# Presentation: 246351

## Understanding the Pre-IDE Program:  FDA Perspective

**Elisa D. Harvey, DV.M., Ph.D.**
**Director, IDE and HDE Programs**
**Office of Device Evaluation**
**AdvaMed**
**15****th**** Annual Device Submissions Workshop**
**May 25, 2005**

## Outline

- General information
- Preparation
- Meeting scheduling/planning
- Case studies
- Recommendations

- AdvaMed May 2005 -- PreIDEs

## Meetings with regulated industry are integral to our mission

- Committed to communicating and interacting with our stakeholders
- ODE/OIVD have 400+ meetings/year
- Average 80 meetings per division:                  2 meetings/wk/division                             (not including teleconferences)
- FDAMA (1997):  Early Collaboration meetings became regulation    (Agreement, Determination meetings)

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## Why face to face meetings?

- Benefits (to sponsors and FDA)
- Design testing and development plans that will expedite review and approval
- Save money and time
- More collaborative approach
- Minimize surprises
- Cost (to sponsors and FDA)
- Time and effort
- Money

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## Meetings may be held at any of these points in premarket phase:

**Prior to conducting “proof of concept” animal studies**
**Preclinical**
**Prior to expanding clinical trials from feasibility to pivotal phase**
- Pre-PMA
- Day 100 PMA meetings
- Post-deficiency letter for 510(k) or PMA
- Appeal a final decision on a PMA or 510(k) or an IDE disapproval
- Agreement or determination meeting

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## Prior to Proof of Concept

- Discuss concepts, broad outline of test plan, bench test methodologies (e.g., use of consensus standards, need for animal studies, need for clinical studies)
- Discuss _**possible**_ regulatory pathways
- Discuss potential combination product issues
**Face-to-face meetings are usually not held at this stage (premature).**

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## Preclinical phase

- Prototype evaluated in preliminary animal models
- Proposed clinical application (possibly not specific patient population) and indication for use
- FDA feedback on:
- Bench testing plan – methods, standards
- Animal study protocols
- Feasibility study protocols
- Preliminary guidance on SR/NSR (need for IDE)
- Preliminary (non-binding) guidance on regulatory pathway
**Feedback dependent on focused questions **
**PreIDE meetings/teleconferences  **_**encouraged**_** at this stage**

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## Prior to initiating pivotal trials

- Feasibility studies completed (or nearly so)
- Device design finalized to extent possible
- Animal studies completed (or in follow-up)
- Pivotal trial protocol “fleshed out” (including 1o and 2o endpoints, duration, evaluation methods, statistical analysis)
- Specific indication for use (and patient population) determined

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## Prior to initiating pivotal trials (cont.)

**FDA will give feedback on:**
- Need for further bench/animal studies
- Need for pilot study prior to initiating pivotal study
- Proposed pivotal study protocol: endpoints, duration, evaluation, statistical analysis plan
- Proposed regulatory pathway
- Proposed indication for use
- Preliminary nonbinding feedback on expedited status, need for advisory panel meeting
**Feedback dependent on focused questions **
**Meetings/teleconferences with FDA  **_**encouraged**_** at this stage**

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## Scheduling informal pre-IDE meetings  (not determination or agreement meetings)

- Planning/scheduling may be done by   project manager (usually 3-4 weeks       after preIDE received)
**Complete** pre-meeting package needed before  meeting will be scheduled
- Divisions may have checklists/other guidelines for what is expected in pre-meeting package:  **Check!**
- Expect meeting to be cancelled/postponed   if extensive new information submitted after meeting scheduled

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## Pre-IDEs:  What they are and what they are not

- Tool to provide informal feedback on:
- Preclinical test plan
- Clinical/statistical test plan
- NSR/Exempt investigations
- OUS investigations
- NOT intended to be:
- A tool for negotiation
- An iterative process
- Modular review
- Review of _data _(“pre-510(k)”, “pre-PMA”)
- As in depth as an IDE or marketing application review
- Legally binding
- Method for dispute resolution

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## Meeting Preparation:  Complete package must be submitted in advance

- FDA must have the complete pre-meeting package in order to schedule meeting:
- Received by branch chief; review team determined
- Assigned to lead reviewer
- Copies prepared (or requested) and distributed
- Internal pre-meeting/sponsor meeting scheduled
- Team members review package, prepare memos prior to pre-meeting
- Internal pre-meeting held to discuss issues, reach consensus and obtain further information from team/management

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## Meeting Preparation:                          Agenda and attendee list

- Sponsors responsible for agenda--no meeting will be scheduled without one
- Include time allocated to each topic
- Your time and FDA’s time valuable – make the most of it (i.e., minimize time on background information, maximize time for discussion)
- Expect that the meeting will begin **and end** on time (typically one hour maximum)
- Submit list of attendees (and their affiliations) in advance
- Sign in sheet will be circulated during meeting, copied and provided to sponsor

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## Meeting Preparation: Focused questions

- During internal pre-meeting, FDA team discusses deficiencies/issues
- Meeting centers around discussing  focused questions provided by sponsor
- Efficient use of resources
- Ensures that your most pressing questions are addressed
- Should be focused, not general (garbage in/garbage out)

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## Case studies

- DISCLAIMER:These case studies are fictional.  Any resemblance to an actual product and/or meeting, is unintentional!

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## Case Study #1: ABC Technologies

- Start-up company w/new technology for embolization agent intended for AVMs in cerebrovasculature
- Technology licensed from European university
- Professor/inventor completed feasibility studies and is conducting a 30 patient study in Europe
- Company submitted pre-IDE outlining plans for GLP animal study and 10 patient study, which, with 30 patient European study, they feel will support 510(k)
- Two questions submitted:
- Are the animal and clinical studies adequate to support marketing approval?
- Do you agree with the proposed regulatory pathway?

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## Case #1: ABC Technologies

- Meeting scheduled for one hour; attendees included professor/inventor of technology, CEO, chief scientist and VP for Regulatory Affairs
- CEO spent 15 minutes describing how company was founded, showed pictures of their buildings and facilities, described in detail each member of scientific advisory board and explained their sources of funding
- Professor/inventor spent next 15 minutes talking about his research, his experience with product and mentioned that he was now testing prototype that eluted drugs
- Chief Scientific Officer spoke for next 20 minutes and described device in detail (including all previous design iterations) described how it worked, reviewed bench test results, reviewed animal results and re-iterated that they had decided, after submitting the pre-IDE, to change the product to elute drugs and therefore would be changing some of  endpoints and evaluation criteria.

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## Case #1: ABC Technologies

- In the (rushed!) last 10 minutes, the company was told (to their surprise and dismay):
- _Significantly_ more preclinical studies would be needed for the drug-eluting version, and since FDA did not know of this change, FDA was not prepared to give them any of the needed advice
- 10 patient feasibility study not adequate to support a marketing application, and further discussions now needed with CDER since sponsor planned on incorporating major change to device design
- FDA did not feel it was appropriate to discuss regulatory pathway at this early stage of development but similar products had all been reviewed as PMAs, with randomized controlled clinical trials

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## Case #1:  ABC Technologies –      What went wrong?

- The company:
- Made major change to device design after submitting pre-IDE
- Did not do their homework on predicate and/or comparable devices
- Did not manage meeting time well
- Did not ask specific or focused enough questions of FDA

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## Case #2: XYZ Technologies

- Start-up company with new technology for treatment of wrinkles
- Technology is injectable product that including a degradable hydrogel, human collagen and lidocaine
- Biocompatibility and animal studies completed;  feasibility study underway in Canada
- Pre-IDE package includes manufacturing information, animal study results, feasibility study results and detailed proposed protocol for controlled 30 patient pilot study followed by controlled pivotal study of 150 patients

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## Case #2:  XYZ Technologies

- Following focused questions submitted:
- Are the procedures for procuring and treating the human collagen acceptable?
- Is the biocompatibility testing plan adequate or will additional immunogenicity studies be needed?
- Are there any drug issues related to the inclusion of lidocaine?
- Is the primary endpoint and timing of evaluation assessments acceptable?
- Is the length of follow-up acceptable?
- Would our PMA application be appropriate for expedited review?

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## Case #2: XYZ Technologies

- Meeting scheduled for one hour; attending for company were CEO, Chief Scientific Officer, VP of Regulatory Affairs, principal investigator for pivotal study and  principal investigator for Canadian feasibility study.  Attending for FDA, in addition to CDRH review team, were CDRH and CDER product jurisdiction officers.
- The company began with 15 minute overview of  technology and review of preclinical studies and clinical results to date.
- Next, each member of FDA team asked questions and provided input. Each focused question was discussed and answered.
- List of action items and next steps were discussed.
- Meeting ended 5 minutes early, allowing everyone from the company team to make it to the airport in plenty of time for their flights.

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## Case #2:  XYZ Technologies –What went right?

- No surprise changes to protocol    or device design
- Company did their homework on the device type and generally knew what would be needed
- Focused questions were appropriate
- Limited time was used wisely

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## Recommendations

- FDA is doing our homework before your meeting; please do yours!
- Think carefully about what you want to get from a meeting – are you ready to talk with FDA?
- If you must make changes to device or protocol after pre-IDE package has been submitted, be prepared to cancel and reschedule
- Manage your meeting time carefully
- Bring right people to discuss focused questions
- Ask for clarification

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## Recommendations

- Do not expect FDA to:
- Make guarantees or binding commitments (unless it is a determination or agreement meeting)
- Approve study or clear/approve device at  meeting
- Act as a consultant
- Give special treatment or favors
- Hold to informal feedback provided years ago – technology does not stay constant
- Have a series of meetings on the same topics – make the most of THIS meeting

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## More Information

- CDRH Website:  Device Advice
- 	_[http://](http://www.fda.gov/cdrh/devadvice/ide/approval.shtml#pre_ide)__[www.fda.gov/cdrh/devadvice/ide/approval.shtml#pre_ide](http://www.fda.gov/cdrh/devadvice/ide/approval.shtml#pre_ide)_
- Contact information:
- Elisa Harvey
- (301) 594-1190 x 106
- elisa.harvey@fda.hhs.gov

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