48940 Federal Register / Vol. 62, No. 181 / Thursday, September 18, 1997 / Rules and Regulations

Drug labeler code Firm name and address

* * * * * * *

038782 ...................................................................................................... K. C. Pharmacal, Inc., 8345 Melrose Dr., Lenexa, KS 66214

* * * * * * *

Dated: September 4, 1997.

George A. Mitchell,

Acting Director, Center for Veterinary

Medicine.

[FR Doc. 97–24736 Filed 9–17–97; 8:45 am]

BILLING CODE 4160–01–F

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Food and Drug Administration

21 CFR Part 524

Ophthalmic and Topical Dosage Form

New Animal Drugs; Cyclosporine

AGENCY: Food and Drug Administration,

HHS.

ACTION: Final rule.

SUMMARY: The Food and Drug

Administration (FDA) is amending the

animal drug regulations to reflect

approval of a supplemental new animal

drug application (NADA) filed by

Schering-Plough Animal Health. The

supplemental NADA provides for use of

cyclosporine ophthalmic ointment on

dogs for management of chronic

superficial keratitis (CSK) and changing

the approved label claim to management

of chronic keratoconjunctivitis sicca

(KCS).

EFFECTIVE DATE: September 18, 1997.

FOR FURTHER INFORMATION CONTACT:

Melanie R. Berson, Center for Veterinary

Medicine (HFV–110), Food and Drug

Administration, 7500 Standish Pl.,

Rockville, MD 20855, 301–594–1612.

SUPPLEMENTARY INFORMATION: ScheringPlough Animal Health, Schering-Plough

Corp., P.O. Box 529, Kenilworth, NJ

07033, has filed supplemental NADA

141–052 Optimmune (cyclosporine)

ophthalmic ointment that provides for

use on dogs for the management of

chronic superficial keratitis (CSK) and

changing the approved label claim from

treatment to management of chronic

keratoconjunctivitis sicca (KCS) in dogs.

The term management reflects the

complexity of the therapy for the

diseases. The drug is limited to use by

or on the order of a licensed

veterinarian. The supplement is

approved as of August 26, 1997, and the

regulations are revised in 21 CFR

524.575(c)(2) to reflect the approval.

The basis of approval is discussed in the

freedom of information summary.

In accordance with the freedom of

information provisions of 21 CFR part

20 and 514.11(e)(2)(ii), a summary of

safety and effectiveness data and

information submitted to support

approval of this application may be seen

in the Dockets Management Branch

(HFA–305), Food and Drug

Administration, 12420 Parklawn Dr.,

rm. 1–23, Rockville, MD 20857, between

9 a.m. and 4 p.m., Monday through

Friday.

Under section 512(c)(2)(F)(iii) of the

Federal Food, Drug, and Cosmetic Act,

this approval for use in nonfoodproducing animals qualifies for 3 years

of marketing exclusivity beginning

August 26, 1997, because the

supplemental application contains

substantial evidence of the effectiveness

of the drug involved, studies of animal

safety or, in the case of food-producing

animals, human food safety studies

(other than bioequivalence or residue

studies) required for approval of the

application and conducted or sponsored

by the applicant. The 3 years of

marketing exclusivity applies only to

the new indication for management of

CSK in dogs.

FDA has carefully considered the

potential environmental effects of this

action and has concluded that the action

will not have a significant impact on the

human environment, and that an

environmental impact statement is not

required. FDA’s finding of no significant

impact and the evidence supporting that

finding, contained in an environmental

assessment, may be seen in the Dockets

Management Branch (address above).

List of Subjects in 21 CFR Part 524

Animal drugs.

Therefore, under the Federal Food,

Drug, and Cosmetic Act and under

authority delegated to the Commissioner

of Food and Drugs and redelegated to

the Center for Veterinary Medicine, 21

CFR part 524 is amended as follows:

PART 524—OPHTHALMIC AND

TOPICAL DOSAGE FORM NEW

ANIMAL DRUGS

1. The authority citation for 21 CFR

part 524 continues to read as follows:

Authority: Sec. 512 of the Federal Food,

Drug, and Cosmetic Act (21 U.S.C. 360b).

2. Section 524.575 is amended by

revising paragraph (c)(2) to read as

follows:

§ 524.575 Cyclosporine ophthalmic

ointment.

* * * * *

(c) * * *

(2) Indications for use. For

management of chronic

keratoconjunctivitis sicca (KCS) and

chronic superficial keratitis (CSK) in

dogs.

* * * * *

Dated: September 10, 1997.

Michael J. Blackwell,

Deputy Director, Center for Veterinary

Medicine.

[FR Doc. 97–24850 Filed 9–17–97; 8:45 am]

BILLING CODE 4160–01–F

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Food and Drug Administration

21 CFR Part 812

[Docket No. 96N–0299]

Investigational Device Exemptions;

Treatment Use

AGENCY: Food and Drug Administration,

HHS.

ACTION: Final rule.

SUMMARY: The Food and Drug

Administration (FDA) is establishing

procedures to allow for the treatment

use of investigational devices. These

procedures are intended to facilitate the

availability of promising new

therapeutic and diagnostic devices to

desperately ill patients as early in the

device development process as possible,

i.e., before general marketing begins,

and to obtain additional data on the

device’s safety and effectiveness. These

procedures apply to patients with

serious or immediately life-threatening

diseases or conditions for which no

comparable or satisfactory alternative

device, drug, or other therapy exists.

DATES: The regulation is effective

January 16, 1998.
Federal Register / Vol. 62, No. 181 / Thursday, September 18, 1997 / Rules and Regulations 48941

FOR FURTHER INFORMATION CONTACT:

Joanne R. Less, Office of Device

Evaluation (HFZ–403), Center for

Devices and Radiological Health

(CDRH), Food and Drug Administration,

9200 Corporate Blvd., Rockville, MD

20850, 301–594–1190.

SUPPLEMENTARY INFORMATION:

I. Background

In the Federal Register of May 22,

1987 (52 FR 19466), FDA published a

final rule that codified procedures

authorizing the treatment use of

investigational new drugs (IND’s)

(hereinafter referred to as the treatment

IND regulation). In publishing the

treatment IND regulation, FDA was

responding to an increased demand

from patients as well as from health

professionals to permit broader

availability of investigational drugs to

treat serious diseases for which there

were no satisfactory alternative

treatments. For similar reasons, in the

Federal Register of December 19, 1996

(61 FR 66954), FDA proposed to amend

its Investigational Device Exemptions

(IDE) regulation (part 812 (21 CFR part

812)) to allow for the treatment use of

investigational devices (hereinafter

referred to as the treatment IDE

regulation). With minor exceptions, the

proposal paralleled the treatment IND

regulation and extended those

provisions to cover the treatment use of

investigational devices, including

diagnostic devices. The final rule

generally codifies the proposal, with

some exceptions discussed below.

Similar to the proposed rule, this final

rule is intended to facilitate the

availability of promising new devices to

patients as early in the device

development process as possible while

safeguarding against commercialization

of the device and ensuring the integrity

of controlled clinical trials.

FDA received six comments on the

proposed rule. These comments were

from an institutional review board (IRB),

a medical device consultant, a medical

device manufacturers’ association, a

medical device manufacturer, an

association of surgeons, and a

consumer. The comments generally

supported the agency’s proposal to

provide for expanded access to

investigational devices under a

treatment IDE. A number of comments

sought clarification of specific points, or

responded to specific questions raised

in the preamble to the proposed rule. No

comments opposed codification of the

treatment procedures. Interested

persons were given until March 19,

1997, to comment on the proposed rule.

II. Highlights of the Final Rule

FDA has retained the basic framework

of the proposed rule. Treatment use of

an investigational device will be

considered when: (1) The device is

intended to treat or diagnose a serious

or immediately life-threatening disease

or condition; (2) there is no comparable

or satisfactory alternative device

available to treat or diagnose the disease

or condition in the intended patient

population; (3) the device is under

investigation in a controlled clinical

trial for the same use under an approved

IDE, or all clinical trials have been

completed; and (4) the sponsor of the

controlled clinical trial is pursuing

marketing approval/clearance of the

investigational device with due

diligence.

Each application for treatment use

shall include, among other things, an

explanation of the rationale for the use

of the device; the criteria for patient

selection; a description of clinical

procedures; laboratory tests, or other

measures to be used to monitor the

effects of the device and to minimize

risk; written procedures for monitoring

the treatment use; information that is

relevant to the safety and effectiveness

of the device for the intended treatment

use; and a written protocol describing

the treatment use.

Treatment use may begin 30 days after

FDA receives the treatment IDE

submission, unless FDA notifies the

sponsor earlier than 30 days that the

treatment use may or may not begin.

FDA may approve the treatment use as

proposed, approve it with modification,

disapprove it, or withdraw approval of

the treatment IDE if FDA finds that

certain criteria are satisfied.

Safeguards for treatment use of an

investigational device include the:

Distribution of the device through

qualified experts; maintenance of

adequate manufacturing facilities; the

submission of certain reports; and

compliance with the regulations

governing informed consent and

institutional review boards (IRB’s).

The sponsor of a treatment IDE shall

submit progress reports to all reviewing

IRB’s and FDA and shall be responsible

for submitting all other reports required

under § 812.150.

In response to comments, FDA has

made the following changes in the final

rule.

FDA has streamlined the reporting

requirements in § 812.36(f). First, FDA

decreased the frequency with which

sponsors must submit progress reports

under § 812.36(f). Under the final rule,

the sponsor of a treatment IDE is

required to submit progress reports on a

semi-annual basis, rather than quarterly,

to all reviewing IRB’s and FDA. Upon

filing of a marketing application, the

requirement for progress reports is

further reduced to annual reporting in

accordance with § 812.150. Second,

FDA limited the type of information that

is to be submitted in a progress report.

Under the final rule, these reports are

required to include only the number of

patients treated with the device under

the treatment IDE, the names of the

investigators participating in the

treatment IDE, and a brief description of

the sponsor’s efforts to pursue

marketing approval/clearance of the

device.

FDA has modified the rule with

respect to cost recovery by adding new

§ 812.36(c)(1)(x). In accordance with

this provision, if the device is to be sold,

the price to be charged is to be based on

manufacturing and handling costs only.

This decision was based on the fact that

under the general IDE, sponsors are

permitted to recover, among other costs,

research and development costs.

Because the research and development

expenditures already are being

recovered under the general IDE, FDA

concluded that cost recovery under the

treatment IDE should be limited to that

of supplying the device for the

treatment use, i.e., manufacturing and

handling costs.

FDA is clarifying the final rule to state

that treatment use must be for the same

use as that studied under an approved

IDE. The preamble to the proposed rule

addressed this point at 61 FR 66954 at

66955, column 3, and FDA believes it is

important to include it in the codified

language. See § 812.36(b)(3). This

change reflects the fact that it is those

indications studied in the controlled

clinical trial for which the agency

would have the preliminary evidence of

safety and effectiveness needed to

support the treatment use.

III. Summary and Analysis of

Comments and FDA’s Responses

A. General Comments

1. One comment stated that the

example FDA provided in the preamble

to the proposed rule of an approved

device that would have met the

treatment IDE criteria, i.e.,

nonthoracotomy (transvenous)

defibrillation leads, was inappropriate.

According to the comment, unless

patients in need of such leads had a

complicating disease or condition that

prevented surgery, the surgical

placement of approved defibrillation

leads would have been a satisfactory

alternative to the nonthoracotomy

(transvenous) defibrillation leads. The
48942 Federal Register / Vol. 62, No. 181 / Thursday, September 18, 1997 / Rules and Regulations

comment stated that placement of the

transvenous leads may present less risk

to the patient than the surgical

placement of defibrillation leads. The

comment noted, however, that the

regulation does not incorporate risk

considerations. If the intent of the

regulation is to permit the use of a

device based on risk, then the comment

suggested that § 812.36(b)(2) be

rewritten to include risk-benefit

considerations.

FDA agrees that risk/benefit

considerations should be part of

treatment IDE decisionmaking, but

believes that the agency has already

addressed this concern adequately in

the criteria established under

§ 812.36(b)(1) and (b)(2), in conjunction

with the bases for disapproval or

withdrawal of a treatment IDE under

§ 812.36(d)(2)(iii) and (d)(2)(iv). In the

example FDA provided, clinical data

from the general IDE showed that

nonthoracotomy (transvenous)

defibrillation leads addressed an unmet

medical need in a defined patient

population, i.e., those patients with

postradiation mediastinal fibrosis who

could not undergo surgical placement of

the approved defibrillation leads. FDA’s

evaluation of a treatment IDE in this

context would necessarily include full

consideration of the potential risks and

benefits of the device, given the clinical

and other scientific information known

to date, in light of the seriousness of the

disease or condition and availability of

alternative therapies.

In addition, FDA notes that once a

treatment IDE is made available

generally, there still remains a risk/

benefit consideration for individual

patients within the intended patient

population. In this situation, the

physician and patient would need to

decide, based on the available clinical

information and the individual patient’s

condition, whether the treatment use

device would expose that patient to an

acceptable level of risk. This is a caseby-case decision to be made by the

doctor and the patient.

2. A comment stated that the

preamble to the proposed rule could be

improved by providing fewer ‘‘disease’’

examples, and providing more examples

of surgical uses, implants, or injury/

accident references, where devices

might be utilized.

In response to the recommendation,

the agency is providing the following

examples to better explain when a

treatment IDE would be appropriate.

One example of an approved device

that would have met the treatment use

criteria is an interactive wound and

burn dressing indicated for use as a

temporary covering for surgically

excised full-thickness and deep partialthickness thermal burns in patients who

require such a temporary covering prior

to autograft placement. This device

would have met the treatment IDE

criteria because: (1) The device is

intended to treat immediately lifethreatening conditions, i.e., fullthickness and deep partial-thickness

thermal burns; (2) there were no

comparable or satisfactory alternative

devices (the only alternative therapy

(cadaver skin) is severely limited in

supply and has a risk of disease

transmission); (3) the device was under

investigation in a controlled clinical

trial for the same use under an approved

IDE; and (4) the sponsor of the

controlled clinical trial was pursuing

marketing approval of the device with

due diligence.

Another example of an approved

device that would have met the

treatment use criteria is the low density

lipoprotein (LDL) apheresis system

indicated for use in performing low

density lipoprotein cholesterol (LDL–C)

apheresis to acutely remove LDL–C from

the plasma of the following high risk

patient populations for whom diet has

been ineffective and maximum drug

therapy has either been ineffective or

not tolerated: functional

hypercholesterolemic homozygotes with

LDL–C > 500/mg/dl; functional

hypercholesterolemic heterozygotes

with LDL–C ≥ 300 mg/dl; and functional

hypercholesterolemic heterozygotes

with LDL–C ≥ 200 mg/dl and

documented coronary heart disease.

This device would have met the

treatment IDE criteria because: (1) The

device is intended to treat serious

conditions, i.e., functional

hypercholesterolemic homozygotes/

heterozygotes with certain LDL–C

levels; (2) there were no comparable or

satisfactory alternative devices (the only

alternative therapies available to treat

these high risk patients are diet, which

can be ineffective, and maximum drug

therapy, which can be either ineffective

or not tolerated); (3) the device was

under investigation in a controlled

clinical trial for the same use under an

approved IDE; and (4) the sponsor of the

controlled clinical trial was pursuing

marketing approval of the device with

due diligence.

Again, these are illustrative examples

only.

3. Two comments requested that FDA

discuss the differences and

relationships among treatment IDE’s,

emergency use devices, the Office of

Device Evaluation’s (ODE)

memorandum on ‘‘Continued Access to

Investigational Devices During

Premarket Approval Application (PMA)

Preparation and Review,’’ expedited

review, and custom devices. One of the

comments recommended that CDRH

issue separate guidance delineating the

differences and relationships among

these policies/regulations.

With the exception of custom devices,

FDA has issued guidance on all of the

topics identified in the previous

comments. The agency has provided the

following summary of each of these

policies and has also identified key

similarities and differences between

them and the treatment IDE regulation.

1. ‘‘Guidance for the Emergency Use of

Unapproved Medical Devices’’

Under FDA’s ‘‘Guidance for the

Emergency Use of Unapproved Medical

Devices’’ (hereinafter referred to as the

Emergency Use Policy), that appeared in

the Federal Register of October 22, 1985

(50 FR 42866), an unapproved medical

device is a device that is utilized for a

purpose, condition, or use for which the

device requires, but does not have, an

approved application for premarket

approval under section 515 of the

Federal Food, Drug, and Cosmetic Act

(the act) (21 U.S.C. 360e) or an approved

IDE under section 520(g) of the act (21

U.S.C. 360j(g)). Normally, an

unapproved device may be used in

human subjects only if it is approved for

clinical testing under an IDE.

Emergency use of an unapproved

device, however, may occur when an

IDE for the device does not exist, when

a physician wants to use the device in

a way not approved under the IDE, or

when a physician or institution is not

approved under the IDE.

The Emergency Use Policy is different

from the treatment IDE regulation in

significant ways. First, the Emergency

Use Policy is designed for just that—

emergencies—and is applied on an

individual patient basis. To qualify for

emergency use, the treating physician

must conclude that: (1) The patient has

a life-threatening condition that needs

immediate treatment; (2) no generally

acceptable alternative treatment for the

condition exists; and (3) there is no time

to obtain FDA approval due to the

immediate need of the patient.

By contrast, treatment use of an

investigational device is designed to

operate prospectively under a protocol

that may cover a large number of

patients, so that a treatment IDE

application would be submitted to and

approved by the agency before patients

are treated with the device. Also, the

Emergency Use Policy is limited to lifethreatening situations, whereas a

treatment IDE allows use of the device

for serious diseases in addition to those

that are immediately life-threatening.
Federal Register / Vol. 62, No. 181 / Thursday, September 18, 1997 / Rules and Regulations 48943

2. ‘‘Continued Access to Investigational

Devices During Premarket Approval

Application (PMA) Preparation and

Review’’

Under ODE’s policy entitled

‘‘Continued Access to Investigational

Devices During PMA Preparation and

Review’’ (hereinafter referred to as the

Continued Access Policy), sponsors of

clinical investigations are permitted to

continue to enroll subjects while a

marketing application is being prepared

by the sponsor or reviewed by ODE if

there is: (1) A public health need for the

device; or (2) preliminary evidence that

the device is likely to be effective and

no significant safety concerns have been

identified for the proposed indication.

By allowing sponsors to continue to

enroll patients while a marketing

application is being prepared and/or

reviewed, the Continued Access Policy

allows increased patient access and the

collection of additional safety and

effectiveness data to support the

marketing application or address new

questions regarding the investigational

device. The Continued Access Policy

may be applied to any clinical

investigation that meets the criteria

identified above; however, it is intended

to be applied late in the device

development process, i.e., after the

controlled clinical trial has been

completed.

There is significant overlap between

the treatment IDE regulation and the

Continued Access Policy. Both the

Continued Access Policy and the

treatment IDE regulation are intended to

provide additional access to an

unapproved device, once preliminary

evidence regarding safety and

effectiveness is available to FDA.

However, because a treatment IDE can

be submitted earlier in the IDE process,

i.e., once promising evidence of safety

and effectiveness has been collected

under the IDE but while the clinical

study is ongoing, it could provide access

to a wider group of patients at an earlier

stage in the IDE process. The treatment

IDE regulation also has a more narrow

application than the Continued Access

Policy in that treatment use is intended

to address only those patients who have

an immediately life-threatening or

serious disease or condition whereas the

Continued Access Policy, which is

applied later in the process, may be

considered for any clinical study.

3.‘‘PMA/510(k) Expedited Review’’

According to ODE’s ‘‘PMA/510(k)

Expedited Review’’ policy (hereinafter

referred to as the Expedited Review

Policy), expedited review of a marketing

application may be considered for a

device intended for or meeting at least

one of the following criteria: (1) Lifethreatening or irreversibly debilitating

condition with no alternative modality.

The condition or potential condition/

disease is serious or life-threatening or

presents a risk of serious morbidity and

no alternative legally marketed

diagnostic/therapeutic modality exists;

(2) life-threatening or irreversibly

debilitating condition with approved

alternatives, but where the new device

provides for clinically important earlier

diagnosis or significant advances in

safety and/or effectiveness over the

existing alternatives; (3) a revolutionary

(breakthrough) device, i.e., the device

represents a clear clinically meaningful

advantage over existing technology

defined as having a major increase in

effectiveness or reduced risk compared

to existing technology; and (4) a specific

public health benefit, i.e., the

availability of the device is otherwise in

the best interest of the public health.

Under the Expedited Review Policy,

granting expedited review ensures that

the marketing application will receive

priority review, i.e., review before other

pending PMA’s or 510(k)s. Therefore,

the Expedited Review Policy differs

from the treatment IDE regulation in

that expedited review pertains to the

review priority given to marketing

applications, whereas treatment use

pertains to expanding access to patients

of a device during the course of the

clinical investigation.

As stated previously, FDA intends to

interpret the criteria for treatment IDE’s

in the same way CDRH applies the

criteria for expedited review of

marketing applications. FDA anticipates

that most requests for treatment use

would involve devices that meet the

criteria for expedited review, i.e., the

device: (1) Is intended for a lifethreatening or irreversibly debilitating

condition for which there is no

alternative therapy or for which the

device provides a significant advance in

safety and effectiveness over the

existing alternatives; or (2) meets a

specific public health need. These

criteria are similar because the same

public health considerations that justify

expanding access to an investigational

product also justify giving a marketing

application for that device top priority.

In both cases, the likely patient benefit

warrants special policies.

4. Custom Devices

FDA has not issued a guidance

document concerning custom devices,

but a custom device is defined in

§ 12.3(b). A custom device is one that:

(1) Necessarily deviates from devices

generally available or from an applicable

performance standard or premarket approval

requirement in order to comply with the

order of an individual physician or dentist;

(2) is not generally available to, or generally

used by, other physicians or dentists; (3) is

not generally available in finished form for

purchase or for dispensing upon

prescription; (4) is not offered for commercial

distribution through labeling or advertising;

and (5) is intended for use by an individual

patient named in the order of a physician or

dentist, and is to be made in a specific form

for that patient, or is intended to meet the

special needs of the physician or dentist in

the course of professional practice.

Because all the preceding criteria must

be met for a device to qualify as a

custom device and because the use of a

custom device is exempt from the IDE

regulation (§ 812.2(c)(7)), the provision

usually covers only a single device and

is not frequently applicable.

FDA believes that the existing

guidance documents on these topics,

together with the preceding discussion,

satisfies the concern raised in the

comment.

4. One comment suggested that FDA

add a reference to the Emergency Use

Policy to permit shipment of devices in

emergency situations such as those in

21 CFR 312.36. The same comment

asked FDA to clarify that IRB review is

not necessary in the case of emergency

use for a single patient.

Emergency use for a single patient is

governed by FDA’s Emergency Use

Policy. As noted previously in the

Emergency Use Policy, an unapproved

device may be shipped without FDA

approval to a physician who is faced

with an emergency situation that meets

the outlined criteria.

The comment’s request for

clarification regarding IRB review in the

case of an emergency use for a single

patient is also addressed in the

Emergency Use Policy. Under this

guidance, in the event that a device is

needed to treat a life-threatening disease

or condition, FDA would expect the

physician to follow as many patient

protection procedures as possible. These

include, among other things, obtaining

the IRB chairperson’s concurrence and

complying with the institution’s

requirements regarding such use.

Therefore, IRB approval for emergency

use would only be required if such

review were necessary under the

procedures of that particular institution.

5. One comment raised a concern that

the treatment IDE review procedures

and reporting requirements will create

additional work that will delay FDA’s

review of PMA’s.

FDA disagrees. As stated in the

preamble to the proposed, FDA

anticipates a limited number of

treatment IDE’s and has estimated it is
48944 Federal Register / Vol. 62, No. 181 / Thursday, September 18, 1997 / Rules and Regulations

likely to receive six annually. (See 61

FR 66954 at 66959.) Although these

treatment IDE’s will create additional

work for the agency, such a limited

number will not cause delays in FDA’s

review of PMA’s. Moreover, in the 10

years since the treatment IND rule was

issued, the agency has not experienced

delays in the review of new drug

applications due to the additional work

created by the treatment IND review

procedures and reporting requirements.

B. Specific Comments

1. A comment noted that § 812.36(a)

defines an ‘‘immediately life-threatening

disease or condition,’’ but does not

define a ‘‘serious disease or condition.’’

The comment asserted that the term

‘‘serious’’ disease or condition should

either be defined in or omitted from the

regulation because it is likely to be a

‘‘gray area’’ with regard to interpretation

of the regulation. The comment

preferred that the term ‘‘serious’’ be

omitted because the diseases intended

to be included under this definition, i.e.,

early stages of breast cancer,

proliferative vitreoretinopathy, and

advanced Parkinson’s disease, would

meet the definition of an ‘‘immediately

life-threatening disease or condition.’’

FDA does not intend to add a

definition of ‘‘serious disease or

condition’’ to the final rule. The agency

has concluded that defining the term

‘‘serious disease or condition’’ could be

unduly restrictive and limit the agency’s

discretion when determining whether

certain stages of a disease or condition

are ‘‘serious.’’ In addition, the agency’s

experience under the treatment IND

regulation demonstrates that a

definition is unnecessary; the agency

has been successful in identifying the

serious diseases or conditions

appropriate to treatment IND even

though the term is undefined in that

regulation. If a sponsor is not sure of

whether a particular stage of a disease

or condition would be considered

‘‘serious,’’ the sponsor should contact

the appropriate review division in ODE

for clarification.

FDA did not omit the term ‘‘serious

disease or condition’’ from the

regulation because, contrary to the

comment’s assertion, the diseases or

conditions intended to be included

under the serious disease or condition

definition would not meet the definition

of immediately life-threatening disease

or condition in all circumstances. For

example, advanced Parkinson’s disease

would normally be considered a serious

disease or condition rather than an

immediately life-threatening disease

state, i.e., there is not a reasonable

likelihood that death will occur within

a matter of months nor is premature

death likely without early treatment.

2. One comment stated that the

definition of ‘‘immediately lifethreatening disease or condition’’ is

severe in its limitations. As a result, the

comment suggested that FDA adopt the

definition used for expedited review,

i.e., a condition or disease that is

irreversibly debilitating with no

alternative treatment modalities or

meets a specific public health need. The

comment believed that this would cover

serious disease states but not restrict

those diseases to those likely to result in

imminent death. The comment stated

that this definition is appropriate

because FDA intends to interpret the

criteria for treatment use IDE’s in the

same way FDA applies the criteria for

expedited review of PMA’s.

FDA disagrees with the

recommendation to modify the

definition of ‘‘immediately lifethreatening disease or condition.’’ As

stated in the preamble to the proposed

rule, with minor exceptions, the

treatment IDE regulation parallels the

treatment IND regulation and extends

those provisions to cover treatment use

of investigational devices. FDA does not

believe that this definition will be

problematic in light of the fact that FDA

is adopting the same definition in the

treatment IDE regulation that is used in

the treatment IND regulation. Since the

implementation of the treatment IND

regulation in 1987, FDA has not had any

experience that would indicate that the

definition is severe in its limitations.

The agency also believes that adopting

the same definition of immediately lifethreatening disease or condition in both

treatment regulations will promote

consistency.

3. One comment recommended that

FDA expand the definition of an

‘‘immediately life-threatening disease or

condition’’ to include diseases or

conditions that threaten the integrity of

the nervous system. According to the

comment, an investigational device

might prevent devastating neurological

illness even though death is not

imminent.

FDA disagrees with expanding the

definition of immediately lifethreatening disease or condition to

include neurological illnesses not

resulting in imminent death because the

agency intended that such illnesses be

included under the definition of a

serious disease or condition. For

example, as stated in the proposed rule,

advanced Parkinson’s disease, which

causes severe neurological impairment,

would be considered a serious disease

or condition appropriate for a treatment

IDE. (See 61 FR 66954 at 66955.)

Likewise, advanced multiple sclerosis

would also be considered a serious

disease or condition because, although

it does not result in imminent death, it

causes severe neurological impairment.

4. A comment requested that

§ 812.36(b)(3) be clarified to read that

patients who were in the ‘‘parent’’

controlled clinical trial under the

approved IDE be allowed to continue

under the treatment IDE, after the parent

controlled clinical trial has been

completed, but before FDA approval is

received. The comment referred to the

July 15, 1996, memorandum entitled,

‘‘Continued Access to Investigational

Devices During Premarket Approval

Application (PMA) Preparation and

Review.’’

FDA agrees that patients who were

originally enrolled in the ‘‘parent’’

controlled clinical trial, which is now

complete, could qualify for continued

access to the device under the

Continued Access Policy described in

section III.A.2 of this document. The

agency does not believe a change to the

regulation is needed to accommodate

this situation.

5. In the preamble to the proposed

rule in § 812.36(e), FDA solicited

comments on the appropriate approach

to take with respect to charging for

devices under treatment IDE’s. (See 61

FR 66954 at 66958.) Specifically, FDA

posed the following questions in

connection with § 812.36(e):

1. Do the IDE and Treatment IDE

Regulations Provide Sufficient

Protection Against Commercialization?

FDA received one comment, which

stated that the IDE regulation, the

proposed rule on treatment IDE’s,

market forces, and expedited review

procedures, where appropriate, protect

against commercialization of devices

distributed under IDE’s or treatment

IDE’s. First, according to the comment,

§§ 812.40 and 812.43 and proposed

§ 812.36(e) limit distribution of

investigational devices by ensuring that

only qualified investigators receive the

device. Failure of the manufacturer to

control distribution often draws

attention from competitors who report

such violations to FDA, thus adding an

additional commercialization control

element. Secondly, the comment

pointed out that § 812.7(c) and proposed

§ 812.36(e) prohibit sponsors from

unduly prolonging an investigation.

Thirdly, according to the comment,

proposed § 812.36(f) adds another layer

of control over commercialization of

treatment investigational devices by

requiring sponsors to provide a

description of their efforts to pursue

marketing approval/clearance of the

device in the progress reports which are
Federal Register / Vol. 62, No. 181 / Thursday, September 18, 1997 / Rules and Regulations 48945

to be submitted to both FDA and the

IRB’s. Finally, the comment noted that

if a device meets the criteria for a

treatment IDE, it will also meet the

criteria for expedited review of PMA’s.

Accordingly, the comment suggested

that in cases where a treatment IDE is

approved, expedited review of the PMA

should be automatically granted.

Expedited reviews should add another

layer of control against clinical trial

prolongation once the trial has been

completed and the PMA is pending

because it is anticipated that the PMA

would be reviewed more quickly.

FDA agrees that the IDE and treatment

IDE regulations should provide

sufficient protection against

commercialization of the investigational

device. In the general IDE regulation,

§ 812.7(c) prohibits sponsors from

unduly prolonging an investigation,

§ 812.43(b) limits distribution of the

investigational device to qualified

investigators, and § 812.150(b)(5)

requires the submission of progress

reports to FDA and the IRB’s. Under

§ 812.36(e), sponsors of treatment IDE’s

are subject to all of the requirements of

the general IDE regulation. Sponsors of

treatment IDE’s are also subject to

§ 812.36(f), which requires sponsors to

describe their efforts to pursue

marketing approval/clearance of the

device in their progress reports.

2. Is It Appropriate for Sponsors to

Recover Research and Development

Costs in Addition to the Costs of

Manufacturing and Handling of an

Investigational Device?

One comment stated that it is not

appropriate for sponsors to recover

research and development costs when

charging for devices under a treatment

IDE because the assignment of such

costs to the limited number of devices

under the treatment IDE will result in

the device being extremely costly and,

therefore, not used. The comment also

stated that delaying recovery of the

research and development costs until

device approval will provide an

incentive for the sponsor to obtain such

approval.

Three other comments stated that

sponsors should be able to recover

research and development costs as well

as manufacturing and handling costs, as

is the case with IDE’s in general.

According to two of the comments, not

allowing sponsors to recover these costs

will result in a reduction of the number

of IDE’s and treatment IDE’s. One of the

comments noted that charging a lower

price for a device under a treatment IDE

than under the IDE in general could

dissuade sponsors from submitting

treatment IDE applications. According

to the second comment, the majority of

devices that would be under treatment

IDE’s are breakthrough technologies

developed by small start-up and

medium sized companies, which often

depend upon venture capital to develop

new devices. The comment further

asserted that these companies cannot

afford the costs of a clinical trial unless

they are compensated. Alternatively, the

comment noted that larger companies

may opt not to apply for an IDE or

treatment IDE if the costs of research,

development, manufacturing, and

handling as well as the expense of the

trial itself cannot be adequately

recovered by postapproval sales.

Upon consideration of the comments,

FDA has decided that it is not

appropriate for sponsors to recover

research and development costs under

treatment IDE’s. FDA acknowledges that

the investment cost of developing a

device may be high and that the actual

cost recovered by the sponsor may be a

factor in proceeding with development

of the device. (See 43 FR 20726 at

20742.) Nevertheless, it is a wellestablished principle, that no profit

should be made on experimental

devices. (See 45 FR 3732 at 3741,

January 18, 1980; Medical Devices;

Procedures for IDE’s; Final rule.) Based

on this principle, and on the fact that

research and development expenditures

may be recovered under the general IDE,

FDA has concluded that cost recovery

during a treatment IDE should be

limited to those direct costs of

supplying the device for the treatment

use, i.e., manufacturing and handling

costs. In this way, manufacturers would

not incur additional costs as a result of

participating in a treatment IDE. FDA

recognizes, however, that manufacturing

and handling costs per unit may be

higher during production of a limited

number of units than during full

commercial distribution.

3. Should Prior FDA Approval for

Charging Be Required?

One comment stated that

§ 812.20(b)(8), which requires a sponsor

to justify why the price charged for the

device does not exceed research,

development, manufacturing, and

handling costs, should also be part of

the treatment IDE application. Another

comment believed that sponsors should

inform FDA in the treatment IDE

application if and how much they

intend to charge for the device. The

comment stated that the sponsor should

provide a justification for the charge

based on actual manufacturing and

handling costs only, and FDA approval

of the charge would be implied when

FDA approves the treatment IDE

application. Another comment stated

that prior FDA approval of costs is not

appropriate because such approval

would result in a longer treatment IDE

approval process.

FDA agrees that, as with IDE’s in

general, prior approval for charging for

the treatment use device should be

required. Therefore, FDA has added

§ 812.36(c)(1)(x), which states that if the

device is to be sold, the treatment IDE

sponsor is required to submit the price

charged for the treatment use device and

a statement indicating that the price is

based on manufacturing and handling

costs only.

FDA disagrees that prior approval of

costs will result in a longer approval

process for treatment IDE applications.

Under § 812.30(a) of the general IDE

regulation, FDA is required to notify a

sponsor in writing of its decision to

approve the investigation as proposed,

approve it with modifications, or

disapprove it within 30 days of receipt

of the application. That review includes

a review of the sponsor’s decision to

charge for the device. Under

§ 812.36(d)(1), FDA is also required to

review treatment IDE applications

within the 30-day timeframe; there is no

reason to assume the approval process

for treatment IDE’s will be protracted.

6. According to one comment on

§ 812.36(f), quarterly reports to the IRB’s

and FDA should be subject to

restrictions intended to protect

confidential information.

FDA agrees that treatment IDE

progress reports ordinarily should be

kept confidential. As provided for under

§ 812.38(a) of the IDE regulation in

general, FDA will not disclose the

existence of an IDE until FDA approves

a marketing application for the device

unless its existence has previously been

publicly disclosed or acknowledged.

Even if the existence of an IDE has been

disclosed or acknowledged by the

sponsor, as is likely with respect to

treatment IDE’s, the information

contained in an IDE or treatment IDE,

including progress reports submitted

under § 812.36, is generally protected

from disclosure.

A second comment on proposed

§ 812.36(f) alleged that quarterly

reporting is an unnecessary burden on

sponsors. The comment noted that the

parallel IND regulation does not require

additional quarterly reporting. The

comment also alleged that this

requirement conflicts with the

Paperwork Reduction Act, in that it

adds a layer of paperwork never before

required for IDE’s. According to the

comment, the adverse reporting

procedures for IDE’s would provide

enough safeguards for treatment IDE’s

without adding a new layer of

paperwork.
48946 Federal Register / Vol. 62, No. 181 / Thursday, September 18, 1997 / Rules and Regulations

FDA agrees in part with the comment.

Upon reconsideration, FDA has

concluded that such frequent reporting,

in addition to the annual reporting

requirement under the regular IDE, is

not necessary. Therefore, FDA has

revised the reporting requirements to

include those elements needed to

monitor the size and scope of the

treatment IDE, and to assess the

sponsor’s due diligence in seeking

marketing approval. Under final

§ 812.36(f), the sponsor of a treatment

IDE is required to submit progress

reports on a semi-annual basis to all

reviewing IRB’s and FDA until the filing

of a marketing application. These

reports shall be based on the period of

time since initial approval of the

treatment IDE and shall include only

three items: (1) The number of patients

treated with the device under the

treatment IDE; (2) the names of the

investigators participating in the

treatment IDE; and (3) a brief

description of the sponsor’s efforts to

pursue marketing approval/clearance of

the device. Upon filing of a marketing

application, progress reports will be

required to be submitted annually in

accordance with § 812.150(b)(5). At the

sponsor’s option, the annual report for

the treatment IDE may be combined

with the annual report for the general

IDE or may be submitted separately.

FDA disagrees that the submission of

progress reports conflicts with the

Paperwork Reduction Act. In

accordance with § 812.150(b)(4), the

sponsor of an IDE is required to submit

to FDA, at 6-month intervals, a current

list of all investigators participating in

the investigation. Furthermore, under

§ 812.150(b)(5), at regular intervals and

at least yearly, the sponsor of an IDE is

required to submit progress reports to

all reviewing IRB’s and FDA. Under

final § 812.36(f), the sponsor of a

treatment IDE will be required to submit

reports on the treatment use at 6 month

intervals, the same frequency required

for updating information about

investigators of controlled clinical trials.

Although the content of the semi-annual

report differs, the information required

is minimal, but nevertheless necessary,

to maintain control over the treatment

use. Therefore, FDA believes that semiannual reporting for treatment IDE’s is

consistent with the reporting

requirements for IDE’s in general and

does not conflict with the Paperwork

Reduction Act.

Finally, FDA agrees that the adverse

event reporting requirements for IDE’s

in general should provide adequate

patient protection for treatment IDE’s.

(See § 812.150(b)(1).) Under final

§ 812.36(f), semi-annual progress reports

for treatment IDE’s are no longer

required to include a summary of

anticipated and unanticipated adverse

device effects because this information

will be captured in the annual progress

reports of § 812.150(b)(5) and by the 10-

day reporting requirements of

§ 812.150(b)(1).

IV. Environmental Impact

The agency has determined under 21

CFR 25.24(a)(8) that this final rule is of

a type that does not individually or

cumulatively have a significant effect on

the human environment. Therefore,

neither an environmental assessment

nor an environmental impact statement

is required.

V. Analysis of Impacts

FDA has examined the impacts of the

final rule under Executive Order 12866

and the Regulatory Flexibility Act (5

U.S.C.601–612) (as amended by subtitle

D of the Small Business Regulatory

Fairness Act of 1996 (Pub. L. 104–121),

and the Unfunded Mandates Reform Act

of 1995 (Pub. L. 104–4). Executive Order

12866 directs agencies to assess all costs

and benefits of available regulatory

alternatives and, when regulation is

necessary, to select regulatory

approaches that maximize net benefits

(including potential economic,

environmental, public health and safety

and other advantages; distributive

impacts; and equity). The agency

believes that this final rule is consistent

with the regulatory philosophy and

principles identified in the Executive

Order. In addition, the final rule is not

a significant regulatory action as defined

by the Executive Order and so is not

subject to review under the Executive

Order.

The Regulatory Flexibility Act

requires agencies to analyze regulatory

options that would minimize any

significant impact of a rule on small

entities. Because relevant information

should already be available to FDA in

the sponsor’s IDE, limited additional

information relative to the safety and

effectiveness of the device for treatment

use would be required in the treatment

IDE application. In fact, applications for

treatment use may be submitted as

supplements to the IDE for the

controlled clinical trial in order to

eliminate additional burden that could

result if sponsors were required to

submit new applications. As a result,

this final rule will not impose

significant economic impact on any

small entities. The Commissioner,

therefore, certifies that the final rule

will not have a significant economic

impact on a substantial number of small

entities. In addition, this final rule will

not impose costs of $100 million or

more on either the private sector or

State, local, and tribal governments in

the aggregate, and therefore a summary

statement of analysis pursuant to

section 202(a) of the Unfunded

Mandates Reform Act of 1995 is not

required.

VI. Paperwork Reduction Act of 1995

This final rule contains information

collections requirements that are subject

to review by the OMB under the

Paperwork Reduction Act of 1995 (44

U.S.C. 3501–3520). The title,

description, and respondent description

of the information collection

requirements are shown below with an

estimate of the annual reporting and

recordkeeping burden. Included in the

estimate is the time for reviewing

instructions, searching existing data

sources, gathering and maintaining the

data needed, and completing and

reviewing the collection of information.

Title: Investigational Device

Exemptions; Treatment Use.

Description: This regulation

establishes the procedures for the

treatment use of investigational devices.

The purpose of this regulation is to

permit broader availability of

investigational devices to treat serious

or immediately life-threatening diseases

or conditions for which there are no

satisfactory alternative treatments.

Under the final rule, treatment use of an

investigational device would only be

considered when the following criteria

are satisfied: (1) The device is intended

to treat or diagnose a serious or

immediately life-threatening disease or

condition; (2) there is no comparable or

satisfactory alternative device or other

therapy available to treat or diagnose

that stage of the disease or condition in

the intended patient population; (3) the

device is under investigation in a

controlled clinical trial for the same use

under an approved IDE, or all clinical

trials have been completed; and (4) the

sponsor of the controlled clinical trial is

pursuing marketing approval/clearance

of the investigational device with due

diligence.

The burdens connected with the

requirements for applications for

treatment use are limited, but consistent

with protecting patient safety and

monitoring proper use. Each application

would include, among other things, an

explanation of the rationale for the use

of the device; the criteria for patient

selection; a description of clinical

procedures, laboratory tests, or other

measures to be used to monitor the

effects of the device and to minimize

risk; written procedures for monitoring

the treatment use; information that is
Federal Register / Vol. 62, No. 181 / Thursday, September 18, 1997 / Rules and Regulations 48947

relevant to the safety and effectiveness

of the device for the intended treatment

use; and a written protocol describing

the treatment use. Sponsors of an

approved treatment IDE would be

required to submit semi-annual progress

reports until a marketing application is

filed, and annual reports thereafter.

Description of Respondents:

Businesses or other for profit

organizations.

ESTIMATED ANNUAL REPORTING BURDEN

21 CFR Section No. of

Respondents

Annual

Frequency per

Response

Total Annual

Responses

Hours per

Response Total Hours

812.36(c) 6 1 6 120 720

812.36(c) 6 2 12 20 240

Total 960

There are no operating and maintenance costs or capital costs associated with this information collection.

Based on its experience with the

treatment use of drugs and FDA’s

knowledge of the types of devices that

may meet the treatment use criteria,

FDA estimates that an average of six

applications will be submitted each

year. Based upon FDA’s knowledge of

the preparation of IDE’s, FDA estimates

that it will take approximately 120

hours to prepare a treatment use IDE.

Thus, the total annual burden for

preparing applications will be 720

hours.

Prior to the effective date of this final

rule, FDA will publish a notice in the

Federal Register announcing OMB’s

decision to approve, modify, or

disapprove the information collection

requirements in this final rule. An

agency may not conduct or sponsor, and

a person is not required to respond to,

a collection of information unless it

displays a currently valid OMB control

number.

List of Subjects in 21 CFR Part 812

Health records, Medical devices,

Medical research, Reporting and

recordkeeping requirements.

Therefore, under the Federal Food,

Drug, and Cosmetic Act, and under

authority delegated to the Commissioner

of Food and Drugs, 21 CFR part 812 is

amended as follows:

PART 812—INVESTIGATIONAL

DEVICE EXEMPTIONS

1. The authority citation for 21 CFR

part 812 continues to read as follows:

Authority: Secs. 301, 501, 502, 503, 505,

506, 507, 510, 513–516, 518–520, 701, 702,

704, 721, 801, 802, 803 of the Federal Food,

Drug, and Cosmetic Act (21 U.S.C. 331, 351,

352, 353, 355, 356, 357, 360, 360c–360f,

360h–360j, 371, 372, 374, 379e, 381, 382,

383); secs. 215, 301,351, 354–360F of the

Public Health Service Act (42 U.S.C. 216,

241, 262, 263b–263n).

2. New § 812.36 is added to subpart B

to read as follows:

§ 812.36 Treatment use of an

investigational device.

(a) General. A device that is not

approved for marketing may be under

clinical investigation for a serious or

immediately life-threatening disease or

condition in patients for whom no

comparable or satisfactory alternative

device or other therapy is available.

During the clinical trial or prior to final

action on the marketing application, it

may be appropriate to use the device in

the treatment of patients not in the trial

under the provisions of a treatment

investigational device exemption (IDE).

The purpose of this section is to

facilitate the availability of promising

new devices to desperately ill patients

as early in the device development

process as possible, before general

marketing begins, and to obtain

additional data on the device’s safety

and effectiveness. In the case of a

serious disease, a device ordinarily may

be made available for treatment use

under this section after all clinical trials

have been completed. In the case of an

immediately life-threatening disease, a

device may be made available for

treatment use under this section prior to

the completion of all clinical trials. For

the purpose of this section, an

‘‘immediately life-threatening’’ disease

means a stage of a disease in which

there is a reasonable likelihood that

death will occur within a matter of

months or in which premature death is

likely without early treatment. For

purposes of this section, ‘‘treatment

use’’of a device includes the use of a

device for diagnostic purposes.

(b) Criteria. FDA shall consider the

use of an investigational device under a

treatment IDE if:

(1) The device is intended to treat or

diagnose a serious or immediately lifethreatening disease or condition;

(2) There is no comparable or

satisfactory alternative device or other

therapy available to treat or diagnose

that stage of the disease or condition in

the intended patient population;

(3) The device is under investigation

in a controlled clinical trial for the same

use under an approved IDE, or such

clinical trials have been completed; and

(4) The sponsor of the investigation is

actively pursuing marketing approval/

clearance of the investigational device

with due diligence.

(c) Applications for treatment use. (1)

A treatment IDE application shall

include, in the following order:

(i) The name, address, and telephone

number of the sponsor of the treatment

IDE;

(ii) The intended use of the device,

the criteria for patient selection, and a

written protocol describing the

treatment use;

(iii) An explanation of the rationale

for use of the device, including, as

appropriate, either a list of the available

regimens that ordinarily should be tried

before using the investigational device

or an explanation of why the use of the

investigational device is preferable to

the use of available marketed

treatments;

(iv) A description of clinical

procedures, laboratory tests, or other

measures that will be used to evaluate

the effects of the device and to minimize

risk;

(v) Written procedures for monitoring

the treatment use and the name and

address of the monitor;

(vi) Instructions for use for the device

and all other labeling as required under

§ 812.5(a) and (b);

(vii) Information that is relevant to the

safety and effectiveness of the device for

the intended treatment use. Information

from other IDE’s may be incorporated by

reference to support the treatment use;

(viii) A statement of the sponsor’s

commitment to meet all applicable

responsibilities under this part and part

56 of this chapter and to ensure

compliance of all participating

investigators with the informed consent

requirements of part 50 of this chapter;

(ix) An example of the agreement to

be signed by all investigators

participating in the treatment IDE and
48948 Federal Register / Vol. 62, No. 181 / Thursday, September 18, 1997 / Rules and Regulations

certification that no investigator will be

added to the treatment IDE before the

agreement is signed; and

(x) If the device is to be sold, the price

to be charged and a statement indicating

that the price is based on manufacturing

and handling costs only.

(2) A licensed practitioner who

receives an investigational device for

treatment use under a treatment IDE is

an ‘‘investigator’’ under the IDE and is

responsible for meeting all applicable

investigator responsibilities under this

part and parts 50 and 56 of this chapter.

(d) FDA action on treatment IDE

applications. (1) Approval of treatment

IDE’s. Treatment use may begin 30 days

after FDA receives the treatment IDE

submission at the address specified in

§ 812.19, unless FDA notifies the

sponsor in writing earlier than the 30

days that the treatment use may or may

not begin. FDA may approve the

treatment use as proposed or approve it

with modifications.

(2) Disapproval or withdrawal of

approval of treatment IDE’s. FDA may

disapprove or withdraw approval of a

treatment IDE if:

(i) The criteria specified in § 812.36(b)

are not met or the treatment IDE does

not contain the information required in

§ 812.36(c);

(ii) FDA determines that any of the

grounds for disapproval or withdrawal

of approval listed in § 812.30(b)(1)

through (b)(5) apply;

(iii) The device is intended for a

serious disease or condition and there is

insufficient evidence of safety and

effectiveness to support such use;

(iv) The device is intended for an

immediately life-threatening disease or

condition and the available scientific

evidence, taken as a whole, fails to

provide a reasonable basis for

concluding that the device:

(A) May be effective for its intended

use in its intended population; or

(B) Would not expose the patients to

whom the device is to be administered

to an unreasonable and significant

additional risk of illness or injury;

(v) There is reasonable evidence that

the treatment use is impeding

enrollment in, or otherwise interfering

with the conduct or completion of, a

controlled investigation of the same or

another investigational device;

(vi) The device has received

marketing approval/clearance or a

comparable device or therapy becomes

available to treat or diagnose the same

indication in the same patient

population for which the investigational

device is being used;

(vii) The sponsor of the controlled

clinical trial is not pursuing marketing

approval/clearance with due diligence;

(viii) Approval of the IDE for the

controlled clinical investigation of the

device has been withdrawn; or

(ix) The clinical investigator(s) named

in the treatment IDE are not qualified by

reason of their scientific training and/or

experience to use the investigational

device for the intended treatment use.

(3) Notice of disapproval or

withdrawal. If FDA disapproves or

proposes to withdraw approval of a

treatment IDE, FDA will follow the

procedures set forth in § 812.30(c).

(e) Safeguards. Treatment use of an

investigational device is conditioned

upon the sponsor and investigators

complying with the safeguards of the

IDE process and the regulations

governing informed consent (part 50 of

this chapter) and institutional review

boards (part 56 of this chapter).

(f) Reporting requirements. The

sponsor of a treatment IDE shall submit

progress reports on a semi-annual basis

to all reviewing IRB’s and FDA until the

filing of a marketing application. These

reports shall be based on the period of

time since initial approval of the

treatment IDE and shall include the

number of patients treated with the

device under the treatment IDE, the

names of the investigators participating

in the treatment IDE, and a brief

description of the sponsor’s efforts to

pursue marketing approval/clearance of

the device. Upon filing of a marketing

application, progress reports shall be

submitted annually in accordance with

§ 812.150(b)(5). The sponsor of a

treatment IDE is responsible for

submitting all other reports required

under § 812.150.

3. Section 812.150 is amended by

revising paragraph (b)(5) to read as

follows:

§ 812.150 Reports.

* * * * *

(b) * * *

(5) Progress reports. At regular

intervals, and at least yearly, a sponsor

shall submit progress reports to all

reviewing IRB’s. In the case of a

significant risk device, a sponsor shall

also submit progress reports to FDA. A

sponsor of a treatment IDE shall submit

semi-annual progress reports to all

reviewing IRB’s and FDA in accordance

with § 812.36(f) and annual reports in

accordance with this section.

* * * * *

Dated: August 20, 1997.

William B. Schultz,

Deputy Commissioner for Policy.

[FR Doc. 97–24735 Filed 9–17–97; 8:45 am]

BILLING CODE 4160–01–F

FEDERAL MEDIATION AND

CONCILIATION SERVICE

29 CFR Part 1404

Expedited Arbitration

AGENCY: Federal Mediation and

Conciliation Service.

ACTION: Final rule.

SUMMARY: This addition to the

arbitration regulations is intended to

create a new service know as ‘‘expedited

arbitration.’’ This service will provide a

streamlined arbitration process for nonprecedential and non-complex

grievance arbitration cases while

encouraging the parties to select new

arbitrators in order to enhance their

career development. This new service is

the result of specific recommendations

of the Arbitration Focus Group by FMCS

on March 27, 1997.

EFFECTIVE DATE: This regulation is

effective October 1, 1997.

FOR FURTHER INFORMATION CONTACT:

Peter Regner, 202–606–8181.

SUPPLEMENTARY INFORMATION: The

Federal Mediation and Conciliation

Service, in an effort to receive public

input on its proposed new service of

expedited arbitration, published the

draft version of its proposed rule in the

June 30, 1997 issue of the Federal

Register (62 FR 35112). Nine arbitrators

responded in writing to the proposed

rule. In general, all individuals

supported the new service. Almost all of

them, however, objected to limiting

eligibility to deliver this service to those

arbitrators listed on the FMCS Roster of

Arbitrators for five (5) years or less.

More specific information about the

public response is contained in the

following section-by-section analysis.

Subpart D—Expedited Arbitration

Section 1404.17 Policy

The first section was further clarified

by adding the ‘‘unique’’ issues would

also be inappropriate for expedited

arbitration, as would complex or

precedential issues.

Section 1404.18 Procedures for

Requesting Expedited Panels

Subsection (d). The procedures for

requesting expedited arbitrators were

modified slightly by allowing the parties

to select a second arbitrator from the

panel submitted to them in the event

their first choice was not available to

serve. This was in response to one

comment opposing a direct appointment

by FMCS in the event the original

arbitrator selected by the parties was not

able to serve. The parties now have an

additional option.