Federal Register / Vol. 60, No. 66 / Thursday, April 6, 1995 / Notices 17535

which shall be considered the filing

date for purposes of the act.

Interested persons may submit

relevant information on the application

to the Dockets Management Branch

(address above) in two copies (except

that individuals may submit single

copies) and identified with the docket

number found in brackets in the

heading of this document. These

submissions may be seen in the Dockets

Management Branch between 9 a.m. and

4 p.m., Monday through Friday.

The agency encourages any person

who submits relevant information on

the application to do so by April 17,

1995, and to provide an additional copy

of the submission directly to the contact

person identified above, to facilitate

consideration of the information during

the 30-day review period.

This notice is issued under the

Federal Food, Drug, and Cosmetic Act

(sec. 802 (21 U.S.C. 382)) and under

authority delegated to the Commissioner

of Food and Drugs (21 CFR 5.10) and

redelegated to the Center for Veterinary

Medicine (21 CFR 5.44).

Dated: March 24, 1995.

Robert C. Livingston,

Director, Office of New Animal Drug

Evaluation, Center for Veterinary Medicine.

[FR Doc. 95–8451 Filed 4–5–95; 8:45 am]

BILLING CODE 4160–01–F

[Docket No. 95D–0052]

Changes To Be Reported for Product

and Establishment License

Applications; Guidance

AGENCY: Food and Drug Administration,

HHS.

ACTION: Notice.

SUMMARY: The Food and Drug

Administration (FDA) is issuing a

guidance document entitled ‘‘Changes

to be Reported for Product and

Establishment License Applications;

Guidance.’’ The guidance document is

intended to provide manufacturers of

licensed biological products guidance

on changes in manufacturing

procedures and establishments which

may be implemented with and without

prior approval by the Director, Center

for Biologics Evaluation and Research

(CBER). This document does not apply

to manufacturers of Whole Blood, blood

components, Source Leukocytes, and

Source Plasma, and it does not address

labeling changes. By following this

guidance document, manufacturers of

licensed biologicals may, in some

instances, reduce their reporting burden

and facilitate implementation of certain

changes.

DATES: Written comments may be

submitted at any time.

ADDRESSES: Submit written comments

to the Dockets Management Branch

(HFA–305), Food and Drug

Administration, rm. 1–23, 12420

Parklawn Dr., Rockville, MD 20857.

Comments should be identified with the

docket number found in brackets in the

heading of this document. Two copies

of any comments are to be submitted

except that individuals may submit one

copy. A copy of the guidance document

and received comments are available in

the Dockets Management Branch

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

through Friday.

FOR FURTHER INFORMATION CONTACT:

Stephen M. Ripley, Center for Biologics

Evaluation and Research (HFM–635),

Food and Drug Administration, 1401

Rockville Pike, Rockville, MD 20852–

1448, 301–594–3074.

SUPPLEMENTARY INFORMATION: Under

§ 601.12 Changes to be reported (21 CFR

601.12), manufacturers are required to

report important proposed changes in

location, equipment, management and

responsible personnel, or in

manufacturing methods and labeling, of

any product for which a license is in

effect or for which an application for

license is pending, to the Director,

CBER. Such reports are to be filed by the

manufacturer not less than 30 days in

advance of the time that such changes

are intended to be made except in case

of an emergency. Proposed changes in

manufacturing methods and labeling

may not become effective until

notification of acceptance is received

from the Director, CBER.

Reporting changes under § 601.12

represents a significant workload for the

industry and the agency. In addition,

regulated industry has expressed

concern about delays in implementing

changes and inconsistencies in

reporting requirements for product

license applications (PLA’s),

establishment license applications

(ELA’s), and new drug applications

(NDA’s). To reduce the reporting burden

on manufacturers of biological products

and to facilitate the approval process,

FDA is issuing this guidance document,

which describes CBER’s current

interpretation of § 601.12(a) and (b).

The guidance document is not

intended to affect the reporting

requirements currently specified in

§ 601.12, but to provide clarifying

descriptions of the types of changes that

are currently considered to be

‘‘important’’ within the meaning of that

section. In addition, the document

clarifies the types of changes which may

be implemented 30 days after

submission of a supplement and those

which must await approval of a

supplement prior to implementation.

Thus, the guidance document outlines

three categories for reporting changes,

based on the importance and nature of

the changes. The document lists

examples of changes that would fall into

each category.

This document does not apply to

changes in manufacturing processes and

facilities associated with the

manufacture of Whole Blood, blood

components, Source Leukocytes, or

Source Plasma. CBER is currently

evaluating reporting requirements in

those areas. In addition, the guidance

document does not address labeling

changes. However, in the Federal

Register of August 3, 1994 (59 FR

39570), FDA published a notice of

availability for the revised Office of

Establishment Licensing and Product

Surveillance Advertising and

Promotional Labeling Staff (APLS)

Procedural Guidance Document. The

APLS Procedural Guidance document

details the approach that manufacturers

and distributors should follow in

submitting advertising and promotional

material for review by CBER. The APLS

Procedural Guidance Document also

provides guidance on CBER’s current

interpretation of § 601.12 as it applies to

reporting important proposed changes

in labeling; specifically, promotional

labeling of biological products for which

a license is in effect or for which an

application for a license is pending.

As with other guidance documents,

FDA does not intend this document to

be all inclusive. The document is

intended to provide information and

does not set forth requirements.

Manufacturers may follow the guidance

or may choose to use alternative

procedures even though they are not

provided in this document. If a

manufacturer chooses to use alternative

procedures, that manufacturer may wish

to discuss the matter further with CBER

to prevent expenditure of resources on

activities that FDA may later determine

to be unacceptable.

This guidance document is not

binding on either FDA or licensed

manufacturers of biological products

and does not create or confer any rights,

privileges, or benefits for or on any

person.

Interested persons may submit to the

Dockets Management Branch (address

above) written comments on the

guidance document. Received

comments will be considered to

determine if further revision to the

guidance document is necessary.

The text of the guidance document

follows:
17536 Federal Register / Vol. 60, No. 66 / Thursday, April 6, 1995 / Notices

Food and Drug Administration, Center for

Biologics Evaluation and Research (CBER),

Changes to be Reported for Product and

Establishment License Applications;

Guidance

I. Introduction and Background

A significant number of supplements to

approved biological product and

establishment license applications submitted

to CBER during an average year involve

changes which fall under § 601.12 Changes to

be reported (21 CFR 601.12).

Under this regulation, important proposed

changes in location, equipment, management

and responsible personnel, or in

manufacturing methods and labeling, are

required to be reported to CBER not less than

30 days in advance of the time such changes

are intended to be made (§ 601.12(a)).

Proposed changes in manufacturing methods

and labeling may not become effective until

notification of acceptance is received from

the Director, CBER (§ 601.12(b)).

This document is not intended to affect the

reporting requirements in § 601.12, but to

provide clarifying descriptions of those

requirements. This guidance does not apply

to manufacturers of Whole Blood, blood

components, Source Leukocytes, and Source

Plasma. Guidance on reporting requirements

in those areas is currently under evaluation

within CBER. In addition, this document

does not address labeling changes. For

guidance on the submission of advertising

and promotional material, see the Office of

Establishment Licensing and Product

Surveillance Advertising and Promotional

Labeling Staff (APLS) Procedural Guidance

Document (August 1994).

To facilitate the approval process, CBER

performed a review of the types of changes

being reported and assessed the relative

impact of each change on product purity,

potency, and safety. Results of this analysis

have provided CBER the rationale for

describing three categories of changes based

on potential effect on product safety, purity,

and potency, with each category associated

with a different notification mechanism. In

general, the types of changes for which CBER

recommends less stringent reporting

represent changes which, for the most part,

have not been associated with demonstrable

effects on product purity, potency, or safety,

and/or which are readily amenable to on-site

scrutiny during inspection of the production

facility. In many instances, manufacturers

will need to evaluate changes addressed in

the three categories using validated standard

operating procedures (SOP’s) or

specifications.

Regardless of whether a supplement is

required to be filed, the manufacturer in

making such changes must conform to the

current good manufacturing practice (CGMP)

requirements of the Federal Food, Drug, and

Cosmetic Act (21 U.S.C. 351(a)(2)(B)) and the

regulations in 21 CFR parts 210 and 211.

Changes affecting the method of manufacture

require validation under the CGMP

regulations. In addition, manufacturers must

comply with the recordkeeping requirements

under the CGMP regulations and ensure that

relevant records are readily available for FDA

inspection.

This document identifies and categorizes

the types of changes in manufacturing

processes and establishments which may be

implemented with and without prior

approval by CBER.

This guidance document is not binding on

either FDA or licensed manufacturers of

biological products and does not create or

confer any rights, privileges, or benefits for

or on any person. It does, however, describe

CBER’s current interpretation of § 601.12.

Where this document reiterates a

requirement imposed by statute or regulation,

the force and effect as law of the requirement

is not changed in any way by virtue of its

inclusion in this document.

Section A of this document contains

general definitions of each category of change

as it pertains to notification or reporting

requirements outlined in § 601.12(a) and (b).

This section also defines a Periodic Report

for Category I changes. Section B of this

document provides instruction on sending

submissions to CBER. Section C of this

document augments these definitions with

selected examples of modifications

appropriately falling under each category.

Section D of this document contains

guidance on categorizing proposed changes

which may not be listed in section C. Section

E of this document discusses the kind of

information the agency is asking

manufacturers to submit in a Periodic Report.

II. Guidance and Rationale

A. Definitions

General definitions of each category of

reporting changes are as follows:

1. Category I—Change(s) for Which No

Supplement Submission is Required and

Which May be Described in a Periodic Report

This category includes modifications to

procedures, process parameters, components,

manufacturing methods, reagents, equipment

and facilities which do not rise to the level

of the ‘‘important’’ changes required to be

reported under § 601.12. These are changes

that are designed to tighten control on the

production process, or have not been

associated with adverse impact on product

safety, purity or potency. Manufacturers

should qualify and, as necessary, validate

such changes before implementing them.

These changes should be shown not to affect

the integrity of the product. For this category,

the manufacturer generates and retains all

relevant data defining (and, as necessary,

validating) changes which are implemented.

In order to expedite the agency’s review of

changes, such data should be readily

accessible for FDA-establishment

inspections. The agency recommends that the

firm notify CBER in a Periodic Report (see

description below) of the changes and dates

of implementation.

2. Category II—Change(s) Requiring a

Supplement Submission and Which May be

Implemented Prior to CBER Approval

This category includes modifications to

location, equipment, management, and

personnel that do not change manufacturing

methods, but have the potential to adversely

affect product safety, purity, and potency.

For these changes, the manufacturer should

submit a standard supplement, accompanied

by all relevant supporting data, with a

request to implement not less than 30 days

following the supplement’s receipt by CBER’s

Document Control Center. Such supplements

should be clearly marked ‘‘Category II

Supplement, Changes to be Implemented’’ at

the top of the cover letter. CBER will confirm

the submission and its receipt date in the

reference number assignment letter. CBER

intends to follow relevant application review

policies in assigning supplement review.

CBER will process Category II changes as

establishment or product license application

supplements and will take official action on

such supplements on, before, or after this 30-

day period. If CBER officials do not contact

the sponsor via telephone or written

correspondence within 30 days following the

documented receipt date to question or reject

the ‘‘Category II’’ status, the manufacturer

may implement the change. CBER may

communicate with the firm during this 30

day period for clarification or to advise that

the change is considered to be a Category III

supplement (see description below).

Manufacturers should be aware that

Category II changes are implemented subject

to agency approval. The agency may refuse

to approve a supplement for a change that

has already been implemented. In assessing

a manufacturer’s plans to correct a problem,

the agency intends to consider the

manufacturer’s reasons for making the

change and the alternatives available to the

manufacturer, among other things. If the

circumstances warrant, the agency may

require the change to be immediately

discontinued. When circumstances permit, it

is FDA’s intent to allow manufacturers to

correct a problem with minimal expense and

without unnecessary waste.

3. Category III—Change(s) Which Require

CBER Approval Prior to Implementation

This category includes changes in

manufacturing methods and requires

manufactures to submit all relevant

supporting documentation and await CBER’s

approval prior to implementation. As with

Category II submissions, CBER intends to

follow relevant application review policies in

assigning supplement review.

4. Periodic Reports

A Periodic Report is a voluntary written

report submitted every 6 months listing and

briefly describing Category I changes and

providing the date of implementation of such

changes. Reports should include separate

descriptions of EACH change affecting a

licensed product and should identify for each

change the specific establishment location

involved. (See section E of this document for

requested information.)

B. Where to Submit Supplements and

Periodic Reports

Three copies of all supplements and

periodic reports should be submitted to the

Center for Biologics Evaluation and Research

(HFM–99), Food and Drug Administration,

1401 Rockville Pike, suite 200N, Rockville,

MD 20852–1448.
Federal Register / Vol. 60, No. 66 / Thursday, April 6, 1995 / Notices 17537

C. Selected Examples

1. Category I

CBER currently considers the following

examples to be changes that will not

ordinarily rise to the level of the ‘‘important’’

changes required to be reported under

§ 601.12. These changes need not be

submitted to CBER prior to implementation

and may be submitted in a periodic report as

‘‘Category I changes.’’ This listing provides

representative samples of Category I changes

and is not all inclusive.

i. Change in purchasing source of approved

final fill components (stoppers, vials, seals)

that meet established specifications. This

does not include change(s) in composition of

such components or suppliers of ancillary

chemicals and drug products such as

diluents.

ii. Change in harvesting and/or pooling

procedures which does not affect method of

manufacture, recovery, storage conditions,

sensitivity of detection of adventitious

agents, or production scale; e.g., collection in

smaller quantities to improve process

efficiency.

iii. Changes in cell inoculum; e.g, mode of

expansion (attached versus suspension;

bioreactor versus spinner), cell density,

staging of culture. This excludes viral

products; e.g., vaccines and in vitro

diagnostic kits.

iv. Change in storage conditions of

reference standard or panel based on stability

data generated with an FDA-approved

protocol.

v. Extension of dating period for in-house

reference standards, based on real-time data,

according to an FDA-approved protocol.

vi. Replacement of inhouse reference

standard or reference panel (or panel

member) according to FDA-approved

standard operating procedures (SOP’s) and

specifications.

vii. Tightening of specifications for

reference standard or lot release analyses.

viii. Establishment of new Working Cell

Bank derived from previously approved

Master Cell Bank according to an FDAapproved SOP.

ix. Narrowing (tightening) of specifications

for intermediates and endproducts to provide

greater assurance of product purity and

potency.

x. Use of alternative storage containers for

intermediates, with no change in sterility,

depyrogenation status, or composition of

container.

xi. Change in storage conditions of

inprocess intermediates based on data from

an FDA-approved stability protocol (labeling

not affected).

xii. Change in bulk pool size for

formulation without process scale-up.

xiii. Batch size changes for ancillary

components (specimen diluents, positive

and/or negative controls, substrate buffers,

etc.) where all equipment contact surfaces

remain chemically identical to approved

equipment.

xiv. Change in the number of vials per fill

with no scale-up or impact on parameters

defined in the environmental assessment.

xv. Change in shipping conditions (e.g.,

temperature, packaging, custody) based upon

data derived from studies following an FDAapproved protocol.

xvi. Rework of biologic product which has

failed final release testing using FDAapproved rework protocol. Note: Any lot of

product subject to rework should be so noted

on the product release protocol.

xvii. Change in stability test protocol to

include more stringent parameters; e.g.,

additional assays, tightened specifications,

etc.

xviii. Replacement of equipment with that

of identical design and operating principle

involving no change in process parameters.

xix. The following modifications of areas

not used for production or storage of

intermediate or finished product (such as

testing laboratories, materials storage,

warehouse, employee break areas, etc.):

(a) Addition of outside areas that do not

adversely affect the product

manufacturing area or utility systems;

(b) Expansion or reorganization of off-site

support space that does not affect the

product manufacturing areas;

(c) Modification to or relocation of support

space within a product manufacturing

facility that does not affect plant utility

systems and flow patterns, or adversely

affect product purity or environmental

conditions (e.g., addition of half

partitions or benches).

xx. The relocation of equipment within

appropriate areas of approved facilities, not

increasing risk to product purity or integrity

of testing (e.g., relocation of fermentor in

fermentation suite).

xxi. Upgrade in air quality, material, or

personnel flow where product specifications

remain unchanged. Involves no change in

equipment or physical structure of

production area.

xxii. Changes in personnel other than the

Responsible Head (21 CFR 600.10) or

individuals serving in a capacity of

alternative or temporary Responsible Head.

2. Category II

CBER currently considers the following

examples to be ‘‘important’’ proposed

changes in location, equipment, management

and responsible personnel. These changes

must be reported pursuant to § 601.12(a) and

meet the definition of a ‘‘Category II

Supplement.’’ This listing provides

representative samples of Category II changes

and is not all inclusive.

i. Addition of back-up systems for

manufacturing processes which are identical

to the primary system and serve as an

alternate resource (not expansion of capacity)

within an approved production area.

ii. Upgrade to production air handling or

water systems using like equipment and not

affecting established specifications; e.g.,

removal of dead legs in water for injection

(WFI) system. (Does not include replacement

of parts or routine repair and maintenance

(Category I).)

iii. Replacement of equipment with that of

similar, but not identical, design and

operating principle that does not affect the

process methodology.

iv. Expansion of existing manufacturing

support systems (WFI, heating, ventilation,

and air-conditioning (HVAC)); e.g., adding an

additional WFI loop.

v. Relocation of operations within the same

production area of an approved facility with

no change in equipment or room

classification.

vi. Modification of an approved

manufacturing area which does not adversely

affect safety, purity or potency of product;

e.g., adding new interior partitions or walls

to increase control over the environment and

replacing or adding new surfaces to enhance

cleaning.

vii. Change in Responsible Head (21 CFR

600.10) or individuals serving in a capacity

of alternative or temporary Responsible

Head.

3. Category III.

CBER currently considers the following

examples to be ‘‘important’’ proposed

changes in manufacturing methods. These

changes require CBER approval before they

may be implemented under § 601.12(b), and

meet the definition of a ‘‘Category III

Supplement.’’ This listing provides

representative samples of Category III

changes and is not all inclusive.

i. Establishment of new Master Cell Bank.

ii. Change in inhouse reference standard or

reference panel (panel member) resulting in

modification of reference specifications.

iii. Establishment of alternate test method

for reference standards, release panels,

product intermediates, or endproduct.

iv. Replacement of existing test method

with new procedure or method; e.g., change

from radioimmunoassay (RIA) to enzymelinked immunosorbent assay (ELISA).

v. Change in process parameters; e.g.,

growth cycle, chromatographic medium,

process time and/or temperature, filtration

process.

vi. Change in sequence of processing steps,

including addition of processing step; e.g.,

viral removal or inactivation.

vii. Change in production scale (up or

down) involving changes in equipment,

process parameters, or process methodology.

viii. Change in chemistry or formulation of

solutions used during processing.

ix. Changes in conjugation chemistry or

process.

x. Change in composition of the biological

product or ancillary components.

xi. Change in dosage form.

xii. Any change which results in detectable

relaxing of product specifications and

modification in potency, sensitivity, or

specificity.

xiii. Change in fill volume (per vial) from

an approved production batch size and/or

scale.

xiv. Reprocessing of product without a

previously approved reprocessing protocol.

xv. Change in stability testing program;

e.g., substitution of analytical methods or

potency assay, broadening of acceptance

criteria, change in storage temperature,

change in test algorithm.

xvi. Extension of dating period for

intermediate or endproduct.

xvii. Change in storage conditions for

licensed final product or intermediate based

on real-time data from FDA-approved

stability protocol (labeling affected).

xviii. The following changes in

manufacturing location that affect process
17538 Federal Register / Vol. 60, No. 66 / Thursday, April 6, 1995 / Notices

conditions and thereby have the potential to

affect product safety, purity, or potency:

(a) Use of a previously unapproved

manufacturing area or facility;

(b) Change in air quality, water quality,

material, or personnel flow for licensed

product manufacturing areas.

(c) Change from single product

manufacturing to multiple product

manufacturing using same equipment

and/or personnel.

(d) Renovation to physical structure that

alters product, material, and/or

personnel flow.

xix. Addition to or replacement of an FDAapproved manufacturing step performed

under contract to a second facility.

D. Categorization of Proposed Changes

Before implementing a change which is not

identified above or does not clearly fit into

one of the defined categories, manufacturers

should discuss the proposed change with

CBER. If guidance is not sought, the change

should be reported in the form of a Category

III supplement, subject to CBER approval

prior to implementation.

Requests for information regarding

categorization of proposed changes not

included in the above categories may be

addressed to the Director of the appropriate

applications Division within the Office with

assigned product, or establishment,

responsibility at the Center for Biologics

Evaluation and Research (HFM–99), Food

and Drug Administration, 1401 Rockville

Pike, suite 200N, Rockville, MD 20852–1448.

E. Information Requested for Category I

Periodic Reports

FDA requests that manufacturers submit

the following information for each Category

I change in the order shown: (1) Name of the

manufacturer; (2) the establishment license

number; (3) the report dates (time period

covered by the report); (4) the product(s)

affected (list each one); (5) the change

implemented, including: (a) A brief

description and reason for the change and/or

modification, (b) the establishment location

involved, (c) the date the change was

implemented, and (d) a cross-reference to the

Approved Validation Protocol or Standard

Operating Procedure, if applicable; and (6)

the signature of the Responsible Head and

the date signed.

Dated: March 31, 1995.

William B. Schultz,

Deputy Commissioner for Policy.

[FR Doc. 95–8382 Filed 4–5–95; 8:45 am]

BILLING CODE 4160–01–F

[Docket No. 93F–0201]

Asahi Denka Kogyo K. K.; Withdrawal

of Food Additive Petition

AGENCY: Food and Drug Administration,

HHS.

ACTION: Notice.

SUMMARY: The Food and Drug

Administration (FDA) is announcing the

withdrawal, without prejudice to a

future filing, of a food additive petition

(FAP 3B4378) proposing that the food

additive regulations be amended to

provide for the safe use of sodium 2,2′-

methylenebis(4,6-di-tert-butylphenyl)

phosphate as a clarifying agent in

polypropylene articles intended for

contact with food to include the use at

temperatures up to and including retort

conditions.

FOR FURTHER INFORMATION CONTACT:

Helen R. Thorsheim, Center for Food

Safety and Applied Nutrition (HFS–

216), Food and Drug Administration,

200 C St. SW., Washington, DC 20204,

202–418–3092.

SUPPLEMENTARY INFORMATION: In a notice

published in the Federal Register of

July 29, 1993 (58 FR 40656), FDA

announced that a food additive petition

(FAP 3B4378) had been filed by Asahi

Denka Kogyo K. K., c/o Japan Technical

Information Center, Inc., 1002

Pennsylvania Ave. SE., Washington, DC

20003. The petition proposed to amend

the food additive regulations in

§ 178.3295 Clarifying agents for

polymers (21 CFR 178.3295) to provide

for the safe use of sodium 2,2′-

methylenebis(4,6-di-tert-butylphenyl)

phosphate as a clarifying agent in

polypropylene articles

intended for contact with food to

include the use at temperatures up to

and including retort conditions. Asahi

Denka Kogyo K. K. has now withdrawn

the petition without prejudice to a

future filing (21 CFR 171.7)

Dated: March 22, 1995.

Eugene C. Coleman,

Acting Director, Office of Premarket

Approval, Center for Food Safety and Applied

Nutrition.

[FR Doc. 95–8515 Filed 4–5–95; 8:45 am]

BILLING CODE 4160–01–F

[Docket No. 94F–0121]

BASF Corp.; Withdrawal of Food

Additive Petition

AGENCY: Food and Drug Administration,

HHS.

ACTION: Notice.

SUMMARY: The Food and Drug

Administration (FDA) is announcing the

withdrawal, without prejudice to a

future filing, of a food additive petition

(FAP 3B4384) proposing that the food

additive regulations be amended to

provide for the safe use of

hydroxypropyl acrylate and butanediol

diacrylate as monomers in the

production of acrylic polymers intended

for use in food packaging adhesives.

FOR FURTHER INFORMATION CONTACT:

Diane E. Robertson, Center for Food

Safety and Applied Nutrition (HFS–

216), Food and Drug Administration,

200 C St. SW., Washington, DC 20204,

202–418–3089.

SUPPLEMENTARY INFORMATION: In a notice

published in the Federal Register of

April 25, 1994 (59 FR 19730), FDA

announced that a food additive petition

(FAP 3B4384) had been filed by BASF

Corp., 9401 Arrow Point Blvd., suite

200, Charlotte, NC 28273. The petition

proposed to amend the food additive

regulations in § 175.105 Adhesives (21

CFR 175.105) to provide for the safe use

of hydroxypropyl acrylate and

butanediol diacrylate as monomers in

the production of acrylic polymers

intended for use in food packaging

adhesives. BASF Corp. has now

withdrawn the petition without

prejudice to a future filing (21 CFR

171.7).

Dated: March 22, 1995.

Eugene C. Coleman,

Acting Director, Office of Premarket

Approval, Center for Food Safety and Applied

Nutrition.

[FR Doc. 95–8516 Filed 4–5–95; 8:45 am]

BILLING CODE 4160–01–F

Health Care Financing Administration

[BPO–130–N]

Medicare and Medicaid Programs;

Quarterly Listing of Program

Issuances and Coverage Decisions—

Fourth Quarter 1994

AGENCY: Health Care Financing

Administration (HCFA), HHS.

ACTION: Notice.

SUMMARY: This notice lists HCFA

manual instructions, substantive and

interpretive regulations and other

Federal Register notices, and statements

of policy that were published during

October, November, and December of

1994 that relate to the Medicare and

Medicaid programs. Section 1871(c) of

the Social Security Act requires that we

publish a list of Medicare issuances in

the Federal Register at least every 3

months. Although we are not mandated

to do so by statute, for the sake of

completeness of the listing, we are

including all Medicaid issuances and

Medicare and Medicaid substantive and

interpretive regulations (proposed and

final) published during this timeframe.

We are also providing the content of

revisions to the Medicare Coverage

Issues Manual published between

October 1 and December 31, 1994. On

August 21, 1989, we published the

content of the Manual (54 FR 34555)

and indicated that we will publish