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Most medical devices require authorization by the

Food and Drug Administration (FDA) under the

Federal Food, Drug, and Cosmetic Act (FDCA) in

order to be legally marketed in the United States. Such author-

ization may be clearance o a premarket notication (510(k)

clearance), de novo classication, or approval o a premarket

application (PMA). Each o these, in turn, may require varying

levels o supporting bench or clinical data, depending upon the

type o device and its intended use.

A sound regulatory strategy requires an understanding o

the pathway to market and data requirements applicable to

a proposed device. Tere are several ways to obtain advance

inormation rom FDA on these issues. Each approach has its

strengths and weaknesses. It is worth knowing the ways inwhich FDA can be approached, the pros and cons o each type

o approach, and how to improve communications with FDA

in order to gain the best possible understanding o the require-

ments that will likely pertain to your proposed device. Te

discussion below will address the available options.

FDAs WebsiteTe Device Centers website (www.da.gov/cdrh) is a good place

to start the research, because it is quick, ree and ofen quite

useul. Te 510(k) database can be used to search or potential

predicate devices. In many cases, there will be a 510(k) sum-

mary that can provide inormation on other predicate devices

and the data provided to support clearance. Unortunately, this

inormation is ofen presented in airly general terms. Nonethe-

less it can still be helpul. For example, the 510(k) summary will

usually provide at least an indication as to whether clinical data

were required. In rare cases, FDA also may post its 510(k) deci-

sion memo, which will be somewhat more detailed.

I useul predicate devices are identied, it is possible to obtain

the underlying 510(k) submission via a Freedom o Inorma-

tion Act request to FDA.1 Unortunately, it is unpredictable how

long FDA will take to respond and it may take more time than

is practical. It is a good idea to check whether FOI Services (aprivate rm) has already obtained the 510(k) in question (www.

oiservices.com), in which case it can be downloaded or a ee.

by Jefrey K. Shapiro

Mr. Shapirois a Director at the law rm of

Hyman, Phelps & McNamara PC

in Washington, DC.

The Pathway to Market forYour Medical Device:A Primer on Obtaining Information from FDA

w w w . f d l i . o r gUpdate May/June 2008

Medical DevicesUpdate 2008, Issue 3With Permission from FDLI, www

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FDAs guidance document data-

base also should be reviewed. In some

instances, FDA has published guidance

that will reveal the likely pathway (e.g.,

510(k) v. PMA) and/or the typical data

required to support a 510(k) submissionor PMA ling. Tese documents, when

available, usually will provide a detailed

map o the path to market.

I a proposed device is in Class III

and approval has already been granted

to other devices in the same class, FDAs

PMA database may be useul. Every

approved device will have a summary

o saety and eectiveness (SSE) posted

in the database discussing in detail the

approved labeling or the device and the

preclinical and clinical data submitted to

support approval. Even i the proposed

device has somewhat dierent technol-

ogy or intended use (thus, potentially

altering the data requirements), a prior

SSE will provide a wealth o inormation

about the road ahead.

Informal ConsultationAfer making the most o FDAs website,

it may be appropriate to contact FDA

ocials to obtain more inormation. A

useul approach is to identiy ocials

who would likely review a 510(k) or PMA

or the proposed device.

In the Device Centers Oce o Device

Evaluation (ODE), there are ve divi-

sions, each encompassing a varying

number o branches that review spe-

cic types o devices. For example, the

Division o Reproductive, Abdominal,and Radiological Devices has a Division

Director, a Deputy Director and our

branch chies. I your device were intend-

ed or obstetric use (as an example), you

might call or e-mail Colin Pollard, cur-

rently chie o the Obstetrics/Gynecology

Devices Branch, to initiate discussions.

I the device is an in vitro diagnostic,

then the Oce o In Vitro Diagnostic

Device Evaluation and Saety (OIVD)

is the analog o ODE. Tis oce, too, is

organized by division. However, instead

o searching or a branch chie, you

would look or the relevant Associate

Director. For example, in the Divisiono Chemistry and oxicology Devices,

the Associate Director or Chemistry is

currently Carol Benson.

I the device is intended to be used

in combination with drugs or biologics,

there may be jurisdictional questions

as to which Center (Drug, Device or

Biologics) has primary jurisdiction.2

Tese issues can be discussed inormally

with the Oce o Combination Products

(OCP) and/or the product jurisdiction

ocers attached to each Center.3

Inormal contacts with agency o-

cials will yield inormation or opin-

ions that are not legally binding upon

the agency.4 Furthermore, when FDA

responds to questions, the answers

are only as valid as the inormation

provided as the basis or the questions.

Tus, it is critical to provide accurate

and complete inormation to your con-tact at FDA. Despite these limitations,

inormal contacts with FDA are usually

the least expensive and astest way to

elicit a great deal o helpul advice.

PreIDE ProgramFDAs preIDE program is the agencys

basic mechanism or interactive presub-

mission communications with industry.

Te current Director o ODEs Investiga-

tional Device Exemption (IDE) Program,Captain Stephen P. Rhodes, USPHS, has

estimated that ODE and OIVD have

a combined average o more than 400

meetings per year, not including tele-

phone or e-mail interactions.5

Te benet o this extensive outreach

eort is to help industry with design

testing and development plans that will

expedite review and approval. Early

interaction also allows FDA personnel

to amiliarize themselves with the new

technologies. Although there is a cost in

time and money to both agency and in-

dustry, the benet is generally perceived

to exceed the cost.Tere are many possible time points

in the premarket process where industry

may request advice. Prior to proo o

concept, it is possible to discuss concepts,

testing plan (in broad outline), bench

test methodologies, possible regulatory

pathways, and potential combination

product issues. ypically, FDA considers

it premature to discuss these matters in

a ace-to-ace meeting, so telephone and

e-mail contact are generally oered.

At the preclinical and clinical phases,

FDA encourages preIDE meetings

and teleconerences. At the preclinical

phase, FDAs eedback may be sought on

bench testing plans, animal study pro-

tocols, and easibility study protocols. In

addition, FDA may be willing to provide

preliminary eedback on the regulatory

pathway and guidance as to whether an

IDE approval will be required or anyclinical study (i.e., whether the device

qualies as signicant risk under the

IDE regulations).6

At the clinical phase, FDAs eedback

may be sought on the need or urther

bench/animal studies, the need or a pilot

study prior to initiating the pivotal study,

proposed study protocols, the regulatory

pathway, and proposed indication or

use. In addition, FDA may be willing toprovide preliminary eedback on issues

such as whether the device qualies or

expedited status and the need or an

advisory panel meeting.

o obtain a preIDE meeting, a rm

must submit a complete pre-meeting

package that includes a device descrip-

tion, pre-clinical test plan/results,

clinical/statistical test plan, and other

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Medical Devices

inormation necessary or FDA to un-

derstand the device and the issues or

which eedback is sought. It is essential

to prepare a list o ocus questions or

which FDAs eedback is sought. Te

process o preparing this list o questions

will help the rm determine the key out-

standing scientic and regulatory issues.

Te list will also guide FDAs preparation

and may help prevent the meeting rom

wandering o course.

Some Divisions have their own

checklists and guidelines as to what

must be in the pre-meeting package,

so it is important to inquire. Once the

package is submitted to FDA, a project

manager is assigned and a meeting will

be scheduled. ypically, these meetingsare scheduled to occur 4 to 6 weeks afer

submission. I signicant new inorma-

tion becomes available afer the package

is submitted (e.g., device modications,

changes to study design), it may be nec-

essary to reschedule the meeting. As the

meeting approaches, it will be necessary

to provide a proposed agenda to FDA

and exchange lists o attendees.

Te preIDE process is typically

ocused on study design and testing

issues. Yet, it may be the best op-

portunity to obtain FDAs eedback

on the regulatory pathway to market.

Tis regulatory issue is intimately

linked to study design, since studies to

support PMA approval are generally

more extensive than those supporting

510(k) clearance or de novo classica-

tion. Nonetheless, the regulatory issues

sometimes are lost in the scienticdiscussion o study design. Tereore,

unless it is clear that a proposed device

will require PMA approval, it is a good

idea to provide FDA in the preIDE

package with a specic analysis o the

proposed pathway to market (e.g., pro-

posed predicate devices and substantial

equivalence argument) and to include

at least one ocus question asking or

FDAs eedback on this issue.

FDAs preIDE program is not itera-

tive. Generally, FDA will grant a single

meeting or the same topic. Tus, it is

important to think through careully the

timing o the meeting and its objectives.

You should view it as your meeting

in the sense that you are responsible or

determining what questions need to be

answered, or ensuring that FDA actually

answers those questions, and or seeking

clarication or elaboration when FDAs

answers do not seem clear or complete.

It is important to bring the right team

to the meeting with all o the expertise

necessary to discuss the ocus questions

you have developed.

FDAs advice at a preIDE meeting isnot legally binding and may change in

light o technological and regulatory

evolution. Tus, it is important to main-

tain contact with FDA on these issues i

your development program extends over

several years.

Finally, i a binding commitment is

needed, FDA by statute oers deter-

mination7 and agreement8 meet-

ings. In general, the ormer is or PMA

devices and allows a written request to

or a determination o the type o valid

scientic evidence that will be neces-

sary to demonstrate that the device is

eective or its intended use. Te latter

generally allows a binding agreement

between FDA and the sponsor or ap-

plicant regarding the parameters o an

investigational plan (including a clinical

protocol).9 Tese two types o meetings

are not widely used, but they may be ap-propriate in some circumstances.

The 510(k) ProgramFDA regulates devices under a risk-based

scheme, in which devices determined

to be substantially equivalent to law-

ully marketed Class I and II devices are

cleared to market subject to postmarket

controls. A 510(k) review is, in essence,

a classication proceeding during which

FDA determines whether a proposed de-

vice is substantially equivalent (SE) or not

substantially equivalent (NSE) to a Class I

or II device already cleared to market.10

FDA will nd a device SE i it has the

same intended use and either the same

technological characteristics as a predi-

cate device or dierent technological

characteristics that 1) do not raise new

types o questions o saety and eective-

ness, and 2) data are provided to dem-

onstrate that the proposed device is at

least as sae and eective as the predicate.

As a practical matter, this review does

examine saety and eectiveness to a de-

gree, at least to the extent o determining

equivalence to a device already cleared tomarket. It is not, however, a ull review o

saety and eectiveness. As a legal matter,

FDAs issuance o a clearance letter is

actually an order classiying the device

into Class I or II based upon substantial

equivalence.

I a proposed device is ound NSE, it

will generally require a PMA approval or

de novo classication. 11 Tis may happen

i the proposed device does not have a

predicate device, presents a new intended

use, or has dierent technological charac-

teristics compared to the predicate device

and raises new questions o saety or e-

ectiveness. FDA can make the oregoing

determinations without a review o data.

In addition, FDA may nd a device NSE i

the data provided do not demonstrate that

the device is at least as sae and eective

as the predicate device. In this situation,

it may be possible to generate appropriatedata to ultimately support clearance o a

new 510(k) submission rather than move

to the de novo or PMA pathways.

An important implication o the

oregoing discussion is that the 510(k)

process itsel may be an appropriate way

to obtain FDAs ruling on the classica-

tion o the device, without the necessity

to conduct a study and provide data. I

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a 510(k) is submitted and ound to be

NSE or lack o data, a new 510(k) may

be submitted afer the appropriate test-

ing has been perormed. I the 510(k) is

submitted and ound to be NSE or the

other reasons mentioned above, that is

a denitive ruling that the device is in

Class III, requiring de novo classication

or PMA approval.

A 513(g) RequestAn option or obtaining written advice

about the classication o a device is a

513(g) request.12 It is named or Section

513(g) o the FDCA, which provides:

Within 60 days o the receipt

o a written request o any person

or inormation respecting theclass in which a device has been

classied or the requirements

applicable to a device under this

Act, [FDA] shall provide such

person a written statement o the

classication (i any) o such de-

vice and the requirements o this

Act applicable to the device.

A 513(g) request is airly simple to

prepare. Generally speaking, it should

include a cover letter, a complete devicedescription, an Indications or Use

statement, and either proposed labeling

or labeling o a similar device already on

the market. A user ee is now required

or each 513(g) request.13 Within 60 days,

and sometimes sooner, FDA will provide

a written response that is binding unless

amended or revoked in writing.14 Te

advice in response to a 513(g) request

only covers the device as described in theinitial request. I the device is modied

(or was not accurate in the rst place),

the 513(g) response may not apply.

A 513(g) request can be used or a wide

range o inquiries. Tese include whether

a product is subject to FDA regulation at

all, whether it is regulated as a device (ver-

sus a cosmetic, biologic or drug), whether

it is within an exemption rom 510(k)

requirements, whether a 510(k) is needed

or a modication to the device, and

whether a device with a new technology

or intended use must undergo a 510(k) or

PMA pathway to market.

Tere has sometimes been uncertainty

about whether a particular stand alone

sofware product is subject to medical

device regulation. FDA has withdrawn

its 1989 draf policy statement, FDA

Policy or the Regulation o Computer

Products. Tis guidance had never

been nalized but had provided opera-

tional policy guidance to industry and

agency sta or many years. Some agency

ocials have said that the principles em-

bodied in the draf guidance still apply

in most cases. Nonetheless, FDA has no

current written guidance on the regula-

tion o stand alone sofware products.

A 513(g) request can be used to elicit

ormal advice as to whether a particular

stand alone sofware product will be

regulated as a medical device and the

requirements that will apply.

Request for DesignationA combination product raises the

question about which Center will have

primary jurisdiction (i.e., Drug, Device

or Biologic). A Request or Designa-

tion (RFD) can be submitted to the

OCP seeking a written ruling as to which

center will have primary jurisdiction.

Tis process and the requirements or an

RFD are set orth in 21 C.F.R. Part 3. Te

OCP must make its written jurisdictional

determination within 60 days o ling.

Tere is no user ee or an RFD.15

Final ThoughtsIt is critical to obtain inormation rom

FDA on the requirements applicable to a

proposed device. It will typically require

signicant time and unding resources

to do so. Tereore, when developing a

business and regulatory strategy, it is es-

sential to build in this inormation gath-

ering process. Tis is particularly true

or novel or complex devices, or which

it is virtually impossible to successully

conduct a clinical study and prepare an

appropriate 510(k) submission or PMA

ling without consulting FDA in ad-

vance. It is essential to develop a careul

strategy or communicating with FDA

using the right tools at the right time in

the development process. Hopeully, the

oregoing discussion will help get you

started in ormulating a successul strat-

egy that wi ll result in a smooth pathway

to market or your device.

1 5 U.S.C. 552; 21 C.F.R. Part 20.

2 Te Device Centers ormal name is the Center or

Devices and Radiological Health (CDRH). Te Drug

Centers ormal name is the Center or Drug Evalu-ation and Research (CDER). Te Biologics Centers

ormal name is the Center or Biologics Evaluation

and Research (CBER).

3 Currently, these are: Stephen Rhodes, CAP,

USPHS, CDRH; Virginia Behr, CDER; and Sheryl

Lard-Whiteord, PhD, CBER.

4 21 C.F.R. 10.85(k).

5 Slide presented during AdvaMed AudioConerence

(Oct. 17, 2007).

6 21 C.F.R. 812.3(m).

7 FDCA, 513(a)(3)(D).

8 FDCA, 520(g)(7).

9 FDAs descript ion o these two types o meetings can

be ound in Early Collaboration Meetings

Under the FDA Modernization Act (FDAMA); FinalGuidance or Industry and or CDRH Sta.

10 Substantia l equivalence may also be claimed to a

pre-amendment device (on the market prior to May

28, 1976), or which PMA applications have not been

called. Tere are also Class I and II devices that are

exempt rom the 510(k) requirement.

11 In de novo classication under Section 513()(2) o

the FDCA, FDA essentially creates a new classica-

tion or novel low risk devices that lack a predicate

device. Te process requires an additional 60 days,

and usually includes the development o special regu-

latory controls or the device. Once the classication

exists, uture devices may seek 510(k) clearance based

upon substantial equivalence to the de novo device.

12 An original and one copy o the 513(g) request shouldbe mailed to the 513(g) Coordinator, Oce o Device

Evaluation, Center or Devices and Radiological

Health c/o Document Mail Center (HFZ-401), 9200

Corporate Boulevard, Rockville, Maryland 20850.

Te current contact person is Lawrence J. (Jake)

Romanell, Program Operations Sta, ODE, CDRH.

13 In Fiscal Year 2008, the standard ee is $2,498 and the

small business discounted ee is $1,249.

14 See 21 C.F.R. 10.85(e).

15 For a detai led treatment o combination products,

see Fox and Shapiro, Combination Products: How

to Develop the Optimal Strategic Path or Approval

(FDANews 2006) (www.danews.com).