Federal Register / Vol. 66, No. 103 / Tuesday, May 29, 2001 / Notices 29149

Polyvalent Bacterial Vaccines with ‘‘no

U.S. Standard of Potency,’’

manufactured by Hollister-Stier

Laboratories, LLC, U.S. license 1272,

became effective August 3, 2000. The

revocation of the biologics license for

the manufacture of Diphtheria and

Tetanus Toxoids and Pertussis Vaccine

Adsorbed, Diphtheria and Tetanus

Toxoids Adsorbed, Diphtheria Toxoid

Adsorbed, and Tetanus Toxoid

Adsorbed, manufactured by BioPort

Corp., U.S. license 1260, became

effective November 20, 2000. Other

products under these licenses are not

affected by this revocation.

FOR FURTHER INFORMATION CONTACT:

Astrid L. Szeto, Center for Biologics

Evaluation and Research (HFM–17),

Food and Drug Administration, 1401

Rockville Pike, Rockville, MD 20852–

1448, 301–827–6210.

SUPPLEMENTARY INFORMATION: In a notice

published in the Federal Register of

May 15, 2000 (65 FR 31003), FDA

issued a proposed order to accept the

conclusions and recommendations of

the Vaccines and Related Biological

Products Advisory Committee

(VRBPAC) and the Panel on Review of

Allergenic Extracts (the Allergenics

Panel) concerning the safety,

effectiveness, and labeling of certain

bacterial vaccines and related biological

products that were previously classified

into Category IIIA (remaining on the

market pending further studies in

support of effectiveness). On the basis of

the Allergenics Panel and the VRBPAC

findings, FDA proposed to reclassify

certain Category IIIA products into

Category I (safe, effective, and not

misbranded) or Category II (unsafe,

ineffective, or misbranded). This action

was taken under the reclassification

review procedures specified in 21 CFR

601.26. The proposed order also

announced the agency’s intention to

revoke the biologics licenses for those

bacterial vaccines and related products

classified as Category II (unsafe,

ineffective, or misbranded).

Certain Category IIIA bacterial

vaccines and toxoids with standards of

potency listed in the proposed order

were classified into two categories based

upon their use as a primary immunogen

or as a booster. Diphtheria and Tetanus

Toxoids Adsorbed, and Tetanus Toxoid

Adsorbed manufactured by BioPort

Corp. were recommended by the

VRBPAC for classification into Category

II (unsafe, ineffective, or misbranded)

for primary immunization and Category

I (safe, effective, and not misbranded)

for booster immunization.

Similarly, certain bacterial vaccines

and related biological products listed in

the proposed order were recommended

for classification into Category II for

both diagnosis and immunotherapy by

the Allergenics Panel. Polyvalent

Bacterial Vaccines with ‘‘no U.S.

Standard of Potency,’’ manufactured by

Hollister-Stier Laboratories, LLC, was

recommended for classification into

Category II for both diagnosis and

immunotherapy by the Allergenics

Panel.

FDA agreed with the

recommendations of the VRBPAC and

the Allergenics Panel to reclassify the

above cited products into Category II for

their respective indications, and in the

proposed order provided notice of the

agency’s intent to revoke the licenses to

manufacture these products. On June

19, 2000, Hollister-Stier Laboratories,

LLC, submitted a letter to FDA

voluntarily requesting revocation of its

license to manufacture Polyvalent

Bacterial Vaccines with ‘‘no U.S.

Standard of Potency.’’ On August 9,

2000, BioPort Corp. submitted a letter to

FDA voluntarily requesting revocation

of its license to manufacture Diphtheria

and Tetanus Toxoids Adsorbed, and

Tetanus Toxoid Adsorbed. In its August

9, 2000, letter, BioPort Corp. also

voluntarily requested revocation of its

license to manufacture Diphtheria and

Tetanus Toxoids and Pertussis Vaccine

Adsorbed, and Diphtheria Toxoid

Adsorbed, although these products were

not included in the proposed order.

The proposed order announced that

the agency would publish a notice of

opportunity for a hearing on the

revocation of the license of each product

classified in Category II. BioPort Corp.

and Hollister-Stier Laboratories waived

their opportunity for a hearing when

they voluntarily requested license

revocation for their reclassified Category

II products.

Accordingly, under the provisions of

21 CFR 601.5(a), section 351 of the

Public Health Service Act, and under

authority delegated to the Commissioner

of Food and Drugs (21 CFR 5.10) and

redelegated to the Director, Center for

Biologics Evaluation and Research (21

CFR 5.68), FDA revoked the biologics

license issued to Hollister-Stier,

Laboratories, LLC, U.S. license 1272, for

the manufacture of Polyvalent Bacterial

Vaccines with ‘‘no U.S. Standard of

Potency,’’ effective August 3, 2000; and

FDA revoked the biologics license

issued to BioPort Corp., U.S. license

1260, for the manufacture of Diphtheria

and Tetanus Toxoids and Pertussis

Vaccine Adsorbed, Diphtheria and

Tetanus Toxoids Adsorbed, Diphtheria

Toxoid Adsorbed, and Tetanus Toxoid

Adsorbed effective November 20, 2000.

Dated: May 9, 2001.

Kathryn C. Zoon,

Director, Center for Biologics Evaluation and

Research.

[FR Doc. 01–13306 Filed 5–25–01; 8:45 am]

BILLING CODE 4160–01–S

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Food and Drug Administration

[Docket No. 96P–0484]

Blood Products Advisory Committee,

Medical Devices Panel;

Reclassification of Autopheresis-C

System From Class III to Class II

AGENCY: Food and Drug Administration,

HHS.

ACTION: Notice of panel

recommendation.

SUMMARY: The Food and Drug

Administration (FDA) is issuing for

public comment the recommendation of

the Blood Products Advisory

Committee, Medical Devices Panel (the

Panel) to reclassify the Autopheresis-C

System, intended for routine collection

of blood and blood components, from

class III to class II. The Panel made this

recommendation after reviewing the

reclassification petition submitted by

Baxter Healthcare Corp. (Baxter). FDA is

also issuing for public comment its

tentative findings on the Panel’s

recommendation. After considering any

public comments on the Panel’s

recommendation and FDA’s tentative

findings, FDA will approve or deny the

reclassification petition by order in the

form of a letter to the petitioner. FDA’s

decision on the reclassification petition

will be announced in the Federal

Register.

DATES: Submit written comments by

August 13, 2001.

ADDRESSES: Submit written comments

to the Dockets Management Branch

(HFA–305), Food and Drug

Administration, 5630 Fishers Lane, rm.

1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT:

Paula S. McKeever, Center for Biologics

Evaluation and Research (HFM–17),

Food and Drug Administration, 1401

Rockville Pike, Rockville, MD 20852–

1448, 301–827–6210.

SUPPLEMENTARY INFORMATION:

I. Background (Regulatory Authorities)

The Federal Food, Drug, and Comestic

Act (the act) (21 U.S.C. 301 et seq.), as

amended by the Medical Device

Amendments of 1976 (the 1976

amendments) (Public Law 94–295), the

29150 Federal Register / Vol. 66, No. 103 / Tuesday, May 29, 2001 / Notices

Safe Medical Devices Act of 1990

(Public Law 101–629), and the Food and

Drug Administration Modernization Act

of 1997 (Public Law 105–115),

established a comprehensive system for

the regulation of medical devices

intended for human use. Section 513 of

the act (21 U.S.C. 360c) established

three categories (classes) of devices,

depending on the regulatory controls

needed to provide reasonable assurance

of their safety and effectiveness. The

three categories of devices are class I

(general controls), class II (special

controls), and class III (premarket

approval).

Under section 513 of the act, devices

that were in commercial distribution

before May 28, 1976 (the date of

enactment of the 1976 amendments),

generally referred to as preamendments

devices, are classified after FDA has: (1)

Received a recommendation from a

device classification Panel (an FDA

advisory committee); (2) published the

Panel’s recommendation for comment,

along with a proposed regulation

classifying the device; and (3) published

a final regulation classifying the device.

FDA has classified most

preamendments devices under these

procedures.

Devices that were not in commercial

distribution prior to May 28, 1976,

generally referred to as postamendments

devices, are classified automatically by

statute (section 513(f) of the act) into

class III without any FDA rulemaking

process. Those devices remain in class

III and require premarket approval,

unless and until the device is

reclassified into class I or II or FDA

issues an order finding the device to be

substantially equivalent, under section

513(i) of the act, to a predicate device

that does not require premarket

approval. The agency determines

whether new devices are substantially

equivalent to previously offered devices

by means of premarket notification

procedures in section 510(k) of the act

(21 U.S.C. 360(k)) and 21 CFR part 807

of the regulations.

A preamendments device that has

been classified into class III may be

marketed, by means of premarket

notification procedures, without

submission of a premarket approval

application (PMA) until FDA issues a

final regulation under section 515(b) of

the act (21 U.S.C. 360e(b)) requiring

premarket approval.

Reclassification of classified

postamendments devices is governed by

section 513(f)(3) of the act. This section

provides that FDA may initiate the

reclassification of a device classified

into class III under section 513(f)(1) of

the act, or the manufacturer or importer

of a device may petition the Secretary of

Health and Human Services (the

Secretary) for the issuance of an order

classifying the device in class I or class

II. FDA’s regulations in § 860.134 (21

CFR 860.134) set forth the procedures

for the filing and review of a petition for

reclassification of such class III devices.

In order to change the classification of

the device, it is necessary that the

proposed new class have sufficient

regulatory controls to provide

reasonable assurance of the safety and

effectiveness of the device for its

intended use.

Under section 513(f)(3)(B)(i) of the

act, the Secretary may, for good cause

shown, refer a petition to a device

classification panel. The Panel shall

make a recommendation to the

Secretary respecting approval or denial

of the petition. Any such

recommendation shall contain: (1) A

summary of the reasons for the

recommendation, (2) a summary of the

data upon which the recommendation is

based, and (3) an identification of the

risks to health (if any) presented by the

device with respect to which the

petition was filed.

II. Regulatory History of the Device

The Autopheresis-C System,

intended for the routine collection of

blood and blood components, is a

postamendments device classified into

class III under section 513(f)(1) of the

act. Therefore, the device can not be

placed in commercial distribution for

the routine collection of blood and

blood components unless it is

reclassified under section 513(f)(3) of

the act, or subject to an approved PMA

under section 515 of the act. This action

is taken in accordance with section

513(f)(3) of the act and § 860.134 of the

regulations, based on information

submitted in a petition for

reclassification by Baxter on June 17,

1996, requesting reclassification of the

Autopheresis-C System, intended for

routine collection of blood and blood

components, from class III to class II.

Although Baxter submitted its petition

for reclassification under section 513(e)

of the act, the request should have been

submitted under section 513(f)(3), and

therefore FDA has considered the

petition filed under section 513(f)(3).

Consistent with the act and the

regulation, FDA referred the petition to

the Panel for its recommendation on the

requested change in classification. The

Panel met on September 26, 1996, at a

public meeting.

III. Device Description

The Autopheresis-C System,

intended for routine collection of blood

and blood components, is an automated

plasmapheresis system. It utilizes a

spinning membrane separation device to

achieve rapid and gentle separation by

filtration of whole blood into

concentrated cellular components for

reinfusion and into plasma for

collection.

The instrument uses a system of

pumps and sensors controlled by a

microprocessor and it incorporates a

variety of safety and alarm system

functions. It uses a fully automated

processing program to collect a preset

volume of plasma from a donor. Plasma

collection in the Autopheresis-C

System involves sequential phases of

collection of plasma from the donor and

reinfusion of the residual red blood cell

concentrate back to the donor.

The Autopheresis-C System is

currently employed in commercial

plasma centers where it is used to

collect Source Plasma, and it is also

found in blood centers and hospital

blood banks where it is used for the

collection of plasma for preparation of

fresh frozen plasma.

IV. Recommendations of the Panel

At a public meeting on September 27,

1996, the Panel unanimously

recommended that the Autopheresis-C

System, intended for routine collection

of blood and blood components, be

reclassified from class III to class II. The

Panel also recommended that

subsequent membrane-based blood cell

separators be classified as class II

devices, if in the opinion of FDA they

are substantially equivalent to the

Autopheresis-C System, the predicate

device. The Panel believed that class II

with the special controls of a periodic

report filed annually for a minimum of

3 years with emphasis on adverse

reactions would provide reasonable

assurance of the safety and effectiveness

of the device.

V. Risks to Health

FDA has identified the following risks

associated with apheresis blood

donation and processing: (1) The

potential loss of blood due to leaks; (2)

thrombosis due to activation of factors

by foreign surfaces; (3) toxic reaction to

citrate or heparin anticoagulant; (4)

damage to red cells, activation of

compliment, and denaturation of

proteins; (5) potential for sepsis and

fever due to bacterial contamination of

the donor’s blood returned to the donor;

(6) infectious disease risk to the donor

or to the operator due to leaks; (7)

electrical shock hazard; (8) donor stress

reaction due to removal or loss of blood;

and (9) reservoir rupture.

Federal Register / Vol. 66, No. 103 / Tuesday, May 29, 2001 / Notices 29151

1 For assistance see the guidance document

entitled ‘‘The New 510(k) Paradigm: Alternate

Approaches to Demonstrating Substantial

Equivalence in Premarket Notifications,’’ March

1998, at http://www.fda.gov/cdrh.

2 For assistance see the guidance document

entitled ‘‘Deciding When to Submit a 510(k) for a

Change to an Existing Device,’’ January 1997, at

http://www.fda.gov/cdrh.

Some of the reported adverse donor

reactions are: (1) Allergic reaction; (2)

vasovagal or syncopal reaction; (3)

citrate toxicity; (4) hematoma; (5)

hematuria or hemoglobinuria; (6)

hypovolemic reaction; (6) myocardial

infarct in three cases unrelated to the

donation procedure; (7) mesenteric

thrombosis unrelated to the donation

procedure; (8) chest pains; (9) high

blood pressure; (10) blood clotting; (11)

nonresponsive donor during or after the

donation procedure; (12) death of a

donor several days following an

apheresis unrelated to the procedure;

(13) blood spray; and (14) tubing

separation.

VI. Summary of Reasons for

Recommendation

After reviewing the data and

information contained in the petition

and provided by FDA, and after

consideration of the open discussions

during the Panel meeting and the Panel

members’ personal knowledge of and

clinical experience with the device, the

Panel gave the following reasons in

support of its recommendation to

reclassify the Autopheresis-C System,

intended for routine collection of blood

and blood components, as the predicate

device and the subsequent generic type

of filtration-based blood cell separator

for use in routine collection of donor

plasma from class III to class II.

The Panel believes that the

Autopheresis-C System and

subsequent generic type of filtrationbased blood cell separator should be

reclassified into class II because special

controls, in addition to general controls,

provide reasonable assurance of the

safety and effectiveness of the device,

and there is sufficient information to

establish special controls to provide

such assurance.

VII. Summary of Data Upon Which the

Panel Recommendation Is Based

In addition to the potential risks of

the Autopheresis-C System and

subsequent generic types of filtrationbased blood cell separators described

above, there is sufficient information

about the benefits of the device.

Specifically, the Autopheresis-C

System has been used since 1986, and

the data presented by Baxter showed no

evidence of cellular or protein damage

to the donor blood; the procedure was

well tolerated by the donor; and the

instrument was safe and effective for

plasma collection. The period from 1986

to 1996 showed that a 0.03 percent of

donations were associated with some

type of event which were reported to

Baxter.

Based on the available information,

FDA believes that the special controls

discussed below are capable of

providing reasonable assurance of the

safety and effectiveness of the

Autopheresis-C System, intended for

routine collection of blood and blood

components, and subsequent generic

types of filtration-based blood cell

separators with regard to the identified

risks to health of this device.

VIII. Special Controls

In addition to general controls, FDA

believes that the following special

control is adequate to address the risks

to health described for this device. The

manufacturer must file an annual report

with FDA on the anniversary date of

reclassification for 3 consecutive years.

A manufacturer of a device determined

to be substantially equivalent1 to the

Autopheresis-C System, intended for

routine collection of blood and blood

components, also is required to comply

with the same general and special

controls. Any subsequent change to the

device requiring the submission a

premarket notification in accordance

with section 510(k)2 of the act, should

be included in the annual report.

Unless FDA specifies otherwise, each

annual report (special control) must

include:

1. A summary of adverse donor

reactions reported by the users to the

manufacturer that do not meet the

threshold for medical device reporting

under 21 CFR part 803;

2. Any change to the device,

including but not limited to:

• new indications for use of the

device;

• labeling changes, including

operation manual changes;

• computer software changes,

hardware changes, and disposable item

changes, e.g., collection bags, tubing,

filters;

3. Equipment failures, including

software, hardware, and disposable item

failures, e.g., collection bags, tubing,

filters.

IX. FDA’s Tentative Findings

The Panel and FDA believe that the

Autopheresis-C System, intended for

routine collection of blood and blood

components, and subsequent generic

types of filtration-based blood cell

separators should be classified into class

II because special controls, in addition

to general controls, would provide

reasonable assurance of the safety and

effectiveness of the device, and there is

sufficient information to establish

special controls to provide such

assurance.

However, any change in the

indication for use, i.e., for therapeutic

purposes, would require a PMA since

these devices are not included in the

reclassification action.

X. References

The following references have been

placed on display in the Dockets

Management Branch and may be seen

by interested persons between 9 a.m.

and 4 p.m., Monday through Friday.

1. Petition for reclassification of the

Autopheresis-C System from class III to

class II by Baxter Healthcare Corp., June 17,

1996.

2. Transcript of the Blood Products

Advisory Committee, 52d Meeting,

September 27, 1996.

XI. Environmental Impact

The agency has determined under 21

CFR 25.34(b) 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.

XII. Analysis of Impacts

FDA has examined the impacts of the

notice 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 (Public Law 104–121), and

the Unfunded Mandates Reform Act of

1995 (Public Law 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 reclassification

action is consistent with the regulatory

philosophy and principles identified in

the Executive order. In addition, the

reclassification action 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

29152 Federal Register / Vol. 66, No. 103 / Tuesday, May 29, 2001 / Notices

entities. Reclassification of the device

from class III to class II will relieve

manufacturers of the cost of complying

with the premarket approval

requirements in section 515 of the act.

Because reclassification will reduce

regulatory costs with respect to this

device, it will impose no significant

economic impact on any small entities,

and it may permit small potential

competitors to enter the marketplace by

lowering their costs. The agency

therefore certifies that this

reclassification action, if finalized, will

not have a significant economic impact

on a substantial number of small

entities. In addition, this reclassification

action 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 under section 202(a) of the

Unfunded Mandates Reform Act of 1995

is not required.

XIII. Request for Comments

Interested persons may submit to the

Dockets Management Branch (address

above) written comments regarding this

document by August 13, 2001. Two

copies of any comment are to 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. Received comments may be

seen in the Dockets Management Branch

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

through Friday.

Dated: May 17, 2001.

Margaret M. Dotzel,

Associate Commissioner for Policy.

[FR Doc. 01–13302 Filed 5–25–01; 8:45 am]

BILLING CODE 4160–01–S

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Food and Drug Administration

Science Advisory Board to the

National Center for Toxicological

Research; Notice of Meeting

AGENCY: Food and Drug Administration,

HHS.

ACTION: Notice.

This notice announces a forthcoming

meeting of a public advisory committee

of the Food and Drug Administration

(FDA). At least one portion of the

meeting will be closed to the public.

Name of Committee: Science

Advisory Board to the National Center

for Toxicological Research (NCTR).

General Function of the Committee:

The board advises the Director, NCTR,

in establishing, implementing, and

evaluating the research programs that

assist the Commissioner of Food and

Drugs (the Commissioner) in fulfilling

regulatory responsibilities. The board

provides an extra-agency review in

ensuring that the research programs at

NCTR are scientifically sound and

pertinent.

Date and Time: The meeting will be

held on June 11, 2001, 1 p.m. to 5:30

p.m., and June 12, 2001, 8:30 a.m. to 1

p.m.

Location: NCTR, Bldg. #12,

Conference Center, Jefferson, AR.

Contact: Leonard M. Schechtman,

NCTR (HFT–10), Food and Drug

Administration, 5600 Fishers Lane,

Rockville, MD 20857, 301–827–6696, or

FDA Advisory Committee Information

Line, 1–800–741–8138 (301–443–0572

in the Washington, DC area), code

12559. Please call the Information Line

for up-to-date information on this

meeting.

Agenda: The board will be presented

with progress reports on the

implementation of recommendations

made by the board at its last meeting on

NCTR’s research programs in endocrine

disrupter knowledge base and

microbiology. The NCTR director will

provide a center update and a

discussion of future research directions.

A proposal will be made to the board

that it consider establishing a

subcommittee on scientific

opportunities to improve regulatory

science through collaboration with

external stakeholders. A report will be

provided to the board on the activities

of an existing subcommittee with a

similar focus (Advisory Committee for

Pharmaceutical Science, Nonclinical

Studies Subcommittee) NCTR division

directors will discuss the

accomplishments and future directions

for their divisions.

Procedure: On June 11, 2001, from 1

p.m. to 5:30 p.m., and June 12, 2001,

from 8:30 a.m. to 12 noon, the meeting

is open to the public. Interested persons

may present data, information, or views,

orally or in writing, on issues pending

before the committee. Written

submissions may be made to the contact

person by May 18, 2001. Oral

presentations from the public will be

scheduled between approximately 11

a.m. and 12 noon on June 12, 2001.

Time allotted for each presentation may

be limited. Those desiring to make

formal oral presentations should notify

the contact person before May 18, 2001,

and submit a brief statement of the

general nature of the evidence or

arguments they wish to present, the

names and addresses of proposed

participants, and an indication of the

approximate time requested to make

their presentation.

Closed Committee Deliberations: On

June 12, 2001, from 12 noon to 1 p.m.,

the meeting will be closed to permit

discussion where disclosure would

constitute a clearly unwarranted

invasion of personal privacy (5 U.S.C.

552b(c)(6)). This portion of the meeting

will be closed to permit discussion of

information concerning individuals

associated with the research programs at

NCTR.

The Commissioner approves the

scheduling of meetings at locations

outside the Washington, DC area on the

basis of the criteria of 21 CFR 14.22 of

FDA’s regulations relating to public

advisory committees.

Notice of this meeting is given under

the Federal Advisory Committee Act (5

U.S.C. app. 2).

Dated: May 22, 2001.

Linda A. Suydam,

Senior Associate Commissioner.

[FR Doc. 01–13378 Filed 5–25–01; 8:45 am]

BILLING CODE 4160–01–S

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

National Institutes of Health

Proposed Collection: Comment

Request; a Study of Motivations and

Deterrents to Blood Donation in the

United States

SUMMARY: In compliance with the

requirement of section 3506(c)(2)(A) of

the Paperwork Reduction Act of 1995,

for opportunity for public comment on

proposed data collection projects, the

National Heart, Lung, and Blood

Institute (NHLBI), the National

Institutes of Health (NIH), will publish

periodic summaries of proposed

projects to be submitted to the Office of

Management and Budget (OMB) for

review and approval.

Proposed Collection

Title: A Study of Motivations and

Deterrents to Blood Donation in the

United States. Type of Information

Collection Request: NEW. Need and Use

of Information Collection: There are

serious blood shortages in the U.S. and

the situation is predicted to worsen

unless corrective measures are initiated.

Through a randomized, anonymous

mail survey of individuals who have

donated blood at one of the five blood

centers participating in the NHLBI

Retrovirus Donor Study (REDS), this

study will examine the personal, or