Worldwide Medical Device Regulatory Updates

As medical device quality assurance and regulatory affairs professionals, it can be challenging to stay on top of changes happening in our industry. Few people have the time to read lengthy articles these days and although many online newsletters exist, they are often packed with PR releases, ads or unrelated information. That\'s why we started this blog for QA/RA professionals in the medical device and IVD industry. The idea is to give you short updates on quality and regulatory topics that may be of interest to you. No fluff, just straight to the point. We hope you\'ll enjoy the content.

FDA Explains Electronic Study Data Submission Expectations

New guidance from the US Food and Drug Administration spells out how medical device manufacturers and study sponsors should format standardized study data for electronic submission.

The guidance pertains to submissions of clinical and non-clinical data related to Investigational Device Exemptions (IDEs), premarket notifications (510(k)s) and premarket approval applications (PMAs) submitted to the Center for Devices and Radiological Health, the Center for Biologics Evaluation and Research and other medical device and pharmaceutical review divisions of the FDA.

Planning and Provision of Standardized Data
First, study sponsors should include descriptions of their standardized study submission plans in their IDEs. These plans must also be included in the Data Management Plan sections of sponsors’ IDE study protocols, and lay out which data standards sponsors intend to use. (Any studies that will not be standardized should also be described, along with explanations for using non-standardized studies.)

Controlled Terminologies
Second, the guidance recommends that study sponsors utilize terminology standards such as CDRH Event Problem Codes as part of their standardized electronic submission efforts. This makes FDA analysis of study data more efficient. The FDA Study Data Standards Resources Web Page lists all terminology standards currently accepted by agency divisions.

Standardization of Previously Collected Nonstandard Data
In cases where study data elements cannot be readily converted to standardized formats, sponsors should document why such data could not be fully standardized. In addition, sponsors should identify which studies contain nonstandard data that were converted to standard formats.

Data Validation
Sponsors should also conduct data validation prior to sending their submissions to the FDA. The agency recognizes two major validation rules: technical validation rules to ensure data submitted conforms to standards, and business validation rules to ensure that data will support relevant business processes as intended.

FDA Meetings
Finally, the guidance recommends using FDA-sponsor meetings such as pre-IDE meetings to point out any outstanding study data standardization issues. In addition, sponsors and manufacturers can send technical questions at any time to CDRH and/or CBER technical support teams.

Markets: USATags: 510(k), 510k, clinical study, FDA, IDE, investigational device exemption, medical device, PMA

Author: Stewart EisenhartDate: February 22, 2012

FDA Clarifies IDE Approval Process

Through new guidance published this month, the US Food and Drug Administration has clarified its review and approval process for its Investigational Device Exemption (IDE) regulations, and has also proposed steps to allow clinical investigations of high-risk medical devices in some instances where IDE approvals have not been finalized.

Approval of an IDE submission must occur before a manufacturer can begin clinical investigations of its device. The guidance explains four outcomes of its IDE review process: approval, approval with conditions, staged approval with or without conditions, and disapproval.

IDE Approval

If a manufacturer’s IDE application obtains FDA approval without conditions, the firm may begin clinical investigation efforts according to the terms set forth in the agency’s approval letter.

IDE Approval with Conditions

In instances where the FDA approves an IDE application with conditions, manufacturers may begin clinical investigations provided that they submit data to address outstanding issues within 45 days. If the agency takes issue with sponsors’ informed consent documents, however, those issues must be resolved before clinical investigations begin.

Issues often garnering approvals with conditions by the FDA include proposed study data analysis methods; late-stage follow-up procedures and assessments; divergences from appropriate study endpoints; and requests for additional information related to non-clinical testing issues.

Failure to submit supplements to the FDA within the 45-day timeframe will result in disapproval of an IDE application.

Staged Approval with or without Conditions

The new FDA guidance introduces staged approval and staged approval with conditions to the IDE approval process. Under these scenarios, manufacturers may begin limited subject enrollments for their investigations while simultaneously addressing issues raised by the regulatory about their IDE applications. (Once outstanding questions have been resolved, sponsors could then expand their study enrollments.)

Staged clinical investigations are warranted, according to the guidance, in instances where obtaining clinical data of a device’s safety characteristics is deemed necessary, requiring review of data from subjects in early stages of a clinical investigation before allowing a wider pool of subjects to be added to the investigation.

Staged investigations are also valuable when existing data supports enrolling a limited number of subjects in a clinical investigation while also conducting long-term non-clinical testing. The FDA would require validation of non-clinical testing results before allowing full enrollment in the sponsor’s clinical investigation.

IDE Disapproval

If the FDA disapproves an IDE application, the sponsor must submit an amendment to its IDE to address deficiencies; only following subsequent approval or approval with conditions by the agency may that sponsor proceed with its clinical investigation.

The guidance identifies five common factors for IDE disapproval:

Failure to comply with any relevant FDA requirement
IDE application contains false information or omits required information
Request for additional information is not addressed within required timeframe
Device’s health benefits do not outweigh the risk its use poses to patients, or it is ineffective
Inadequacies in the sponsor’s report of prior investigations, manufacturing processes or monitoring process of its investigation

Key Factors for Consideration

The FDA’s guidance also lists some of the major factors its reviewers evaluate in order to determine approval status of IDE applications. These include:

Non-clinical testing data, reviewed to see whether it supports a device’s safety and performance
Category of clinical investigation—feasibility or pivotal—can affect which elements of an IDE application FDA reviewers will examine most carefully
Risk assessment—are the expected risks of a clinical investigation acceptable?
Sudy design elements such as subject safety, enrollment criteria and clinical methodology for feasibility studies, and primary safety and effectiveness endpoints, assessment methodologies and statistical analysis plans for pivotal studies
Informed consent documents must meet requirements of 21 CFR Part 50
Least burdensome approaches to address premarket regulatory issues to ensure appropriate timeframes, efforts and cost-effectiveness for industry participants and FDA personnel

Markets: USATags: clinical investigation, FDA, IDE, investigational device exemption, premarket approval

Author: Stewart EisenhartDate: November 14, 2011

New FDA Guidance on IDEs for Early Feasibility Studies

The US Food and Drug Administration is proposing a new policy for Investigational Device Exemption (IDE) applications for early feasibility studies of high-risk medical devices, according to new guidance from the agency.

The guidance covers early feasibility clinical studies, which are limited clinical investigations conducted early in device development for specific indications, and first in human (FIH) studies, in which devices for specific indications are evaluated for the first time using human test subjects.

New FDA policies regarding early feasibility and FIH studies included in the guidance would allow agency approval of IDE applications for such studies based on less non-clinical data than would be required for traditional feasibility studies. The guidance would also enable timelier device and clinical protocol changes during early feasibility studies but still require compliance with 21 CFR Part 812 IDE regulations.

Reports of Prior Investigations

The guidance lays out specific requirements for 21 CFR Part 812 requirements targeting Reports of Prior Investigations for early feasibility studies. Reports of Prior Investigations should include sections on background, executive summary and detailed reports, as well as information to justify clinical investigation of a medical device.

Information provided in Reports of Prior Investigation should support expectations of acceptable clinical use of a device, and that the device in question functions as the manufacturer intended. Reports should also cover basic device safety issues as well as catastrophic failure modes and risk mitigation processes.

Investigational Plans

Requirements in 21 CFR Part 812 also entail Investigational Plans in order to clarify that early feasibility studies are not being conducted to collect data to support device marketing applications. Components of an Investigational Plan should include risk analysis and mitigation, a clinical protocol, human subject protection measures and monitoring procedures.

Iterations during Early Feasibility Studies

Finally, the guidance emphasizes the need to discuss with the FDA whenever changes need to be made to investigational plans during the pre-IDE process. The guidance would set a new policy to allow more types of modifications to be made to devices and clinical protocols during early feasibility studies using five-day notices without prior FDA approval.

For changes that would require prior FDA approval, the guidance introduces contingent approval—permitting changes based upon acceptable non-clinical test results without requiring additional FDA review—and interactive review, which would boost communication between applicants and the agency during 30-day review timeframes for early feasibility IDE supplements.