[Federal Register Volume 65, Number 233 (Monday, December 4, 2000)]
[Notices]
[Pages 75718-75719]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-30696]


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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.

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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.

[[Page 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 Sec. 201.122 (21 CFR 201.122). If the API appears not 
to meet the requirements for the exemptions in Sec. 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 Sec. 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 Sec. 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 Sec. 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 
Sec. 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 Sec. 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 Sec. 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/ora__import__ia6666.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