Packaging and Handling of Infectious Substances and Select Agents

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Centers for Disease Control and Prevention

42 CFR Part 72

RIN 0920-AA02

Packaging and Handling of Infectious Substances and Select Agents

AGENCY: Centers for Disease Control and Prevention (CDC), HHS.

ACTION: Notice of proposed rulemaking.

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SUMMARY: The Centers for Disease Control and Prevention proposes to

[[Page 58023]]

amend the regulations concerning the interstate shipment of infectious

substances in order to clarify and expand the existing requirements for

proper packaging and handling of these agents. One purpose of the

proposed rule is to ensure that all biological materials that are known

or suspected of containing an infectious substance are packaged for

interstate shipment to minimize the potential for leakage of contents

that could contaminate the environment or come into direct physical

contact with persons handling such packages during transit. A second

purpose is to insure receipt of certain infectious substances. This new

regulation will harmonize CDC regulations with other Federal agencies'

regulations and with international regulations.

It also updates the requirements for facilities transferring or

receiving select agents, incorporating by reference the 4th edition of

the CDC/NIH publication Biosafety in Microbiological and Biomedical

Laboratories.

DATE: Written comments must be received on or before December 27, 1999.

Written comments on the proposed information collection requirements

should also be submitted on or before December 27, 1999.

ADDRESSES: Mail written comments to the following address: Nashandra

Hayes, Office of Health and Safety, Centers for Disease Control and

Prevention, 1600 Clifton Road, Mail Stop--FO5, Atlanta, Georgia 30333.

Mail written comments on the proposed information collection

requirements to: Wendy Taylor, Office of Information and Regulatory

Affairs, Office of Management and Budget, New Executive Office

Building, 725 17th Street, NW, rm. 10235, Washington, DC 20503, Att.:

Desk Officer for CDC.

FOR FURTHER INFORMATION CONTACT: Dr. Jonathan Y. Richmond or Dr.

Richard Knudsen, Office of Health and Safety, Centers for Disease

Control and Prevention, 1600 Clifton Road, NE, Mail Stop F05, Atlanta,

Georgia 30333; telephone (404) 639-2453 or 639-3235, respectively.

SUPPLEMENTARY INFORMATION:

Revised Proposed Notice of Rulemaking

Replaces NPRM at 55 FR 7678, March 2, 1990.

I. Background

Under 42 U.S.C. 264, the Department of Health and Human Services is

authorized to promulgate regulations to prevent the introduction,

transmission and spread of communicable diseases from foreign countries

and between the states. Authority was given to CDC in 1971 to regulate

the interstate shipment of infectious substances. The current

regulations are at 42 CFR part 72. The regulations provide requirements

for minimum packaging and labeling for biological products and

diagnostic specimens, and include a list of infectious agents for which

special tracking is required. These regulations were last updated in

1980.

A Notice of Proposed Rulemaking (NPRM) was published in the Federal

Register on March 2, 1990 (55 FR 7678), to update the existing

packaging requirements for infectious substances. Impetus for that NPRM

came from postal workers and members of Congress who expressed concerns

about the potential risk of exposure to infectious agents for people

who handle improperly packaged or damaged packages of biomedical

material during transit. Persons shipping these materials also stated

that some definitions in the 1980 regulation were unclear. There had

also been changes in the list of infectious agents that required

notification of receipt.

Comments on the 1990 NPRM focused on two major issues. Numerous

parties, including United States Postal Service workers, submitted

comments regarding the transport of clinical specimens for diagnostic

studies. Several parties encouraged CDC to harmonize the proposed

regulation with the international shipping regulations.

Several government agencies and industry groups, in addition to

CDC, regulate the packaging, labeling and shipment of infectious

materials within the United States and internationally.

The Department of Transportation (DOT) Hazardous Materials

regulations, at 49 CFR parts 171-180, regulate the interstate

transportation by surface or air of infectious substances, medical

waste, chemical and radioactive materials. That regulation does not

apply to the transport of clinical or diagnostic specimens, unless

specifically known to contain an infectious substance (49 CFR 173.134).

The United States Postal Service (USPS) regulates the

shipment, by U.S. mail, of etiologic agents, infectious substances,

clinical specimens, biological products, and sharps (e.g., contaminated

needles and other sharp medical materials) and unsterilized containers

(39 CFR and Domestic Mail Manual C023, Etiologic Agent Preparations,

Clinical Specimens, and Biological Products; and International Mail

Manual 135 Mailable Dangerous Goods).

The Department of Labor, Occupational Safety and Health

Administration (OSHA), at 29 CFR 1910.1030, Occupational Exposure to

Bloodborne Pathogens, regulates the worker safety aspects of the

handling, packaging and transport of human blood and body fluids,

unfixed tissues, organs and cell cultures, and other fluids from humans

and animals infected or possibly infected with bloodborne pathogens.

The Department of Commerce (DOC) maintains a list of

controlled items, including certain microorganisms that cannot be

exported from the U.S. (15 CFR parts 768-799). The DOC recommends that

shippers follow the CDC regulation for packaging when a shipment is

allowed to a foreign country.

The United Nations Committee of Experts on the Transport

of Dangerous Goods makes recommendations on the international transport

of infectious substances and clinical specimens. These recommendations

are included in the International Civil Aeronautics Organization (ICAO)

technical instructions, which have been adopted by the International

Air Transport Association (IATA).

--ICAO publishes Technical Instructions for the Safe Transport of

Dangerous Goods by Air, based on the United Nations (UN)

recommendations for the domestic and international transport of

infectious substances and clinical (diagnostic) specimens.

--IATA publishes the Dangerous Goods Regulations (DGR), which further

describe for IATA member airlines, the national and international

recommendations for air transport of infectious substances and clinical

(diagnostic) specimens. The IATA DGR are followed by the domestic and

international member airlines.

CDC's regulation, currently at 42 CFR part 72, provides packaging

and labeling requirements for shipments of infectious materials. There

are several reasons why CDC regulates this area in addition to the

other agencies listed above. The focus of the CDC regulation is on

protection of the public health by minimizing the potential for (1)

Direct physical contact with package contents by persons handling such

packages during transit, (2) Contamination of the environment, and (3)

The spread of disease into the community. The CDC regulations serve by

filling the gaps where there is no governance, by complementing the

requirements of other agencies where there is overlapping authority,

and by providing CDC as a central reporting authority assures

availability of CDC's infectious

[[Page 58024]]

disease expertise to assist in the response when packages are damaged.

Although there had been some review of the requirements of other

agencies when developing the 1990 NPRM, there had not been any

comprehensive attempt to harmonize the various requirements. When

comments to the 1990 NPRM were reviewed, it became clear that there was

confusion among shippers and handlers as to how all the various

requirements of other agencies related to the CDC regulations. Because

of substantive differences in the requirements and use of different

terminology, there was a clear need to harmonize the various

requirements.

In response to the comments on the 1990 NPRM, and as part of the

regulatory reform/reinventing government initiative, CDC has

collaborated with the other agencies and groups to prepare revised

proposed CDC regulations that are in harmony with the other

requirements, thereby reducing the burden on shippers while still

maintaining, or even improving, packaging standards to protect the

public health. In some instances, one or more of the other agencies/

groups will also be revising their requirements as part of our joint

effort to achieve complementary regulations. We invite specific comment

on any requirements contained in the proposed CDC regulations which are

thought to be inconsistent or unclear in relation to the requirements

of any other regulatory authority.

CDC also serves as a Center for Applied Biosafety and Training for

the World Health Organization (WHO) and for the UN. In conjunction with

the National Institutes of Health, CDC has participated in developing

revised international guidelines for the shipment of infectious

materials and diagnostic specimens. This NPRM also reflects the

recommendations of the WHO biosafety advisory group, as published in

1997, in Guidelines for the Safe Transport of Infectious Substances and

Diagnostic Specimens.

As a result of this extensive collaboration, significant changes

have been made to the 1990 NPRM, and a new NPRM is being published to

provide the opportunity for laboratories and other shippers of

infectious materials, persons who transport or handle packages, public

health officials and other affected parties to comment on these

proposed regulations to ensure that the final regulations are both

complementary to other packaging and shipping requirements and

protective of the public health.

CDC believes these regulations will not be an additional burden to

shippers because shippers interested in ensuring the integrity of their

packages are already utilizing comparable packaging. These regulations

will help to ensure that all shippers are aware of and utilize

appropriate packaging when shipping infectious substances, thereby

protecting the public health.

Comparison of CDC's Proposed Packaging and Labeling Requirements

With Other Agencies' and Groups' Packaging and Labeling

Requirements

This NPRM proposes packaging and labeling requirements for: (1)

Clinical specimens because they may contain infectious agents, and (2)

materials known or suspected of containing infectious substances or

toxins.

Table 1 shows which types of infectious materials are covered by

each regulating authority and the scope of that coverage. As noted in

the table, no single agency covers all aspects regarding the shipment

of infectious substances.

Table 1.--Infectious Substances: Comparison of the CDC NPRM \1\ With OSHA,\2\ DOT,\3\ USPS,\4\ and IATA \5\

Packaging and Labeling Requirements

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Regulations

Requirements CDC NPRM \1\ -------------------------------------------------------

OSHA \2\ DOT \3\ USPS \4\ IATA \5\

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Infectious materials:

Biological products................... + + -\6\ + +

Clinical (diagnostic) specimens....... + + -\6\ + +

Cultures and reference stocks......... + + + + +

Packaging materials:

Watertight primary receptacle......... + + + + +

Absorbent material.................... + na + + +

Watertight secondary packaging........ + na + + +

List of contents...................... + na + -\7\ +

Outer packaging....................... + na + + +

Packaging performance standards....... + na + + +

Packaging labels:

Infectious substance/biohazard symbol + + + + +

label................................

Shipping label,\8\ outer packaging.... + na -\9\ + +

Shipping label, secondary packaging... + na na + na

Tracking special infectious substances.... + na na na na

Terminology............................... + + + + +

Shipping modes covered.................... All All All Mail only Air only

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Legend: + = same or very similar to the CDC NPRM; - = significantly different from the CDC NPRM; na = not

addressed in regulation.

\1\ CDC: Centers for Disease Control and Prevention, 42 CFR Part 72 as proposed in this NPRM.

\2\ OSHA: Occupational Safety and Health Administration, 29 CFR 1910.1030.

\3\ DOT: Department of Transportation, 49 CFR Parts 171-180.

\4\ USPS: United States Postal Service, Domestic Mail Manual CO23.

\5\ IATA: International Air Transport Association, Dangerous Goods Regulations.

\6\ Only those biological products and clinical specimens known to contain infectious substances are covered

under 49 CFR 173.134.

\7\ USPS requires a list of contents (manifest) for all sharps mailing containers, but only requires a list of

contents for other items sent via air transportation

\8\ Shipping label: Names, addresses, contact names and phone numbers of person shipping the package and

intended recipient (addressee).

\9\ DOT specifies that the shipper include an emergency response telephone number on the shipping documents (49

CFR 172.604).

[[Page 58025]]

II. Proposed Rule

This proposed rule would amend the existing regulations at 42 CFR

part 72 concerning the interstate shipment of infectious substances to

clarify and expand the existing requirements for proper packaging and

handling of these agents. The purpose of this regulation is to ensure

that all biological materials that contain, or may contain, an

infectious substance are packaged for interstate shipment in a manner

that minimizes the potential for leakage and possible contamination of

the environment, or direct physical contact with the contents by

persons handling such packages during transit. This rule will also

require that infectious agents and toxins capable of causing serious

infection, illness or death be labeled and tracked during shipment.

It also updates the requirements for facilities transferring or

receiving select agents, incorporating by reference the 4th edition of

the CDC/NIH publication Biosafety in Microbiological and Biomedical

Laboratories.

A. Definitions

Biological products--Biological product means a biological product

that is subject to preparation and manufacture in accordance with the

provisions of 9 CFR part 102 (Licensed Veterinary Biological Products),

9 CFR part 103 (Biological Products for Experimental Treatment of

Animals), 9 CFR part 104 (Imported Biological Products), 21 CFR part

312 (Investigational New Drug Application), or 21 CFR parts 600-680

(Biologics) and that, in accordance with such provisions, may be

shipped in interstate traffic. FDA-approved vaccines are exempt from

this regulation.

Only biological products that are known or presumed to contain an

infectious substance are subject to this regulation.

Clinical Specimens--A clinical specimen is any human or animal

material including, but not limited to excreta, secreta, blood and its

components, tissue and tissue fluids, that is collected for the purpose

of diagnosis, research, or other purposes. Formalin-fixed specimens are

excluded. Animal material clinical specimens are subject to the

regulation only if known or suspected of containing human pathogens.

Under the concept of Universal Precautions all bodily fluids of

human origin must be handled as if they are infectious in order to

minimize the potential for exposure to bloodborne pathogens. Section

72.3 in this NPRM meets those requirements.

Some clinical specimens are known or presumed to contain viable

infectious micro-organisms that could result in an infection if an

exposure occurred during a transport mishap. These specimens must be

packaged and labeled as infectious substances (see Sec. 72.4(a)). If

exposure could result in an extremely serious infection or illness in

an exposed worker or the public, such specimens are considered special

infectious substances and must be tracked during shipment.

Infectious substance--CDC has replaced the term ``etiologic agent''

with the DOT and international term ``infectious substance''. For

purposes of this regulation, an infectious substance is any substance,

clinical specimen or culture, isolate, or other derivative of a

clinical specimen that contains, or is suspected of containing a viable

infectious virus, prion, or a viable microorganism, such as a

bacterium, rickettsia, parasite or fungus, that is known or reasonably

believed to cause disease in humans. Toxins known to be pathogenic are

to be packaged and shipped either as infectious substances or as

special infectious substances (Sec. 72.5), as applicable.

Examples of infectious substances include:

1. All cultures containing or suspected of containing a

microorganism that causes or may cause disease in humans;

2. All human or animal clinical specimens that are known or

suspected of containing an infectious microorganism or toxin;

3. Environmental samples to the extent that they are suspected of

containing human pathogens at a level that presents risk of infection.

4. Other specimens not included above and designated as infectious

by a qualified person (e.g., physician, scientist, veterinarian,

nurse).

To maintain consistency with DOT regulations, a qualifying sentence

has been added to the definition of an infectious substance that states

that a microbial toxin that causes disease in humans will be packaged

and shipped as an infectious substance.

Packaging--A change in this NPRM is the adoption of DOT and IATA

terminology to clarify that there is agreement among the various

organizations involved in regulating this area. The terms ``primary

container'', ``secondary container'', and ``outer container'' have been

replaced with the DOT terms and definitions of ``primary receptacle'',

``secondary packaging'', and ``outer packaging'.

Special infectious substance means any of the microbiological

agents or toxins listed in Sec. 72.5 or appendix A to part 72 (proposed

to be recodified as appendix to subpart B). These special infectious

substances include those agents listed in the CDC/NIH publication,

Biosafety in Microbiological and Biomedical Laboratories, as biosafety

level (BSL) 4 and most of the BSL3 agents. Special infectious

substances present a potentially high risk of infection and/or death to

persons exposed to them through either direct contact, aerosol or

ingestion. Therefore, shipments of special infectious substances are

tracked to assure their safe arrival.

B. Transport of Clinical Specimens

Clinical specimens are to be packaged in such a manner that they

will remain intact under conditions that normally occur during transit.

If the primary receptacle were to break or leak during transit, the

specimen would be contained by the absorbent material and by the

secondary packaging, so no material would leak to the outside surface

of the outer packaging.

Packaging requirements for clinical specimens proposed in this NPRM

are similar to those for infectious substances, except that the

proposed performance standards are less rigorous. These packaging and

labeling requirements meet the specifications established by OSHA and

various international agencies.

C. Transport of Infectious Substances

Infectious substances are to be packaged in such a manner that they

would withstand conditions which would normally occur during transit

and would not leak even if the primary receptacle were to break. In

addition, the proposed packaging requirements have been enhanced by

adding a requirement that the packaging be capable of passing a drop

test. The completed package must be capable of passing the tests

specified in 49 CFR 178.609. The requirements established in this NPRM

meet those of DOT, OSHA, various international agencies and are

consistent with the 1999 IATA Dangerous Goods Regulations.

In keeping with DOT and the international guidelines and

regulations, volume/weight limits have been changed to four liters or

four kilograms in a single package (excluding the packaging and coolant

weights). An itemized list of contents must be enclosed between the

secondary packaging and outer packaging. The proposed rule also details

provisions associated with substances shipped refrigerated or frozen

(prefrozen packs,

[[Page 58026]]

wet or dry ice), shipped in liquid nitrogen, or as lyophilized

materials.

The proposed rule requires on the outer packaging a black and white

label bearing the words ``Infectious Substance'', CDC's telephone

number for reporting damaged packages, and the biohazard symbol. The

proposed rule also would require that the name, address, and telephone

number of both the shipper and recipient be affixed to the outer

package.

D. Transport of Special Infectious Substances; Failure to Receive

This proposed rule would be unique in requiring that the most

dangerous human pathogens be shipped as ``special infectious

substances''. These agents include those identified for work at

biosafety level 3 and 4 as specified in the Biosafety in

Microbiological and Biomedical Laboratories publication.

Special infectious substances must be shipped by the carrier and a

system that provides for tracking the shipment and notifying CDC if the

packages are not received. Information gathered by CDC from such

notifications will be useful in identifying problems and implementing

corrective actions.

E. Select Agents

Some of the microorganisms listed as special infectious substances

are also considered to be ``select agents'' and are regulated in 42 CFR

72.6 (Additional Requirements for Facilities Transferring or Receiving

Select Infectious Agents) (proposed here to be renumbered as Section

72.11). The only changes in this proposed rule to Sec. 72.6 are at

Sec. 72.6 (a)(5) (now Sec. 72.11 (a)(5)), and Sec. 72.6 (c)(1) (now

Sec. 72.11(c)(1)), which are revised to incorporate the 4th edition of

the CDC/NIH publication Biosafety in Microbiological and Biomedical

Laboratories.

F. Variations

To promote innovation and allow for new technologies, the proposed

rule would allow the Director, CDC, to approve variations from the

requirements of this subpart if, upon written application, it is found

that such variations provide protection at least equivalent to that

provided by the requirements in this subpart, as finalized, and such

findings are made a matter of official written record.

G. Penalties

Violations of the rule would be subject to criminal penalties as

prescribed in 42 U.S.C. 271 and 18 U.S.C. 3559, 3571. Specifically,

individuals in violation of the rule would be subject to a fine or

imprisonment of not more than one year, or both.

III. Procurement of Labels

Shippers will be able to order a supply of the two shipping labels

described in the regulations from private printers by furnishing them

the exact specifications provided in the final rule, or by purchasing

the labels from the Superintendent of Documents (U.S. Government

Printing Office, Mail Stop: SSOP, Washington, D.C. 20402-9328).

IV. Analysis of Impacts

A. Review Under Executive Order 12866, Sections 202 and 205 of the

Unfunded Mandate Reform Act of 1995 (P.L. 104-4), and by the Regulatory

Flexibility Act (5 U.S.C 603-605)

The Department has examined the potential impact of this proposed

rule as directed by Executive Order 12866, by sections 202 and 205 of

the Unfunded Mandate Reform Act of 1995 (Pub. L. 104-4), and by the

Regulatory Flexibility Act (5 U.S.C. 603-605).

Executive Order 12866 directs Federal agencies to assess the costs

and benefits of available regulatory alternatives, and, when regulation

is necessary, to select regulatory approaches that maximize net

benefits. This proposed rule is designed to ensure that all biological

materials that contain, or may contain, an infectious substance are

packaged in a manner for interstate shipment that minimizes the

potential for leakage and possible contamination of the environment or

direct physical contact with the contents by persons handling such

packages during transit. The proposed rule is designed to complement

other shipping requirements developed by the Departments of Commerce,

Agriculture, and Transportation, the USPS, OSHA, and the International

Air Transport Association and, thereby, to reduce the burden on

shippers while imposing minimal administrative costs, and to prevent

possible serious, harmful effects to public safety and health. (The

proposal has been reviewed by the Office of Management and Budget under

the terms of the Executive Order.)

The Unfunded Mandates Reform Act of 1995, in sections 202 and 205,

requires Federal agencies to prepare several analytic statements before

proposing a rule that may result in expenditures of $100 million by

State, local and tribal governments, or by the private sector in any

one year. Because a final rule resulting from this proposal would not

result in expenditures of this magnitude, such statements are not

necessary.

The Regulatory Flexibility Act requires Federal agencies to prepare

a regulatory flexibility analysis of the potential impact of the

proposed rule on small entities and permits agency heads to certify

that a proposed rule will not, if promulgated, have a significant

economic impact on a substantial number of small entities. CDC does not

know how many small entities will be impacted by this regulation, and

does not know what the economic impact on those small entities would

be. However, CDC believes that packaging requirements set forth in this

rule would not be an additional burden on shippers because this is an

amendment to existing PHS rules with which shippers must comply. In

addition, it will harmonize these rules with other existing regulations

that shippers must follow. CDC believes that this rule will lessen

confusion regarding proper packaging and shipping of infectious

materials and will bring HHS regulations into conformity with other

regulations. CDC is requesting information/comments on the number of

small entities that would be impacted by this NPRM, the economic burden

on those small entities and why the Secretary should not certify that

this rule will have no significant impact on small entities. CDC is

also requesting comments/recommendations on other possible less

burdensome approaches to ensuring that all infectious or potentially

infectious materials are packaged and shipped in a way that minimizes

risks to workers, the public and the environment.

These regulations will help to ensure that all shippers are aware

of and utilize appropriate packaging when shipping infectious

substances, thereby protecting the public health.

B. Review Under the Paperwork Reduction Act of 1995

The proposed rule contains information collection requirements that

are subject to review by the Office of Management and Budget (OMB)

under the Paperwork Reduction Act of 1995. The title, description and

respondent description of the information collection are shown below

with an estimate of the annual reporting burden. The estimate includes

the time for reviewing instructions, gathering and maintaining the

necessary data, and completing and reviewing the collection of

information. With respect to the following collection of information,

CDC invites comments on: (a) Whether the proposed collection of

information is necessary for the proper performance of CDC's public

[[Page 58027]]

health functions, including whether the information shall have

practical utility; (b) the accuracy of CDC's estimate of the burden of

the proposed collection of information including the validity of the

methodology and assumptions used; (c) ways to enhance the quality,

utility, and clarity of the information to be collected; and (d) ways

to minimize the burden of the collection of information on respondents,

including through the use of automatic collection techniques or other

forms of information technology.

Title: Packaging and Handling of Infectious Substances and Select

Agents.

Description: The CDC proposes to amend the regulations concerning

the interstate shipment of infectious substances in order to clarify

and expand requirements for proper packaging and handling of these

agents. The proposed rule would ensure that all biological materials

that may contain an infectious substance are packaged for interstate

shipment in a manner that minimizes the potential for leakage and

possible contamination of the environment or direct physical contact

with the contents by persons handling such packages during transport.

It also updates the requirements for facilities transferring or

receiving select agents, incorporating by reference the 4th edition of

the CDC/NIH publication Biosafety in Microbiological and Biomedical

Laboratories.

Anyone handling damaged or leaking packages of infectious

substances during interstate shipment must isolate the package, notify

the shipper and intended recipient immediately and notify CDC as soon

as feasible (1-800-232-0124). When notifying CDC, the caller should

provide a description of the condition of the package, the name,

address and telephone number of the shipper, and any other pertinent

information, so that information and assistance can be provided, as

necessary, regarding appropriate decontamination and disposal

procedures.

Persons who ship packages containing special infectious substances

must notify the addressee of the date of shipment, and the addressee

must confirm receipt by telephone or other electronic means. If the

shipper does not receive such confirmation within 3 days of anticipated

delivery, the shipper must then contact CDC within 24 hours to enable

the agency to determine whether a public health response is necessary.

Information gathered by CDC from such notifications will also be useful

in identifying problems and implementing corrective actions.

Description of Respondents: Government agencies, universities,

research institutions, laboratories, private companies and others that

ship or receive infectious substances, and government or commercial

carriers of infectious substances.

Estimated Annual Reporting Burden

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Frequency Total

CFR section Number of of annual Hours per Total hours

respondents reporting responses response

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

72.4(b)........................................ 500 1x/yr 50 0.1 5

72.5(b)........................................ 200 10/yr 2,000 0.1 200

72.5(c)........................................ 200 10/yr 2,000 0.1 200

72.5(d)........................................ 20 1/yr 20 0.2 4

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Total 409

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Reporting or Disclosures: These estimates are an approximation of

the average time expected to be necessary for a collection of

information. They are based on past experiences of respondents

reporting such information to CDC. There are no capital costs or

operating and maintenance costs for the respondents associated with

this information collection.

The agency has submitted a copy of this proposed rule to OMB for

its review of this information collection. Interested persons are

requested to submit written comments regarding this information

collection, including suggestions for reducing the burden, to the

Office of Information and Regulatory Affairs, OMB, New Executive Office

Building, 725 17th Street, NW, Rm. 10235, Washington, DC 20503, Att.:

Desk Officer for CDC.

List of subjects in 42 CFR Part 72

Biologics, packaging and containers, Transportation.

Dated: March 12, 1999.

Jeffrey Koplan,

Director, Centers for Disease Control and Prevention.

Dated: May 31, 1999.

Donna E. Shalala,

Secretary, Department of Health and Human Services.

For the reasons stated in the preamble, it is proposed to amend 42

CFR Chapter I, part 72, as follows:

PART 72--PACKAGING AND HANDLING OF INFECTIOUS SUBSTANCES AND SELECT

AGENTS

1. The authority citation for Part 72 is revised to read as

follows:

Authority: 42 U.S.C. 216, 264, 271; 31 U.S.C. 9701; 18 U.S.C.

3559, 3571; 42 U.S.C. 262 note.

2. The heading of part 72 is revised to read as set forth above.

3. Sections 72.1-72.5 are revised.

4. 72.6 is redesignated as Sec. 72.11.

5. A new Sec. 72.6 is added.

6. A heading for subpart A is added and sections Secs. 72.1-72.6

are transferred to subpart A.

7. A heading for subpart B is added and redesignated section 72.11

is transferred to subpart B and amended by revising paragraphs (a)(5)

and (c)(1).

8. Section 72.7 is redesignated as section 72.21.

9. A heading for subpart C is added and redesignated section 72.21

is transferred to subpart C.

10. Appendix A to Part 72 is transferred to subpart B and the

heading is revised to read ``Appendix to Subpart B''.

The additions and revisions to part 72 read as follows:

Subpart A--Interstate Shipment of Biological Materials That Contain

or May Contain Infectious Substances

Sec. 72.1 Purpose.

The purpose of this regulation is to ensure that all materials that

contain or may contain an infectious substance are packaged for

interstate shipment in a manner that minimizes the potential for

leakage and possible contamination of the environment or direct

physical contact with the contents by persons handling such packages

during transit.

[[Page 58028]]

The rule also requires the tracking of shipments of special infectious

substances and requires registration of certain select agents. The

requirements of this subpart are in addition to and not in lieu of any

other packaging or other requirements for the transportation of

infectious substances in interstate traffic as prescribed by the US

Department of Transportation, the US Postal Service and other agencies

of the Federal Government.

Sec. 72.2 Definitions.

As used in this subpart:

Absorbent material means material that is capable of absorbing

liquids. It may be either particulate or non-particulate, but if

particulate, it shall be contained so it does not leak out of the

package.

Biological product means a biological product that is subject to

preparation and manufacture in accordance with the provisions of 9 CFR

part 102 (Licensed Veterinary Biological Products), 9 CFR part 103

(Biological Products for Experimental Treatment of Animals), 9 CFR part

104 (Imported Biological Products), 21 CFR part 312 (Investigational

New Drug Application), or 21 CFR parts 600-680 (Biologics) and that, in

accordance with such provisions, may be shipped in interstate traffic.

Only biological products that are known or presumed to contain an

infectious substance are subject to this regulation. FDA-approved

vaccines are exempt from this regulation.

Clinical specimen (diagnostic specimen) is any human or animal

material including, but not limited to excreta, secreta, blood and its

components, tissue and tissue fluids, that is collected for the

purposes of diagnosis, research, or other purposes. Formalin-fixed

specimens are exempt from this regulation. Animal material clinical

specimens are subject to this regulation only if known or suspected of

containing human pathogens. All human clinical specimens are covered.

Coolant material means material such as ice, dry ice, liquid

nitrogen, and gel packs, that is included in the package to cool the

contents.

Infectious substance (etiologic agent) and infectious material are

considered synonymous. An infectious substance is defined as a

substance containing or suspected of containing an infectious virus,

prion, or a viable microorganism, such as a bacterium, rickettsia,

parasite or fungus, that is known or reasonably believed to cause

disease in humans. Toxins known to be pathogenic to humans are to be

packaged and shipped as infectious substances or special infectious

substances (Sec. 72.5). The term ``infectious substance'' excludes any

medical waste that is regulated under other federal regulations. For

purposes of this regulation, infectious substances include:

(1) All cultures containing or suspected of containing a

microorganism that causes or may cause disease in humans;

(2) All human or animal clinical specimens that are known or

suspected of containing an infectious microorganism or toxin;

(3) Environmental samples if they are suspected of containing human

pathogens at a level that presents risk of infection.

(4) Other specimens not included above and designated as infectious

by a qualified person (e.g., a physician, scientist, veterinarian,

nurse).

Interstate traffic means the movement, including any portion

entirely within a State or possession, from a point of origin in any

State or possession or from outside the Untied States, to a point of

destination in any other State or possession; or form any State or

possession to another country; or between a point of origin and a point

of destination in the same State or possession but through any other

State, possession or contiguous foreign country.

Outer packaging means the container in which a primary receptacle

and secondary package, together with any absorbent materials and

cushioning, is shipped.

Primary receptacle means a tube, vial, bottle, ampule, or similar

item that contains the material being shipped.

Secondary packaging means a container into which the primary

receptacle is placed.

Special infectious substance means any of the microbiological

agents or toxins listed in Sec. 72.5 or appendix to subpart B of this

part, including any human or animal specimens known or suspected of

containing such a microbial agent, or any other microorganism that

could cause serious infection and/or death in persons exposed to them

through either direct contact, aerosol or ingestion. Additional changes

to this list may be made through publication of a notice in the Federal

Register.

Sec. 72.3 Transportation of clinical specimens; minimum packaging

requirements.

(a) General requirements. No person may knowingly transport or

cause to be transported in interstate traffic, directly or indirectly,

any clinical specimen unless such material is packaged, labeled, and

shipped in accordance with the requirements of this section. However,

any clinical specimens known or suspected to contain an infectious

substance shall be labeled and packaged as described under Sec. 72.4.

(1) Clinical specimens shall be packaged to withstand conditions

incident to ordinary handling in transit, including shocks and pressure

changes, so that if leakage of the primary receptacle(s) occurs during

transit, the contents will be contained within the outer packaging.

Required packaging and components are as follows:

(i) A watertight primary receptacle.

(ii) Watertight secondary packaging.

(iii) Absorbent material must be placed between the primary

receptacle(s) and the secondary packaging. If multiple primary

receptacles are placed in a secondary packaging, they msut be placed so

as to ensure that contact between them is prevented. The absorbent

material must be sufficient to absorb the entire contents of all

primary receptacles.

(iv) Outer packaging must be of adequate strength for its capacity,

mass and intended use. Any package with liquid contents shall have

sturdy outer packaging constructed of corrugated cardboard, fiberboard,

wood, metal, or rigid plastic. Styrofoam, plastic bags and paper

envelopes are unacceptable outer packaging for such packages.

(2) The size of the outer package must be at least 100 mm (3.9

inches) in the smallest overall external dimension.

(3) The primary receptacle and the secondary packaging must be

capable of withstanding, without leakage, an internal pressure which

produces a pressure differential of not less than 95kPA (0.95 bar,

13.8lb/in2) in the temperature range of -40 deg. C to

+55 deg. C (-40 deg. F to 131 deg. F).

(4) An itemized list of contents must be enclosed between the

secondary packaging and the outer packaging.

(5) For substances shipped at ambient temperatures or higher, means

of ensuring a leak-proof seal of the primary receptacle, such as a heat

seal, skirted stopper or metal crimp seal must be provided. Screw caps

must be reinforced to ensure they do not leak. Evacuated specimen

collection tubes such as Vacutainer (Becton-Dickinson,

Franklin Lakes, NJ) tubes do not require additional sealing.

(6) For substances shipped refrigerated or frozen (wet ice,

prefrozen packs, dry ice), ice or dry ice must be placed outside the

secondary packaging(s). Interior support must be provided to secure the

secondary packaging(s) in the original position as the ice or dry ice

melts or sublimates, respectively. If ice is used, the outer

[[Page 58029]]

packaging must be leak-proof. If dry ice is used, the outer packaging

must permit the release of carbon dioxide gas. The primary receptacle

must maintain its containment integrity at the temperature of the

refrigerant as well as the temperatures and pressure of air transport

to which the receptacle could be subjected if refrigeration were to be

lost.

(7) For substances shipped in liquid nitrogen, a watertight

material, capable of withstanding cryogenic temperatures must be used

as the primary receptacles. Secondary packaging must also withstand

very low temperatures. All requirements for shipment of liquid nitrogen

must also be observed. The primary receptacle must maintain its

containment integrity at the temperature of the refrigerant as well as

at the temperatures and pressure of air transport to which the

receptacle could be subjected if refrigeration were to be lost.

(8) For lyophilized substances, primary receptacles capable of

containing lyophilized substances must be used (including, but not

limited to, flame-sealed glass ampules or rubber-stoppered glass vials

with metal seals).

(9) The completed package must be capable of withstanding at least

a 1.2 meter drop on a hard unyielding surface without release of its

contents.

(10)(i) Biohazard Labeling is required for the primary receptacle

and outer packaging as described in 29 CFR 1910.1030, Occupational

Exposure to Bloodborne Pathogens.

(ii) The outer packaging shall bear a label as illustrated and

described below:

[GRAPHIC] [TIFF OMITTED] TP28OC99.052

(A) The color of material on which the label is printed shall be

bright orange; the printing shall be black. The color of the biohazard

symbol shall be black.

(B) The label shall be a rectangle measuring 51 mm (2 inches) high

by 102.5 mm (4 inches) long.

(C) The biohazard symbol, measuring 40 mm (1.56 inches) in

diameter, shall be centered on a square measuring 51 mm (2 inches) on

each side.

(D) Size of the letters (Helvetica) on the label shall be as

follows:

Biohazard--16 pt.

Clinical specimens--14 pt.

Packaged in compliance with 42 CFR part 72--6 pt.

In case of damage or leakage, notify--10 pt.

Shipper and Receiver--10 pt.

(iii) The outer packaging shall also bear a shipping label with the

names, addresses, and contact names and telephone numbers of the

individual/institution sending the package and the intended recipient

(addressee).

(b) Leaking packages. The carrier, the receiver, or anyone handling

a package described in paragraph (a) of this section that is leaking,

shall upon discovery of leakage, isolate the package, and immediately,

or as soon as feasible, notify the shipper and intended recipient to

receive instructions on clean-up and disposition of the package.

Sec. 72.4 Transportation of infectious substances; minimum packaging

requirements.

(a) General requirements. No person may knowingly transport or

cause to be transported in interstate traffic, directly or indirectly,

any infectious substance, including clinical specimens or biological

products that are known or presumed to contain infectious substances,

unless such material is packaged, labeled, and shipped in accordance

with the requirements of this section.

(1) Infectious substances shall be packaged to meet the

requirements of Sec. 72.3(a) (1)-(8).

(2) The maximum amount of infectious substances that may be placed

in a single outer shipping package shall not exceed four liters or four

kilograms, excluding the packaging and coolant weights.

(3) In addition, each complete package must be capable of passing

the tests specified in 49 CFR 178.609.

(4)(i) Biohazard Labeling is required for the primary receptacle

and outer package as described in 29 CFR 1910.1030, Occupational

Exposure to Bloodborne Pathogens.

(ii) The outer packaging shall bear a label as illustrated and

described below:

[[Page 58030]]

[GRAPHIC] [TIFF OMITTED] TP28OC99.053

(A) The color of material on which the label is printed shall be

white and the printing shall be in black; the biohazard symbol shall be

in black.

(B) The label shall be a diamond-on-point measuring, at a minimum,

51 mm (4 inches) on each side.

(C) The black biohazard symbol, measuring 21 mm (.81 inches) in

diameter, shall be centered on a square measuring 51 mm (2 inches) on

each side.

(D) Size of the letters (Helvetica) on the label shall be as

follows:

Infectious Substance--16 pt.

Packaged in compliance with 42 CFR Part 72--5 pt.

In case of damage or leakage--7 pt.

Immediately notify--7 pt.

Public Health Authority--7 pt.

In U.S.A.--5 pt

Centers for Disease Control and Prevention--5 pt.

Atlanta, GA--5 pt

1-800-232-0124--5 pt.

6--24 pt.

(E) The number 6 (mandated by the DOT) shall be centered at the

bottom of the label.

(iii) The outer packaging and the secondary packaging shall also

bear labels with the names, addresses, and contact names and telephone

numbers of the individual/institution sending the package and of the

intended recipient (addressee).

(b) Damaged or leaking packages. The carrier, the receiver, or

anyone handling a package described in paragraph (a) of this section

that is damaged or leaking, shall upon discovery of damage or leakage,

isolate the package and immediately, or as soon as feasible, in order

to receive instructions on appropriate decontamination and disposal,

notify the shipper, receiver, and the Centers for Disease Control and

Prevention by telephone at 1-800-232-0124. The caller shall provide a

description of the condition of the package; the name, address and

telephone number of the shipper; and other pertinent information.

(This information collection has been approved by OMB (0920-0199)).

Sec. 72.5 Packaging and method of shipment of special infectious

substances; failure to receive.

(a) List of special infectious substances. (1) The following

microorganisms and toxins are considered special infectious substances

because they present a potentially high risk of infection and/or death

to persons exposed to them through either direct contact, aerosol or

ingestion. Shipments of special infectious substances must be tracked

to assure their safe arrival.

Bacterial Agents

Bacillus anthracis

Bartonella bacilliformis

Brucella, all species

Burkholderia (Pseudomonas) mallei

Burkholderia (Pseudomonas) pseudomallei

Clostridium botulinum

Francisella tularensis

Mycobacterium tuberculosis (drug-resistant strains)

Yersinia pestis

Viral and Rickettsial Agents

Arboviruses assigned to Biosafety level 3 or 4 in the CDC/NIH

publication Biosafety in Microbiological and Biomedical

Laboratories, which may be purchased from the Superintendent of

Documents, U.S. Government Printing Office, Washington, D.C. 20402.

Other Viral Agents

Crimean-Congo hemorrhagic fever virus

Eastern Equine Encephalitis virus

Ebola virus

Hantaan virus (Korean hemorrhagic fever virus)

Hantavirus (all viruses of genus)

Herpesvirus simiae (B virus)

Lassa fever virus

Lymphocytic choriomeningitis virus

Marburg virus

Pox viruses pathogenic for humans (e.g., smallpox, monkeypox)

South American Hemorrhagic fever viruses (Junin, Machupo, Sabia,

Flexal, Guanarito)

Tick-borne Encephalitis complex viruses

Venezuelan Equine Encephalitis virus

Yellow fever virus

Rickettsial Agents:

Rickettsia rickettsiae

Rickettsia prowazekii

Coxiella burnetti

Fungal Agents

Coccidioides immitis

Histoplasma capsulatum

Histoplasma duboisii

Toxins

Toxins listed in appendix to Subpart B of this part are to be

shipped as special infectious substances. Other microbial toxins

known to be pathogenic shall be shipped as infectious substances, as

provided under Sec. 72.4.

(2) This list may be supplemented through publication of a notice

in the Federal Register. Call 1-888-232-3299 (the FAX Information

system in CDC's Office of Health and Safety) for a copy of the current

list, or check the CDC website at http://www.cdc.gov/od/ohs.

(b) Packaging and method of shipment. All materials that contain or

are reasonably believed to contain a special infectious substance shall

be packaged and labeled for interstate shipment according to the

requirements of Sec. 72.4. In addition, the shipper shall: Use a

shipping system that provides for tracking during transport (e.g.,

registered mail or those of certain

[[Page 58031]]

private carriers); Provide 24 hours-per-day telephonic response to

emergency calls from carriers in case of a spill or incident involving

a package containing a special infectious agent; and, Notify the

addressee by telephone or other electronic means of the date of

shipment on the date of shipment, or provide a written schedule of

shipment in advance, and request confirmation of receipt of each

shipment. Records of such notifications shall be retained by the

shipper until notified of receipt.

(c) Confirmation of receipt. Upon receipt, the addressee shall

provide confirmation to the shipper by telephone or other electronic

means.

(d) Failure to receive. When confirmation of receipt of material

designated in paragraph (a) of this section is not received by the

shipper within 3 days following anticipated delivery of the package,

the shipper shall notify the carrier which shall immediately seek to

ascertain the disposition of the package. In addition, the shipper

shall notify the Centers for Disease Control and Prevention within 24

hours by telephone at 1-800-232-0214 to enable the agency to determine

whether a public health response is necessary.

Sec. 72.6 Requirements; variations.

The Director, Centers for Disease Control and Prevention, may

approve variations from the requirements of this subpart if, upon

written application, review and evaluation, it is found that such

variations provide protection at least equivalent to that provided by

compliance with the requirements specified in this subpart, and such

findings are made a matter of official written record.

Sec. 72.7 [Redesignated as Sec. 72.21]

Subpart B--Handling of Select Agents

Sec. 72.11 Additional requirements for facilities transferring or

receiving select agents.

(a) * * *

(5) The requirements for BSL-2, 3, and 4 operations pertaining to

this section are contained in the CDC/NIH publication, ``Biosafety in

Microbiological and Biomedical Laboratories,'' Fourth Edition, May 1999

which is hereby incorporated by reference. The Director of the Federal

Register has approved under 5 U.S.C. 552(a) and 1 CFR part 51 the

incorporation by reference of the above publication. Copies may be

obtained from the Superintendent of Documents, U.S. Government Printing

Office, Washington, DC 20402. Copies may be inspected at the Centers

for Disease Control and Prevention, 1600 Clifton Road, Atlanta,

Georgia, or at the Office of the Federal Register, 800 North Capitol

Street NW, Suite 700, Washington, DC. The manual is also available on

the CDC web site at www.cdc.gov/od/ohs/biosfty/bmbl4/bmbl4toc.htm.

* * * * *

(c) * * *. (1) The Secretary may authorize a state agency or

private entity to register facilities under paragraph (a) of this

section, if the Secretary determines that the registering entity's

criteria for determining the biosafety standards for facilities

handling select agents are consistent with the requirements contained

in the CDC/NIH publication ``Biosafety in Microbiological and

Biomedical Laboratories,'' Fourth Edition.

* * * * *

Subpart C--Penalties

Sec. 72.21 [Redesignated from Sec. 72.7]

Appendix A to Part 72 [Transferred to Subpart B and heading

revised]

Appendix to Subpart B

* * * * *

[FR Doc. 99-27640 Filed 10-27-99; 8:45 am]

BILLING CODE 4163-18-P