# Medical Devices; Guidance for Industry; Premarket Notification (510(k)) Guidance Document for Contact Lens Care Products; Revised; Availability

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URL: https://www.frixlaw.com/law-library/documents/fr%3A97-14750

## Record

- **Collection:** Federal Register
- **Document type:** Notice
- **Published:** June 6, 1997
- **Citation:** 62 FR 31118

## Text

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration
[Docket No. 97D-0191]

Medical Devices; Guidance for Industry; Premarket Notification
(510(k)) Guidance Document for Contact Lens Care Products; Revised;
Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing the
availability of a revised guidance entitled, ``Guidance for Industry;
Premarket Notification (510(k)) Guidance Document for Contact Lens Care
Products.'' The revised guidance sets forth the types of tests the
Center for Devices and Radiological Health (CDRH), FDA, believes are
necessary to provide reasonable assurance of the safety and
effectiveness of contact lens care products. The revised guidance
accompanies a final rule, which appears elsewhere in this issue of the
Federal Register, reclassifying rigid gas permeable contact lens
solution; soft (hydrophilic) contact lens solution; and contact lens
heat disinfecting units from class III (premarket approval) to class II
(special controls).

DATES: Written comments may be submitted at any time.
ADDRESSES: Submit written requests for single copies of the revised
guidance entitled, ``Guidance for Industry Premarket Notification
(510(k)) Guidance Document for Contact Lens Care Products'' (shelf
number 674) to the Division of Small Manufacturers Assistance (HFZ-
220), Center for Devices and Radiological Health, Food and Drug
Administration, 1350 Piccard Dr., Rockville, MD 20850, 301-443-6597
(outside MD 1-800-638-2041). Send two self-addressed adhesive labels to
assist that office in processing your requests. Submit written comments
on the revised guidance to the Dockets Management Branch (HFA-305),
Food and Drug Administration, 12420 Parklawn Dr., rm. 1-23, Rockville,
MD 20857. Requests and comments should be identified with the docket
number found in brackets in the heading of this document. Comments may
be submitted at any time and will be used to determine whether to
revise the guidance further.

FOR FURTHER INFORMATION CONTACT: James F. Saviola, Center for Devices
and Radiological Health (HFZ-460), Food and Drug Administration, 9200
Corporate Blvd., Rockville, MD 20850, 301-594-1744.

SUPPLEMENTARY INFORMATION:

I. The Statutory Requirements

The Safe Medical Devices Act (the SMDA) (Pub. L. 101-629), which
amended the medical device provisions of the Federal Food, Drug, and
Cosmetic Act (the act) (21 U.S.C. 321 et. seq.), contains specific
provisions on transitional devices (i.e., those devices regulated as
new drugs before the Medical Device Amendments of 1976 (Pub. L. 94-295)
became law) (see section 520(l) of the act (21 U.S.C. 360j(l)). In
1976, Congress classified into class III all transitional devices
(i.e., those devices previously regulated as drugs). The legislative
history of the SMDA reflects congressional concern that many
transitional devices were being overregulated in class III (H. Rept.
808, 101st Cong., 2d sess. 26-27 (1990); S. Rept. 513, 101st Cong., 2d
sess. 26-27 (1990)). Congress amended section 520(l) of the act to
direct FDA to collect certain safety and effectiveness information from
the manufacturers of transitional devices that still remain in class
III to determine whether the devices should be reclassified into class
II (special controls) or class I (general controls).
Under section 520(l)(5)(B) of the act, FDA was to publish
regulations by December 1, 1992, either leaving the transitional class
III devices in class III or revising their classification down to class
I or class II. However, as permitted by section 520(l)(5)(C) of the
act, in the Federal Register of November 30, 1992 (57 FR 56586), the
agency published a notice extending the period for issuing such
regulations until December 1, 1993. Due to limited resources, FDA was
unable to publish the regulations before the December 1, 1993,
deadline. In the Federal Register of April 1, 1996 (61 FR 14277), FDA
published a proposed rule to reclassify from class III (premarket
approval) to class II (special controls) the rigid gas permeable
contact lens solution; the soft (hydrophilic) contact lens solution;
and the contact lens heat disinfecting unit. FDA also announced the
availability of a premarket notification (510(k)) draft guidance
document for contact lens care products (61 FR 14330, April 1, 1996).
Interested persons were invited to comment on the guidance document by
May 31, 1996.
Elsewhere in this issue of the Federal Register, FDA is issuing a
final rule reclassifying from class III (premarket approval) to class
II (special controls) all transitional contact lens care products. In
conjunction with the final rule, FDA is announcing the availability of
the revised guidance for premarket notification for the reclassified
contact lens care products entitled, ``Guidance for Industry; Premarket
Notification (510(k)) for Contact Lens Care Products.''

II. The Revised Guidance

The revised guidance sets forth the types of testing that FDA
believes will provide reasonable assurance of the continued safety and
effectiveness of transitional contact lens care products. It also
provides comprehensive

[[Page 31119]]

directions for manufacturers of contact lens care products to follow in
submitting a 510(k) premarket notification submission demonstrating
substantial equivalence of their device to a legally marketed contact
lens care product (predicate device). Information on the battery of
preclinical testing that may demonstrate substantial equivalence is
included in the guidance. If the results of preclinical testing
demonstrate that the device will have new characteristics, clinical
performance data may be needed to establish substantial equivalence. If
clinical performance data are needed, the guidance document suggests
methodologies (e.g., size and scope of the study) to be included in the
investigational protocol.
Other elements of the guidance include: (1) General information on
the regulations and requirements for labeling contact lens care
products; (2) information about 510(k) submission requirements relating
to modifying a marketed contact lens care product; and (3) guidance for
submitting a 510(k) notification for contact lens cases and contact
lens accessories (i.e., mechanical cleaning aids and accessory cleaning
pads).
In the event that clinical trials are necessary, FDA emphasizes
that manufacturers are required to conduct the trials in accordance
with the investigational device exemption regulations in 21 CFR part
812. At this time, FDA considers clinical studies of most contact lens
care products to be nonsignificant risk investigations. For
nonsignificant risk investigations, approval of an institutional review
board (IRB) is necessary before initiating a clinical study, and an
investigational plan and informed consent document must be presented to
an IRB for review and approval. Prior FDA approval is not required.
However, FDA considers some clinical studies of solutions that
contain new active ingredients for ophthalmic use and that are intended
for use directly in the eye to be significant risk investigations that
would require both IRB and FDA review and approvals. Examples of
significant risk investigations requiring FDA and IRB review and
approval include investigations of solutions intended for repeated use
directly in the eye that contain new types of ingredients that have no
history of ophthalmic use, that may require different testing than the
preclinical tests in the guidance, that may contain ingredients that
can perfuse through the cornea, or that may involve overlapping
concerns with other FDA Centers, such as products or studies
incorporating a biologic or a pharmaceutical compound. Sponsors
proposing to conduct such studies should contact James F. Saviola
(address above) concerning the risk status of the proposed
investigation prior to implementing their studies.
Comments received from the public on the draft guidance were
summarized at the July 26, 1996, meeting of the Ophthalmic Devices
Panel of the Medical Devices Advisory Committee.

III. Summary and Analysis of Comments and FDA's Response

Separate comments were received from four individuals and a single
set of comments from industry via the Contact Lens Institute. Comments
were generally categorized as editorial, clarification, and
substantive. The guidance document has been revised to address most of
the editorial, providing clarification and substantive comments.
Comments pertaining to policy and clinical information are
summarized as follows:
1. One comment suggested that FDA change the wording in the
guidance which states that clinical studies of contact lens care
products are nonsignificant risk investigations. The current wording in
the guidance states that this is the case unless the device contains
new active ingredients for ophthalmic use and is intended to be used
directly in the eye.
FDA agrees in part with this comment. However, investigations of
some in-eye products are significant risk investigations (e.g.,
investigations of solutions intended for repeated use directly in the
eye that contain new types of ingredients that have no history of
ophthalmic use, that may require different testing than the preclinical
tests in the guidance, that may contain ingredients that can perfuse
through the cornea, or that may involve overlapping concerns with other
FDA Centers, such as products or studies incorporating a biologic or a
pharmaceutical compound). The guidance has been revised to clarify when
a contact lens care product investigation is considered significant
risk and to recommend that sponsors contact FDA for guidance concerning
risk status of such proposed investigations prior to beginning clinical
studies.
2. One comment stated that discard dates alone will not necessarily
reduce the risk of eye infections caused by contamination during use
and suggested that the statement in the General Manufacturing section
stating that, whenever possible, manufacturers should consider the use
of discard dates after opening, be revised to be more consistent with
21 CFR 800.10(b).
FDA agrees that the guidance should reflect the regulation and has
revised the guidance accordingly. However, FDA believes that discard
dates would help to minimize contamination of lens care products and
that responsible manufacturers should work in this direction.
3. A few comments were received pertaining to recommendations for
clinical trials (e.g., size and scope, study design, and testing
matrix). One comment stated that the studies are too short and may not
uncover complications such as different levels of patient
hypersensitivity. That comment stated that clinical studies for all new
lens care formulations should be, at a minimum, 3 months in length with
at least 100 patients. Also, for products that are substantially the
same as one already on the market with the same indication, clinical
studies would still be necessary.
FDA has designed the guidance to include preclinical testing as the
primary evidence for establishing substantial equivalence, with
supplemental clinical testing as additional confirmatory information.
The clinical recommendations include minimum patient numbers. Sample
sizes are similar to those used in the daily wear contact lens
guidance. FDA has revised the guidance to clarify that a 30 patient/1-
month study is appropriate in certain matrices for products with active
ingredients within marketed concentrations, as well as for higher or
lower concentrations. Under study design, FDA has clarified the
statement that a crossover design with an in vitro analysis is an
example of a method that may be used for clearer effectiveness studies,
rather than stating that it may be the best method to use. The guidance
has been revised to include suggestions for sponsors choosing to
include data from a patient population greater than the minimum size
recommended.
In Appendix B for protocol considerations, FDA has revised the
visit schedule to delete the 2-week visit for trials conducted longer
than 1 month, provided for the use of other suitable well-defined
grading scales (e.g., International Standards Organization Scale), and
revised the investigator-patient ratio section to provide additional
guidance for the number of patients per study site.
4. One comment suggested that the title of the ``Adverse Reaction
Section'' be changed to ``Serious Adverse Reaction.'' Another comment
suggested that the discontinued eye summary

[[Page 31120]]

table be deleted. FDA disagrees with both of these comments. The first
comment invites subjectivity of reporting adverse events.
Discontinuation information could provide important safety or efficacy
information and should be reported.
Comments pertaining to preclinical information are summarized as
follows:
Concerning microbiology, most comments submitted for clarification
or minor changes in test methods have been included in the revised
guidance. Many of these comments addressed preparation of the microbial
challenge used to conduct the test. Substantive comments on the
disinfection efficacy tests, which are the stand alone and regimen
tests, addressed the panel of test organisms, the methodology, and the
performance criteria.
Concerning test organisms, one comment recommended that FDA add to
the current panel of microorganisms used for evaluating antimicrobial
efficacy.
This comment was rejected. FDA believes the current panel is
adequate for determining the substantial equivalence of newly marketed
products. Manufacturers may choose to test products against additional
microorganisms during product evaluation; however, FDA's current policy
is that labeling claims may not highlight product efficacy against
individual microorganisms.
Concerning methodology, comments addressed the need to include
organic load and biofilm in the test procedures.
FDA's position remains unchanged regarding the inclusion of organic
load to establish the substantial equivalence of disinfecting
solutions. FDA did not incorporate two separate comments on organic
load (i.e., one that suggested inclusion of a mild organic load in the
stand alone test procedure and one that recommended elimination of
organic load in the regimen test). Stand alone disinfecting products
are labeled with cleaning instructions to remove organic load. For lens
care regimens with milder disinfecting agents, it is necessary to
include removal of simulated lens deposits during cleaning and rinsing
steps.
FDA rejected a comment to evaluate biofilm in the lens case. The
issue of biofilm formation can be adequately addressed through labeling
recommendations for daily cleaning and frequent lens case replacement.
Concerns were raised on the currently recommended performance
regimen criteria of less than three colony forming units to determine
substantial equivalence of disinfecting regimens.
FDA agrees that manufacturers should have alternative performance
criteria due to limited experience with the revised regimen test
procedure. Therefore, the guidance has been revised to include an
option based on directly comparing regimen test results for the device
with those obtained for a predicate device.
FDA revised the guidance to include the experimental error (+/-0.5
log) in the performance criteria requiring stasis on yeast and mold
counts.
Based on the comments received concerning the bacteriostasis test,
the following revisions have been made in the guidance:
1. A correction to eliminate a microbial rechallenge in the
bacteriostasis test.
2. Including bacteriostasis testing outside of the actual product
container.
FDA has incorporated most suggested clarifications for chemistry
and manufacturing. Revisions include the following for chemistry:
1. A solution compatibility test has been included in all product
test matrices.
2. A wetting angle test is recommended for all conditioning
solutions in the test matrix.
3. The following example has been added as a modification not
requiring a 510(k): Nonsignificant manufacturing changes made in
accordance with 21 CFR 807.81 that meet good manufacturing practice
requirements.
Comments on the protocol for establishing shelf-life concerned
microbiology and chemistry testing.
1. FDA rejected the suggestion that sponsors should submit and/or
reference data from identically packaged contact lens care products to
support shelf-life sterility since a product formulation may affect
microbial growth during storage.
2. FDA has added the statement that manufacturing changes to
smaller bottle sizes from identical materials, using an approved shelf-
life protocol, is an example of a change not requiring a 510(k).
3. FDA has deleted the recommendation for disinfection efficacy
testing at the end of the recommended shelf life.
4. FDA has included container inversion as one example for
maximally testing the container/closure system as clarification, and
not as a specific recommendation.
5. FDA has reevaluated the recommendation for accelerated testing
for establishing shelf life beyond 2 years and the recommendation for 6
months ambient temperature data prior to marketing. The recommendation
that any shelf-life request beyond 2 years should be based on real time
data has been eliminated. The guidance recommends that companies
provide their shelf-life protocol in their 510(k) and certify that they
will have shelf-life data sufficient to support their labeled
expiration date prior to marketing their device.
Toxicology comments received on the product specific test matrices
include:
1. Replacing the current 3-day acute ocular irritation test with a
5-day test.
2. Adding an additional battery of toxicology tests for the higher
than marketed concentrations.
3. Including cytotoxicology and an ocular irritation toxicology
screening test for active ingredients within marketed concentrations
and for lower than marketed concentrations.
FDA's response to these comments are as follows:
1. The suggested 3-day acute ocular irritation test currently in
the guidance is based on historical evidence that if adverse events
occur, they will generally manifest themselves during the 3-day time
period. If a sponsor prefers the 5-day test, this is acceptable.
2. While the additional battery of tests for the higher than
marketed concentrations may be appropriate in some cases depending on
the ingredients, they are not generally appropriate for all product
specific matrices.
3. FDA agrees that toxicology screening is appropriate and the
guidance has been revised accordingly.
Several comments were received concerning labeling. Many of these
suggested editorial changes which have been incorporated in the revised
guidance. The following four labeling comments were rejected:
1. FDA has not deleted the warning, ``To Avoid Contaminating Your
Solution, Do Not Transfer to Other Bottles or Containers.'' This
warning was recommended by the Ophthalmic Devices Panel as one means of
helping to minimize contamination. FDA believes that, at a minimum,
this warning should be on larger-sized bottles.
2. Company phone numbers to which adverse reactions should be
reported is still included as a means of encouraging device reporting
back to the manufacturer.
3. Boxed warnings were included in the ``Write-it-Right'' labeling
example to provide an example of labeling developed according to
specific principles. These warnings remain in the guidance because they
are examples and not specific recommendations.

[[Page 31121]]

4. FDA has revised the labeling examples to make product-specific
warnings more direct.
FDA will continue to evaluate and amend the guidance in the future
if changes are necessary to assure the continued safety and
effectiveness of contact lens care products.

IV. Significance of a Guidance

In the past, guidances have generally been issued under
Sec. 10.90(b) (21 CFR 10.90(b)), which provides for the use of
guidances to state procedures or standards of general applicability
that are not legal requirements, but that are acceptable to FDA. The
agency is now in the process of revising Sec. 10.90(b). Therefore, this
guidance is not being issued under the authority of Sec. 10.90(b). This
guidance document represents the agency's current thinking on the tests
the agency believes necessary to provide reasonable assurance of the
safety and effectiveness of transitional contact lens care products. It
does not create or confer any rights for or on any person and does not
operate to bind FDA or the public. An alternative approach may be used
if such approach satisfies the requirements of the applicable statute,
regulations, or both.

V. Requests for Comments

Interested persons may, at any time, submit to the Dockets
Management Branch and to the contact person (addresses above) comments
on the revised guidance. Two copies of any comments should be
submitted, except that individuals may submit one copy. Comments are to
be identified with the docket number found in brackets in the heading
of this document. The revised guidance and received comments may be
seen in the office above between 9 a.m. and 4 p.m., Monday through
Friday. Comments received will be considered in future revisions of the
guidance.
FDA/CDRH maintains an entry on the World Wide Web (WWW) for easy
access to information including text, graphics, and files that may be
downloaded to a PC with access to the Web. Updated on a regular basis,
the CDRH home page includes the ``Guidance for Industry; Premarket
Notification (510(k)) for Contact Lens Care Products,'' device safety
alerts, Federal Register reprints, information on premarket submissions
(including lists of approved applications and manufacturers'
addresses), small manufacturers' assistance, information on video
conferencing and electronic submissions, mammography matters, and other
device-oriented information. The CDRH home page may be accessed at
http://www.fda.gov/cdrh. ``Guidance for Industry Premarket Notification
(510(k)) Guidance Document for Contact Lens Care Products'' will be
available on the Ophthalmic Guidance Document page at: http://
www.fda.gov/cdrh/ode/ed-op.html. A text-only version of the
CDRH Web site is also available from a computer or VT-100 compatible
terminal by dialing 1-800-222-0185 (terminal settings are 8/1/N). Once
the modem answers, press Enter several times and then select menu
choice 1: FDA Bulletin Board Service. From there follow instructions
for logging in, and at BBS Topics Page, arrow down to the FDA home page
(do not select the first CDRH entry). Then select Medical Devices and
Radiological Health for general information, or arrow down for specific
topics.

Dated: May 28, 1997.
Joseph A. Levitt,
Deputy Director for Regulations Policy, Center for Devices and
Radiological Health.
[FR Doc. 97-14750 Filed 6-5-97; 8:45 am]
BILLING CODE 4160-01-F

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Source: Frix Law Library, https://www.frixlaw.com/law-library/documents/fr%3A97-14750. Public record. Not legal advice.