. This, in turn, will support more efficient analytic processes at the agency. The combined use of various types of data standards is necessary to achieve an acceptable degree of semantic interoperability.”
Although the final rules will represent more initial work for medical device and pharmaceutical companies, the new standards will ultimately result in more efficient internal processes and better relationships with the FDA. The standardization rules can also be viewed as a quality check—if data does not fit the standard templates for data submittal, the information may be incorrect or improperly presented. Catching it internally is far better than having it be flagged and questioned by the FDA. Having the FDA and the manufacturer speak the same language when it comes to data presentation should improve communication, reduce frustration, and lead to faster approvals.