75718 Federal Register / Vol. 65, No. 233 / Monday, December 4, 2000 / Notices

permit FDA to withdraw approval of the

application and has waived its

opportunity for a hearing.

EFFECTIVE DATES: January 3, 2001.

FOR FURTHER INFORMATION CONTACT:

David T. Read, Center for Drug

Evaluation and Research (HFD–7), Food

and Drug Administration, 5600 Fishers

Lane, Rockville, MD 20857, 301–594–

2041.

SUPPLEMENTARY INFORMATION: On July

10, 2000, SangCya Oral Solution

(Cyclosporine Oral Solution, USP)

Modified, 100 milligrams per milliliter,

was the subject of a class II recall under

21 CFR part 7 (Ref. 1). The recall of the

drug product, marketed under ANDA

64–195, arose from data recently

submitted by SangStat to the agency

regarding the bioavailability of the

product in healthy subjects when

administered with apple juice.

Following the recall, SangStat notified

the agency in writing on July 21, 2000,

that the company had decided to

permanently withdraw the product from

the market. On August 4, 2000, SangStat

requested in writing that the agency

withdraw approval of ANDA 64–195.

Subsequently, SangStat provided the

agency with a full and complete waiver

of the company’s right to a hearing

under section 505(e) of the Federal

Food, Drug, and Cosmetic Act (the act)

(21 U.S.C. 355(e)) to allow the agency to

complete the withdrawal of approval

under 21 CFR 314.150(d).

Therefore, under section 505(e) of the

act and under authority delegated to the

Director, Center for Drug Evaluation and

Research (21 CFR 5.82), approval of

ANDA 64–195, and all amendments and

supplements thereto, is hereby

withdrawn, effective January 3, 2001.

The effective date of the withdrawal of

approval is intended to allow patients

the opportunity to complete their

transition to another cyclosporine drug

product (see Ref. 1). Thereafter,

distribution of the product in interstate

commerce without an approved

application is illegal and subject to

regulatory action. Also, on the basis of

the circumstances described above that

led to the recall of the product and its

subsequent removal from the market,

the agency will remove the product

from the agency’s list of drug products

with effective approvals, published

under the title ‘‘Approved Drug

Products with Therapeutic Equivalence

Evaluations.’’ This document serves as

notice of the removal of the product

covered by ANDA 64–195, SangCya

Oral Solution, from the list of approved

drug products.

Reference

The following reference has been

placed on display in the Dockets

Management Branch (HFA–305), Food

and Drug Administration, 5630 Fishers

Lane, rm. 1061, Rockville, MD 20852.

The document may be seen by

interested persons between 9 a.m. and 4

p.m., Monday through Friday. The

document is available on the Internet at:

http:www//fda.gov/bbs/topics/

ANSWERS/ANS01025.html.

1. FDA Talk Paper dated July 10, 2000.

Dated: November 21, 2000.

Janet Woodcock,

Director, Center for Drug Evaluation and

Research.

[FR Doc. 00–30773 Filed 12–1–00; 8:45 am]

BILLING CODE: 3510–22–S

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Food and Drug Administration

[Docket No. 00D–1601]

Guidance for Industry and for FDA

Employees on Import Alert #66–66;

Availability

AGENCY: Food and Drug Administration,

HHS.

ACTION: Notice.

SUMMARY: The Food and Drug

Administration (FDA) is announcing the

availability of the guidance entitled

‘‘Import Alert #66–66, Detention

Without Physical Examination of API’s

That Appear To Be Misbranded Under

502(f)(1) Because They Do Not Meet the

Requirements for the Labeling

Exemptions in 21 CFR 201.122.’’ This

document provides guidance for

industry and FDA employees on FDA’s

interpretation of the Federal Food, Drug,

and Cosmetic Act (the act) and the

labeling exemptions in title 21 of the

Code of Federal Regulations regarding

bulk chemicals that can be used as

active pharmaceutical ingredients

(API’s) and may be destined for

pharmaceutical processors formulating

finished drug products. The document

includes FDA’s guidance to industry

and FDA district offices for detention

without physical examination of API’s

from certain manufacturers.

DATES: Submit written comments on the

guidance to the Dockets Management

Branch (address below) by February 2,

2001. After February 2, 2001, submit

written comments to the contact person

listed below.

ADDRESSES: Submit written requests for

single copies of the guidance document

entitled ‘‘Import Alert #66–66,

Detention Without Physical

Examination of API’s That Appear To

Be Misbranded Under 502(f)(1) Because

They Do Not Meet the Requirements for

the Labeling Exemptions in 21 CFR

201.122’’ to the Division of Import

Operations and Policy (HFC–170),

Office of Regulatory Affairs, Food and

Drug Administration, 5600 Fishers

Lane, Rockville, MD 20857. Send two

self-addressed adhesive labels to assist

that office in processing your requests.

You may fax your request to 301–594–

0413. Submit written comments on this

guidance to the Dockets Management

Branch (HFA–305), Food and Drug

Administration, 5630 Fishers Lane, rm.

1061, Rockville, MD 20852. Comments

should be identified with the docket

number found in brackets in the

heading of this document. See the

SUPPLEMENTARY INFORMATION section for

electronic access to the guidance.

FOR FURTHER INFORMATION CONTACT:

Thaddeus J. Poplawski, Division of

Import Operations and Policy (HFC–

170), Food and Drug Administration,

5600 Fishers Lane, Rockville, MD

20857, 301–443–6553.

SUPPLEMENTARY INFORMATION:

I. Background

A large volume of bulk chemicals that

can be used as API’s in human

medicines are being offered for entry

into the United States. In order to be

used as a pharmaceutical, an API is

required to be included in an FDA

approved new drug application (NDA),

abbreviated new drug application

(ANDA), or investigational new drug

application (IND).

Imported API’s labeled for further

manufacturing and processing or

labeled as chemical substances are

frequently destined for pharmaceutical

processors that formulate finished drug

products under approved NDA’s. These

drug substances, consigned to

individuals or processors who formulate

and distribute human drugs, may be

misbranded under section 502(f)(1) of

the act (21 U.S.C. 352(f)(1)).

Sponsors of IND’s frequently import

from foreign countries either the dosage

form or the API for use in laboratory

research or clinical trials.

Some persons importing API’s have

found that they could obtain entry of

these articles if they simply supply an

NDA or IND number at the point of

entry. FDA is advising its district offices

that they should be alert to the

possibility that: (1) The NDA or IND

number provided does not cover the

source of the particular API or (2) the

persons importing the API have no

authorization to refer to the particular

NDA or IND number.

Federal Register / Vol. 65, No. 233 / Monday, December 4, 2000 / Notices 75719

Section 502(f)(1) of the act provides

that API or bulk chemical that can be

used as an API must have labeling that

lists adequate directions for its use,

unless the API is subject to exemptions

from labeling found in § 201.122 (21

CFR 201.122). If the API appears not to

meet the requirements for the

exemptions in § 201.122, and also lacks

labeling listing adequate directions for

its use, the article may be subject to

refusal of admission under section

801(a)(3) of the act (21 U.S.C. 381(a)(3))

because it appears to be misbranded

under section 502(f)(1) of the act.

A. Exemption Under § 201.122

API labeling invariably lacks adequate

directions for use as required by section

502(f)(1) of the act. However, such drugs

may be subject to an exemption under

§ 201.122. This regulation requires

specific labeling on the package when

adequate directions for use are missing,

such as ‘‘Caution: For manufacturing,

processing, or repacking.’’

However, the exemption under

§ 201.122 will not apply to a substance

intended for a use in the manufacture,

processing, or repacking of the API that

causes the finished article to be a new

drug, unless:

1. An approved NDA covers the

production and delivery of the API to

the application holder by persons

named in the application; or

2. If no application is approved with

respect to the API, the label statement

‘‘Caution: For manufacturing,

processing, or repacking’’ is

immediately supplemented by the

words ‘‘in the preparation of a new drug

or new animal drug limited by Federal

law to investigational use,’’ and the

delivery is made for use only in the

manufacture of such new drug or new

animal drug limited to investigational

use as provided in 21 CFR part 312 or

21 CFR 511.1.

The API/manufacturer combinations

listed in Attachment A to Import Alert

#66–66 appear to represent importations

of API’s to be used for the manufacture,

processing, or repacking of drugs that

the act and regulations require to be the

subject of an approved NDA or a valid

IND. However, either the person

receiving the API or the person

importing the API appears not to meet

the statutory and/or regulatory labeling

requirements. Further, it appears that

the agency has never inspected the

declared manufacturer’s current good

manufacturing practice for that

imported API.

B. Guidance

FDA’s district offices are provided

guidance to detain, without physical

examination, the API’s from the

manufacturers named in the attachment

to this Import Alert.

Districts may detain without physical

examination API’s from the persons

listed in Attachment A to Import Alert

#66–66 because it appears that the API

is misbranded based on its lack of

adequate directions for use as required

by section 502(f)(1) of the act and its

failure to meet the requirements of the

exemption found in § 201.122. Persons

importing these API’s may obtain

release of the detained articles if these

persons can supply evidence

establishing that the article is:

1. Intended for pharmacy

compounding that meets the

requirements of section 503A of the act

(21 U.S.C. 353a), including that the API:

(a) Is accompanied by a valid certificate

of analysis; (b) is manufactured by an

establishment registered under section

510 of the act (21 U.S.C. 360); and (c)

does not appear on a list of drugs

identified in 21 CFR 216.24, that have

been withdrawn or removed from the

market for reasons of safety or

effectiveness.

2. Intended for use in the

manufacture, processing, or repacking of

an over-the-counter (OTC) product or

prescription product that does not

require an NDA; or

3. A new animal drug, or intended for

use in the manufacture, processing, or

repacking of a new animal drug, subject

to an NADA; and, therefore, the API is

not subject to this import alert.

Persons importing API’s may obtain

release of the detained articles by

supplying evidence establishing that the

article is:

1. Intended for use in the

manufacture, processing, or repacking of

a human drug that is itself the subject

of an approved NDA, and that the API

is from the appropriate source; or

2. It is covered by IND requirements

at § 312.110(a).

This guidance is not intended to

address new animal drugs or

investigational new animal drugs

addressed by Import Alert number 68–

09. If the imported API’s are intended

for use in an NADA or INAD

(investigational new animal drug

notice), refer to Import Alert number

68–09.

If the API’s are intended for the

compounding of finished drugs by

pharmacies, persons importing the API’s

must comply with the requirements in

section 503A of the act.

This guidance does not apply to

excipients or API’s intended for use in

OTC drugs or prescription drugs that do

not require a new drug application.

II. Significance of Guidance

This Level 1 guidance is being issued

consistent with FDA’s good guidance

regulation (21 CFR 10.115; 65 FR 56468,

September 19, 2000). The guidance

represents the agency’s current thinking

on the detention without physical

examination of API’s that appear to be

misbranded under 502(f)(1) of the act

because they do not meet the

requirements for the labeling

exemptions in § 201.122. 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 applicable statutes and

regulations.

This guidance document is effective

immediately because prior public

participation to its implementation is

not feasible or appropriate due to the

risk to the public health.

III. Electronic Access

Persons with access to the Internet

may obtain the guidance at http://

www.fda.gov/ora/fiars/

oralimportlia6666.html

IV. Comments

Interested persons may submit to the

Dockets Management Branch (address

above) written comments regarding this

immediately-in-effect guidance by

February 2, 2001. After February 2,

2001, submit written comments

regarding this guidance to the contact

person (address above). Such comments

will be considered when determining

whether to amend the current guidance.

Two copies of any comments 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. The guidance document and

received comments may be seen in the

Dockets Management Branch between 9

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

Friday.

Dated: November 27, 2000.

Dennis E. Baker,

Associate Commissioner for Regulatory

Affairs.

[FR Doc. 00–30696 Filed 12–1–00; 8:45 am]

BILLING CODE 4160–01–F