17208 Federal Register / Vol. 60, No. 65 / Wednesday, April 5, 1995 / Rules and Regulations

(ii) * * *

(D) * * *

(2) Quantitative information

comparing the level of cholesterol in the

product per specified weight with that

of the reference food that it replaces

(e.g., ‘‘Cholesterol lowered from 30 mg

to 22 mg per 3 oz of product.’’) is

declared adjacent to the most prominent

claim or to the nutrition label, except

that if the nutrition label is on the

information panel, the quantitative

information may be located elsewhere

on the information panel in accordance

with § 101.2.

* * * * *

Dated: March 24, 1995.

William B. Schultz,

Deputy Commissioner for Policy.

[FR Doc. 95–8067 Filed 3–31–95; 4:32 pm]

BILLING CODE 4160–01–P

21 CFR Part 876

[Docket No. 92N–0382]

Gastroenterology-Urology Devices;

Effective Date of Requirement for

Premarket Approval of Testicular

Prosthesis

AGENCY: Food and Drug Administration,

HHS.

ACTION: Final rule.

SUMMARY: The Food and Drug

Administration (FDA) is issuing a final

rule to require the filing of a premarket

approval application (PMA) or a notice

of completion of a product development

protocol (PDP) for the testicular

prosthesis, a generic type of a surgically

implanted medical device intended to

simulate the presence of a testicle

within the male scrotum. Commercial

distribution of this device must cease,

unless a manufacturer or importer has

filed with FDA a PMA or a notice of

completion of a PDP for its version of

the testicular prosthesis within 90 days

of the effective date of this regulation.

This regulation reflects FDA’s exercise

of its discretion to require a PMA or

notice of completion of a PDP for

preamendments devices.

EFFECTIVE DATE: April 5, 1995.

FOR FURTHER INFORMATION CONTACT:

Mark D. Kramer, Center for Devices and

Radiological Health (HFZ–470), Food

and Drug Administration, 9200

Corporate Blvd., Rockville, MD 20850,

301–594–2194.

SUPPLEMENTARY INFORMATION:

I. Introduction

In the Federal Register of January 6,

1989 (54 FR 550), the agency identified

the testicular prosthesis as one of the

high-priority devices that would be

subject to PMA or PDP requirements.

This rulemaking is consistent with

FDA’s stated priorities and Congress’

requirement that class III devices are to

be regulated by FDA’s premarket

approval review. This action is being

taken under the Medical Device

Amendments of 1976 (Pub. L. 94–295).

The preamble to this rule responds to

comments received on the proposal to

require the filing of a PMA or a notice

of completion of a PDP.

This regulation is final upon

publication and requires a PMA or a

notice of completion of a PDP for all

testicular prostheses classified under

§ 876.3750 (21 CFR 876.3750) and all

devices that are substantially equivalent

to them. A PMA or a notice of

completion of a PDP for these devices

must be filed with FDA within 90 days

of the effective date of this regulation.

(See section 501(f)(1)(A) of the Federal

Food, Drug, and Cosmetic Act (the act)

(21 U.S.C. 351(f)(1)(A)).)

In the Federal Register of November

23, 1983 (48 FR 53012 at 53024), FDA

issued a final rule classifying the

testicular prosthesis into class III

(premarket approval). Section 876.3750

of FDA’s regulations setting forth the

classification of the testicular prosthesis

intended for medical use applies to: (1)

Any testicular prosthesis that was in

commercial distribution before May 28,

1976, and (2) any device that FDA has

found to be substantially equivalent to

a testicular prosthesis in commercial

distribution before May 28, 1976.

In the Federal Register of January 13,

1993 (58 FR 4116), FDA published a

proposed rule to require the filing,

under section 515(b) of the act (21

U.S.C. 360e(b)), of a PMA or notice of

completion of a PDP for the classified

testicular prosthesis and all

substantially equivalent devices

(hereinafter referred to as the January

1993 proposed rule). In accordance with

section 515(b)(2)(A) of the act, FDA

included in the preamble to the

proposal the agency’s proposed findings

regarding: (1) The degree of risk of

illness or injury designed to be

eliminated or reduced by requiring the

device to meet the premarket approval

requirements of the act, and (2) the

benefits to the public from use of the

device (58 FR 4116 at 4118).

The preamble to the January 1993

proposed rule also provided an

opportunity for interested persons to

submit comments on the proposed rule

and the agency’s proposed findings and,

under section 515(b)(2)(B) of the act (21

U.S.C. 360e(b)(2)(B)), provided the

opportunity for interested persons to

request a change in the classification of

the device based on new information

relevant to its classification. Any

petition requesting a change in the

classification of the testicular prosthesis

was required to be submitted by January

28, 1993. The comment period initially

closed on March 15, 1993. Because of

one request, FDA extended the

comment period for 60 days to May 14,

1993, to ensure adequate time for

preparation and submission of

comments (58 FR 15119, March 19,

1993).

FDA did not receive any petitions

requesting a change in the classification

of the testicular prosthesis. The agency

did receive a total of five comments in

response to the January 1993 proposed

rule. These represent comments from

individuals, manufacturers, and

professional societies. The comments

primarily addressed issues relating to

the significant risks associated with the

use of testicular prostheses, and the

preclinical and clinical data needed to

support a future PMA application.

II. Summary and Analysis of Comments

and FDA’s Response

A. General Comments

1. One comment stated that it appears

that FDA has chosen solid silicone

elastomer testicular implants for

disparate treatment from other silicone

implants, even though the basic

chemistry, ingredients, and many

manufacturing steps are very similar to

other class II implantable silicone

products. The comment requested that

FDA describe the differences between

silicone gel-filled and solid silicone

elastomer testicular implants, and

between silicone gel-filled mammary

prostheses and solid silicone elastomer

testicular prostheses.

FDA disagrees with this comment.

The testicular prosthesis was classified

into class III in 1983 because

insufficient information existed to

determine that general controls would

provide reasonable assurance of the

safety and effectiveness of the device or

to establish a performance standard to

provide this assurance. The possible

risks identified at the time of

classification included: (1) The possible

migration of silicone gel from the

interior of the prosthesis to adjacent

tissue (with or without rupture of the

silicone elastomer shell), and (2)

possible long-term toxic effects of the

silicone polymers from which the

prosthesis is fabricated. Therefore,

requiring premarket approval for the

testicular prosthesis is consistent with

the intent to regulate this device as a

class III device even in 1983. FDA notes

that no requests for a change in
Federal Register / Vol. 60, No. 65 / Wednesday, April 5, 1995 / Rules and Regulations 17209

classification based on new information

relevant to the classification of the

device were submitted in response to

the January 1993 proposed rule.

While FDA recognizes that some of

the risks of silicone gel testicular

prostheses may not necessarily apply to

the solid silicone elastomer testicular

prosthesis, the requirement that PMA’s

be submitted applies to the generic class

of device comprised of all testicular

prostheses. In addition, while FDA

recognizes that some of the risks of

silicone gel mammary prostheses may

not necessarily apply to solid or silicone

gel-filled testicular prostheses, the

testicular prosthesis is similar in

materials and construction to the

silicone gel-filled breast prosthesis and,

therefore, many of the risks associated

with the use of the silicone gel-filled

breast prosthesis may also be associated

with the solid silicone and silicone gelfilled testicular prosthesis.

2. One comment stated that FDA’s

inclusion of prospective clinical data

requirements in the proposed rule has

resulted in a timetable for ultimate PMA

submission that appears unreasonable

and creates an undue burden on

manufacturers. The comment stated

that, had firms initiated PMA studies

prior to the publication of the proposed

rule, they could not have anticipated the

new requirements.

FDA disagrees with this comment.

More than 10 years have passed since

these devices were classified into class

III by final regulation. Furthermore, the

risks to health detailed in the proposed

rule remain consistent with those

identified at the time of classification.

FDA believes that, consistent with

congressional intent, manufacturers

have had notice and ample opportunity

to gather the information necessary to

provide reasonable assurance of the

safety and effectiveness of these devices.

It is not responsible to suggest that

Congress intended manufacturers to

remain passive and not develop PMA’s

until a regulation became final. Indeed,

the act specifically requires submissions

30 months after the final classification

of a preamendments device or within 90

days of a final regulation, whichever is

later. (See section 501(f)(2)(B) of the

act). Thus, it is clear that Congress

intended that manufacturers anticipate a

final regulation and be prepared to

submit appropriate applications or

discontinue distribution of their

devices.

3. One comment stated that FDA’s

treatment of ear and testicular

prostheses (both cosmetic implants) is

disparate, because no psychological data

was required for ear prostheses, and

suggested that the proposed requirement

for psychological data is unprecedented

in the regulation process.

FDA disagrees with this comment. Ear

and testicular prostheses are different

devices, and have been classified by

different panels. Ear prostheses, which

are class II devices, were classified by

the General and Plastic Surgery Panel.

The review of such plastic surgery

prostheses, such as chin prostheses,

takes into consideration the quality of

life of the patient. FDA notes that

psychological data is only part of the

effectiveness evaluation outlined in the

proposed rule. Moreover, the request for

such data is not unprecedented. Such

data also were required in PMA’s for

silicone gel breast implants.

4. One comment stated that FDA

should recognize that the solid silicone

elastomer testicular prostheses available

today are much improved in quality and

are implanted using refined surgical

techniques that minimize many risks

implicated with their early use.

FDA acknowledges that the design of

certain testicular prostheses and

surgical techniques have evolved over

time. FDA believes that neither the

literature nor other data currently

available to FDA definitively describe

differences in the incidence of problems

attributable to device design and/or

variations in surgical procedures.

Sufficient information exists identifying

the risks detailed in the proposed rule

as risks to health associated with the

testicular prosthesis. FDA is requiring

the submission of PMA’s for this device

in order to determine whether these

risks can be controlled to provide

reasonable assurance of the safety and

effectiveness of these devices for their

intended use. Even a decline in the

incidence of these risks would not be a

sufficient reason to abandon the

regulation to require PMA’s for

testicular prostheses, absent a clear

delineation and understanding of those

risks.

5. One comment stated that Congress

never intended ‘‘old’’ (preamendments)

devices to be subjected to the same

scrutiny as ‘‘new’’ devices under the

premarket approval requirements.

FDA disagrees with this comment.

FDA does not believe that Congress

intended to differentiate between ‘‘old’’

and ‘‘new’’ devices with respect to the

requirement that valid scientific

evidence support a PMA approval.

Neither sections 513(a)(3) nor 515(d) of

the act (21 U.S.C. 360c(a)(3)) makes any

distinction between ‘‘old’’ and ‘‘new’’

devices with regard to the requirements

for approval. However, FDA does expect

that more retrospective data, which, by

its historical character, is generally less

detailed and rigorous than prospectively

gathered data, would be available for

use in supporting the approval of ‘‘old’’

as opposed to ‘‘new’’ devices. Scientific

evidence, including retrospectively

gathered data, is acceptable to support

a PMA approval, as long as the data

constitute valid scientific evidence

within the meaning of § 860.7(c)(2) (21

CFR 860.7(c)(2)).

6. One comment stated that the

proposed rule did not address how

amendments to PMA’s submitted prior

to panel review will be handled, and

requested that the agency clarify the

administrative procedures applicable to

such PMA amendments.

PMA amendments submitted prior to

advisory panel review will be evaluated

to determine whether the information is

sufficiently substantive to be considered

a ‘‘major’’ amendment. A major

amendment may extend the review

period for up to 180 days as outlined in

21 CFR 814.37(c)(1).

7. One comment stated that FDA

should refrain from promulgating the

final rule without the specific guidance

documents defining certain preclinical

and clinical testing requirements.

FDA disagrees with this comment.

Section 515(b) of the act does not

require FDA to provide guidance for

tests for PMA’s prior to issuing a call for

PMA’s. While FDA outlined numerous

manufacturing, preclinical, and clinical

studies that suggest the content of a

PMA for a testicular prosthesis, and

issued a detailed guidance document for

such PMA’s in March 1993, that was

discussed at a public meeting of the

Gastroenterology and Urology Devices

Advisory Panel in April 1993, these

tests were suggestive and not intended

to bind a PMA applicant to any specific

study or set of studies. FDA’s ‘‘Draft

Guidance for the Content of PMA

Applications for Testicular Prostheses’’

is available upon request from the

Division of Small Manufacturers

Assistance (HFZ–220), Center for

Devices and Radiological Health, 1350

Piccard Dr., Rockville, MD 20850.

8. One comment suggested that FDA

should reopen the dialogue with

industry, scientific, and medical

communities in order to develop a

consensus on the exact scope and nature

of some of the preclinical, material, and

clinical data requirements.

FDA agrees that the dialogue with

industry and the scientific and medical

communities should remain open

regarding the information needed to

support a PMA. FDA staff have been

and continue to be accessible to discuss

these requirements as requested.
17210 Federal Register / Vol. 60, No. 65 / Wednesday, April 5, 1995 / Rules and Regulations

B. Risks

9. Two comments suggested that the

list of risks do not represent ‘‘significant

risks’’ of testicular prosthesis

implantation. The contention was that

FDA has not clearly differentiated

between significant risks, potential

risks, and potential adverse effects, and

that FDA should limit identification of

risks to those which have been

reasonably shown to be significant risks.

The comment noted that the potential

effects may be divided into short-term

effects and long-term effects.

FDA disagrees with this comment.

The proposed rule clearly differentiated

risks that have been observed with

testicular prostheses from those that are

potential risks. Erosion, extrusion,

displacement, fibrous capsular

contracture, infection, and silicone gel

leakage are risks that have been reported

specifically for the testicular prosthesis.

Carcinogenicity, human reproductive

and teratogenic effects, immune related

connective tissue disorders

(immunological sensitization),

biological effects of silica, and

degradation of polyurethane foam

covering some implants were identified

as potential risks that, based on review

of all available information, FDA

believes are relevant to the testicular

prosthesis. While FDA agrees that the

risks of any implant fall into the broad

categories of short-term and long-term

risks, FDA believes that many of the

risks identified are both short and longterm in nature, rather than exclusively

short or long-term.

10. One comment suggested that since

erosion, extrusion, and/or displacement

are readily correctable by medical

intervention, and since revision surgery

is possible if explant is necessary, they

should not be considered significant

risks. Furthermore, the comment

suggested that displacement is not a

commonly reported adverse event, nor

can the prosthesis migrate to a variety

of locations within the body.

FDA disagrees with this comment.

Insufficient information is available to

determine the frequency of these events

or their effects. Furthermore, because

these risks can necessitate revision

surgery or explant, FDA believes they

are appropriately identified as

significant risks. However, FDA agrees

that it was not accurate to state that the

prosthesis can ‘‘migrate to a variety of

locations within the body,’’ but notes

that the prosthesis can migrate to, in

front of, or behind the contralateral

testis or above the scrotum. The

discussion of this risk has been

modified accordingly.

11. Several comments stated that

certain references cited in the proposed

rule failed to demonstrate a causal

relationship or a strong association

between the implantation of a testicular

prosthesis and the onset of risks, such

as carcinogenicity, teratogenicity, and

autoimmune diseases or connective

tissue disorders.

FDA agrees that the references cited

do not establish or refute the existence

of a causal relationship between

testicular prostheses and these risks.

However, the literature cited by FDA

provides evidence that these potential

risks are associated with the device and

are not trivial. Consequently,

investigation of these risks in support of

a PMA is necessary.

12. Two comments regarding the

potential carcinogenicity of silicone

were received. The comments make the

contention that the animal studies

reported are irrelevant because the

observed sarcomas were solely due to

physical (solid state) carcinogenesis and

such risks are not applicable to humans.

FDA disagrees with these comments.

Carcinogenicity is a putative risk

secondary to implantation of any

material. After review of all available

information, the agency continues to

believe that carcinogenicity is a

potential risk that must be assessed in

a PMA.

13. Three comments were on the

subject of reproductive and teratogenic

effects of the testicular prosthesis. These

comments stated that, because the

majority of prostheses are placed in

middle-aged to elderly men who have

had testicular removal as treatment for

prostatic cancer, the human

reproductive concern is irrelevant.

These comments also stated that: (1)

There are no reports of adverse effects

of testicular prostheses on reproduction,

or teratogenic effects on offspring of

patients with such prostheses; (2) FDA

misinterpreted the results of the

literature cited; and (3) only silicone

rubber or silicone gel products which

contain or are synthesized from

phenylmethyl silicones have potential

effects on the male reproductive system.

FDA agrees with the comments that,

to date, there are no published studies

showing reproductive toxic effects or

teratogenic effects associated with

implantation of silicone materials.

While some authors may have

concluded that silicone is not a

teratogen, FDA believes that there have

been no well-designed studies using

silicone testicular implants to determine

potential human reproductive and

teratogenic risks. FDA believes that

information in the form of welldesigned, single generation animal

studies would be appropriate.

Additionally, a PMA applicant may

choose to submit appropriate human

studies, or properly gathered and

analyzed historical data, to establish the

teratogenic potential of a silicone

testicular prosthesis.

FDA agrees that the requirement for

reproductive toxicity and teratogenicity

information for PMA’s should apply for

those silicone rubber or silicone gel

testicular prostheses which contain or

are synthesized from phenylmethyl

silicones, but the agency notes that this

testing should also be conducted for

other silicones until the reproductive

and teratogenic profiles of these

materials are established.

Finally, FDA agrees that the human

reproductive concern may not apply to

some testicular implant recipients.

However, because a sizable portion of

the implant population consists of

young males, the concern is relevant.

After reviewing all available data, FDA

believes that the prolonged contact

young males would have with the

device presents a potential risk of

reproductive effects and teratogenicity

in humans.

14. Two comments stated that fibrous

capsule formation is a normal wound

healing process and, in the case of a

testicular prosthesis, aids in keeping the

implant in place and preventing

migration to other parts of the body. The

comments stated that this response

occurs following implantation of almost

any material and should not be

considered a complication or adverse

event associated with implantation of

testicular prostheses. One comment

stated that the incidence rate of fibrous

capsular contracture is low, while the

second stated that it has never been

reported; both argued that it should not

be listed as a significant risk.

FDA agrees that fibrous capsule

formation is a normal wound healing

process that can occur following

implantation of almost any material.

The agency disagrees, however, that

fibrous capsular contracture is not a

significant risk of the testicular

prosthesis. Fibrous capsular contracture

may result in excessive scrotal firmness,

discomfort, pain, disfigurement, and

displacement of the implant. Moreover,

sufficient information exists to identify

capsular contracture as a risk to health

associated with the testicular implant.

FDA believes that literature case reports

and product complaints to the

manufacturer do not necessarily capture

all problems with medical devices.

15. Two comments suggested that the

incidence of infection occurs at a rate

consistent with other prosthetic implant

surgeries and is seldom serious and,
Federal Register / Vol. 60, No. 65 / Wednesday, April 5, 1995 / Rules and Regulations 17211

therefore, that infection should not be

considered a significant risk.

FDA disagrees with this comment.

While the incidence of infection may be

similar to other prosthetic devices, data

are needed to specifically quantify its

incidence and effect. Infection often

leads to surgical removal of the implant

and, therefore, is a potentially serious

adverse event. After review of all

available information, FDA continues to

believe that infection is a significant risk

associated with the testicular prosthesis.

16. Several comments were received

on the subject of immune related

connective tissue disorders or

immunological sensitization. The

comments make the following

contentions: (1) Silicone stimulates a

cell-mediated response only when

administered under extraordinary

conditions with an adjuvant; (2) there is

no evidence to date that hard silicone

elastomer has immune system adjuvant

properties; (3) recent surveys of

populations of women with connective

tissue disorders have demonstrated no

increase in disease prevalence in

women with silicone breast implants;

and (4) since scientific studies of

women with silicone mammary

prostheses have not shown a risk for

development of connective tissue

disorders, implantees with silicone

testicular implants, which have less

than one thirtieth the volume of a breast

implant, should also not be at risk of

connective tissue disorders.

FDA disagrees with these comments.

The adjuvant effect of silicone gel is

established in animal studies (Ref. 1). A

recent study (Ref. 2) suggests that some

women with silicone gel-filled breast

prostheses may develop atypical

immunologic reactions. Therefore, the

agency continues to believe that the

potential risk of immune related

connective tissue disorders or

immunological sensitization to

implanted silicone testicular prostheses

must be assessed in a PMA.

17. One comment stated that, while

the scientific evidence to date does not

demonstrate any cause and effect

relationship between the testicular

silicone implant and the subsequent

development of autoimmune diseases,

additional research needs to be

completed.

FDA agrees with this comment.

18. Two comments stated that fumed,

amorphous silica is tightly incorporated

into the silicone elastomer shell of the

testicular prostheses and, as a result, has

very different (and reduced) biological

activity.

FDA does not believe that there is

sufficient information available to

conclude that amorphous (fumed) silica

does not produce the same kind of

biological effects as crystalline silica.

Furthermore, while the silica reinforcer

material may not be extractable, it can

be potentially exposed or shed in the

form of particles from the elastomer by

the process of abrasive wear. Therefore,

FDA believes it is necessary that data

demonstrating the safety of amorphous

silica should be submitted in PMA’s.

C. Benefits

19. One comment stated that it is

important to recognize the value of a

psychological benefit to patients using

these devices, and that although it is

more difficult to document and quantify

a psychological benefit than a physical

benefit, the preponderance of evidence

showing a psychological benefit should

not be underestimated nor undervalued.

FDA agrees with this comment, and

has outlined the data needed to

demonstrate the psychological benefit of

the testicular prosthesis.

D. Manufacturing

20. One comment stated that

cooperation between manufacturers and

raw materials suppliers is necessary in

order to obtain the manufacturing data

required in a PMA.

FDA agrees that a cooperative

relationship between manufacturers and

raw materials suppliers will make the

manufacturing data requirements easier

to complete, but the agency notes that

much of the materials information

needed is on the finished, sterilized

device.

21. One comment suggested that the

manufacturing information section

should be revised to allow the

referencing of master file submissions,

with more limited chemical

characterization (e.g., Fourier Transform

Infrared Spectroscopy (FTIR)) to

confirm chemical composition, and

mechanical testing to establish criteria

for lot to lot variability in the cured

product.

FDA disagrees with this comment.

While proprietary manufacturing

information and, perhaps, testing results

may be part of a master file, additional

information beyond formulation data is

needed to document the safety of the

materials used to construct the device.

The additional information must consist

of testing that is more sensitive to

process variation than routine FTIR and

mechanical tests on the cured product.

The chemical, physical, and mechanical

properties of the final device are

affected not only by the starting raw

materials, but by the chemical reaction,

processing, and subsequent sterilization

of these raw materials to make the final

device. Only the device manufacturer,

not the raw material supplier, has

control over these processes.

Consequently, referral to a device

master file is not, in itself, adequate to

assess the safety of the final sterilized

device.

22. One comment noted that the

supply of silicone raw materials is in

jeopardy due to market withdrawal by

several manufacturers. This comment

suggested that a guidance document is

needed to determine acceptable

equivalency and data requirements.

FDA agrees that market withdrawal of

silicone raw materials by several

manufacturers may limit their

availability. In the Federal Register of

July 6, 1993 (58 FR 36207), FDA

published a notice of availability of a

guidance entitled ‘‘Guidance for

Manufacturers of Silicone Devices

Affected by Withdrawal of Dow Corning

Silastic Materials.’’ The guidance

describes the testing procedures to be

followed by manufacturers in

determining the equivalency of the

materials.

E. Extraction Testing

23. One comment stated that the

concept of exhaustive extraction and

identification and quantification of all

chemicals is relatively recent and thus

requires method development and

validation tantamount to the creation of

a new science.

FDA disagrees with this comment.

Numerous literature references describe

extraction, identification, and

quantification of individual silicone

components from a variety of matrices

using a variety of extraction solvents.

While more limited, references exist for

supercritical fluid extraction of the low

molecular weight components from

silicone elastomers. This is not a new

science. FDA recognizes the difficulty in

quantifying the amount of more than 35

separate components possible given the

materials of interest, however present

state-of-the-art allows this to be done.

24. One comment stated that FDA’s

request for molecular characterization of

elastomer intermediates, outer shell,

patch, and other component parts is not

possible since, with the exception of the

internal gel component, the parts are

composed of solid cured elastomeric

material. Furthermore, the comment

stated that FDA’s request for

determination of residual volatile and

nonvolatile cyclic compounds is a

duplication of the requirement for

analysis of extractables set forth in the

preclinical data section of the proposed

rule.

FDA agrees that this section was

unclear. Because only a limited amount

of chemical characterization can be
17212 Federal Register / Vol. 60, No. 65 / Wednesday, April 5, 1995 / Rules and Regulations

done on highly crosslinked polymers, it

is important to characterize the

immediate precursors to assure the

quality of the base polymers and

crosslinking agents. Regarding the

determination of residual volatile and

nonvolatile cyclic compounds, FDA

agrees that this requirement should

apply only to the individual structural

components (outer shell, patch, internal

gel, suture tab, polyurethane foam

covering, and any other materials) as

they are found in the final sterilized

device as described in the preclinical

data section, and should not apply to

material intermediates and precursors.

25. One comment stated that the

requirement of ‘‘complete identification

and quantification of all chemicals’’ is

untenable and unattainable, and should

be modified to allow manufacturers to

focus on identification and

quantification of those substances

whose presence in the finished device is

known or reasonably anticipated based

on composition of starting materials,

known additives, reaction byproducts,

and potential residues or contaminants

from reagents used in processing.

FDA disagrees with this comment.

Identification and quantification of the

majority of chemicals below a molecular

weight of 1,500 for silicones, as

specified in the guidance, is possible.

For other polymeric materials, different

criteria may be acceptable and should

be discussed with FDA on a case-bycase basis. While FDA agrees that

knowledge of the formulation will assist

in predicting what might be found in

the final product, it will not delineate

what or how much is actually in the

final product nor assess how the

manufacturing process will affect the

final product. Knowledge of the

formulation will also help in selecting

the appropriate analytical methodology

to be used for the analysis.

26. One comment stated that analysis

of extractables and subsequent toxicity

testing should be performed entirely on

the final product, rather than separate

structural components, and that FDA

should establish threshold limits for

extractives based on molecular

characteristics.

FDA agrees with the first part of this

comment, but notes that the analyst

should be aware of the drawback to

testing the final product in toto. For

example, wide variation in the size of

the structural components and their

proximity to each other in the final

device may result in erroneous

conclusions being made regarding the

chemical identity and source of extract

components. Furthermore, the outside

shell of an intact device may preclude

exhaustive extraction of the interior gel

within a reasonable period of time. Nor

does testing of an intact device simulate

a prosthesis that has ruptured in vivo.

Separate testing of the individual

components (materials/adhesives) of the

final device is acceptable provided that

the formulation of the test specimens is

identical to the formulation of the

materials used in the actual device and

has been subjected to the same curing,

post-curing, processing, and

sterilization modes as the final whole

device. Such testing would also allow

an increase in specimen size to

accommodate the collection of sufficient

extract to perform any analytical and

biocompatibility testing. Adjustment of

the analytical results on a weight basis

can then be calculated for the intact

device. Regarding the establishment of

threshold limits, FDA agrees in theory,

but notes that present limited

knowledge of toxicity based on

molecular characteristics, especially

with respect to siloxanes, makes the

establishment of threshold limits

impossible.

27. One comment stated that FDA

should define what is meant by

‘‘exhaustive extraction’’.

FDA’s ‘‘Draft Guidance for the

Content of PMA Applications for

Testicular Prostheses’’ provides detailed

guidance on extraction for silicone

implants. This guidance is available

upon request from the Division of Small

Manufacturers Assistance (HFZ–220)

(see address above in section II A of this

document).

F. Physical Testing

28. One comment stated that it seems

unnecessary for FDA to require

characterization of a physical or

chemical property unless it is relevant

to the intended use of the device.

FDA notes that no specific physical

property tests were cited in the

comment. FDA believes that all of the

physical property tests identified in the

proposed rule are relevant to the

intended use of the device.

29. Two comments stated that the

testicular prosthesis is too small to use

the American Society for Testing and

Materials (ASTM) test methods D412

and D624 as stated in the proposed rule,

which specify specimen size and test

methodology, based on a relationship

between a ratio of thickness to area for

a known coupon size and configuration.

The comment suggested that the ASTM

test methods can be used if slabs

representing the device formulation are

prepared for testing, according to both

ASTM D412 and D624.

FDA agrees with this comment. The

use of downsized dies for testing

smaller samples obtained from finished

sterilized devices may be employed.

Test slabs mimicking the formulation of

the materials used in the actual device

and subjected to the same processing

and sterilization modes could also be

used. This would also apply to the

samples used for testing of the integrity

of adhered or fused joints. Evaluation of

biodegradation effects on physical

properties of elastomeric components

could be accomplished by physical

testing of test slabs explanted from

animals.

30. One manufacturer noted that, in

its experience, there has never been a

case of a testicular implant failure from

shell abrasion, and questioned the need

for abrasion testing. The comment noted

that only two explants had been

received in the manufacturer’s 9-year

history with the device.

FDA disagrees with this comment.

The fact that the manufacturer has

received only two explanted devices in

its 9-year history with the device is not

a sufficient reason for dismissing

abrasion as a potential failure mode for

the device. In addition, other potential

adverse effects are associated with

abrasion, such as release of silica,

inflammation, and granuloma

formation.

G. Biocompatibility Testing

31. Two comments stated that

mutagenicity and other toxicity testing

be required to use mixtures of total

extractables rather than individual

components.

FDA agrees with this comment.

32. One comment noted that

biodegradation testing may require

miniature implants in animals, and

suggested that the biodegradation

studies should consist of microscopy

studies, as well as chemical

characterization which would be

indicative of any degradation process.

FDA agrees with this comment.

33. One comment stated that

histopathology should not be required

for acute toxicity studies because the

duration of the study is insufficient for

developing tissue responses.

FDA agrees with this comment.

34. One comment stated that the

preclinical requirements exceed the

Tripartite Biocompatibility Guidance for

Medical Devices (Ref. 3) and even the

science of biocompatibility testing.

FDA disagrees with this comment.

The agency notes that the

biocompatibility requirements were

based on the Tripartite Biocompatibility

Guidance for Medical Devices.

35. One comment suggested that

testing of nonpolar solvent extracts for

a variety of biocompatibility tests is not
Federal Register / Vol. 60, No. 65 / Wednesday, April 5, 1995 / Rules and Regulations 17213

relevant to the devices currently on the

market.

FDA disagrees with this comment.

The proposed rule suggests that, at a

minimum, ethanol, ethanol/saline (1:9),

and dichloromethane should be used.

Solvents should be chosen that are

expected to solubilize the low molecular

weight migrants in a reasonable period

of time, thus facilitating exhaustive

extraction—not to mimic in vivo

conditions. Inasmuch as the chemical

nature of all the migrants is not known,

it is advisable to use solvents with

varying chemical characteristics.

36. One comment suggested that for

extracts composed of substances

possessing innocuous structures and

having low potential exposures, either

no testing or only minimal testing

should be required.

FDA disagrees with this comment.

There is currently limited knowledge of

what is and what is not ‘‘innocuous’’

based solely on chemical structure. The

potential exposure can only be based on

the maximum amount found in the final

product by analytical tests. However,

since polysiloxanes contain many,

perhaps more than 35, chemical

components as a byproduct of the

synthesis, FDA agrees that it is difficult

to individually test all components

found in the extract. Therefore, FDA

will accept testing of the mixtures of

total extractables rather than of

individual components.

37. One comment stated that the

pharmacokinetics testing outlined

requires methodology that does not

currently exist for solid elastomeric

silicone.

FDA agrees in general with the

comment regarding solid elastomeric

silicone products. However, if the solid

elastomers contain leachable

components, FDA believes they should

be subjected to pharmacokinetics

testing.

H. Clinical Investigations

38. Several comments suggested that

many of the safety and effectiveness

questions raised in the proposed rule

can be addressed by evaluation of the

available published clinical data,

collection and analysis of retrospective

epidemiological data and, if necessary,

initiation of postmarketing followup

studies.

FDA agrees that long-term

retrospective epidemiological data, if

collected properly, can be very useful in

identifying long-term issues pertaining

to safety and effectiveness. However,

FDA believes it is necessary to require

randomized (if at all possible),

prospective studies to establish the

short-term (in this case, up to 5 years or

until physical maturity of the subject)

safety and effectiveness data of the

testicular implant. Only prospective

data collected under a well-designed

protocol can adequately address issues

of safety and effectiveness relevant to

the current population of implant users.

39. One comment stated that FDA

focused almost exclusively on ‘‘wellcontrolled studies’’ while ignoring other

valid scientific evidence as defined in

§ 860.7(c)(2).

FDA disagrees with this comment.

Although § 860.7(f) does allow valid

scientific evidence other than wellcontrolled investigations, § 860.7(e)(2)

notes that ‘‘The valid scientific evidence

used to determine the effectiveness of a

device shall consist principally

[emphasis added] of well-controlled

investigations.’’ Therefore, wellcontrolled investigations are not only

appropriate, but required, with other

‘‘valid scientific evidence’’ to be

considered in a supporting role. In fact,

FDA encourages the submission of all

well-documented, valid retrospective

data, which are presented in an

organized manner.

40. One comment stated that FDA did

not identify the duration of the clinical

trial needed to establish safety and

effectiveness, and suggested that while

life-long data are ideally needed, some

reduced amount of data should be

identified to allow continued

distribution of the testicular prosthesis.

FDA notes that the proposed rule

suggested that 5-year clinical data, or

data collected until the physical

maturity of the subject (whichever

occurs later) is needed, and that postapproval studies will be needed to

address the various long-term issues

identified.

41. Two comments requested

clarification of what would constitute

an adequate control, suggesting that the

controls need to be tailored to the

specific questions being asked, and that

multiple control groups may therefore

be necessary. One comment stated that

meaningful control data may be either

unimportant or impossible to obtain.

One comment suggested that the patient

should be his own control due to the

difficulty in identifying and recruiting

an appropriate control group for a male

without one or both testicles.

FDA agrees that controls need to be

tailored to the specific questions under

investigation, and that multiple control

groups may therefore be necessary. FDA

strongly disagrees that ‘‘meaningful

control data may be unimportant.’’

However, if ‘‘meaningful control data

may be * * * impossible to obtain’’, the

sponsor must rigorously demonstrate

this for the relevant hypothesis. FDA

agrees that it may be very difficult or

impractical to recruit an appropriate

control group. If the sponsor can

satisfactorily demonstrate this to be the

case, the subject may serve as his own

control.

42. One comment noted that

epidemiological clinical testing would

require many years of patient

enrollment to address only hypothetical

concerns.

FDA agrees in part with this

comment. FDA’s ‘‘Guidance to

Manufacturers on the Development of

Required Post-approval Epidemiologic

Study Protocols for Testicular Implants’’

permits manufacturers to document

whether conditions are too rare to detect

in a reasonable study. It also emphasizes

that valid case-control studies and

retrospective cohort studies are

welcome. The guidance is available

upon request from the Division of Small

Manufacturers Assistance (HFZ–220)

(see address above in section II A of this

document).

43. One comment suggested that two

generation human testing would be

needed for teratology testing.

FDA believes that single generation

animal studies, properly gathered and

analyzed historical clinical data, or

other valid scientific evidence would

also be appropriate in determining the

teratogenic potential of the testicular

prosthesis.

I. Need for Psychological Data

44. One comment stated that the

psychological benefits of the testicular

prosthesis do not need to be evaluated

using standardized testing and

quantification of benefits because: (1)

Studies are available in which patient

satisfaction with testicular prostheses

has been assessed; (2) the notion that

the absence of one or both testicles

produces adverse psychological effects

on boys and adult males appears to be

universally accepted; (3) several

anecdotal reports strongly support the

use of testicular prostheses for patients

with congenital or other absence of

testes; and (4) manufacturers make no

claims regarding the psychological

benefit of the device.

FDA disagrees with these comments.

The studies cited were either so small

as to be considered anecdotal, did not

describe the assessment tools used, used

no systematic assessment of the

psychological impact of the prostheses,

or consisted of particular

subpopulations whose applicability to

the general population would be

questionable. These shortcomings

underscore the need for FDA’s request

for a systematic assessment using

reliable and valid measures of the
17214 Federal Register / Vol. 60, No. 65 / Wednesday, April 5, 1995 / Rules and Regulations

psychosocial consequences of testicular

implants. Regardless of the actual

claims made, it is clear that the

testicular prosthesis is implanted for its

psychosocial benefit to the implant

recipient.

45. One comment stated that the

intended use of the testicular prosthesis

is to construct or reconstruct the size

and contour of the male testicle, and

that before and after size measurements

would be sufficient to demonstrate

effectiveness beyond any reasonable

doubt. Furthermore, to expect

manufacturers to conduct psychological

testing in the absence of an FDArecognized validated test instrument is

not appropriate.

FDA disagrees with this comment.

While before and after size

measurements would be sufficient to

show the anatomical effect of the

implant, FDA believes that testicular

prostheses are primarily used for the

psychological benefit. FDA agrees with

an earlier comment which stated that

the psychological benefit should neither

be underestimated nor undervalued.

Finally, FDA notes that section 515(b) of

the act does not require FDA to provide

guidance for tests for PMA’s prior to

issuing a call for PMA’s. While FDA

outlined the principles of the

psychological/psychosocial data needed

in the proposed rule, in the ‘‘Draft

Guidance for Preparation of PMA

Applications for Testicular Prostheses,’’

and at a public meeting of the

Gastroenterology and Urology Devices

Advisory Panel in April 1993, these

tests were suggestive and not intended

to bind a PMA applicant to any specific

study or set of studies.

46. One comment stated that requiring

documentation of psychological benefits

through further well-controlled

presurgical, immediate postsurgical, and

long-term psychological studies using

standardized, validated test instruments

is inappropriate and would appear to

fall outside the intent of the act.

Congress intended that medical devices

perform as intended, not that they

necessarily produce therapeutic effects.

FDA disagrees with this comment.

Section 860.7(e)(1) states that there is

‘‘reasonable assurance that a device is

effective when it can be determined,

based upon valid scientific evidence,

that in a significant portion of the target

population, the use of the device * * *

will provide clinically significant

results.’’ FDA believes that it is

necessary that a PMA demonstrate that

the device has a beneficial therapeutic

effect, rather than merely demonstrating

that a device functions in accordance

with its design.

47. One comment stated that

psychological testing of the juvenile

segment of the potential patient

population is impractical and

inappropriate, and that FDA should

provide specific guidelines on any

required psychological testing.

FDA agrees that it may not be feasible

to effectively assess the psychosocial

impact of testicular prosthesis

implantation on children 12 years of age

and younger. However, FDA believes

that children over 12 years of age should

be tested, since sexuality and the

physical manifestations of sexuality are

psychologically very important to

pubescent and adolescent children.

Manufacturers are encouraged to contact

FDA regarding specific guidelines on

this testing.

III. Findings With Respect to Risks and

Benefits

A. Degree of Risk

1. Extrusion/erosion of the testicular

prosthesis. Extrusion and erosion of the

testicular implant through the scrotal

wall are among the most common

complications associated with the use of

these devices. Prosthesis extrusion is

usually associated with concurrent

wound dehiscence in instances where

the device was inserted through a

scrotal incision. Skin erosion has been

reported following implantation of the

testicular prosthesis due to the presence

of a Dacron suture tab, insertion of an

oversized device, or aggressive

dissection of the subdartos pocket, and

could result in subsequent infection or

device extrusion. It has been suggested

that the rate of extrusion due to wound

dehiscence is between 3 and 8 percent.

2. Displacement of the testicular

prosthesis. Displacement, or migration,

is another commonly reported adverse

event. The prosthesis can migrate in

front of or behind the contralateral testis

or above the scrotum. Displacement can

be caused by either inadequate scrotal

distension prior to insertion or improper

surgical placement/fixation.

3. Fibrous capsular contracture.

Fibrous capsular contracture, the

formation of a constricting fibrous layer

around the prosthesis, has been

associated with the presence of

testicular implants. Capsular

contracture may result in excessive

scrotal firmness, discomfort, pain,

disfigurement, and displacement of the

implant.

Although the etiological factors of

capsular contracture have not been

reported with testicular implants,

several factors have been suggested with

the breast implant, including hematoma,

infection, and foreign body reaction.

Despite these reports, no single factor

has been demonstrated to be the sole

cause of contracture. The etiology of

contracture is not understood.

4. Infection. Infection, a risk of any

surgical implant procedure, is

associated with the use of testicular

implants. As in any implantation

procedure, compromised device sterility

and surgical techniques may be major

contributing factors to this risk. Usually,

the occurrence of infection necessitates

the removal of the prosthesis. It has

been suggested with the silicone gelfilled breast prosthesis that infection

may also contribute to the early

development of capsular contracture.

5. Human carcinogenicity.

Carcinogenesis has been widely

discussed as a reputed risk secondary to

implantation of any material. Evidence

from the literature indicates that, in

animal studies, different forms of

silicone have been associated with

various types of cancer. Cases of several

types of cancer in humans have been

reported in association with various

forms of implanted silicone.

6. Human reproductive and

teratogenic effects. The effect of certain

silicone compounds on the reproductive

potential of the male is largely

unknown. It has been reported that at

least one form of organosiloxane, which

is known to be present in some silicone

gels, mimics estrogens in the male rat

leading to rapid testicular atrophy.

Teratogenesis includes the origin or

mode of production of a malformed

fetus and the disturbed growth

processes involved in the production of

a malformed fetus. Studies using

silicone fluid in animals have been

minimal, and yield contradictory and

inconclusive results. Prolonged contact

with either the solid silicone device, or

the silicone gel-filled membrane and its

components, presents a potential risk of

teratogenicity in humans. Additionally,

the theoretical risk of abnormalities

appearing later in life in normally

appearing offspring also warrants

investigation.

The risk of adverse reproductive and

teratogenic effects from testicular

implants exists only in the subset of

patients who have a single prosthesis

with a unilateral, functional testicle.

7. Immune related connective tissue

disorders—immunological sensitization.

Immunological sensitization may be a

serious risk associated with the

implantation of a testicular prosthesis.

Immune related connective tissue

disorders have been reported in women

who have silicone gel-filled prostheses

or who have had silicone injections in

augmentation mammoplasty. There are

clinical reports of several patients who
Federal Register / Vol. 60, No. 65 / Wednesday, April 5, 1995 / Rules and Regulations 17215

have undergone augmentation

mammoplasty with silicone gel-filled

breast prostheses and later presented

with connective tissue disease-like

syndromes. Because testicular

prostheses consist of similar silicone

elastomers and gels, further study of the

potential risk of immune related

connective tissue disorders in humans

with these implants is warranted.

8. Biological effects of silica.

Amorphous (fumed) silica is bound to

the silicone in the elastomer of the

testicular prosthesis, and may be

fibrogenic and immunogenic. Fumed

silica and the silicone shell each elicit

cellular responses in rats. The biological

effects of silica, particularly the

immunologic component of these

reactions, present a potential risk and

need to be examined.

The following potential risk pertains

only to the gel-filled silicone rubber

testicular prosthesis:

9. Silicone gel leakage and migration.

Silicone gel leakage and migration from

the silicone elastomer envelope, either

from rupture of the envelope or by

leaking of the gel through the envelope

(gel ‘‘bleed’’), are also significant risks of

silicone gel-filled testicular prostheses.

Rupture of the envelope with gel

leakage and subsequent migration may

be secondary to surgical technique or

mechanical stresses such as routine

manual massage, trauma, and wear on

the envelope, and necessitates removal

of the prosthesis. In addition to the

above, silicone gel-filled breast

implants, which are similar to testicular

implants in materials and construction,

are reported to ‘‘bleed’’ micro amounts

of silicone through the intact silicone

elastomer shell into the surrounding

tissues. Although diffusion of silicone

gel through the elastomer shell has not

specifically been measured in the

testicular prosthesis, gel bleed continues

to be a theoretical risk with this device

and needs to be evaluated. Migration of

the gel into the human body presents

the potential for development of adverse

effects such as granulomas or

lymphadenopathy. The ultimate fate of

migrating silicone gel within the body is

currently not well understood.

The following potential risk is

associated only with those testicular

prostheses that are polyurethane foam

covered:

10. Degradation of polyurethane

foam. The polyurethane foam material

that has been used to cover some

testicular prostheses is known to

degrade over time with a potential

breakdown product of 2,4

diaminotoluene (TDA), a known

carcinogen in animals. The fate of the

degraded product in vivo is unknown to

date, and the use of this material in

testicular implants may have been

discontinued. Case reports of the

polyurethane foam covered silicone gelfilled breast implant indicate that there

is greater difficulty with the removal of

this type of prosthesis due to a

fragmented polyurethane shell and/or

capsular tissue ingrowth. Foreign body

responses have been reported

concurrent with the use of the

polyurethane foam covered testicular

prosthesis in humans.

B. Benefits of the Device

The testicular prosthesis is intended

to simulate the presence of a testicle

within the male scrotum, and is

indicated in subjects who are missing

one or both testes due to either

congenital or acquired reasons.

Testicular prosthesis implantation is a

discretionary surgical procedure

performed for psychological, rather than

for other medical reasons.

Testicular prostheses are commonly

used to correct congenital anomalies in

young males who are born without one

or both testicles (i.e., testicular agenesis

or atrophy). Additionally, such devices

are often implanted subsequent to

removal of one or both testes for one of

several reasons: Malignant cancer of the

prostate, testicular cancer, testicular

torsion, cryptorchidism, failed

orchiopexy, epididymitis/orchitis, or

testicular trauma.

Men facing orchiectomy (removal of

the testicles) may experience depression

that accompanies this degenerative

change in body image. Such feelings of

depression have been equated to the

experiences of women who have

undergone mastectomy or hysterectomy.

Shame and feelings of inferiority are

common, and can lead to anxiety,

personality changes, changes in one’s

customary lifestyle, fear of sexual

rejection, and psychogenic impotence. It

has also been reported that a visible

defect in a child’s genital region may

result in feelings of inferiority, leading

to social isolation. Such occurrences

may produce psychologic problems, and

have an affect upon the child’s

emotional development and sexual

identity. Implantation of a testicular

prosthesis may help to alleviate such

feelings in males of all ages, thereby

improving quality of life. The studies

which have been published indicate

that recipients of testicular prostheses

exhibit a high degree of satisfaction with

their surgery.

IV. Final Rule

Under section 515(b)(3) of the act,

FDA is adopting the findings as

published in the preamble to the

proposed rule and is issuing this final

rule to require premarket approval of

the generic type of device, the testicular

prosthesis, by revising § 876.3750(c).

Under the final rule, a PMA or a

notice of completion of a PDP is

required to be filed with FDA within 90

days of the effective date of this

regulation for any testicular prosthesis

that was in commercial distribution

before May 28, 1976, or that has been

found by FDA to be substantially

equivalent to such a device on or before

the 90th day past the effective date of

this regulation. An approved PMA or

declared completed PDP is required to

be in effect for any such device on or

before 180 days after FDA files the

application. Any other testicular

prosthesis that was not in commercial

distribution before May 28, 1976, or that

has not, on or before 90 days after the

effective date of this regulation, been

found by FDA to be substantially

equivalent to a testicular prosthesis that

was in commercial distribution before

May 28, 1976, is required to have an

approved PMA or declared completed

PDP in effect before it may be marketed.

If a PMA or notice of completion of

a PDP for a testicular prosthesis is not

filed on or before the 90th day past the

effective date of this regulation, that

device will be deemed adulterated

under section 501(f)(1)(A) of the act, and

commercial distribution of the device

will be required to cease immediately.

The device may, however, be

distributed for investigational use if the

requirements of the investigational

device exemption (IDE) regulations (21

CFR part 812) are met.

Under § 812.2(d) (21 CFR 812.2(d)) of

the IDE regulations, FDA hereby

stipulates that the exemptions from the

IDE requirements in § 812.2(c)(1) and

(c)(2) will no longer apply to clinical

investigations of the testicular

prosthesis. Further, FDA concludes that

investigational testicular prostheses are

significant risk devices as defined in

§ 812.3(m) and advises that, as of the

effective date of § 876.3750(c), the

requirements of the IDE regulations

regarding significant risk devices will

apply to any clinical investigation of a

testicular prosthesis. For any testicular

prosthesis that is not subject to a timely

filed PMA or notice of completion of a

PDP, an IDE must be in effect under

§ 812.20 on or before 90 days after the

effective date of this regulation or

distribution of the device for

investigational purposes must cease.

FDA advises all persons presently

sponsoring a clinical investigation

involving the testicular prosthesis to

submit an IDE application to FDA no

later than 60 days after the effective date
17216 Federal Register / Vol. 60, No. 65 / Wednesday, April 5, 1995 / Rules and Regulations

of this final rule to avoid the

interruption of ongoing investigations.

V. Environmental Impact

The agency has determined under 21

CFR 25.24(a)(8) and (e)(4) that this

action 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.

VI. Analysis of Impacts

FDA has examined the impacts of the

final rule under Executive Order 12866

and the Regulatory Flexibility Act (Pub.

L. 96–354). 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 the manufacturers of

these devices have been aware for a long

time, more than 10 years, of the need to

prepare PMA’s for these devices, the

agency certifies that the final rule will

not have a significant economic impact

on a substantial number of small

entities. Therefore, under the Regulatory

Flexibility Act, no further analysis is

required.

VII. References

The following references have been

placed on display in the Dockets

Management Branch (HFA–305), Food

and Drug Administration, rm. 1–23,

12420 Parklawn Dr., Rockville, MD

20857 and may be seen by interested

persons between 9 a.m and 4 p.m.

Monday through Friday.

1. Naim, J., and R.J. Lanzafame, ‘‘The

Adjuvant Effect of Silicone Gel on Antibody

Formation in Rats,’’ Immunological

Investigations, 22(2):151–161, 1993.

2. Bridges, A. J., C. Conley, G. Wang, D. E.

Burns, and F. B. Vasey, ‘‘A Clinical and

Immunologic Evaluation of Women With

Silicone Breast Implants and Symptoms of

Rheumatic Disease,’’ Annals of Internal

Medicine, 118(12):929–936, 1993.

3. Tripartite Biocompatibility Guidance for

Medical Devices, Office of Device Evaluation

General Program Memorandum #87–1, April

24, 1987.

List of Subjects in 21 CFR Part 876

Medical devices.

Therefore, under the Federal Food,

Drug, and Cosmetic Act and under

authority delegated to the Commissioner

of Food and Drugs, 21 CFR part 876 is

amended as follows:

PART 876—GASTROENTEROLOGY–

UROLOGY DEVICES

1. The authority citation for 21 CFR

part 876 is revised to read as follows:

Authority: Secs. 501, 510, 513, 515, 520,

522, 701 of the Federal Food, Drug, and

Cosmetic Act (21 U.S.C. 351, 360, 360c, 360e,

360j, 3601, 371).

2. Section 876.3750 is amended by

revising paragraph (c) to read as follows:

§ 876.3750 Testicular prosthesis.

* * * * *

(c) Date premarket approval

application (PMA) or notice of product

development protocol (PDP) is required.

A PMA or notice of completion of a PDP

is required to be filed with the Food and

Drug Administration on or before July 5,

1995, for any testicular prosthesis that

was in commercial distribution before

May 28, 1976, or that has on or before

July 5, 1995, been found to be

substantially equivalent to a testicular

prosthesis that was in commercial

distribution before May 28, 1976. Any

other testicular prosthesis shall have an

approved PMA or a declared completed

PDP in effect before being placed in

commercial distribution.

Dated: March 13, 1995.

D. B. Burlington,

Director, Center for Devices and Radiological

Health.

[FR Doc. 95–8383 Filed 4–4–95; 8:45 am]

BILLING CODE 4160–01–F

DEPARTMENT OF THE TREASURY

Internal Revenue Service

26 CFR Part 1

[TD 8591]

RIN 1545–AT28

Valuation of Plan Distributions

AGENCY: Internal Revenue Service (IRS),

Treasury.

ACTION: Temporary regulations.

SUMMARY: This document contains

temporary regulations that provide

guidance to employers in determining

the present value of an employee’s

benefit under a qualified defined benefit

pension plan, for purposes of the

applicable consent rules and for

purposes of determining the amount of

a distribution made in any form other

than in certain nondecreasing annuity

forms. These temporary regulations are

issued to reflect changes to the

applicable law made by the Retirement

Protection Act of 1994 (RPA ’94), which

is part of the Uruguay Round

Agreements Act of 1994. RPA ’94

amended the law to change the interest

rate, and to specify the mortality table,

for the purposes described above. The

text of these temporary regulations also

serves as the text of the proposed

regulations set forth in the notice of

proposed rulemaking on this subject in

the Proposed Rules section of this issue

of the Federal Register.

DATES: These regulations are effective

April 5, 1995.

These regulations apply to plan years

beginning after December 31, 1994,

except as provided in § 1.417(e)–

1T(d)(8) and (9).

FOR FURTHER INFORMATION CONTACT:

Linda S. F. Marshall, (202) 622–4606

(not a toll-free number).

SUPPLEMENTARY INFORMATION:

Short Description

The temporary regulations in this

document set out rules for computing

the amount of any benefit under a

qualified defined benefit pension plan

that is paid in any form other than

certain annuity forms. These temporary

regulations reflect changes made to the

law in the Retirement Protection Act of

1994 (RPA ’94) Pub. L. 103–465. Under

the new law, if the annuity benefit an

employee could receive under the plan

is converted to a different form of

benefit, the non-annuity benefit cannot

be less than the value that would be

determined using legally required

assumptions regarding life expectancy

(mortality table) and interest rate. This

ensures that the non-annuity benefit

will not be less valuable than the

annuity benefit.

Under these temporary regulations,

the mortality table used under the new

law is the mortality table published by

the IRS (currently a mortality table

commonly used by state insurance

commissioners). The interest rate used

under the new law is the interest rate on

30-year Treasury securities, as

published by the IRS. These temporary

regulations allow an employer to choose

a monthly, quarterly, or annual period

during which the plan’s interest rate

remains constant, and allow an