On March 24, 1997, the FDA CDRH ODE DCLD implemented a program to facilitate reviews of certain types of Premarket Approval (PMA) Supplements are conducted in "real time" using a variety of interactive formats (e.g. meeting, video conference, telephone conference). The benefits of this program include faster review times for manufacturers and more efficient use of FDA staff time.

The following types of changes may be eligible:

• Component changes not effecting clinical performance or Indications for Use, e.g. changes in a buffer reagent formulation; addition of preservative
• Instrument/software changes not affecting or changing Indications for Use
• Stability testing protocols and tentative open-vial or reconstituted stability dating
• Sterilization changes to another known method (e.g. ETO to gamma)
• Minor design changes; e.g. including generations of instruments on which an assay can be used; modifications to packaging; addition of automated dilution protocol
• Material changes, to another well-recognized material
• Minor labeling changes; e.g. additions of caution statements in the package insert; proprietary product name changes
• Supplements which contain requests similar to other previously approved supplements
• Protocols for post-approval studies
• Other types of changes not impacting Indications for Use that do not require a substantial review or documentation.

Manufacturing site changes are not eligible for review in this program. Cite guidance document, also, Supplements with detailed clinical data generally are not eligible for the program due to the complexity of reviewing these data. [sic]

For borderline changes, you should contact DCLD to determine whether the change is appropriate for real-time review. Mark it "Real-Time Supplement."

Complete the "Real Time Review Request Form for PMA Supplements." The form is available on the FDA website www.fda.gov/cdrh/ode/realtime.pdf. Fax the completed request form to "Branch Chief, DCLD" at (301) 594-5940. The form will be faxed back after FDA decision is made regarding acceptance of the Supplement for real time review; the decision is documented on the form.

If your request for real time review has been accepted, contact the FDA reviewing branch approximately 2 weeks before submitting the PMA Supplement to schedule a face-to-face real time meeting, if desired.

The PMA Supplement must be received by the reviewing branch at least 2 working days prior to the scheduled real time review meeting. If this time frame is not met, the meeting will be rescheduled or the supplement will be reviewed in the standard time and format.

The following is the FDA-suggested agenda for the meeting:

• Brief presentation by the applicant
• Discussion of issues and objectives
• Breakout into scientific discipline groups, if appropriate
• Break for DCLD staff discussion
• Same day DCLD verbal feedback to applicant

DCLD will fax the action letter no more than 5 working days after completion of the meeting and verbal feedback, with hard copy to follow.

Pre-scheduling is not needed for teleconferences.

No, but if early in the process (soon after submission), you believe that your submitted PMA Supplement fits this program, contact Branch Chief or Deputy Director, DCLD, for discussion. If concurrence is reached, schedule the meeting.

No. For PMA Supplements only.

Contact [information not available] at [information not available] to discuss.

From Doc Mail, the PMA supplement is sent to the PMA staff for logging in, prior to being sent to the reviewing branch of DCLD. If you notify DCLD, they will let the PMA staff know that the application should be expedited.

Company has 48 hrs. to get response back, in order to continue R-T. Otherwise, FDA will issue "not approvable" letter.