Import for Export; Reporting and Recordkeeping Requirements for Unapproved or Violative Products Imported for Further Processing or Incorporation and Subsequent Export

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 1

[Docket No. 98N-0496]

RIN 0910-AB24

Import for Export; Reporting and Recordkeeping Requirements for

Unapproved or Violative Products Imported for Further Processing or

Incorporation and Subsequent Export

AGENCY: Food and Drug Administration, HHS.

ACTION: Proposed rule.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA) is proposing reporting

and recordkeeping regulations to implement certain sections of the

Federal Food, Drug, and Cosmetic Act (the act) as amended by the FDA

Export Reform and Enhancement Act of 1996. The proposed rule would

require an importer to report to FDA each time it imports an unapproved

or otherwise violative article that is to be exported after further

processing or incorporation into another product in the United States

and to keep records to ensure that the article is so processed or

incorporated and then exported, and that any portion of the import that

is not exported is destroyed.

DATES: Submit written comments by February 8, 1999. Written comments on

the information collection requirements should be submitted by December

24, 1998.

ADDRESSES: Submit written comments to the Dockets Management Branch

(HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061,

Rockville, MD 20852. Submit written comments on the information

collection requirements to the Office of Information and Regulatory

Affairs, OMB, New Executive Office Bldg., 725 17th St. NW., Washington,

DC 20503. Attn: Desk Officer for FDA.

FOR FURTHER INFORMATION CONTACT:

For general information: Marvin A. Blumberg, Division of Import

Operations and Policy (HFC-171), Food and Drug Administration, 5600

Fishers Lane, Rockville, MD 20857, 301-443-6553.

For information concerning blood products: Kimberly A. Cressotti,

Division of Case Management (HFM-610), Center for Biologics Evaluation

and Research, Food and Drug Administration, 1401 Rockville Pike, suite

200N, Rockville, MD 20852-1448, 301-827-6201.

SUPPLEMENTARY INFORMATION:

I. Background

The FDA Export Reform and Enhancement Act of 1996 (Pub. L. 104-134,

amended by Pub. L. 104-180, August 6, 1996) became law on April 26,

1996. One provision of the new law, now codified at section 801(d)(3)

of the act (21 U.S.C 381 (d)(3)), allows importation of any component

of a drug, component part or accessory of a device, or other article of

device requiring further processing, and any food or color additive, or

dietary supplement, if it is to be further processed or incorporated

into a product that is to be exported from the United States by the

initial owner or consignee in accordance with section 801(e) or 802 of

the act (21 U.S.C 382), or section 351(h) of the PHS Act (42 U.S.C. 262

(h)). (For purposes of section 801(d) of the act, FDA interprets the

term ``component'' broadly to include anything used in, or in the

manufacture of, a drug, biologic, or device, as well as a finished

final product that will be further processed in the United States.

Thus, for example, the term includes bulk drugs, unapproved foreign

versions of drugs approved for use in the United States, active and

inactive ingredients of a drug or biologic, pieces of a device, and

completed devices.) Under section 801(d)(3) of the act, the initial

owner or consignee must submit a statement regarding the imported

article to FDA at the time of initial importation. Any component of a

drug; any component, part, article, or accessory of a device; any food

additive, color additive; or any dietary supplement imported under

section 801(d) of the act that is not incorporated or further processed

by the initial owner or consignee must be destroyed or exported (see

section 801(d)(3)(C) of the act). Section 801(d)(3)(B) of the act

further requires the initial owner or consignee to maintain records

identifying the use and exportation or disposition of the imported

article, including portions that were destroyed, and, upon request from

FDA, to submit a report that accounts for the exportation or

disposition of the imported article and the manner in which the initial

owner or consignee complied with the requirements in section 801(d) of

the act.

This provision of the act is generally known as the ``import-for-

export'' provision.

Another new provision, now codified at section 801(d)(4) of the

act, places additional requirements on the import-for-export of blood,

blood components, source plasma, source leukocytes, or a component,

accessory, or part (hereinafter referred to as ``blood products''), and

of tissue and components or parts of tissue. Section 801(d)(4) of the

act prohibits the importation of blood products unless they comply with

section 351(a) of the PHS Act or FDA permits the importation under FDA-

determined appropriate circumstances and conditions. (Section 351(a) of

the PHS Act pertains to the licensing of biological products.)

Section 801(d)(4) of the act also prohibits the importation of

tissues and their components, under section 801(d)(3) of the act,

unless the importation complies with section 361 of the PHS Act (42

U.S.C. 264). Section 361 of the PHS Act authorizes FDA to issue

regulations to control communicable disease, and, for human tissues

intended for transplantation, these regulations are found at part 1270

(21 CFR part 1270). FDA, therefore, interprets section 801(d)(4) of the

act as meaning that a person importing human tissue for transplantation

for further processing or incorporation into a product destined for

export must comply with part 1270. Under Sec. 1270.42 published in the

Federal Register of July 29, 1997 (62 FR 40429), the importer of record

must notify the director of the FDA district having jurisdiction over

the port of entry or notify his or her designee, and the human tissue

must be quarantined until released by FDA.

Human tissue intended for transplantation may be imported and

further processed or incorporated into other products without meeting

the screening and testing requirements of part 1270 if the human tissue

is kept in quarantine at all times (see Sec. 1270.3

[[Page 64931]]

(definition of ``quarantine'')). However, as indicated in Sec. 1270.31

(62 FR 40429, July 29, 1997), the owner or consignee in the United

States must prepare and follow written procedures for designating and

identifying quarantined human tissue and preventing infectious disease

contamination or cross-contamination during processing.

FDA considers live animal cells, tissues, and organs intended to be

transplanted, implanted, or used for ex-vivo perfusion in humans

(xenogeneic products) to be biological products. Nonliving animal

cells, tissues, and organs intended for transplantation or implantation

into humans may be either biological products or devices. Animal cells,

tissues, and organs imported into the United States under section

801(d) of the act which FDA considers to be biological products or

devices would be expected to comply with proposed Sec. 1.84(b).

All veterinary biologics (e.g., vaccines, bacterins, allergens,

antibodies, antitoxins, toxoids, etc.) and animal-origin materials that

could represent a disease risk to U.S. livestock, including animal

products, by-products, and biological materials that contain or have

been in contact with certain organisms or animal materials) are

regulated by the U.S. Department of Agriculture's (USDA) Animal and

Plant Health Inspection Service. An importer must obtain a USDA permit

before importing any of these materials.

The proposed rule would establish the requirements for requesting a

determination from FDA to allow importation of blood products, and

would establish reporting, labeling, and recordkeeping requirements for

all imported articles under the import-for-export provision. These

would be the minimum requirements necessary to comply with the import-

for-export provision in the act and are intended to enable the importer

to ensure, and the agency to monitor, that imported substances are

further processed or incorporated into one of the specified FDA-

regulated products while in the United States, and are then exported or

destroyed without entering domestic commerce. Although the act does not

define the term ``further processed,'' given the legislative intent to

allow manufacturing and processing activities not previously permitted

under the act, FDA interprets the term ``further processed'' to cover a

wide range of activities, including packaging or labeling of finished

products and specialized processing (such as sterilization) of a

product. However, the agency does not consider a product to be

``further processed'' if it is merely stored in the United States

before being exported elsewhere.

II. Description of the Proposed Rule

A. Request for Determination Regarding the Importation of Blood, Blood

Components, Source Plasma, Source Leukocytes, or Their Components,

Accessories, or Parts

As stated earlier, section 801(d)(4) of the act prohibits the

importation of blood, blood components, source plasma, or source

leukocytes, or ``a component, accessory, or part thereof,'' unless they

comply with section 351(a) of the PHS Act or meet ``appropriate

circumstances and conditions'' as determined by FDA. The agency

interprets the phrase concerning compliance with section 351(a) of the

PHS Act as requiring products to be licensed, and also interprets

section 801(d)(4) of the act to include blood or plasma derivatives or

intermediates. With respect to the determination of ``appropriate

circumstances and conditions,'' FDA interprets the phrase as applying

to unlicensed blood products and will decide on a case-by-case basis

whether blood products that do not comply with section 351(a) of the

PHS Act should be allowed into the United States under section

801(d)(4) of the act. This decision will be based, in part, on the

agency's assessment of the adequacy of the safeguards to prevent

diversion into U.S. commerce, contamination of, or commingling with

products licensed or approved by FDA for use in the United States.

Consequently, proposed Sec. 1.84(a) would describe the process for

requesting a determination that an unlicensed blood product meets the

appropriate circumstances and conditions to allow its importation into

the United States. Proposed Sec. 1.84(a)(1) would require a person who

intends to import an unlicensed blood product into the United States

for further processing or incorporation into a product destined for

export to request a determination from FDA before importing the blood

product. The request, under proposed Sec. 1.84(a)(2), would contain the

following:

1. The names and addresses of the foreign manufacturer of the

article to be imported and the initial owner or consignee in the United

States that would be responsible for the further processing or

incorporation of the article into another product;

2. The specific identity of the article to be imported and details

as to how it will be further processed or incorporated into a product

for export;

3. A description of the standard operating procedures and

safeguards that will be used to ensure that the imported articles or

products incorporating the imported articles are not diverted to

domestic use in the United States and are segregated from, and not

comingled with, products or components intended for use in the United

States. For example, this may consist of quarantine procedures used for

segregating imported blood, blood components, or final products from

products intended for use in the United States and validation data for

procedures to clean equipment and facilities used for manufacturing

both products for use in the United States and for manufacturing

products for export;

4. General donor screening documentation or criteria, in English.

The request for determination should not include individual donor

screening questionnaires;

5. A copy of the product label translated (if necessary) into

English (described in greater detail below); and

6. A certification that all blood and blood products will be tested

for infectious disease agents such as HIV-1, HIV-2, hepatitis B virus,

hepatitis C virus, HTLV-I, HTLV-II, and Treponema pallidum. Proposed

Sec. 1.84(a) would permit the infectious agent tests to be performed

using test kits other than those licensed or approved by FDA; in such

cases, a copy of the labeling, including manufacturer's test kit

instructions, for the test kit used, translated into English, would be

included in the request for determination.

Requests for determination, under proposed Sec. 1.84(a)(3), would

be submitted to the Division of Case Management (HFM-610), Center for

Biologics Evaluation and Research (CBER). CBER will develop procedures

and timeframes for reviewing these requests.

A request for determination would be submitted to and approved by

CBER before importation of the first shipment of the unlicensed

biological product. Once CBER has approved a request for determination,

future shipments of the same product may be imported for export without

an additional request for determination so long as the importer,

consignee, and all other conditions upon which the determination was

based remain unchanged.

Proposed Sec. 1.84(a)(4) would require the initial owner or

consignee to maintain records regarding the request for determination

and to make those records available to FDA upon request.

[[Page 64932]]

Under proposed Sec. 1.84(a)(5), FDA would notify, in writing, the

person requesting the determination if the agency grants permission to

import the blood product.

These proposed regulations for blood, blood components, source

plasma, source leukocytes, or their components, accessories, or parts

are intended to help prevent any recurrence of situations in which

blood products not approved for use in the United States are used in

products that are then distributed into U.S. commerce. In one such

case, a manufacturer imported unlicensed source plasma for use in the

manufacture of hepatitis test kits, and these kits were later

distributed in the United States. Consistent with section 801(d)(4) of

the act, the agency is proposing rules to ensure that blood products

that are not licensed or approved for use in the United States are not

used in products distributed in the United States.

B. Reporting Requirements

As stated earlier, section 801(d)(3)(A) of the act requires the

importer to submit, ``at the time of initial importation,'' a statement

to the agency indicating that the imported article is intended to be

further processed or incorporated by the initial owner or consignee

into a drug, biological product, device, food, food additive, color

additive, or dietary supplement that will be exported by such owner or

consignee from the United States in compliance with section 801(e) or

802 of the act or section 351(h) of the PHS Act.

Accordingly, proposed Sec. 1.84(b)(1) would require an importer to

submit a statement to FDA each time the importer imports an article

under the import-for-export provisions of the act. The statement would

be required each time the product enters the United States, even if the

imported article has been previously imported. The statement, under

proposed Sec. 1.84(b)(2), would include, but not be limited to, the

following:

1. A formal declaration of the purpose for which the article is

being imported prior to export (how it will be further processed, or

the name or description of the product into which it will be

incorporated in the United States), and that it will not be sold or

offered for sale in the United States;

2. The name or description of the article (including any scientific

or technical name);

3. Any product coding, batch, lot, or other identifying numbers;

4. The name and address of the foreign manufacturer of the imported

article; and

5. The name and address of the initial owner or consignee in the

United States responsible for the further processing or incorporation

of the article into another product.

For blood products, proposed Sec. 1.84(b)(2) would also require the

importer to include a copy of the determination from FDA granting

permission to import the product.

The statements would be sent to the FDA district having

jurisdiction over the port of entry at which the article will be

offered for import. Proposed Sec. 1.84(b)(3) would require the importer

to retain a copy of the statement as part of its records for the

imported article.

C. Shipping Package Label Requirements

To facilitate identification of articles imported into the United

States under the import-for-export provisions in section 801(d)(3) and

(d)(4) of the act, FDA is proposing certain label requirements for

shipping containers. Under proposed Sec. 1.84(c), the importer, initial

owner, or consignee would be responsible for permanently affixing to

the shipping container, package or crate a label, in English,

indicating that the shipping container, package, or crate contains

article(s) that are intended for export from the United States after

further processing or incorporation into another product, and may not

be sold or offered for sale in the United States. The label would also

name or describe the imported article(s); provide any product coding,

batch, lot, or other identifying numbers; provide the foreign

manufacturer's name and address; identify the imported article's

country of origin (if different from that of manufacturer); and contain

any appropriate warning or special handling label. For example, if an

imported blood product tested positive for an infectious agent,

proposed Sec. 1.84(c)(6) would require the shipping package label to

indicate the agent for which the product tested positive and

prominently display the term ``BIOHAZARD.''

D. Label Requirements for Imported Blood Products

Proposed Sec. 1.84(d) would require a foreign supplier of blood,

blood components, source plasma, source leukocytes, or a component,

accessory, or part thereof (including blood or plasma derivatives or

intermediates) that is not licensed under section 351(a) of the PHS Act

and is to be imported under section 801(d)(4) of the act, to label the

products, in English, with the following information:

1. A properly descriptive name;

2. Name(s) and address(es) of establishments collecting, preparing,

labeling, or pooling the source material;

3. Donor, lot, or pool numbers relating the unit to the donor;

4. The recommended storage temperature (in degrees Celsius);

5. The quantity of the product;

6. The statement, ``Import for Export;''

7. The statement, ``Not for Use in Products Subject to Licensure

Under Section 351 of the Public Health Service Act;''

8. The statement, ``For Manufacturing Use Only'' or ``For

Manufacturing into Noninjectable Products Only;''

9. A statement indicating that the product has been tested for

infectious disease agents, including, but not limited to, HIV-1, HIV-2,

hepatitis B virus, hepatitis C virus, HTLV-I, HTLV-II, and Treponema

pallidum. The infectious agent tests may be performed using test kits

other than those licensed or approved by FDA and should be the same

tests described in the request for determination under proposed

Sec. 1.84(a).

10. If the product tested positive for any infectious agent listed

in proposed Sec. 1.84(d)(9), the product's label would indicate the

agent(s) for which the product tested positive and display the term

``BIOHAZARD'' prominently and in bold letters; and

11. Any other appropriate warnings or special handling instructions

as determined by the importer.

A copy of the label, under proposed Sec. 1.84(a), would be included

in the initial request for determination that the blood product meets

the ``appropriate circumstances and conditions'' for importation under

section 801(d)(4) of the act.

The requirements in proposed Sec. 1.84(d) would be in addition to

the shipping package label requirements in proposed Sec. 1.84(c).

FDA also notes that regulations issued by other Federal agencies

and departments may apply to the imported products (see, e.g., 9 CFR

parts 92 et al.; 19 CFR part 12; 42 CFR part 72; 49 CFR part 173, U.S.

Postal Service regulations, 39 CFR parts 124 and 125).

E. Recordkeeping Requirements

Section 801(d)(3)(B) of the act requires that ``the initial owner

or consignee responsible for such imported article maintain records

that identify the use of such imported article.'' Proposed Sec. 1.84(e)

would require the initial owner or consignee responsible for the

article imported into the United States under the import-for-export

provision to have

[[Page 64933]]

a place of business in the United States, to maintain identifying

records for 5 years after the date on which the imported article was

exported (after further processing or incorporation into another

product) or destroyed, and to make the identifying records available

for inspection by the agency. The identifying records would include the

following information:

1. The name or description of the article (including any scientific

or technical name);

2. Any product coding, batch, lot, or other identifying numbers;

3. The name and address of the foreign manufacturer of the imported

article;

4. How the article will be or was further processed, and the name

or description of any product into which it will be or was incorporated

in the United States;

5. The signature of the responsible individual at the importing

firm;

6. The name and address of the firm in the United States where the

article will be further processed or incorporated into another product;

7. The disposition of the imported article, including quantity and

methods of disposition (i.e., manufacturing records showing how

specific articles were used or destroyed and the dates of receipt, use,

destruction, or re-exportation, as that information becomes available);

8. Any product coding, lot, batch, or other identification number

for the further-processed article or product incorporating the imported

article;

9. A copy of the label to be applied to the shipping package,

container, or crate used to export the further-processed article or

product incorporating the imported article (indicating that it contains

articles that may not to be sold or offered for sale in the United

States and are intended for export only);

10. The name and address of the foreign purchaser of the further-

processed article or product incorporating the imported article; and

11. For blood, blood components, source plasma, source leukocytes,

or a component, accessory, or part thereof (including blood or plasma

derivatives or intermediates) that is not licensed under section 351(a)

of the PHS Act and is to be imported under section 801(d)(4) of the

act, documentation of the agreement between the foreign material

supplier and the U.S. manufacturer. Proposed Sec. 1.84(e)(2)(xi) would

require this documentation to outline the specific contractual

relationship, the foreign manufacturing specifications, and the U.S.

manufacturer's plan for auditing the foreign supplier to ensure

compliance with the terms of the contract.

Additionally, proposed Sec. 1.84(e)(2)(xi) would require the

initial owner or consignee of imported blood, blood components, source

plasma, source leukocytes, or a component, accessory, or part thereof

(including blood or plasma derivatives or intermediates) to have

written standard operating procedures to ensure that such products or

articles incorporating such products are not diverted to domestic use

in the United States and are kept segregated from and are not comingled

with products or components intended for use in the United States.

These procedures could, for example, include quarantine procedures for

segregating imported blood, blood components, or final products from

products intended for use in the United States and validation data for

procedures used to clean equipment and manufacturing facilities that

produce both products for distribution in the United States and

products for export only.

FDA emphasizes that companies must also comply with the applicable

requirements of section 801(e) or 802 of the act or section 351(h) of

the PHS Act. (Persons who seek to import tissues or their parts or

components must also comply with section 361 of the PHS Act.) Those

statutory provisions may impose additional requirements on the exported

product as well as requirements on notification to FDA, labeling, and

records.

F. Registration and Listing Requirements for Persons Who Import and

Further Process or Incorporate Blood Products That Are Not Licensed

Under With Section 351(a) of the PHS Act

As an additional condition for importing blood products that are

not licensed under section 351(a) of the PHS Act, proposed Sec. 1.84(f)

would require that the person in the United States who will be further

processing or incorporating the imported article register with the FDA

and list the blood product(s) that it will be processing or

incorporating into other products or update its registration and

listing. The listing would include a description of the imported

article as well as the final product for export. The proposal would

require that the registration and listing information be sent to the

appropriate registration office listed in 21 CFR part 207 or part 607.

This registration and listing will enable FDA to track all blood

products imported under section 801(d)(4) of the act that are not

licensed under section 351(a) of the PHS Act and to monitor the

products so that they do not enter domestic commerce. Additionally, for

blood products to be exported after further manufacture into final

dosage form under section 351(h) of the PHS Act, such registration and

listing will enable FDA to evaluate, if appropriate, the person who

will be further processing or incorporating the imported article to

ensure that compliance with current good manufacturing practices, or,

consistent with section 802(f)(1) of the act, conformance with

international manufacturing standards as certified by an international

standards organization recognized by FDA, as specified by section

351(h)(3) of the PHS Act. Section 802(f)(1) of the act requires all

products exported under section 802 of the act to be in substantial

conformity with current good manufacturing practices or to meet

international standards as certified by an international standards

organization recognized by FDA. At this time, FDA has not formally

recognized any international standards or international standards

organizations for purposes of section 802(f)(1) of the act.

III. Environmental Impact

The agency has determined under 21 CFR 25.30(h) and (j) 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.

IV. Analysis of Impacts

FDA has examined the impacts of the proposed rule under Executive

Order 12866 and the Regulatory Flexibility Act (5 U.S.C. 601-612).

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).

According to Executive Order 12866, a regulatory action is

economically significant if it meets any one of a number of specified

conditions, including having an annual effect on the economy of $100

million or adversely affecting in a material way a sector of the

economy, competition, or jobs. A regulation is considered significant

under Executive Order 12866 if it raises novel legal or policy issues.

The agency believes that this proposed rule is consistent with the

regulatory philosophy and principles identified in the Executive Order.

In

[[Page 64934]]

addition the proposed rule is not a significant regulatory action as

defined by the Executive Order. The agency also believes that the

recordkeeping and reporting requirements encompassed in the proposed

rule will not have a significant effect on the economy. FDA estimates

the industry's total recordkeeping and reporting costs to be $40,000

and $61,500, respectively. These estimates are based on an estimated

cost of $100 per record and an average wage or $30 per hour for each

report (with a total of 2,050 reports). Thus, the proposed rule's cost

to industry would be $101,500.

The Regulatory Flexibility Act requires the agency to analyze

options that would minimize any significant impact of a rule on small

businesses. This proposed rule would entail only minimal reporting and

recordkeeping as necessary to identify substances and their use that

have been imported under the ``import for export'' provisions of the

act. The required reporting and recordkeeping is necessary to enable

the importer to ensure, and the agency to monitor, that such imported

substances are further processed or incorporated into another product

while in the United States, and are then exported or destroyed, as

required by the act. Indeed, the ``import-for-export'' provisions of

the act that these proposed regulations would implement might create

new economic opportunities for U.S. businesses, including small

businesses. Thus, the agency certifies that the proposed rule will not

have a significant economic impact on a substantial number of small

businesses. Therefore, under the Regulatory Flexibility Act, the agency

is not required to conduct further analysis.

V. Paperwork Reduction Act of 1995

This proposed rule contains information collection requirements

that are subject to public comment and review by the Office of

Management and Budget (OMB) under the Paperwork Reduction Act of 1995

(44 U.S.C. 3501-3520). The title, description, and respondent

description for the information collection requirements are shown below

with an estimate of the annual reporting and recordkeeping burden.

Included in the estimate is the time for reviewing instructions,

searching existing data sources, gathering and maintaining the data

needed, and completing and reviewing each collection of information.

FDA invites comments on: (1) Whether the proposed collection of

information is necessary for the proper performance of FDA's functions,

including whether the information will have practical utility; (2) the

accuracy of FDA's estimate of the burden of the proposed collection of

information, including the validity of the methodology and assumptions

used; (3) ways to enhance the quality, utility, and clarity of the

information to be collected; and (4) ways to minimize the burden of the

collection of information on respondents, including through the use of

automated collection techniques, when appropriate, and other forms of

information technology.

Title: Import for Export; FDA Export Reform and Enhancement Act of

1996; Reporting and Recordkeeping Requirements for Unapproved or

Violative Products Imported for Further Processing or Incorporation and

Subsequent Export.

Description: The proposed rule would require an importer to report

to FDA each time that it is importing an article that is to be exported

after further processing or incorporation into another product in the

United States, and to keep records enabling him to ensure, and FDA to

monitor, that the article is so processed or incorporated and then

exported, and that any portion of the import that is not exported is

destroyed. This proposed rule is to implement section 801(d)(3) and

(d)(4) of the act as amended by the FDA Export Reform and Enhancement

Act of 1996.

Description of Respondents: Persons and businesses, including small

businesses.

The estimated burden associated with the information collection

requirements for this proposed rule is 10,050 hours.

FDA estimates the burden of this collection of information as

follows:

Table 1.-- Estimated Annual Recordkeeping Burden1

----------------------------------------------------------------------------------------------------------------

Annual

21 CFR Section No. of Frequency per Total Annual Hours per Total Hours

Recordkeepers Recordkeeping Records Recordkeeper

----------------------------------------------------------------------------------------------------------------

1.84(e) 75 5 375 20 7,500

1.84(e)(xi) 25 1 25 20 500

8,000

----------------------------------------------------------------------------------------------------------------

\1\There are no operating and maintenance costs or capital costs associated with this collection of information.

Table 2.-- Estimated Annual Reporting Burden1

----------------------------------------------------------------------------------------------------------------

No. of

21 CFR Section No. Of Responses per Total Annual Hours per Total Hours

Respondents Respondent Responses Response

----------------------------------------------------------------------------------------------------------------

1.84(a) 25 1 25 46 1,150

1.84(b) 75 5 375 1 375

1.84(c) 75 5 375 1 375

1.84(d) 25 1 25 5 125

1.84(f) 25 1 25 1 25

2,050

----------------------------------------------------------------------------------------------------------------

\1\There are no operating and maintenance costs or capital costs associated with this collection of information.

The above estimates were based on normal operating burdens for the

preparation and submission of information to FDA for imported products,

the actual number of firms and import for export entries in fiscal year

(FY) 1997, and projections of the future number of firms and import for

export entries. In FY 1997, 41 firms, on 175 different occasions,

brought products into the United States under the import for export

authority at an average rate of 4.27 entries per firm (although most

firms only used the import for export authority once in FY

[[Page 64935]]

1997). The agency anticipates more firms (particularly firms involved

with blood and blood products) to use the import for export authority

in the future and, therefore, estimates the maximum number of

respondents or recordkeepers to be 75 (an increase of 29 over FY 1997).

FDA's estimates for the hours per record or report are based on

estimates from persons familiar with export operations. The records or

reports would, in many situations, be derived from normal business

records for imported products, so the burden should be very minimal and

should also be consistent with current recordkeeping practices.

The agency has submitted the information collection requirements of

this proposed rule to OMB for review. Interested persons are requested

to send comments regarding information collection by December 24, 1998,

to OMB (address above).

VI. Request for Comments

Interested persons may on or before February 8, 1999, submit to the

Dockets Management Branch (address above) written comments regarding

this notice. 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. Received comments will be on file with the Dockets Management

Branch (address above) and may be seen in that office between 9:00 a.m.

and 4:00 p.m., Monday through Friday.

List of Subjects in 21 CFR Part 1

Cosmetics, Drugs, Exports, Food labeling, Imports, Labeling,

Reporting and recordkeeping requirements.

Therefore, under the Federal Food, Drug, and Cosmetic Act, the

Public Health Service Act, and authority delegated to the Commissioner

of Food and Drugs, it is proposed that 21 CFR part 1 be amended as

follows:

PART 1--GENERAL ENFORCEMENT REGULATIONS

1. The authority citation for 21 CFR part 1 is revised to read as

follows:

Authority: 15 U.S.C. 1453, 1454, 1455; 21 U.S.C. 321, 343, 352,

355, 360b, 362, 371, 374, 381, 382, 393; 42 U.S.C. 216, 262, 264.

2. Section 1.84 is added to subpart E to read as follows:

Sec. 1.84 Import for export: Request for determination and reporting

and recordkeeping requirements for unapproved or violative products

imported for further processing or incorporation into specified

products and subsequent export.

(a) Request for determination regarding the importation of blood,

blood components, source plasma, source leukocytes, or their

components, accessories, or parts. (1) A person who intends to import

blood, blood components, source plasma, source leukocytes, or their

components, accessories, or parts (including blood or plasma

derivatives or intermediates) that are not licensed under section

351(a) of the Public Health Service Act (the PHS Act) shall, before

importing the product into the United States under section 801(d)(4) of

the Federal Food, Drug, and Cosmetic act (the act), request a

determination that such importation is permitted.

(2) The request shall contain the following information:

(i) The names and addresses of the foreign manufacturer of the

article to be imported and the initial owner or consignee in the United

States that would be responsible for the further processing or

incorporation of the article into another product;

(ii) The specific identity of the article to be imported and

details as to how the imported article will be further processed or

incorporated into a product for export;

(iii) A description of the standard operating procedures and

safeguards that the initial owner or consignee in the United States

will use or implement to ensure that the imported articles or products

incorporating such articles are segregated from and not comingled with

products, components, accessories, or parts intended for use in the

United States (e.g., quarantine procedures used for segregating

imported blood, blood components, or final products from products

intended for use in the United States, including validation data for

procedures to clean equipment and facilities used in manufacturing

products for use in the United States and products for export);

(iv) General donor screening questionnaire or criteria, translated

into English, that will be used to screen donors;

(v) A certification that tests for infectious disease will be

performed by the foreign supplier on the blood, blood components,

source plasma, or source leukocytes, or their components, accessories,

or parts (including blood or plasma derivatives or intermediates) at

the time of donation and before importation to the United States, and

the expected results of such tests. The infectious disease agents that

shall be tested for include, but are not limited to: HIV-1, HIV-2,

hepatitis B virus, hepatitis C virus, HTLV-I, HTLV-II, and Treponema

palladum. A request under paragraph (a) of this section may be based

upon infectious agent tests performed using test kits other than those

licensed or approved by the Food and Drug Administration (FDA). In such

cases, a copy of the labeling for the test kit used, translated into

English, shall be included in the submission; and

(vi) A copy of the label described in paragraph (d) of this

section.

(3) The request for determination shall be submitted to Office of

Compliance, Division of Case Management (HFM-610), Center for Biologics

Evaluation and Research, Food and Drug Administration, 1401 Rockville

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

(4) Records pertaining to the request for determination shall be

maintained and made available for FDA review upon request.

(5) If FDA determines that the blood, blood component, source

plasma, or source leukocyte, or component, accessory, or part meets the

appropriate circumstances and conditions to permit its importation into

the United States, FDA shall, in writing, notify the person requesting

the determination that it has granted permission to import the article.

(b) Reporting requirements. (1) A person wishing to import articles

specified in paragraphs (b)(l)(i) through (b)(l)(iv) of this section

that may not be sold or offered for sale in the United States, but

which the initial owner or consignee intends to have further processed

or incorporated into a drug, biological product, device, food, food

additive, color additive, or dietary supplement in the United States,

and which the initial owner or consignee will export from the United

States in accordance with sections 801(e) or 802 of the act or section

351(h) of the PHS Act, shall submit to the FDA district with

jurisdiction over the port of entry, with each import entry, a

statement containing information described in paragraph (b)(2) of this

section. The articles for which this reporting requirement apply are:

(i) A component of a drug (including a drug, veterinary drug, and

biological for use in humans);

(ii) A component part or accessory of a device, or other article of

device requiring further processing, which is ready or suitable for use

for health-related purposes;

(iii) A food or color additive; and

(iv) A dietary supplement.

[[Page 64936]]

(2) The statement that shall be supplied to FDA with each import

entry shall include, but is not limited to, the following information:

(i) A formal declaration of the purpose for which the article is

being imported before export (how it will be further processed, or the

name or description of the product into which it will be incorporated

in the United States) and that it will not be sold or offered for sale

in the United States;

(ii) The name or description of the article (including any

scientific or technical name);

(iii) Any product coding, batch, lot, or other identifying numbers;

(iv) The name and address of the foreign manufacturer of the

imported article (if different from the name of the foreign shipper

identified in the import records at the U.S. Customs Service);

(v) The name and address of the initial owner or consignee in the

United States and, if different, the address in the United States where

the article will be further processed or incorporated into any product

listed in paragraph (b)(1) of this section; and

(vi) In addition to the information described in paragraphs

(b)(l)(i) through (b)(l)(iv) of this section, for blood, blood

components, source plasma, source leukocytes, or a component,

accessory, or part thereof (including blood or plasma derivatives or

intermediates) that are not licensed under section 351(a) of the PHS

Act and are to be imported under section 801(d)(4) of the act, the

statement shall include a copy of the determination by the agency

granting permission to import the product.

(3) The initial owner or consignee also shall keep a copy of the

statement as part of its records for the article.

(c) Shipping-package label requirements. The importer, initial

owner, or consignee of articles to be imported into the United States

for further processing or incorporation into a product for export shall

permanently affix, to the articles' shipping container, package or

crate, a label that provides the following information in English:

(1) Contains article(s) that are intended for export from the

United States after further processing or incorporation into articles

intended for export, and may not be sold or offered for sale in the

United States;

(2) The name or description of the article(s) (including any

scientific or technical name);

(3) The product coding, batch, lot, or other identifying numbers;

(4) The name and address of the responsible foreign manufacturer of

the imported article(s);

(5) The country of origin (if different from that of responsible

manufacturer); and

(6) Any appropriate warning or special-handling label, such as

``BIOHAZARD'' for products potentially contaminated with an infectious

agent.

(d) Label requirements for blood products. The foreign supplier of

blood, blood component, source plasma, source leukocyte, or a

component, accessory, or part thereof (including blood or plasma

derivatives or intermediates) that is not licensed under section 351(a)

of the PHS Act and is to be imported under section 801(d)(4) of the

act, shall label the product in English with the following information:

(1) A properly descriptive name;

(2) Name(s) and address(es) of establishments collecting,

preparing, labeling, or pooling the source material;

(3) Donor, lot, or pool numbers relating the unit to the donor;

(4) The recommended storage temperature (in degrees Celsius);

(5) The quantity of the product;

(6) The statement, ``Import for Export;''

(7) The statement, ``Not for Use in Products Subject to Licensure

Under Section 351 of the Public Health Service Act;''

(8) The statement, ``For Manufacturing Use Only'' or ``For

Manufacturing into Noninjectable Products Only;''

(9) A statement indicating that the product has been tested for

infectious disease agents, including, but not limited to: HIV-1, HIV-2,

hepatitis B virus, hepatitis C virus, HTLV-I, HTLV-II, and Treponema

palladum. A request under paragraph (a) of this section may be based

upon infectious agent tests performed using test kits other than those

licensed or approved by FDA. In such cases, a copy of the label for the

test kit used, translated into English, shall accompany the request;

(10) If the product has tested positive for any infectious agent as

required in paragraph (d)(9) of this section, the product's label shall

indicate the agent(s) for which the product has tested positive, and

the term ``BIOHAZARD'' shall be prominently displayed in bold letters;

and

(11) Any other appropriate warnings or special handling

instructions as determined by the importer.

(e) Recordkeeping requirements. (1) The initial owner or consignee

who is responsible for the article offered for import shall have a

place of business in the United States.

(2) The initial owner or consignee responsible for the article

offered for import shall maintain identifying records for 5 years after

exportation or destruction of the imported article, and shall make

those identifying records available for inspection by the agency. The

identifying records shall include the following information:

(i) The name or description of the article (including any

scientific or technical name);

(ii) Any product coding, batch, lot, or other identifying numbers;

(iii) The name and address of the foreign manufacturer of the

imported article;

(iv) How the article will be or was further processed, and the name

or description of any product into which it will be or was incorporated

in the United States;

(v) The signature of the responsible individual at the importing

firm;

(vi) The name and address of the firm in the United States where

the article will be or was further processed or incorporated into

another product;

(vii) The disposition of the imported article (i.e., manufacturing

records showing how specific articles were used or destroyed and the

dates of receipt, use, destruction, or re-exportation, as that

information becomes available);

(viii) Any product coding, lot, batch, or other identification

number for the further-processed article or product incorporating the

imported article;

(ix) A copy of the label to be applied to the shipping package,

container, or crate used to export the further-processed article or

product incorporating the imported article (indicating that it contains

articles that may not be sold or offered for sale in the United States

and are intended for export only);

(x) The name and address of the foreign purchaser of the further-

processed article or product incorporating the imported article; and

(xi) Additionally, for blood, blood components, source plasma,

source leukocytes, or a component, accessory, or part thereof

(including blood or plasma derivatives or intermediates) that is not

licensed under section 351(a) of the PHS Act and is to be imported

under section 801(d)(4) of the act, the records shall include

documentation of the agreement between the foreign material supplier

and the U.S. manufacturer. The documentation shall outline the specific

contractual relationship, the foreign manufacturing specifications, and

the U.S. manufacturer's plan for auditing the foreign supplier to

ensure compliance with the terms of the contract. The initial owner or

consignee shall have written standard operating procedures to ensure

that such products are not

[[Page 64937]]

diverted to domestic use in the United States and are kept segregated

from and not comingled with products or components intended for use in

the United States (e.g., quarantine procedures used for segregating

imported blood, blood components, or final products from products

intended for use in the United States, including validation data for

procedures to clean equipment and facilities used for manufacturing

products for use in the United States and exported products).

(f) Registration and listing requirements. Each person who intends

to further process or incorporate blood, blood components, source

plasma, source leukocytes, or a component, accessory, or part thereof

(including blood or plasma derivatives or intermediates) that is not

licensed under section 351(a) of the PHS Act and is to be imported

under section 801(d)(4) of the act, shall register with FDA and list

the blood product to be further processed or incorporated into other

products, or update its registration and listing, and include in the

listing a description of the imported material as well as the final

product for export. The information shall be sent to the appropriate

registration office listed in parts 207 or 607 of this chapter.

Dated: November 14, 1998.

William K. Hubbard,

Associate Commissioner for Policy Coordination.

[FR Doc. 98-31351 Filed 11-23-98; 8:45 am]

BILLING CODE 4160-01-F