EXCERPT FROM CODE OF FEDERAL REGULATIONS, TITLE 9, PART 122— ORGANISMS AND VECTORS ^*

9 CFR Ch. I (1-1-88 Edition) Animal and Plant Health Inspection Service, USDA

Part 122—Organisms And Vectors

AUTHORITY: Sec. 2, 32 Stat. 792, 37 Stat. 832–833; 21 U.S.C. 111, 151–158.

EDITORIAL NOTE: For nomenclature changes, see 36 FR 24928, Dec. 24, 1971.

§ 122.1 Definitions.

The following words, when used in the regulations in this Part 122, shall be construed, respectively, to mean:

(a)

Department. The U.S. Department of Agriculture.

(b)

Secretary. ''Secretary" means the Secretary of Agriculture of the United States, or any officer or employee of the Department to whom authority has heretofore been delegated, or to whom authority may hereafter be delegated, to act in his stead.

(c)

Veterinary Services. The Veterinary Services unit of the Department.

(d)

Deputy Administrator. The Deputy Administrator, Veterinary Services or any officer or employee of the Veterinary Services to whom authority has heretofore lawfully been delegated, or may hereafter lawfully be delegated, to act in his stead.

(e)

Organisms. All cultures or collections of organisms or their derivatives, which may introduce or disseminate any contagious or infectious disease of animals (including poultry).

(f)

Vectors. All animals (including poultry) such as mice, pigeons, guinea pigs, rats, ferrets, rabbits, chickens, dogs, and the like, which have been treated or inoculated with organisms, or which are diseased or infected with any contagious, infectious, or communicable disease of animals or poultry or which have been exposed to any such disease.

(g)

Permittee. A person who resides in the United States or operates a business establishment within the United States, to whom a permit to import or transport organisms or vectors has been issued under the regulations.

(h)

Person. Any individual, firm, partnership, corporation, company, society, association, or other organized group of any of the foregoing, or any agent, officer, or employee of any thereof.

[31 FR 81, Jan. 5, 1966]

§ 122.2 Permits required.

No organisms or vectors shall be imported into the United States or transported from one State or Territory or the District of Columbia to another State or Territory or the District of Columbia without a permit issued by the Secretary and in compliance with the terms thereof: Provided, That no permit shall be required under this section for importation of organisms for which an import permit has been issued pursuant to Part 102 of this subchapter or for transportation of organisms produced at establishments licensed under Part 102 of this subchapter. As a condition of issuance of permits under this section, the permittee shall agree in writing to observe the safeguards prescribed by the Deputy Administrator for public protection with respect to the particular importation or transportation.

(Approved by the Office of Management and Budget under control number 0579–0013)

[28 FR 7896, Aug. 2, 1963. Redesignated at 31 FR 81, Jan. 5, 1966 and amended at 48 FR 57473, Dec. 30, 1983]

§ 122.3 Application for permits.

The Secretary may issue, at his discretion, a permit as specified in § 122.2 when proper safeguards are set up as provided in § 122.2 to protect the public. Application for such a permit shall be made in advance of shipment, and each permit shall specify the name and address of the consignee, the true name and character of each of the organisms or vectors involved, and the use to which each will be put.

(Approved by the Office of Management and Budget under control number 0579–0015)

[23 FR 10065, Dec. 23, 1958. Redesignated at 31 FR 81, Jan. 5, 1966 and amended at 48 FR 57473, Dec. 30, 1983]

§ 122.4 Suspension or revocation of permits.

(a)

Any permit for the importation or transportation of organisms or vectors issued under this part may be formally suspended or revoked after opportunity for hearing has been accorded the permittee, as provided in Part 123 of this subchapter, if the Secretary finds that the permittee has failed to observe the safeguards and instructions prescribed by the Deputy Administrator with respect to the particular importation or transportation or that such importation or transportation for any other reason may result in the introduction or dissemination from a foreign country into the United States, or from one State, Territory or the District of Columbia to another, of the contagion of any contagious, infectious or communicable disease of animals (including poultry).

(b)

In cases of wilfulness or where the public health, interest or safety so requires, however, the Secretary may without hearing informally suspend such a permit upon the grounds set forth in paragraph (a) of this section, pending determination of formal proceedings under Part 123 of this subchapter for suspension or revocation of the permit.

[23 FR 10065, Dec. 23, 1958. Redesignated at 31 FR 81, Jan. 5, 1966]

STATEMENT FROM USDA'S ANIMAL AND PLANT HEALTH AND INSPECTION SERVICE ON REQUIREMENTS FOR IMPORTING CELL CULTURES ^**

IMPORTING CELL CULTURES: REQUIREMENTS TO PROTECT U.S. AGRICULTURE

Some researchers don't know it—and others have found out the hard way—but they need a permit from the U.S. Department of Agriculture to bring cell cultures into the United States. USDA's Animal and Plant Health Inspection Service requires permits for importing cells or their culture medium because of the possibility they might carry foreign animal diseases that could devastate a highly susceptible U.S. livestock population.

Cell cultures and similar materials arriving in this country without permits are confiscated and destroyed by agricultural inspectors at U.S. ports of entry. Inspectors have scientific backgrounds and don't like having to set back research. But at that point there is no alternative. Protection against introduction of organisms from abroad must be built into the import procedure ahead of time.

A major concern is foot-and-mouth disease (FMD), which is found throughout most of the world. Two of the six FMD outbreaks that occurred in the United States early in this century were traced to contaminated cowpox vaccine. FMD has not occurred in the United States since 1929, when stringent import laws were enacted.

Although scientists have exchanged cell lines for many years, there is a large increase in this activity. One reason is the great popularity of monoclonal antibodies as research tools because of their high specificity and reproducibility. Monoclonal antibodies are produced by hybridomas, which are lines of hybrid cells formed by fusing mammalian cells. Fetal calf serum, a possible source of FMD virus, is used to produce virtually all such cultures.

Before most cell lines can be imported, safety tests must be conducted at the APHIS Foreign Animal Disease Diagnostic Laboratory at Plum Island, N.Y., a high-security facility located off the northeastern tip of Long Island. Generally, the tests employ recently developed in vitro methods, which are considerably faster and less expensive than previous safety tests conducted in living animals. However, tests for FMD still require the use of live animals.

To get an import permit, complete the questionnaire "Importation Information" and fill out VS Form 16-3. Send both documents to:

Organisms and Vectors Section

Import-Export and Emergency Planning Staff

VS-APHIS-USDA

6505 Belcrest Road

Hyattsville, MD 20782

(Phone: 301-436-5453)

Applicants will be notified if a safety test is required. If so, they will be told the estimated cost, and they must then deposit funds to cover this cost. Importers bringing in cell cultures or hybridoma cells on a regular basis can establish an escrow account, which avoids the need to forward funds for each import. A minimum of four vials, each containing at least 1 million cells from a uniform lot, is required for a safety test.

The normal working time for issuing a permit, completing safety tests, and transferring the imported material is 60 to 90 days. To expedite the procedure, APHIS may issue a permit for the material to be shipped to the Foreign Animal Disease Diagnostic Laboratory at Plum Island, N.Y., pending receipt of the funds. However, actual testing will not begin until the funds are in hand. Cost of testing varies. In early 1986, an in vivo safety test using susceptible host animals cost from $2,000 to $3,000. However, it sometimes was possible to cut costs by pooling samples for host animal tests. Cost of in vitro safety tests was about $500 per test, depending on the animal diseases present in the country of origin and the intended use of the material being imported.

Safety testing may not be required for some cell cultures imported for human diagnostic or research purposes. Some examples are cultured human bone marrow cells, amniocentesis samples, or cells to be karyotyped.

Official information on Federal requirements for importing cell cultures (including hybridomas) is published in Veterinary Services Memorandum 593.1, March 11, 1986, which is available from the Organisms and Vectors Section. This group can also provide additional details and answer questions from prospective importers.

Researchers should plan their imports as far in advance as possible. That way, the actual import will proceed smoothly and expeditiously when the time comes.

VETERINARY SERVICES MARCH 1986 MEMORANDUM ON IMPORTATION OF CELL CULTURES INCLUDING HYBRIDOMAS

Veterinary Services Memorandum 593.1

I.

PURPOSE

The purpose of this memorandum is to provide updated information on importing cell cultures, including hybridomas, that may require safety testing.

II.

CANCELLATIONS

This memorandum replaces VS Notice dated June 25, 1985.

III.

POLICY

It is Veterinary Services policy that no animal-origin biological materials such as cell cultures, monoclonal antibodies, or related material may be imported into the United States without a Veterinary Services (VS) permit (VS Form 16-3A).

IV.

GENERAL

A.

To obtain an import permit, an application (VS Form 16-3) should be submitted to:

Import-Export Staff, Organisms and Vectors

VS, APHIS, USDA

6505 Belcrest Road

Hyattsville, MD 20782

A sample copy of the application (Form 16-3) is enclosed (Attachment 1). Applicants must also complete the questionnaire entitled "Importation Information" (Attachment 2) and submit it with their application.

B.

The information requested in these forms is necessary for proper evaluation of the request. Incomplete information will result in denials or delays in processing the application. Based upon the information submitted by the applicant, a determination will be made if the material to be imported requires safety testing to ensure it is free from livestock pathogens. Safety testing can be conducted at the Foreign Animal Disease Diagnostic Laboratory (FADDL), Plum Island, New York.

C.

Applicants will be advised if a safety test is required and will be given an estimate of the cost for conducting the test. Applicants desiring to have material safety tested must enter into a Cooperative Trust Fund Agreement with APHIS, VS, and deposit sufficient funds to cover the estimated cost for safety testing in advance. The Import-Export Animals and Products Staff will initiate the Cooperative Trust Fund Agreement. In order to expedite the procedure, VS may issue a permit for the material to be shipped to FADDL pending receipt of the funds and Cooperative Trust Fund Agreement. However, the signed Cooperative Agreement, plus the necessary funds, must have been received by VS before testing can be scheduled at FADDL.

D.

The normal working time for issuing a permit for importing material to Plum Island, New York, completing safety tests, and transferring the imported material to the applicant is 60 to 90 days. A minimum of four vials, each containing at least one million cells from a uniform lot, is required for a safety test.

E.

Once the safety test is completed and a determination made that the imported material is free from livestock pathogens, the remainder of the imported material will be released directly to the importer under conditions specified in the permit (Attachment 3).

F.

If an importer wishes to import cell cultures and/or hybridoma cells on a regular basis, the applicant may enter into a continuous Cooperative Trust Fund Agreement with VS and establish an escrow account to ensure no unnecessary delay will occur because of lack of funds (Attachment 4).

G.

Presently, in vivo safety tests utilizing susceptible host animals usually cost approximately $2,000 to $3,000 per test. Sometimes it is possible to reduce the cost by pooling samples in one host animal test. Scientists at FADDL have developed in vitro safety tests to detect certain livestock pathogens resulting in substantial cost savings for importers. In vitro safety tests for additional diseases are being developed. Current cost for in vitro tests is approximately $500 per test depending upon animal disease present in the country of origin and the intended use of material being imported.

H.

Safety testing may not be required for some cell cultures imported for human diagnostic purposes and research. Examples of material which would qualify without safety testing include cultured human bone marrow cells, amniocentesis samples, or cells to be karyotyped.

Applications for such cell cultures will be individually evaluated.

I.

The following classification of cell cultures is based on intended use and generally indicates the level of safety testing required.

Class I Cell cultures to be used for the production of products such as vaccines, hormones, or other biologicals to be used in livestock, poultry, or for commercial distribution.

Requirement: These cell cultures must be safety tested at FDDL using susceptible host animals, approved in vitro test, and/or laboratory animals.

Class II Cell cultures to be used only for in vitro studies and not to be used in animals other than primates.

Requirements: These cultures may not require safety testing. The material may be sent directly to the importer when no safety testing is required. The permit (VS form 16-3A) will specify restrictions such as "FOR IN VITRO LABORATORY TESTS: DO NOT INOCULATE INTO LIVESTOCK, BIRDS, OR LABORATORY ANIMALS."

J.

Cell cultures imported under permit which do not require a safety test may not be distributed to other laboratories without prior approval from USDA, APHIS, VS. Applications for the distribution of imported material should be submitted to the USDA, APHIS, VS, Import-Export Staff, Organisms and Vectors.

J.K. Atwell

Deputy Administrator

Veterinary Services

4 Enclosures

Figure

Attachment 1—VS Form 16-3 Application for Permit to Import Controlled Material or to Import or Transport Organisms or Vectors

Figure

Attachment 2—Importation Information Questionnaire for Cell Lines

Figure

Attachment 3—VS Form 16-3A Veterinary Permit, International and Domestic Control Organisms and Vectors

Attachment 4—Procedure to Complete Trust Fund Agreement for Safety Testing of Cell Cultures, Including Hybridomas

When the applicant has been advised by the Import-Export Animals and Products Staff that a safety test is required (see VS Memorandum No. 593.1, dated March 11, 1986), the following steps will be taken to obtain the Cooperative Trust Fund Agreement:

1.

A copy of the application with other pertinent information will be submitted to FADDL, Plum Island, New York, to obtain cost estimates for the required safety tests.

2.

The total cost estimate will be sent to the applicant.

3.

The Import-Export Staff will then draft the Cooperative Trust Fund Agreement.

4.

The VS Executive Office will review the draft document for policy compliance, proper format, and funding requirements.

5.

The Import-Export Staff will finalize and send five copies of the Cooperative Trust Fund Agreement to the Cooperator for signature.

6.

If the agreement is acceptable, the Cooperator will sign all copies and return the agreement to the Import-Export Staff with a check for the total cost of the tests made payable to the United States Department of Agriculture, Animal and Plant Health Inspection Service, Veterinary Services.

7.

The Import-Export staff will deliver the check and Cooperative Trust Fund Agreement to the VS Executive Office for a document number, final signature and processing.

8.

Two copies of the executed Cooperative Trust Fund Agreement will be sent to the Cooperator for their records.

9.

If an importer wishes to import cell cultures and/or hybridoma cells on a regular basis, the importer should inform the Import-Export Staff during initial discussions. The importer may enter into a continuous Cooperative Trust Fund Agreement with VS and establish a revolving trust fund account.

Figure

VS Form 16-18 Authorized Entry Label

EXCERPT FROM, AND INSTRUCTIONS BASED ON, CODE OF FEDERAL REGULATIONS, TITLE 42, PART 71—FOREIGN QUARANTINE: IMPORTATION OF ETIOLOGICAL AGENTS, HOSTS, AND VECTORS

UNITED STATES DEPARTMENT OF HEALTH AND HUMAN SERVICES

Public Health Service

42 CFR - Part 71

Foreign Quarantine

Importation of Etiological Agents, Hosts, and Vectors

§71.54. Etiological Agents, Hosts, and Vectors

(a)

A person may not import into the United States, nor distribute after importation, any etiological agent or any arthropod or other animal host or vector of human disease, or any exotic living arthropod or other animal capable of being a host or vector of human disease unless accompanied by a permit issued by the Director.

(b)

Any import coming within the provisions of this section will not be released from custody prior to receipt by the District Director of the U.S. Customs Service of a permit issued by the Director.

INSTRUCTIONS

1.

Classes of Imports Requiring Permits. It is impracticable to list all of the several hundred species of etiological agents and vectors that may be covered by §71.54. Certain classes of imports over which the maintenance of surveillance is important and for which permits must be obtained from the Director, Centers for Disease Control, Public Health Service, Department of Health and Human Services, or his/her authorized representative, follow:

a.

Any living insect, or other living arthropod, known to be or suspected of being infected with any disease transmissible to man; also, if alive, any bedbugs, fleas, flies, lice, mites, mosquitoes, or ticks, even if uninfected. This includes eggs, larvae, pupae, and nymphs as well as adult forms.

b.

Any animal known to be or suspected of being infected with any disease transmissible to man.

c.

All live bats.

d.

Unsterilized specimens of human and animal tissue (including blood), body discharges or excretions, or similar material, when known to be or suspected of being infected with disease transmissible to man.

e.

Any culture of living bacteria, virus, or similar organism known to cause or suspected of causing human diseases.

f.

Any snails capable of transmitting schistosomiasis. No mollusks are to be admitted without a permit from either the Public Health Service or the Department of Agriculture. Any shipment of mollusks with a permit from either agency should be cleared immediately.

2.

Advice to Customs. In applying this section, Customs officers may request advice of the nearest quarantine office or Program headquarters if a question should arise as to the necessity for a permit in any individual instance. In giving advice, quarantine officers should be guided by the principle that the intent of this section is to keep out of the United States communicable diseases and also vectors or hosts not commonly found in this country. When an importation does not seem likely to bring in disease or a vector or host, advice should be given to the effect that a permit is not required. In case of doubt concerning admissibility, quarantine officers should promptly make inquiry of Program headquarters.

3.

Blanket Permits. Blanket permits, limited as to time and material, are occasionally issued. The original blanket permit is retained in the office to which it is issued. When it is used as authority to import quarantinable material, a certified or photostatic copy of it should accompany the shipment. The copy is cancelled and collected as in the case of a single entry permit.

4.

To obtain an importation permit, one should complete the attached permit application form and send to: Office of Biosafety, Centers for Disease Control, Atlanta, Georgia 30333. A permit is issued to the recipient, and may be conditional upon one or more of the items indicated on the attached sample permit.

Figure

Importation or Transfer Authorization Label (CDC 0.1007)

Figure

Shipper's Declaration for Dangerous Goods (Sample Form)

Figure

EXCERPT FROM CODE OF FEDERAL REGULATIONS, TITLE 42, PART 72— INTERSTATE SHIPMENT OF ETIOLOGIC AGENTS

Figure

Notice to Carrier Label (CDC)

Footnotes

*

Code of Federal Regulations. 1988. Part 122, Organisms and Vectors, in Chapter 1, Animal and Plant Health Inspection Service.

**

Reprinted from APHIS Facts, June 1986. Washington, DC: U.S. Department of Agriculture, Animal and Plant Health Inspection Service.

The importation and interstate transport of infectious agents is subject to several federal regulations. In this appendix, most of the relevant regulations and forms are reproduced for the information of those who will use this report. Federal regulations and forms are subject to revision, and the reader is urged to consult the most up-to-date version of the Code of Federal Regulations, as well as relevant offices in the U.S. Department of Agriculture and the Public Health Service, to remain abreast of changes that may have occurred.