[Federal Register: November 27, 2001 (Volume 66, Number 228)]
[Rules and Regulations]
[Page 59138-59161]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr27no01-4]
=======================================================================
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Parts 207, 607, and 807
[Docket No. 98N-1215]
RIN 0910-AB21
Foreign Establishment Registration and Listing
AGENCY: Food and Drug Administration, HHS.
ACTION: Final rule.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA) is issuing a final rule
to amend its regulations pertaining to the registration of foreign
establishments and the listing of human drugs, animal drugs, biological
products, and devices. The final rule requires foreign establishments
whose products are imported or offered for import into the United
States to register with FDA and to identify a United States agent. The
final rule implements section 417 of the Food and Drug Administration
Modernization Act of 1997 (FDAMA) as it pertains to foreign
establishment registration.
DATES: This rule is effective February 11, 2002.
Compliance date: FDA will begin enforcing the requirements in 21
CFR part 207 on May 28, 2002, and in 21 CFR part 807 on April 26, 2002.
ADDRESSES: Submit written or electronic comments to the Dockets
Management Branch (HFA-305), Food and Drug Administration, 5630 Fishers
Lane, rm. 1061, Rockville, MD 20852. Submit electronic comments to
http://www.fda.gov/dockets/ecomments.
FOR FURTHER INFORMATION CONTACT: Philip L. Chao, Office of Policy,
Planning, and Legislation (HF-23), Food and Drug Administration, 5600
Fishers Lane, Rockville, MD 20857, 301-827-3380.
SUPPLEMENTARY INFORMATION:
I. Introduction
In the Federal Register of May 14, 1999 (64 FR 26330), FDA
published a proposed rule to implement section 417
[[Page 59139]]
of FDAMA (Public Law 105-115). Section 417 of FDAMA amended section
510(i) of the Federal Food, Drug, and Cosmetic Act (the act) (21 U.S.C.
360(i)) to require, in part, that:
(1) Any establishment within any foreign country engaged in the
manufacture, preparation, propagation, compounding, or processing of
a drug or a device that is imported or offered for import into the
United States shall register with the Secretary the name and place
of business of the establishment and the name of the United States
agent for the establishment.
(2) The establishment shall also provide the information
required by subsection (j).
(Section 510(j) of the act pertains to product listing.)
Generally speaking, before FDAMA's enactment, foreign
establishments could, but were not required to, register with FDA. FDA,
through its regulations, did require foreign establishments to list
their products regardless of whether the foreign establishment was
registered (see, e.g., former section 510(i) of the act, 21 CFR
207.40(a), 38 FR 6257, 6258 through 6259, and 6262 through 6263 (March
7, 1973) (final rule implementing the Drug Listing Act of 1972)). This
difference in registration and listing requirements confused some
foreign establishments and led some to not comply with the listing
requirement. Additionally, the lack of registration information on
foreign establishments sometimes made it difficult to determine the
source of specific imported products, particularly products that were
impure, counterfeit products, or products whose safety or efficacy had
not been established.
FDAMA changed this situation by requiring all foreign
establishments engaged in the manufacture, preparation, propagation,
compounding, or processing of a drug or a device that is imported or
offered for import into the United States to register. It also
emphasized that foreign establishments must list their products and
required, for the first time, foreign establishments to identify a
United States agent.
Consequently, the proposed rule sought to amend the establishment
registration and listing regulations in part 207 (21 CFR part 207)
(human and animal drugs and biologics), part 607 (21 CFR part 607)
(human blood and blood products), and part 807 (21 CFR part 807) (human
devices). In general, the proposal removed the distinctions between
domestic and foreign establishments where appropriate, required foreign
establishments to identify a United States agent, and described some of
the United States agent's duties.
The proposal also made minor technical amendments, such as updating
addresses of FDA offices and the names of marketing applications, to be
consistent with current FDA practices.
The comment period for the proposed rule was originally scheduled
to end on July 28, 1999. On July 23, 1999, the Government of Canada
requested that FDA extend the comment period for 60 days, stating that
the proposed requirements could present significant cost and compliance
burdens on small and medium-sized Canadian establishments. The
Government of Canada requested the extension so that it could: (1)
Ensure that affected Canadian establishments were aware of the proposed
rule, and (2) prepare informed comments. The request arrived too late
for FDA to announce an extension of the comment period, so FDA
published a document in the Federal Register of August 9, 1999 (64 FR
43114), reopening the comment period from August 9, 1999, to October 8,
1999.
II. Comments on the Proposed Rule
FDA received over 35 comments on the proposed rule. Domestic and
foreign establishments, particularly Canadian establishments, submitted
most comments, although the Government of Canada, the trade agency for
the Government of Ontario, Canada, Canadian and American trade
associations, law firms, and FDA employees also submitted comments.
To make it easier to identify comments and FDA's responses to the
comments, the word Comment in parenthesis, will appear before the
description of the comment, and the word Response in parenthesis, will
appear before FDA's response. FDA has also numbered each comment to
make it easier to identify a particular comment. The number assigned to
each comment is purely for organizational purposes and does not signify
the comment's value or importance or the order in which it was
submitted.
A. General Comments
Several comments addressed general issues that were not directed to
any particular codified provision.
(Comment 1) Two comments expressed general support for the rule.
One comment said that the rule brings a`` desired level of consistency
in requirements for both domestic and international manufacturing
activities'' and will enable FDA to identify and locate firms and
products made abroad, thus enhancing public health and safety.
In contrast, one comment, submitted by a law firm in the United
States, asserted that FDA should not require foreign establishments to
register if their products are not commercially distributed in the
United States. As an example, the comment said the rule should not
apply if the product is sent to a foreign trade zone. The comment
acknowledged that section 510(i) of the act does not expressly say that
the product must be imported or offered for import into the United
States ``for commercial distribution,'' but claimed that section 510(j)
of the act suggests that only those who manufacture, prepare,
propagate, compound, or process products for commercial distribution
must register. The comment further claimed that excluding some foreign
establishments from the registration requirement would also be
consistent with FDAMA because FDAMA sought to reduce regulatory
burdens.
(Response) FDA agrees, in part, with the comment, but only to the
extent that it involves products that are shipped to foreign trade
zones and never enter domestic commerce. In brief, a foreign trade zone
(also known as a Free Trade Zone) is a federally sanctioned site where
foreign and domestic goods are considered to be outside of the U. S.
Customs territory. While in a foreign trade zone, the goods can be
stored, tested, sampled, displayed, repaired, manipulated, assembled,
salvaged, repackaged, cleaned, processed, relabeled, mixed, destroyed,
or inspected (and, if approved by the foreign trade zone board,
manufactured). If the goods are reexported from the foreign trade zone,
no customs duties are paid, but if the goods enter U. S. commerce,
duties would apply.
It is important to note that, while the U. S. Customs Service does
not assess duties on goods in a foreign trade zone, those goods are
subject to FDA's jurisdiction. However, FDA agrees that if a foreign
establishment sends human drugs, animal drugs, devices, or biological
products to a foreign trade zone and the product is re-exported from
the foreign trade zone to another country without ever entering U. S.
commerce, the foreign establishment is not required to register or list
the products that were sent to the foreign trade zone. (These foreign
establishments may voluntarily register and list their products, but
the final rule does not require them to do so).
If the goods do enter U. S. commerce from a foreign trade zone, the
foreign establishment must register and list its products. In this
situation, the foreign establishment is like any other foreign
establishment that exports a product to the United States. In other
words, if the
[[Page 59140]]
goods are sold in the United States, the fact that those goods may have
initially entered the United States through a foreign trade zone does
not relieve the foreign establishment from registration and listing
requirements.
FDA, therefore, has amended the foreign establishment registration
and listing provisions at Secs. 207.40(a), 607.40(a), and 807.40(a) to
exclude drugs and devices that enter a foreign trade zone and are re-
exported from the United States without ever entering domestic
commerce.
(Comment 2) The same comment, in asking FDA to exempt foreign
establishments from registration and listing requirements if their
products are imported into the United States but are not marketed in
the United States, suggested registering these foreign establishments
is ``simply not necessary'' and that FDA defer to foreign authorities
in such cases. The comment stated that foreign countries, whether
exporting or receiving a product, can impose their own registration
requirements on foreign manufacturers. The comment added that FDA is
authorized to enter cooperative arrangements with foreign countries to
determine whether drugs or devices should enter the United States.
(Response) FDA agrees, in part, and disagrees, in part, with the
comment. The agency agrees that it is unnecessary to require a foreign
establishment to register and list its products provided that the
product enters the United States through a foreign trade zone and is
later re-exported without ever entering domestic commerce. However, the
fact that a foreign country may have its own registration requirements
or that FDA may enter cooperative arrangements with foreign countries
does not, by itself, justify an exemption from the act's registration
and listing requirements. Foreign registration requirements may differ
considerably from FDA's requirements or may not exist at all; likewise,
cooperative arrangements may not exist or would have to be negotiated
in order to obtain registration information from a foreign government.
(Comment 3) One comment asked FDA to work with the U. S. Customs
Service in order to prevent any unnecessary interruption in the flow of
goods and to facilitate communications between agencies at ports of
entry.
(Response) FDA has worked and will continue to work closely with
the Customs Service on various issues affecting the importation and
exportation of FDA-regulated products and will notify the Customs
Service about this final rule. Additionally, FDA will ``phase-in'' the
rule so that foreign establishments will have an opportunity to adjust
to these regulatory requirements. (Details concerning registration
schedules for parts 207, 607, and 807 appear later in this document in
section II.F entitled ``Registration Schedules.'') Consequently, the
rule should not create any ``unnecessary interruption'' in imports of
human drugs, animal drugs, biologics, blood and blood products, or
devices.
B. Comments on the United States Agent Requirement
1. Comments on the Number of United States Agents, Including Requests
to Exempt Firms in Certain Countries From Having a United States Agent
As stated earlier, section 510(i) of the act requires foreign
establishments to identify a United States agent. The preamble to the
proposed rule explained that FDA interpreted this provision as
requiring the agent to be an individual, firm, or company physically
located in the United States (see 64 FR 26330 at 26331). The preamble
to the proposed rule added that the United States agent could not be a
mailbox, answering machine or answering service, or any other place
where an individual acting as the foreign establishment's agent is not
physically present and that FDA interprets section 510(i) of the act as
requiring only one agent for each foreign establishment.
(Comment 4) Some comments would amend the rule to allow or to
require more than one agent per establishment. Two comments advocated
one agent per product, and one of these comments said that foreign
establishments should identify the United States agent as part of a
drug master file or veterinary master file. One comment supported
requiring one United States agent for each product and U. S. customer.
Other comments suggested that a foreign establishment should be able to
designate more than one agent or as many agents as it wished. In
general, these comments explained that a foreign establishment may
supply multiple U. S. companies or have multiple U. S. distributors.
The comments said that, under these circumstances, a foreign
establishment cannot select one company or distributor as its United
States agent due to potential conflicts of interest, potential harm to
the foreign establishment's proprietary interests, or frequent changes
in its distributors. Some comments said that a distributor could not be
a United States agent for more than one foreign establishment. One
comment also argued that FDA already has names and addresses of agents
for each product as part of a drug master file, so FDA should allow
foreign establishments to have more than one United States agent.
(Response) Section 510(i) of the act clearly and unequivocally
requires foreign establishments to register the name of a United States
agent. As stated in the preamble to the proposed rule, FDA interprets
section 510(i) of the act as allowing only one United States agent for
each foreign establishment because section 510(i) of the act refers to
the United States agent in singular, rather than plural, terms (see 64
FR 26330 at 26331). FDA continues to believe that this interpretation
is efficient (because FDA would communicate or interact with only one
United States agent rather than multiple agents who represent, or
purport to represent, the same foreign establishment) and consistent
with the statutory language. Thus, FDA declines to amend the rule to
increase the number of United States agents per foreign establishment.
FDA also declines to amend the rule to have foreign establishments
identify the United States agent as part of their drug master files or
veterinary master files. Section 510(i)(1) of the act considers the
United States agent to be part of a foreign establishment's
registration requirement, so requiring a foreign establishment to name
its United States agent as part of the registration process is
consistent with the act.
(Comment 5) Many comments, particularly from Canadian sources,
objected to having any United States agent. These comments would revise
the rule to eliminate or suspend a United States agent requirement,
either for Canadian firms or for firms in countries meeting certain
criteria. The comments offered numerous reasons why FDA should not
require certain foreign firms, particularly Canadian firms, to have a
United States agent. The reasons cited most often were (in no
particular order): (a) The requirement will be expensive; (b) the
requirement results in a competitive disadvantage for Canadian firms
doing business in the United States because Canada does not impose
similar obligations on U. S. firms; (c) an agent will not be as
knowledgeable as company officials concerning the company's products or
training an agent to be knowledgeable will be burdensome, expensive,
and time-consuming; (d) Canada and the United States share time zones,
business ethics, language, and communications capabilities so a United
States agent will not significantly enhance communications between FDA
and Canadian firms; (e) FDA has not shown any need for a United States
agent; (f)
[[Page 59141]]
firms with a history of good communications with FDA should be exempt
from the United States agent requirement; and (g) the requirement will
act as a trade barrier between Canada and the United States. One
comment said a United States agent is unnecessary because FDA can work
with the U. S. Customs Service to prevent unapproved devices from
entering the United States. Some Canadian firms indicated that they
would ask the Canadian Government to impose similar requirements
against U. S. firms if FDA did not create an exemption.
A few comments suggested that FDA create exemptions for Canadian
firms or firms in countries meeting certain criteria. One comment from
an United States trade association advocated an exemption from the
United States agent requirement for ``establishments in those countries
with whom the United States has negotiated free trade agreements,''
arguing that FDA's ``interpretation'' of section 417 of FDAMA may pose
an ``unreasonable barrier to trade,'' that registration and listing
information should be enough to protect consumers, and that ``we run
the risk of our partners in these agreements placing similar burdens on
American companies.'' Other comments would exempt firms in countries
that have no communications problems with the United States or FDA;
countries that do not have a similar agent requirement that applies
against U. S. firms; or countries where English is spoken and where
firms can communicate directly with FDA.
(Response) FDA appreciates the concerns expressed by the comments.
However, section 510(i) of the act does not contain any mechanism or
any criteria for exempting certain foreign establishments or foreign
establishments located in certain countries, in geographical regions,
or in countries with no communications problems with the United States
or FDA. Neither does it provide for a deferral of the United States
agent requirement. The statutory language is clear--a foreign
establishment ``shall register * * * the name of the United States
agent for the establishment'' (see section 510(i) of the act). The most
logical interpretation of the term, ``United States agent,'' is that
the agent must be in the United States. If Congress intended foreign
establishments to be able to designate agents outside the United
States, the words ``United States'' would be unnecessary in section
510(i) of the act. Indeed, if Congress intended to require foreign
establishments to be able to designate agents outside the United
States, there would be no need for any agent at all because FDA could
simply contact the foreign establishment directly. It is a well settled
principle of statutory interpretation that, ``Absent clear
congressional intent to the contrary, we will assume the legislature
did not intend to pass vain or meaningless legislation'' (Coyne &
Delany v. Blue Cross & Blue Shield of Virginia, 102 F.3d 712, 715 (4th
Cir. 1996); see also Halverson v. Slater, 129 F.3d 180, 185 (D.C. Cir.
1997) (Congress cannot be presumed to do a futile thing).) Thus, the
most straightforward reading of section 510(i) of the act is that
foreign establishments must register the name of a United States agent
and that the United States agent must be in the United States. So,
despite the assertions made by one comment, one cannot fairly criticize
FDA's ``interpretation'' of the act as being erroneous or claim that
FDA's interpretation of the act is creating an ``unreasonable barrier''
to trade.
FDA sees no need to alter the rule based on those comments claiming
that the United States agent requirement will create competitive
disadvantages or trade barriers, increase costs to foreign
establishments, or lead foreign countries to impose similar
requirements against U. S. firms. The United States agent requirement
is consistent with U. S. trade obligations under the relevant
international agreements.
(Comment 6) One comment explained that small businesses might find
the United States agent requirement to be economically feasible if
multiple foreign establishments could share the same agent.
(Response) FDA has no objections to having one United States agent
represent multiple foreign establishments. However, FDA reminds firms
to select their United States agents carefully to guard against any
conflict of interest and to account for any confidentiality or other
business concerns.
2. Comments on the United States Agent's Duties or Responsibilities
(Comment 7) The preamble to the proposed rule cautioned foreign
establishments to select their agents carefully due to potential
conflicts of interest and issues involving trade secrets or
confidential commercial information (see 64 FR 26330 at 26334). One
comment acknowledged FDA's advice, but said that FDA's interest in
enhanced communication and rapid acquisition of information would be
best served if foreign establishments could determine the number of
agents they need according to their business and proprietary needs.
Another comment said that the rule would compel foreign establishments
to designate persons other than their U. S. distributors as their
United States agents because foreign establishments might be unwilling
to give a distributor potential access to confidential information. The
comment said this would increase costs of retaining a United States
agent.
(Response) FDA disagrees with the comments. FDA expects to initiate
most, if not all, communications between the agency and a United States
agent. Thus, it would obviously be more efficient if FDA only had to
contact one United States agent for a particular foreign establishment
rather than sort through a list of agents to determine whether a
foreign establishment had designated or authorized a particular agent
to address a particular issue.
As for advising foreign establishments to select their United
States agents carefully, FDA was emphasizing that its interactions with
a United States agent could involve proprietary information,
particularly in emergency situations (see 64 FR 26330 at 26334). FDA
must be able to communicate freely with a United States agent in these
situations; otherwise, if the United States agent is unable or
unauthorized to speak to FDA, the United States agent has little or no
value in serving as a contact between FDA and the foreign
establishment. FDA takes no position whether a foreign establishment
should select a U. S. distributor to be its United States agent.
(Comment 8) Several comments addressed the United States agent's
duties under the rule. Under proposed Secs. 207.40(c)(2), 607.40(d)(2),
and 807.40(d)(2), the United States agent would be responsible for
assisting FDA in communications with the foreign establishment,
responding to questions concerning the foreign establishment's products
that are imported or offered for import into the United States, and
assisting FDA in scheduling inspections of the foreign establishment.
The proposal also authorized FDA to provide information or documents to
the United States agent if FDA is unable to contact the foreign
establishment directly or expeditiously.
One comment said that the agent's duties were very flexible,
reasonable, and represented a ``vast improvement'' over an earlier
approach taken by FDA for device manufacturers, while another comment
said the proposed rule appropriately imposed no duty on the agent to
file annual submissions for devices. In contrast, other comments
misinterpreted the rule as requiring the United States agent to submit
all documents, such as premarket
[[Page 59142]]
notifications, annual certifications, and registration and listing
information, to FDA, or to be the only contact between a foreign
establishment and FDA. The comments argued that the agent would only
become an obstacle to communications between FDA and foreign
establishments or, in the case of device firms, would be performing the
same duties as the firm's official correspondent.
(Response) FDA intentionally imposed very few duties on the United
States agent. Thus, contrary to the views expressed in some comments,
FDA is not requiring the agent to submit all documents--or any
particular document--to FDA on behalf of a foreign establishment or to
be a foreign establishment's sole contact with FDA. The final rule,
like the proposal, only requires that the agent assist FDA in
communications with the foreign establishment, to respond to questions
concerning the foreign establishment's products that are imported or
offered for import into the United States, and to assist FDA in
scheduling inspections of the foreign establishment. The final rule
also authorizes FDA to provide information or documents to the United
States agent if FDA is unable to contact the foreign establishment
directly or expeditiously. Foreign establishments have the discretion
to give their United States agents additional tasks and may always
contact FDA directly, with or without their United States agents.
FDA does wish to clarify, however, that the United States agent, as
established in section 510(i) of the act and this final rule, is
different, both in the underlying legal authority for the requirement
and its application to FDA-regulated products, from the ``U.S.-
designated agent'' in the existing Sec. 807.40(c). The ``U.S.-
designated agent'' applied solely to device manufacturers, and FDA
stayed the effective date of the ``U.S.-designated agent'' requirement
in the Federal Register of July 23, 1996 (61 FR 38345). (In fact,
because this final rule rewrites Sec. 807.40 entirely, the ``U.S.-
designated agent'' language from Sec. 807.40 no longer appears.) In
contrast, the United States agent requirement applies to human drug,
animal drug, biologics (including blood and blood products), and device
establishments, and is required by section 510(i) of the act. Section
510(i) of the act did not create any specific duties for the United
States agent, and so FDA, under this rulemaking, prescribed very few
duties for the United States agent.
(Comment 9) One comment stated that, at the port of entry, the
importer of record has the burden of resolving any import problems. The
comment said that because the U. S. Customs Service and FDA regulate
imports, it is unclear how regulatory differences between the Customs
Service and FDA would be reconciled. The comment said that if a foreign
establishment selects company A as its United States agent, company A's
role in resolving import problems would be unclear if another company
was the importer of record.
(Response) The comment misinterprets the rule. The United States
agent, under parts 207, 607, and 807, has no duties or responsibilities
to the Customs Service. Furthermore, with regard to imported products,
the final rule requires the United States agent to respond to questions
regarding the foreign establishment's products that are imported or
offered for import into the United States (see, e.g.,
Sec. 207.40(c)(2)). The preamble to the proposed rule indicated that
these questions might concern the product's distribution in the United
States (see 64 FR 26330 at 26333). In other words, the rule does not
require the United States agent to respond to inquiries from the
Customs Service. The final rule does not require the United States
agent to resolve any import problems alone or to resolve any import
problems immediately at a port of entry. The final rule does not
require the United States agent to be responsible for legal issues
surrounding the product's admission into the United States. In the
comment's hypothetical example, FDA regulations would not require
company A to resolve import problems raised by FDA or the Customs
Service, although FDA believes that the United States agent could play
an important role in resolving such problems by facilitating
communication with the foreign establishment, working with the importer
of record, or even, when appropriate, helping resolve the problem.
3. Miscellaneous Comments Regarding the United States Agent Requirement
(Comment 10) Several comments asked about the United States agent's
liability. One comment asked FDA to clarify that FDA would not hold the
agent legally responsible if, after the agent had made reasonable
attempts to transmit documents or information to the foreign
establishment, the foreign establishment failed to respond adequately
to FDA. The comment suggested that FDA revise the rule to limit the
agent's liability to ``a fulfillment of the agent's responsibility * *
* on behalf of the foreign firm'' and to not hold the agent liable for
any violation of the act by the foreign firm. Another comment expressed
a similar opinion, stating that FDA had not considered whether a United
States agent would be liable for the foreign establishment's actions.
Another comment expressed concern about the United States agent's
exposure to litigation from parties in the United States who sue the
foreign establishment. Two other comments said that they had surveyed
various U. S. firms or contacted U. S. attorneys and found that none
were willing to act as a United States agent; one comment indicated
that U. S. firms were concerned about their potential legal liability.
(Response) In general, FDA does not intend to hold the United
States agent responsible for violations of the act committed by a
foreign establishment. FDA wants the United States agent to assist in
communications with the foreign establishment, to respond to questions
about the foreign establishment's products, and to help schedule
inspections of the foreign establishment. If a foreign establishment
violates the act, FDA would pursue action against that foreign
establishment. Examples of instances where FDA might take action
against the United States agent would be where the agent submitted
false information to FDA or the agent and the foreign establishment
were effectively the same entity. Given the limited nature of the
United States agent's potential liability to FDA, the agency declines
to amend the rule to address liability issues.
As for the United States agent's liability in third party
litigation (i.e., situations where a private party sues the foreign
establishment and attempts to attach or enforce a judgment by attaching
the United States agent's assets), such issues are beyond the scope of
this rule. FDA does not have authority to insulate United States agents
from such litigation, and such litigation would be a matter of State,
rather than Federal, law.
(Comment 11) One comment asked FDA to provide additional support
and details on the United States agent requirement. The comment
suggested that FDA should identify persons who can serve as United
States agents and make that information publicly available through
FDA's website or other publications. The comment also said FDA should
consider its enforcement needs regarding office location, personnel
qualifications, and necessary communications capabilities.
(Response) Given the final rule's broad, general descriptions of
the United States agent's duties, details regarding the United States
agent's office location, the agent's personnel qualifications, and
communications
[[Page 59143]]
capabilities are not necessary at this time. If such details become
necessary or desirable in the future, FDA will consider whether
additional documents, such as a guidance document or rulemaking, are
needed.
As for identifying persons who might serve as United States agents,
FDA's Center for Devices and Radiological Health is considering whether
to list persons who have expressed an interest in being United States
agents. The list would be made available over the Internet, but FDA
cautions that the list should not be interpreted as endorsing any
person on the list or as suggesting that those persons are particularly
trained or qualified to act as United States agents.
(Comment 12) The proposed rule would require a foreign
establishment to report changes in the United States agent's name,
address, or phone number within 5 days of the change. The preamble to
the proposed rule invited comment as to whether a United States agent
should be able to report such changes to FDA itself (see 64 FR 26330 at
26333). The preamble to the proposed rule explained that, on rare
occasions, FDA has contacted individuals whom their establishments had
identified as their agent or representative only to find that the
individual had terminated its relationship with the establishment or
was unaware that the establishment had designated that individual as
its representative (id.).
One comment would permit a United States agent to notify FDA about
changes to its name or address or even whether a person no longer
serves as a foreign establishment's United States agent.
(Response) FDA agrees and has revised Secs. 207.40(c)(3),
607.40(d)(3), and 807.40(b)(3) so that United States agents may report
changes themselves.
(Comment 13) Several comments supported discussions between FDA and
its Canadian counterparts to reach an agreement that would eliminate
the need for a United States agent for Canadian firms or let Canadian
authorities act on FDA's behalf on matters involving Canadian firms.
Another comment stated that it understood that the U. S. Department of
Agriculture and FDA had a ``reciprocal relationship'' with the Canadian
Food Inspection Agency (CFIA) that enables U. S. regulatory authorities
to inspect Canadian firms where possible and, where geographically
impossible, obtain information from Canadian authorities regarding a
Canadian firm's products, their origin, inspection status, and other
information.
(Response) Although FDA and its Canadian counterparts have a
history of cooperation on regulatory matters of mutual interest,
section 510(i) of the act and other laws administered by FDA do not
contain a mechanism for exempting countries from the United States
agent requirement. Consequently, negotiations seeking an administrative
exemption from the United States agent requirement would not be
productive.
Similarly, an agreement with a foreign country regarding inspection
results does not relieve foreign manufacturers from complying with
section 510(i) of the act. Neither does it relieve FDA from enforcing
section 510(i) of the act.
(Comment 14) Several comments asserted that trade agreements
restricted the ability of the United States to require foreign
establishments to have a United States agent. Most comments referred to
the North American Free Trade Agreement (NAFTA), the United States-
Canada Free Trade Agreement, and/or the General Agreement on Tariffs
and Trade (GATT) to declare that a United States agent requirement
would hinder trade or would be an unreasonable barrier to trade. Other
comments simply referred to unnamed trade agreements and did not
explain how the United States agent requirement violated those trade
agreements. One comment stated that NAFTA provides for recovery of lost
profits under certain conditions and that FDA must consider NAFTA
matters before issuing regulations that could affect North American
trade. Another comment said that NAFTA prevents the United States from
requiring foreign establishments to have a United States agent when
Canada does not have a similar requirement for U. S. firms.
Other comments raised other trade issues, stating that the United
States agent requirement will prompt some foreign establishments to
withdraw from the U. S. market, resulting in an adverse effect on U. S.
consumers. Some comments suggested that they would ask their
governments to enact similar requirements against U. S. companies. A
small number of comments feared that other countries, after discovering
that the United States requires foreign establishments to have an
agent, would enact similar legislation or claimed that their own
foreign country did not impose such requirements on U. S.
establishments.
(Response) FDA disagrees with the comments that suggested that the
rule violates relevant trade agreements. Both GATT and NAFTA permit
parties to adopt measures for the protection of human health as well as
measures to secure compliance with permissible laws. The rule
accurately implements the legitimate public health objectives of
facilitating communication and scheduling of inspections with foreign
establishments and is not a disguised restriction on trade.
Furthermore, it does not violate the national treatment provisions of
the trade agreements because the requirement parallels the domestic
registration requirements of providing the name of an accessible
individual responsible to the establishment.
As for those comments claiming that the rule will prompt some
foreign establishments to withdraw from the U. S. market or lead to
foreign legislation targeting U. S. companies, such matters are
speculative and outside the scope of this regulation.
As for those comments claiming that their own country does not have
a similar requirement that would apply against U. S. establishments,
FDA is aware of several agent-like requirements imposed by foreign
countries. These requirements vary in the obligations imposed and the
industries affected, but, regardless of their nature, the existence or
non-existence of foreign statutory requirements does not alter the fact
that section 510(i) of the act requires foreign establishments to have
a United States agent.
(Comment 15) Most comments did not object to requiring foreign
establishments to register their establishments. The comments often
explained that their own country's laws or regulations required
establishments to register or that FDA would be treating domestic and
foreign establishments alike. However, one comment objected to having a
United States agent because, it argued, FDA does not require
establishments in the United States to have an agent. The comment also
criticized the ``U.S.-designated agent'' requirement (which never
became effective) as treating foreign establishments differently than
U. S. establishments.
(Response) Section 510(i) of the act clearly requires foreign
establishments engaged in the manufacture, preparation, propagation,
compounding, or processing of a drug or a device that is imported or
offered for import into the United States to register and to name a
United States agent. Although the comment is correct that the act does
not impose a United States agent requirement on U. S. establishments,
there would be no need to amend the act to impose such a requirement on
U. S. establishments because, by virtue of being located in the United
States, they already should have employees located
[[Page 59144]]
in the United States whom FDA can contact when necessary.
C. Comments on Proposed Changes to Part 207 (Human Drugs, Biologics,
and Animal Drugs)
1. General Comments
(Comment 16) One comment said that foreign establishments that make
a bulk chemical intermediate do not have to register or list because a
bulk chemical intermediate is not a drug. The comment then suggested
that, because a new drug application (NDA) holder processes both bulk
chemical intermediates and bulk drug substances into a finished drug
product, there is no valid basis for requiring a foreign bulk drug
substance manufacturer to register if a foreign bulk chemical
intermediate manufacturer does not register. The comment suggested that
the NDA holder simply list both foreign suppliers in the NDA rather
than require a foreign bulk drug substance establishment to register.
(Response) FDA declines to revise the rule as suggested by the
comment. The comment's claim regarding different regulatory burdens
between bulk chemical intermediate product manufacturers and bulk drug
substance manufacturers is misleading because it neglects to consider
the role of each substance in a drug. Chemical intermediates, in
general, are materials that are produced during a manufacturing process
and undergo further molecular change or processing before they become
an active pharmaceutical ingredient. Bulk drug substances, under
Sec. 207.3(a)(4), are substances that are represented for use in a drug
and that, ``when used in the manufacturing, processing, or packaging of
a drug, becomes an active ingredient or finished dosage form of the
drug * * *.'' Thus, chemical intermediates and bulk drug substances are
not alike.
In other words, a chemical intermediate undergoes one or more
molecular changes during manufacturing to become a different chemical,
but the chemical intermediate, in its original form, is not intended or
suitable for use as an active ingredient. Requiring establishments that
manufacture chemical intermediates to register and to list, therefore,
would not provide much helpful information to FDA and, for that reason,
is not necessary to protect the public health.
In contrast, if a firm makes a bulk drug substance, the bulk drug
substance does not require molecular change to become pharmacologically
active. Thus, because a bulk drug substance, like a finished drug, may
provide pharmacological activity, it makes sense to require
establishments that manufacture bulk drug substances to register and
list.
(Comment 17) One comment asked FDA to clarify which biological
products fall under part 207 and to explain the rationale for including
or excluding biological products from part 207. The comment offered no
reason why this clarification was necessary.
(Response) Deciding whether a biological product should be
registered under parts 207, 607, or 807 depends largely on how the
product is defined. In brief, section 201(g)(1)(B) and (g)(1)(C) of the
act (21 U.S.C. 321(g)(1)(B) and (g)(1)(C)) defines ``drug'' as
``articles intended for use in the diagnosis, cure, mitigation,
treatment, or prevention of disease in man or other animals'' and as
``articles (other than food) intended to affect the structure or any
function of the body of man or other animals.'' Section 201(h) of the
act, in part, defines ``device'' as ``an instrument, apparatus,
implement, machine, contrivance, implant, in vitro reagent, or other
similar or related article, including any component, part, or
accessory'' which is ``intended for use in the diagnosis of disease or
other conditions, or in the cure, mitigation, treatment, or prevention
of disease in man or other animals'' or ``intended to affect the
structure or any function of the body of man or other animals'' and
``which does not achieve its primary intended purposes through chemical
action within or on the body of man or other animals and which is not
dependent upon being metabolized for the achievement of its primary
intended purposes.''
Section 510(i) of the act, in turn, requires foreign establishments
engaged in the manufacture, preparation, propagation, compounding, or
processing of a drug or device that is imported or offered for import
into the United States to register the name and place of business of
the establishment and the name of a United States agent and to provide
listing information. Thus, if a biologic meets the definition of drug
or device, as defined in the act, a foreign manufacturer for that
biologic must register (including the name of its United States agent)
and submit listing information. Implementing regulations for the
registration and listing requirements in section 510 of the act are
divided among parts 207 (drugs (including biologics) and animal drugs),
607 (blood and blood products), and 807 (devices).
It is impractical to explain further which biologics may or may not
be regulated under part 207 or to explain the rationale for their
inclusion or exclusion. FDA's experience demonstrates that, despite
FDA's intentions to provide advice or clarity, whenever the agency
attempts to provide complete descriptions of the products that are
subject to a particular regulation or part, the descriptions are either
misconstrued as being exhaustive or definitive (so that persons whose
products are not identified or even slightly different from the
products mentioned in the description claim that they are exempt from
the rule) or must be constantly revised to add new products and to
remove old products. FDA, therefore, finds it more practical, less
confusing, and a better use of its resources to refrain from providing
the detailed explanations sought by the comment. If an establishment is
unsure which registration and listing requirements apply, it should
contact the Center for Biologics Evaluation and Research (CBER).
2. Definitions (Sec. 207.3)
Proposed Sec. 207.3 defined two terms: ``commercial distribution''
and ``United States agent.'' The proposal in Sec. 207.3(a)(5) defined
``commercial distribution'' as:
any distribution of a human drug except for investigational use
under part 312 of this chapter, and any distribution of an animal
drug or animal feed bearing or containing an animal drug for
noninvestigational uses, but the term does not include internal or
interplant transfer of a bulk drug substance between registered
establishments within the same parent, subsidiary, and/or affiliate
company. For foreign establishments, the term ``commercial
distribution'' shall have the same meaning except that the term
shall not include distribution of any drug that is neither imported
nor offered for import into the United States.
FDA meant to clarify that, for foreign establishments, commercial
distribution does not include distribution of a human or animal drug
that is neither imported nor offered for import into the United States.
This change was intended to reflect the statutory language limiting the
registration requirement to those foreign establishments that are
``engaged in the manufacture, preparation, propagation, compounding, or
processing of a drug or a device that is imported or offered for import
into the United States'' (emphasis added), as well as the definition of
``interstate commerce'' in section 201(b) of the act.
(Comment 18) One comment sought further clarification of the term
``commercial distribution'' and how it determined who must register
under
[[Page 59145]]
Sec. 207.20. The comment asked whether a foreign establishment that
supplies a bulk active drug ingredient to the U. S. holder of an NDA
for incorporation into a finished product must register and list its
products and whether the act of supplying the bulk active drug
ingredient was ``commercial distribution.'' The comment asserted that
if FDA required the foreign bulk active ingredient establishment to
register and list, it would impose a greater obligation on the foreign
establishment than on an affiliated company of the NDA holder. The
comment asserted that the transfer or shipment of bulk drug substances
between affiliates does not constitute commercial distribution.
(Response) Section 510(i) of the act applies to any foreign
establishment engaged in the ``manufacture, preparation, propagation,
compounding, or processing of a drug or device that is imported or
offered for import into the United States * * * .'' Section 201(g)(1)
of the act defines ``drug,'' in part, as ``articles intended for use as
a component'' of a drug. Thus, a foreign bulk drug manufacturer who
ships bulk active ingredients to a U. S. firm is subject to section
510(i) of the act and must register the foreign establishment
(including a United States agent) and list its products.
FDA disagrees with the comment's assertion that requiring a foreign
bulk drug manufacturer to register and list would impose a greater duty
than one that would apply to an NDA holder's affiliate company. Under
Sec. 207.3(a)(5), only internal or interplant transfers of bulk drug
substances between registered establishments within the same parent,
subsidiary, and/or affiliate company fall outside the definition of
``commercial distribution.'' Thus, under Sec. 207.3(a)(5), an affiliate
firm would have to be registered just like the foreign establishment.
(Comment 19) One comment sought additional definitions or
explanations of terms in part 207. The comment said FDA should amend
the definitions to state specifically that establishments, both foreign
and domestic, that make biological products must register and list. The
comment claimed that biologics manufacturers are sometimes unaware that
they must register and list. The comment also asked FDA to clarify
whether biologic source suppliers must register.
(Response) FDA declines to amend the rule to include an express
reference to biologics establishments. Part 207 already contains
sufficient indications to show that the requirements apply to biologics
establishments, so further clarification is unnecessary, and the
statutory definition of ``drug,'' in section 201 of the act, includes
biological products.
Furthermore, revising part 207 to include an express reference to
biologics establishments might increase any confusion in the biologics
industry or force FDA to make similar changes throughout title 21 of
the CFR each time the word ``drug'' appears. Otherwise, a biologics
firm might argue that the absence of an express reference to biologics
in any given regulation meant that the regulation did not apply to
biologics. The result would be confusion as to which rules did or did
not apply to biologics. While it might ultimately be beneficial for FDA
to examine all of its regulations to clarify their scope or coverage, a
large scale reexamination and editorial effort is outside the scope of
this rule.
As for the question whether biologics source suppliers must
register, registration is required if the product that is imported or
offered for import to the United States meets the definition of
``drug'' in section 201(g) or ``device'' in section 201(h) of the act
and if the foreign establishment is not otherwise exempt from the
registration requirement.
(Comment 20) Proposed Sec. 207.3(a)(11) defined ``United States
agent'' as ``a person residing or maintaining a place of business in
the United States whom a foreign establishment designates as its
agent.'' FDA received no comments on the definition in
Sec. 207.3(a)(11), but one comment did address the identical definition
at Sec. 807.3. The comment noted that the preamble to the proposed rule
stated that the definition of ``United States agent'' excluded
mailboxes, answering machines or services, or other places where an
individual acting as the foreign establishment's agent is not
physically present (see 64 FR 26330 at 26331). The comment suggested
that FDA revise the definition of ``United States agent'' to mention
these exclusions.
(Response) FDA agrees with the comment and has revised the
definition of ``United States agent'' in Secs. 207.3(a)(11), 607.3(j),
and 807.3(r) accordingly.
3. Establishment Registration and Product Listing for Human Blood and
Blood Products and for Medical Devices (Sec. 207.7)
Proposed Sec. 207.7(a) would revise the address for the office in
CBER that receives the registration and listing information.
FDA received no comments on this provision and has finalized it
without change.
4. Exemptions for Establishments (Sec. 207.10)
Proposed Sec. 207.10 would delete the word ``domestic'' from its
title, so that the provision pertains to exemptions for both foreign
and domestic establishments. The proposal would also revise the
description of establishments that are exempt from registration.
FDA received no comments on this provision and has finalized it
without change.
5. Who Must Register and Submit a Drug List (Sec. 207.20)
Proposed Sec. 207.20(a) would clarify that the exemptions are under
section 510(g) of the act or subpart B (``Exemptions'') of part 207.
This would be an editorial change to place all exemptions that apply to
drug manufacturers in subpart B of part 207 and would remove all
exemptions from subpart D.
The proposal would also revise paragraph (a) of Sec. 207.20 so that
the language requiring owners and operators to register their
establishments and to list drugs, whether or not the output of the
establishment or any particular drug so listed enters interstate
commerce, would apply only to domestic firms. FDA proposed this change
because it does not intend to require foreign establishments to list
drugs that do not enter interstate commerce by being imported or
offered for import into the United States.
The proposal would also make some minor edits to Sec. 207.20(a) by:
(a) Deleting the phrase ``at this time'' because the phrase is
unnecessary, (b) moving the parenthetical language referring to Type B
and Type C medicated feed so that it refers accurately to animal feeds
bearing or containing an animal drug rather than to animal feeds
generally, and (c) revising the parenthetical language so that it
refers to Type B ``or'' Type C medicated feed. The proposed rule would
also add ``abbreviated new drug applications'' and ``abbreviated new
animal drug applications'' to the list of marketing applications in
Sec. 207.20(c). These applications were inadvertently omitted from
previous rulemakings amending part 207.
(Comment 21) In the preamble to the proposed rule, FDA noted that
Sec. 207.20(a) permits a company to submit listing information on
behalf of a parent, subsidiary, and/or affiliate company for all
establishments when operations are
[[Page 59146]]
conducted at more than one establishment and there exists joint
ownership and control among all the establishments. FDA interpreted
this provision, and similar provisions at Secs. 607.20(a) and
807.20(a), as including foreign establishments to which the same
conditions apply (see 64 FR 26330 at 26332).
One comment asked FDA to explain what `` affiliate companies '' and
`` joint ownership and control '' are. The comment said that the rule
allows reporting by affiliate companies where there is joint ownership
and control, but does not explain what those terms mean.
(Response) The act and a commonly used law dictionary can provide
some help on interpreting the terms `` affiliate companies '' and ``
joint ownership and control.'' Section 735(9) of the act (21 U.S.C.
379g(9)) defines ``affiliate,'' for purposes of fees relating to drugs,
as meaning ``a business entity that has a relationship with a second
business entity if, directly or indirectly--(A) one business entity
controls, or has the power to control, the other business entity; or
(B) a third party controls, or has power to control both of the
business entities.'' This definition is similar to one that appears in
Black's Law Dictionary, which defines ``affiliation,'' in terms of
corporations, as legally enforceable control of stock of corporations
by the same interests (see Black's Law Dictionary 80 (4th ed. 1968)).
Thus, an ``affiliate company'' is one that is legally controlled,
directly or indirectly, by another company or can be controlled by
another company; mere business links are not sufficient. Black's Law
Dictionary defines ``joint owners'' as ``two or more persons who
jointly own and hold title to property'' and ``control'' as ``power or
authority to manage, direct, superintend, restrict, regulate, direct,
govern, administer, or oversee'' (id. at 1260 and 399). Thus, ``joint
ownership and control'' suggests that two or more persons own the
companies at issue and share managerial or supervisory
responsibilities.
(Comment 22) One comment suggested that FDA revise Sec. 207.20(a)
and similar language in Secs. 607.20(a) and 807.20(a) to allow a
foreign parent company to register and list on behalf of its foreign
subsidiaries. The comment explained that the rule allows parent
companies to list on behalf of their subsidiaries, but does not allow
them to register their subsidiaries. The comment suggested that section
510(i) and (j) of the act give FDA the flexibility to allow parent
companies to register on behalf of their subsidiaries and that this
would also enable foreign establishments to name a single official who
would be responsible for registration and listing information, thereby
facilitating the development of a single, unified registration and
listing system.
(Response) FDA agrees with the comment and has amended
Secs. 207.20(a), 607.20(a), and 807.20(a) to allow parent companies to
register and list on behalf of their subsidiaries.
(Comment 23) One comment said that FDA should ``recognize'' that
distributors may list drug products and that the manufacturers of those
drug products, whether foreign or domestic, should not have to list the
same drugs. The comment asserted that the Drug Listing Act of 1972 was
not intended to require ``dual listing'' by a manufacturer if a
distributor supplied the same information. The comment said FDA's
current practice (which requires manufacturers to list drugs even if a
distributor lists those drugs) is contrary to the Drug Listing Act of
1972, FDA's regulations at Sec. 207.20(b), and the Paperwork Reduction
Act. The comment said requiring ``additional'' listing has no practical
utility, is wasteful to the regulated industry, and costly to
consumers.
(Response) Although the comment is outside the scope of the rule in
the sense that it has no direct bearing on foreign establishment
registration, listing, or the United States agent requirement, FDA
disagrees with the comment. Section 207.20(b) applies to owners and
operators of establishments that are ``not otherwise required to
register under section 510 of the act'' and that ``distribute under
their own label or trade name a drug manufactured or processed by a
registered establishment'' (emphases added). It states that these
owners and operators may elect to submit listing information directly
to FDA and to obtain a Labeler Code. The regulation, therefore, clearly
states that these distributors: (1) Do not have to register (whereas
manufacturers must register); (2) are distributing drugs under their
own label or trade name (which will be different from the labels and
names used by the manufacturer); and (3) have discretion to decide
whether they wish to list the drugs (because Sec. 207.20(b) says that
these persons ``may elect'' to submit listing information to FDA).
More importantly, the comment overlooks the value in having these
distributors and manufacturers list drugs. Section 207.20(b) applies
where the distributor uses its own label or trade name on a drug, but
does not manufacture the drug itself. So, if these distributors and
drug manufacturers list the drugs that they put into commercial
distribution, FDA will be able to link the distributor's drugs back to
their manufacturer(s) even though the distributor is using a different
label or name for the drug.
To illustrate how this works, assume that a distributor, named
Delta, distributes two drugs that it calls Alpha and Beta. Alpha is
made by a U. S. manufacturer, named Domestic Co., which sells Alpha
under the name X, while Beta is made by a foreign manufacturer, named
Foreign Co., and sold under the name Y. If, as the comment apparently
requests, Delta--but not Domestic Co., or Foreign Co., had to list the
drugs, FDA might find it difficult to link Alpha and Beta to their
respective manufacturers. If, on the other hand, the manufacturers, but
not Delta, had to list the drugs, FDA might find it difficult to know
that drug X and Alpha are the same or that drug Y and Beta are the
same. When viewed from this perspective, the drug listing information
from both the distributor and manufacturers serves the practical
purpose of providing a link between seemingly different drugs, and so,
contrary to the comment, the drug listing information is not redundant
or unnecessary.
(Comment 24) One comment said that FDA, in the past, has allowed
foreign drug establishments to authorize a representative to register
and list on its behalf. The comment asked FDA to clarify that foreign
drug establishments may continue this practice.
(Response) Foreign drug establishments may continue to have
representatives register and submit drug listing information on their
behalf. Neither section 510(i) of the act, nor this final rule,
requires foreign drug establishments to complete or to submit
registration and listing information themselves, but foreign drug
establishments are responsible for the accuracy of the information
submitted to FDA and for complying with the registration and listing
requirements.
(Comment 25) One comment suggested that if a biologic intermediate
is licensed, then the license holder for the intermediate and the
license holder for the final product must register and list the
product.
(Response) In general, if an establishment has a licensed
biological product, the establishment, whether foreign or domestic,
must register and list its products. FDA would consider the product to
fall within the definition of ``drug'' or ``device'' in section 201(g)
or (h) of the act, so section 510(i) of the act would require
registration and product listing.
[[Page 59147]]
(Comment 26) One comment asked whether biologics source suppliers
must register.
(Response) As stated earlier, registration is required if the
product that is imported or offered for import to the United States
meets the definition of ``drug'' or ``device'' in section 201(g) or (h)
of the act and if the establishment is not otherwise exempt from the
registration requirement.
If the establishment is unsure about whether or not they should
register, they should contact the appropriate product review division
in CBER. If the establishment is unsure about which product review
division to contact, they should contact the Office of Compliance and
Biologics Quality at 301-827-6190 for assistance.
(Comment 27) One comment claimed that, because the rule excluded
establishments whose drugs are not imported or offered for import into
the United States, the rule contradicted FDA's ``Policy Statement
Concerning Cooperative Manufacturing Arrangements for Licensed
Biologics'' (hereinafter referred to as ``the cooperative manufacturing
policy''), which appeared in the Federal Register on November 25, 1992
(57 FR 55544). The comment focused on foreign manufacturers of bulk
substances who sell their products to other foreign manufacturers who
use them in making a finished product.
(Response) The cooperative manufacturing policy discussed several
types of manufacturing arrangements for establishments who wish to
cooperate in the manufacture of a licensed biological product and made
no distinctions between foreign and domestic manufacturers. FDA drafted
the policy statement to describe the then-current licensing policies in
CBER ``for meeting the increased demand for flexible manufacturing
arrangements'' (57 FR 55544).
The first manufacturing arrangement discussed in the policy
concerned short supply arrangements. In a short supply arrangement, a
manufacturer obtains materials from another facility under certain
conditions because the manufacturer needs to obtain source materials
only due to ``unusual circumstances where the source material is scarce
or growth requirements so peculiar that production is uncommon'' (57 FR
55544 at 55545). The policy was silent as to whether firms who provide
source material under a short supply arrangement must register or list,
so it neither supports nor conflicts with this rule. FDA advises
foreign establishments who provide source material under a short supply
arrangement to register and to list if they meet the terms in section
510(i) of the act and this final rule. In other words, registration and
listing is required if the foreign establishment is engaged in
manufacturing, preparing, propagating, compounding, or processing a
drug or device that is imported or offered for import into the United
States (and the establishment does not otherwise qualify for an
exemption from the registration and listing requirements).
The second arrangement discussed in the policy concerned divided
manufacturing arrangements where two registered manufacturers jointly
participate in manufacturing a product (emphasis added). Under this
scenario, both manufacturers are manufacturing the product, so, even if
the manufacturers were both foreign establishments, they would be
subject to the registration requirements in this rule because they are
engaged in the manufacture, preparation, propagation, compounding, or
processing of a drug or device that is imported or offered for import
into the United States. So, the policy, as it applies to divided
manufacturing arrangements, does not conflict with the rule.
The third and fourth arrangements discussed in the policy pertain
to shared and contract manufacturing arrangements. In shared
manufacturing arrangements, two or more manufacturers may perform
different manufacturing tasks, but are not licensed to perform all
manufacturing aspects. The policy advised manufacturers in shared
manufacturing arrangements to register and to list in accordance with
part 207. If the manufacturers are located in a foreign country, FDA
considers both to be manufacturing a product to be imported or offered
for import into the United States and would expect both manufacturers
to register and to list the products that are being imported or offered
for import. Consequently, the policy does not conflict with the rule.
As for contract manufacturing arrangements, these arrangements
involve a licensed manufacturer who engages another manufacturing
facility (referred to as the ``contract manufacturer'') to perform all
or some of the steps to manufacture a biological product (see 57 FR
55544 at 55546). Clearly, the licensed manufacturer, as the entity who
obtains marketing approval and sells the product, must register and
list its product even if the licensed manufacturer is a foreign
establishment. Registration and listing would be required because,
under section 510(i) of the act, the licensed manufacturer is
manufacturing, preparing, propagating, compounding, or processing a
drug that is imported or offered for import into the United States. The
same would be true for foreign contract manufacturers; if a foreign
contract manufacturer's manufacturing steps can be considered to be
manufacturing, preparing, propagating, compounding, or processing a
drug that is imported or offered for import into the United States,
then the foreign contract manufacturer falls within section 510(i) of
the act and must register and list.
FDA further notes that the cooperative manufacturing policy
statement simply represents FDA's advice whereas this rule implements
section 510(i) of the act and creates enforceable obligations.
Therefore, even if there were any conflict between the policy statement
and this rule, foreign establishments must comply with this rule.
6. Times for Registration and Drug Listing (Sec. 207.21)
Proposed Sec. 207.21 would correct an administrative oversight by
adding ``abbreviated new drug applications'' and ``abbreviated new
animal drug applications'' to the list of marketing applications in
that section. The effect would be to state, expressly, that an owner or
operator of an establishment that has just begun manufacturing or
processing drugs should register within 5 days after submitting an NDA,
abbreviated new drug application, new animal drug application,
abbreviated new animal drug application, medicated feed mill license
application, antibiotic application, or a biologics license application
to manufacture a biological product.
(Comment 28) One comment said FDA failed to address biological
manufacturing sites that are currently licensed, but not registered.
The comment asked when these firms should register.
(Response) FDA recently began efforts to create an electronic
registration program for all establishments, both foreign and domestic,
that are subject to part 207. As a result, FDA is amending
Sec. 207.21(a) to delete the registration schedule and its reference to
Form FDA-2656 (Registration of Drug Establishment).
Foreign establishments subject to part 207 should register by May
28, 2002.
(Comment 29) One comment said that FDA should create a special
schedule for foreign establishment registration, rather than use the
existing schedule, because foreign establishments might find it
difficult to register quickly or immediately (depending on when the
[[Page 59148]]
rule becomes effective). The comment said FDA should also consider the
implications of company mergers, name changes, burdens of complying
with new registration schedules, and multiple product types.
(Response) As stated above, foreign establishments subject to part
207 should register by May 28, 2002. This should give foreign
establishments sufficient time to comply with the registration and
listing requirements even if they are aware of impending mergers, name
changes, or other future business considerations.
7. Information Required in Registration and Drug Listing (Sec. 207.25)
Section 207.25(b)(2) requires the numbers for various marketing
applications to be included in the drug listing information submitted
to the agency. For example, if an NDA were assigned number 20-570, the
application number that would be included in the drug listing
information would be NDA 20-570.
The proposed rule would add abbreviated new animal drug
applications to the list of marketing applications in Sec. 207.25. This
action was necessary because abbreviated new animal drug applications
were inadvertently omitted.
(Comment 30) One comment asked whether Sec. 207.25(b)(3), which
requires an establishment to provide the ``license number of the
manufacturer'' as part of the drug product listing form, applies to
numbers assigned to biologics license applications.
(Response) When FDA approves a biologics license application, the
applicant receives a United States license number. The United States
license number is different from the biologics license application
number and is the number that should be reported on the drug listing
form for biological products in Sec. 207.25(b)(3).
8. Inspection of Registrations and Drug Listings (Sec. 207.37)
Proposed Sec. 207.37(a) would update the addresses in the Center
for Drug Evaluation and Research (CDER) where copies of registration
forms filed by establishments are available for inspection and would
state that copies of registration forms submitted by foreign
establishments are available for inspection at the Office of Compliance
in CDER. Copies of forms submitted by domestic establishments would
continue to be available for inspection at FDA district offices and at
the Office of Compliance in CDER.
The proposal would also update the addresses in Sec. 207.37(b).
(Comment 31) One comment claimed the current procedures for
examining drug listing information are ``cumbersome and inconvenient''
and that FDA should makes its processes more transparent and its
procedures readily available. The comment said FDA should post the
information on the Internet.
(Response) In general, FDA has taken various steps to make
information more readily available. The agency will take the comment's
suggestion under advisement, but, due to resource limitations and other
agency priorities, it cannot, at this time, make drug listing
information available electronically or estimate when it will be able
to do so.
9. Drug Listing Requirements for Foreign Drug Establishments
(Sec. 207.40)
Proposed Sec. 207.40(a) would require foreign establishments whose
drugs are imported or offered for import into the United States to
comply with the establishment registration and listing requirements in
subpart C of part 207 (``Procedures for domestic drug
establishments''), unless exempt under subpart B of part 207
(``Exemptions''). Proposed Sec. 207.40(b) would prohibit the
importation of drugs from unregistered foreign establishments, prohibit
the importation of unlisted drugs, and require foreign establishments
to submit registration and listing information, including labels and
labeling, in English. Proposed Sec. 207.40(c) would, among other
things, require each foreign establishment to submit the name, address,
and phone number of its United States agent as part of the
establishment's initial and updated registration information, and to
describe the United States agent's responsibilities.
(Comment 32 and Response) FDA, on its own initiative, is revising
the reference to drugs imported for investigational use in
Sec. 207.40(b). The rule stated that drugs for investigational use must
comply with 21 CFR part 312. FDA is revising the provision to add a
reference to part 511 (21 CFR part 511) because investigational new
animal drugs are subject to part 511. This change should have no effect
on foreign establishments because the Center for Veterinary Medicine
has not required foreign establishments to list investigational new
animal drugs.
FDA is also revising Sec. 207.40(b) and its prohibition on the
importation or the offer to import drugs from unregistered foreign
establishments. FDA is adding a reference to section 801(d)(3) of the
act (21 U.S.C. 381(d)(3)) so that drugs imported under section
801(d)(3) of the act may be admitted into the United States even if the
foreign establishment is not registered. The agency is taking this step
because section 801(d)(3) of the act imposes very few restrictions on
the admission of drug components that are imported into the United
States for further processing or incorporation into a product that will
be exported from the United States. The agency is making similar
changes to Secs. 607.40(b) and 807.40(c).
(Comment 33) Proposed Sec. 207.40(c)(2) would require the United
States agent to assist FDA in communications with the foreign drug
establishment, respond to questions concerning the foreign drug
establishment's products that are imported or offered for import into
the United States, and assist FDA in scheduling inspections of the
foreign drug establishment. One comment would revise the rule to allow
multinational companies with many foreign affiliates to designate an
employee at the foreign affiliate as the United States agent and to
list an employee in the United States as an alternate. The comment said
this would make communications between FDA and foreign establishments
more efficient because the foreign employee would be able to answer
questions more directly and schedule inspections more readily.
(Response) FDA declines to revise the rule as suggested by the
comment. FDA reiterates that it interprets the term ``United States
agent'' as meaning that the agent is physically located in the United
States. If the United States agent could be located in any foreign
country, section 510(i) of the act would not have to refer to a
``United States'' agent. Indeed, if the agent could be in any foreign
country, the agent requirement might even by invalid or questioned as
an intrusion into a foreign country's corporate or employment laws.
So, the rule does not prevent a multinational firm from designating
an employee located in the United States as its agent who could, if
necessary, consult a foreign employee to respond to any questions FDA
might have, schedule an inspection, or work with a foreign employee on
other issues relevant to the United States agent's duties.
(Comment 34) Proposed Sec. 207.40(c)(3) would require foreign
establishments to report changes in the United States agent's name,
address, or phone number within 5 days of the change. One comment
stated that there may not be an adequate number of firms or persons who
can act as United States agents and that foreign establishments will
have to identify and locate such persons. The comment asked FDA to
provide 30 days,
[[Page 59149]]
rather than 5 days, for foreign establishments to identify its United
States agent. Similarly, another comment said a 5-day period is too
short and asked FDA to allow 10-business days or 14-calendar days.
(Response) FDA has revised Sec. 207.40(c)(3), and similar
requirements at Secs. 607.40(d)(3), and 807.40(b)(3), to give foreign
establishments and United States agents 10-business days to report
changes.
(Comment 35) As stated earlier, one comment asserted that FDA
should not require foreign establishments to register if their products
are not commercially distributed in the United States. The comment said
that foreign establishments which send goods to a foreign trade zone
and later re-export those goods from the United States without entering
them into U. S. commerce should be exempt from registration
requirements.
(Response) FDA agrees with the comment, but only as it pertains to
foreign establishments who send products into foreign trade zones and
whose products are re-exported from the United States without having
entered domestic commerce. FDA, therefore, has amended Secs. 207.40(a),
607.40(a), and 807.40(a) accordingly.
D. Proposed Changes to Part 607 (Human Blood and Blood Products)
1. Definitions (Sec. 607.3)
a. Definition of ``commercial distribution.'' Proposed
Sec. 607.3(e) would revise the definition of ``commercial
distribution'' to state that, for foreign establishments, commercial
distribution does not include distribution of any blood or blood
product that is neither imported nor offered for import into the United
States. The preamble to the proposed rule explained that this change
was intended to make the definition, insofar as foreign establishments
are concerned, consistent with the language of section 510(i)(1) of the
act.
FDA received no comments on this provision and has finalized it
without change.
b. Definition of ``United States agent.'' Proposed Sec. 607.3(j)
would define ``United States agent'' as ``any person residing or
maintaining a place of business in the United States whom a foreign
establishment designates as its agent.'' This definition was identical
to that in proposed Sec. 207.3(a)(11).
(Comment 36) FDA received no comments addressing proposed
Sec. 607.3(j). However, as stated earlier, the agency did receive a
comment which sought to revise the identical definition at Sec. 807.3
to expressly exclude mailboxes, answering machines or services, or
other places where an individual acting as the foreign establishment's
agent is not physically present.
(Response) FDA agrees with the comment and has revised the
definition of ``United States agent'' in Sec. 607.3(j) and the
identical definitions in Secs. 207.3(a)(11) and 807.3(r), accordingly.
2. Establishment Registration and Product Listing of Blood Banks and
Other Firms Manufacturing Human Blood and Blood Products (Sec. 607.7)
Section 607.7(b) and (c) provides an address for CBER from which
registration forms may be obtained and to which they may be sent. The
proposed rule would amend Sec. 607.7(b) and (c) to update the address.
FDA received no comments on this provision and has finalized it
without change.
3. Who Must Register and Submit a Blood Product List (Sec. 607.20)
Proposed Sec. 607.20(a) would revise the description of owners and
operators who must register their establishments and list their
products. The proposal would clarify that only domestic firms must
register and submit a list of every blood product in commercial
distribution, ``whether or not the output of such blood product
establishment or any particular blood product so listed enters
interstate commerce.'' This would mean that foreign establishments do
not have to list blood products that are not sold or offered for sale
in the United States.
(Comment 37) As stated earlier, one comment suggested that FDA
revise Sec. 207.20(a) and similar language in Secs. 607.20(a) and
807.20(a) to allow a foreign parent company to register and list on
behalf of its foreign subsidiaries. The comment explained that the rule
allows parent companies to list on behalf of their subsidiaries, but
does not allow them to register their subsidiaries.
(Response) FDA agrees with the comment and has amended
Secs. 207.20(a), 607.20(a), and 807.20(a) to allow parent companies to
register and list on behalf of their subsidiaries.
4. How and Where to Register Establishments and List Blood Products
(Sec. 607.22)
Proposed Sec. 607.22 would update the addresses from which
registration and listing forms may be obtained. The proposal would also
delete the language in Sec. 607.22(b) concerning tapes for computer
input and the submission of proposed formats for FDA review and
approval because the option for using computer tapes was never used.
FDA received no comments on this provision and has finalized it
without change.
5. Information Required for Establishment Registration and Blood
Product Listing (Sec. 607.25)
Proposed Sec. 607.25(a) would delete the word ``ZIP'' from the
phrase ``post office ZIP code.'' FDA proposed this change because many
foreign countries do not use the term ``ZIP'' code.
FDA received no comments on this provision and has finalized it
without change. However, the agency, on its own initiative, is also
amending Sec. 607.25(b)(3) regarding the registration number of a
parent establishment. Section 607.25(b)(3), as revised, now clarifies
that for each blood product listed, the registration number of the
parent establishment is required and that ``an establishment not owned,
operated, or controlled by another firm or establishment is its own
parent establishment.'' FDA is making this change to be consistent with
changes to the Form FDA 2830 (Blood Establishment Registration and
Product Listing).
6. Amendments to Establishment Registration (Sec. 607.26)
Currently, Sec. 607.26 requires changes in individual ownership,
``corporate or partnership structure location or blood-product handling
activity'' to be reported. The proposal would revise this language to
read as ``Changes in individual ownership, corporate or partnership
structure, location, or blood-product handling activity'' to clarify
that changes in corporate or partnership structure or location or
blood-product handling activity are to be reported.
FDA received no comments on this provision and has finalized it
without change.
7. Additional Blood Product Listing Information (Sec. 607.31)
Proposed Sec. 607.31(a) would authorize the Director of CBER,
rather than the Commissioner of Food and Drugs (the Commissioner), to
perform various actions, such as making a request or a finding, before
requiring additional blood product listing information. The proposal
reflected the fact that the center director, rather than the
Commissioner, performs those functions.
The proposal would also delete Sec. 607.31(b) that pertains to the
voluntary reporting of information on the quantity
[[Page 59150]]
of blood product distributed. FDA proposed to delete the text in
paragraph (b) of Sec. 607.31 because the form specified in the rule,
Form FD-2831 (Blood Establishment Resource Summary), is obsolete, and
the provision has not been used.
FDA received no comments on this provision and has finalized it
without change.
8. Notification of Registrant; Blood Product Establishment Registration
Number and NDC Labeler Code (Sec. 607.35)
Section 607.35(a) currently states that the Commissioner will
provide a validated copy of Form FD-2830 to the location shown for the
registering establishment. The proposal would amend Sec. 607.35(a) to
state that a copy will also be sent to the reporting official if that
official is at another address. The proposal would also substitute the
``Director of the Center for Biologics Evaluation and Research'' for
the ``Commissioner'' because the center director, rather than the
Commissioner, is the official who provides the validated copy.
FDA received no comments on this provision and has finalized it
without change.
9. Inspection of Establishment Registrations and Blood Product Listings
(Sec. 607.37)
Proposed Sec. 607.37 would update the addresses where filed forms
are available for inspection or where requests for information
regarding blood establishment registration and listing should be sent.
FDA received no comments on this provision and has finalized it
without change.
10. Establishment Registration and Blood Product Listing Requirements
for Foreign Blood Product Establishments (Sec. 607.40)
Proposed Sec. 607.40(a) would require foreign establishments to
comply with establishment registration requirements in addition to
blood product listing requirements. To complement this change, the
proposal would revise the title to Sec. 607.40 to read as
``Establishment registration and blood product listing requirements for
foreign blood product establishments.''
Proposed Sec. 607.40(b) would enable FDA to prohibit the
importation of blood products from unregistered foreign establishments,
in addition to prohibiting the importation of unlisted blood products.
This prohibition would be similar to Sec. 207.40(b) and would be
consistent with sections 301(p) and 501(a) (21 U.S.C. 331(p) and
351(a)), and 801(a) of the act. Proposed Sec. 607.40(b) would also add
establishment registration information to types of information that
must be submitted in the English language.
Proposed Sec. 607.40(c) would require foreign blood product
establishments to submit the name and address of the establishment and
the name of the individual responsible for submitting the establishment
registration and product listing information as part of the
establishment registration and blood product listing. Proposed
Sec. 607.40(c) would also require foreign establishments to report any
changes in their registration or listing information.
Proposed Sec. 607.40(d) would require each foreign blood product
establishment to submit the name, address, and phone number of one
United States agent as part of its initial and updated registration
information and describe the United States agent's responsibilities.
Changes to the United States agent's name, address, or phone number
would, under proposed Sec. 607.40(d), be reported to FDA within 5 days
of the change.
(Comment 38) FDA received no comments on this provision, but, as
stated earlier, one comment asserted that FDA should not require
foreign establishments to register if their products are not
commercially distributed in the United States. The comment said that
foreign establishments which send goods to a foreign trade zone and
later re-export those goods from the United States without entering
them into United States commerce should be exempt from registration
requirements.
(Response) FDA agrees with the comment, but only as it pertains to
foreign establishments who send products into foreign trade zones and
whose products are re-exported from the United States without having
entered domestic commerce. FDA, therefore, has amended Secs. 207.40(a),
607.40(a), and 807.40(a) accordingly.
(Comment 39) FDA received no comments on Sec. 607.40, but, as
stated earlier, received comments on similar language in Sec. 207.40
regarding the time period for reporting changes to the United States
agent's name, address, or phone number. The comments would increase the
time period to 10-business days or 14-calendar days.
(Response) FDA agrees with the comment and has revised
Secs. 207.40(c)(3), 607.40(d)(3), and 807.40(b)(3) to give foreign
establishments and United States agents 10 business days to report
changes.
11. Exemptions for Blood Product Establishments (Sec. 607.65)
Proposed Sec. 607.65 would revise paragraphs (c), (d), and (e) so
that the exemptions described in those paragraphs would apply to both
foreign and domestic persons or establishments. For example, proposed
Sec. 607.65(c) would exempt domestic and foreign persons who
manufacture blood products solely for use in research, teaching, or
analysis, while proposed Sec. 607.65(d) would exempt carriers, both
foreign and domestic, who receive, carry, hold, or deliver blood
products in their usual course of business. Proposed Sec. 607.65(e)
would exempt domestic and foreign persons who engage solely in the
manufacture of in vitro diagnostic blood products and reagents that are
not subject to licensing under section 351 of the Public Health Service
Act (PHS Act) (42 U.S.C. 262).
FDA received no comments on this provision and has finalized it
without change.
12. Miscellaneous Biologics Comments
(Comment 40) One comment said that the document entitled ``Policy
Statement Concerning Cooperative Manufacturing Arrangements for
Licensed Biologics,'' which appeared in the Federal Register on
November 25, 1992 (57 FR 55544), discusses registration requirements
for firms in cooperative manufacturing arrangements, but does not
specifically address ``who was responsible for the registration process
(i.e., the license holder of the final product versus the establishment
owner of the bulk drug substance').''
(Response) FDA issued the cooperative manufacturing policy in 1992,
6 years before FDAMA amended section 510(i) of the act to require
foreign establishments to register. While FDA is currently updating the
policy, comments concerning the policy are outside the scope of this
rule.
Yet with regard to the comment's cooperative manufacturing
scenario, section 510(i) of the act requires any establishment within
any foreign country engaged in the manufacture, preparation,
propagation, compounding, or processing of a drug or device that is
imported or offered for import into the United States to register the
name and place of business of the establishment and the name of a
United States agent for the establishment. Thus, in a cooperative
manufacturing arrangement, if a foreign bulk drug substance
establishment imports or offers to import the bulk drug into the United
States, the foreign establishment must
[[Page 59151]]
register. Likewise, the license holder of the final product, whether
foreign or domestic, must register because, by obtaining the license
(and presumably intending to sell the drug), the license holder is
engaged in the manufacture, preparation, propagation, compounding, or
processing of a drug (see section 510(a)(1), (b), and (i) of the act).
E. Proposed Changes to Part 807 (Devices)
1. Definitions (Sec. 807.3)
a. Definition of ``commercial distribution.'' Section 807.3(b)
currently defines ``commercial distribution,'' in part, as ``any
distribution of a device intended for human use which is held or
offered for sale * * * .''
Similar to the proposed changes to Secs. 207.3 and 607.3, the
proposed rule would create a new Sec. 807.3(b)(4) to state that, for
foreign establishments, commercial distribution does not include
distribution of a device that is neither imported nor offered for
import into the United States.
FDA received no comments on this provision and has finalized it
without change.
b. Definition of ``United States agent.'' Proposed Sec. 807.3(r)
would define a ``United States agent'' as ``any person residing or
maintaining a place of business in the United States whom a foreign
establishment designates as its agent.''
(Comment 41) As stated earlier, FDA received one comment on the
definition of United States agent. The comment noted that the preamble
to the proposed rule stated that the definition of ``United States
agent'' excluded mailboxes, answering machines or services, or other
places where an individual acting as the foreign establishment's agent
is not physically present (see 64 FR 26330 at 26331). The comment
suggested that FDA revise the definition of ``United States agent'' to
mention these exclusions.
(Response) FDA agrees with the comment and has revised the
definition of ``United States agent'' in Secs. 207.3(a)(11), 607.3(j),
and 807.3(r) accordingly.
2. Who Must Register and Submit a Device List (Sec. 807.20)
Section 807.20(a) currently requires an ``owner or operator of an
establishment not exempt under section 510(g) of the act'' or subpart D
of part 807 who is engaged in the manufacture, preparation,
propagation, compounding, assembly, or processing of a device intended
for human use to register and to submit listing information. It also
states that an owner or operator shall register and list devices
``whether or not the output of the establishments or any particular
device so listed enters interstate commerce.''
Proposed Sec. 807.20(a) would clarify that an owner or operator
``shall'' register and list (unless it is otherwise exempt from such
requirements). The proposal would also clarify that the language
requiring owners and operators to register their establishments and to
list devices, even if the devices do not enter interstate commerce,
applies only to domestic firms.
The proposal would also amend the title of subpart B of part 807,
``Procedures for Domestic Device Establishments,'' to remove the word
``domestic.'' This would reflect the fact that the act's registration
and listing requirements now apply both to domestic establishments and
to foreign establishments whose devices are imported or offered for
import into the United States.
The proposal would also delete Sec. 807.20(a)(6) pertaining to
persons acting as the U.S.-designated agent.
(Comment 42) One comment asked if a foreign establishment that
supplies components to U. S. manufacturers must register and list if
the U. S. manufacturer incorporates those components into a device.
(Response) Section 807.65(a) states that a ``manufacturer of raw
materials or components to be used in the manufacturer or assembly of a
device who would not otherwise be required to register under the
provisions of this part'' is exempt from the registration requirements.
(Comment 43) One comment asked if devices that are licensed under
section 351 of the PHS Act must be listed and whether their
manufacturers must be registered.
(Response) Section 510(i) of the act makes no distinction between
establishments whose products are subject to the act or whose products
are subject to the PHS Act. It requires all foreign establishments that
are engaged in the manufacture, preparation, propagation, compounding,
or processing of a drug or device that is imported or offered for
import into the United States to register (including the name of a
United States agent) and to list their products.
Consequently, if a foreign establishment has devices that are
licensed under section 351 of the PHS Act, then that foreign
establishment must register and list its products. Most devices that
are licensed under section 351 of the PHS Act will contain or use blood
or blood components, so establishments that manufacture such licensed
products would be subject to the registration and listing requirements
for blood and blood products (part 607) rather than the registration
and listing requirements for devices. FDA has revised Sec. 607.3(b) to
state expressly that, for purposes of the blood and blood product
registration and listing requirements, blood and blood products include
products which meet the definition of a device under the act and are
licensed under section 351 of the PHS Act.
(Comment 44) One comment asked FDA to clarify whether foreign
establishments may continue to authorize an initial importer in the
United States to list devices on the foreign establishment's behalf.
The comment explained that, in the past, FDA has allowed initial
importers to list devices if the foreign establishment certifies that
it does not ship its devices to anyone else in the United States. The
comment added that, under Sec. 807.25(d), the official correspondent
for the foreign establishment would remain as the contact point for
registration and listing matters.
(Response) The final rule requires foreign manufacturers to
register and to list. In other words, FDA is discontinuing its policy
that allowed ``sole'' initial importers to list devices. FDA is
discontinuing the policy because, even though importers believed they
were the ``sole'' importer, FDA sometimes found there were multiple
``sole'' importers. Each importer listed devices, and the lists would
differ. The submission of multiple, and sometimes different, device
lists from persons who claimed to be the ``sole'' initial importer for
a particular foreign establishment created confusion and uncertainty
about the device lists. Therefore, FDA is requiring foreign
establishments to register and to list their devices and will not
accept lists from ``sole'' initial importers.
(Comment 45) One comment asked FDA to clarify whether contract
manufacturers must register or list devices. The comment explained that
proposed Sec. 807.20(a)(2) suggests that contract manufacturers do not
have to list devices, but does not expressly exempt contract
manufacturers from the registration requirements. The comment added
that Sec. 807.20(c) appears to exempt contract manufacturers from
registration requirements and suggested that both foreign and domestic
contract manufacturers be exempt from registration requirements.
(Response) The comment is correct that Sec. 807.20(a)(2) exempts
contract manufacturers from the listing
[[Page 59152]]
requirements, while the language in Sec. 807.20(c)(1) was intended to
exempt contract manufacturers from registration and listing
requirements. However, the agency is considering more substantial
revisions to part 807, and these revisions will include changes to the
requirements for contract manufacturers. As a result, FDA declines to
amend Sec. 807.20(a)(2) and (c)(1) as suggested by the comment, and the
agency encourages foreign contract manufacturers to register.
(Comment 46) One comment noted that, under Sec. 807.20(a)(2),
contract manufacturers do not have to list devices, and that
Sec. 807.22(c)(1) does not require initial importers to submit a list
of devices. The comment suggested that FDA move the language regarding
initial importers from Sec. 807.22(c)(1) to Sec. 807.20(a)(2) to
enhance clarity and consistency.
(Response) The comment goes beyond the scope of the rule. While FDA
agrees that Secs. 807.20(a)(2) and 807.22(c)(1) could be written more
clearly and consistently, the agency is considering more substantial
revisions to part 807. Therefore, FDA declines to amend this rule to
make the changes suggested by the comment.
(Comment 47) As stated earlier, one comment suggested that FDA
revise Sec. 207.20(a) and similar language in Secs. 607.20(a) and
807.20(a) to allow a foreign parent company to register and list on
behalf of its foreign subsidiaries. The comment explained that the rule
allows parent companies to list on behalf of their subsidiaries, but
does not allow them to register their subsidiaries.
(Response) FDA agrees with the comment and has amended
Secs. 207.20(a), 607.20(a), and 807.20(a) to allow parent companies to
register and list on behalf of their subsidiaries.
3. Information Required or Requested for Establishment Registration and
Device Listing (Sec. 807.25)
Proposed Sec. 807.25 would delete the word ``ZIP'' from the term,
``post office ZIP Code,'' because the term ``ZIP Code'' is not used in
many foreign countries.
FDA received no comments on this provision and has finalized it
without change.
4. Establishment Registration and Device Listing for United States
Agents of Foreign Establishments (Sec. 807.40)
Proposed Sec. 807.40 would delete the existing language in
Sec. 807.40 entirely and replace it with general descriptions of the
foreign establishment's obligations and the United States agent's role.
The proposal would also use the term ``foreign establishment,'' rather
than ``foreign manufacturer,'' and revise the title to Sec. 807.40 to
be more consistent with section 510 of the act.
Proposed Sec. 807.40(a) would require any foreign establishment
engaged in the manufacture, preparation, propagation, compounding, or
processing of a device that is imported or offered for import into the
United States to register and list its devices in conformance with
subpart B of part 807 (``Procedures for Device Establishments''). This
would have foreign establishments comply with the same procedures as
domestic establishments.
The proposal would also require the official correspondent for the
foreign establishment to facilitate communication between the
establishment's management and FDA. This change complements the
requirement for an official correspondent in Sec. 807.25(d).
Proposed Sec. 807.40(b) would require each registered foreign
establishment to submit the name, address, and phone number of its
United States agent as part of its registration information. The
proposal would also require the agent to reside or maintain a place of
business in the United States, but would allow (rather than require) a
foreign establishment to designate its United States agent as its
official correspondent. The preamble to the proposed rule explained
that designating the United States agent as the official correspondent
may be more efficient than having a separate United States agent and an
official correspondent, but the proposed rule would give foreign
establishments flexibility in deciding how to allocate their resources
in this area and what the United States agent's responsibilities would
be (see 64 FR 26330 at 26337). The preamble to the proposed rule also
noted that electronic product manufacturers, under Sec. 1005.25 (21 CFR
1005.25), must designate a permanent resident of the United States as
the manufacturer's agent upon whom service of process may be made for
and on behalf of the manufacturer as provided in section 360(d) of the
Radiation Control for Health and Safety Act of 1968. The preamble to
the proposed rule suggested that manufacturers of products that are
both medical devices and electronic products might wish to consider
whether their agents, under Sec. 1005.25, can also serve as their
United States agent under proposed Sec. 807.40 and perform the duties
expected of a United States agent (id.).
Like proposed Secs. 207.40 and 607.40, proposed Sec. 807.40(b)
would require the United States agent, upon request from FDA, to assist
the agency in communications with the foreign establishment, to respond
to questions regarding devices imported or offered for import, and to
assist FDA in scheduling inspections of the foreign establishment.
Proposed Sec. 807.40(b) would also enable FDA, when it is unable to
contact the foreign manufacturer directly or expeditiously, to provide
information or documents to the United States agent and for that act to
be considered equivalent to providing the same information or documents
to the foreign establishment, and would further require a foreign
establishment to report to FDA changes in the United States agent's
name, address, or phone number within 10 days of the change.
Proposed Sec. 807.40(c), like proposed Secs. 207.40(b) and
607.40(b), would prohibit the importation of devices that have not been
listed or manufactured, prepared, propagated, compounded, or processed
at a registered foreign establishment.
(Comment 48) One comment noted that Sec. 807.40(a) requires the
official correspondent to facilitate communications between a firm and
FDA while proposed Sec. 807.40(b)(2) would require the United States
agent to facilitate communications between a foreign establishment and
FDA. The comment suggested revising Sec. 807.40(a) to require the
official correspondent to facilitate communications pertaining to
registration and listing. The comment said this would help distinguish
between the official correspondent and the United States agent.
(Response) FDA agrees with the comment and has revised
Sec. 807.40(a) accordingly. This change would make the official
correspondent's role, for foreign establishments, more consistent with
that for domestic establishments, as seen in Sec. 807.25(d) (official
correspondent for a domestic establishment is the point of contact for
matters relating to registration and listing).
(Comment 49) As stated earlier, one comment asserted that FDA
should not require foreign establishments to register if their products
are not commercially distributed in the United States. The comment said
that foreign establishments which send goods to a foreign trade zone
and later re-export those goods from the United States without entering
them into U. S. commerce should be exempt from registration
requirements.
(Response) FDA agrees with the comment, but only as it pertains to
foreign establishments who send products into foreign trade zones and
[[Page 59153]]
whose products are re-exported from the United States without having
entered domestic commerce. FDA, therefore, has amended Secs. 207.40(a),
607.40(a), and 807.40(a) accordingly.
(Comment 50) Two comments sought to exempt foreign establishments
from the United States agent requirement if the foreign establishment
makes class I devices. The comments asserted that these devices present
little or no risk to consumers so requiring these establishments to
have a United States agent would increase costs to those establishments
and provide little or no benefit.
(Response) FDA declines to amend the rule as suggested by the
comments. Section 510(i) of the act does not base the United States
agent requirement on a product's level of risk, and FDA's
interpretation of section 510(i) of the act would be more consistent
and fair if it applied the United States agent requirement to all
foreign establishments regardless of their device classifications.
Additionally, Sec. 807.40 only requires the United States agent to
assist in communications with the foreign establishment, to respond to
questions regarding devices imported or offered for import, and to
assist in scheduling inspections of the foreign establishment. These
duties are not dependent on a device's classification. For example, FDA
might ask the United States agent to help schedule an inspection of the
foreign establishment. Such assistance could facilitate the inspection,
regardless of the device classification for the foreign establishment's
products.
5. Miscellaneous Device Comments
(Comment 51) One comment would revise the title for part 807 to
delete the word ``distributors.'' The comment said that FDA does not
require distributors to register or list devices.
(Response) The proposed rule used an incorrect title for part 807;
the current title for part 807 refers to manufacturers and initial
importers of devices and does not refer to distributors. Therefore, no
changes are necessary.
(Comment 52) One comment offered several suggestions on how to
revise the registration and listing forms for device establishments.
The comment would also redesignate the forms and make corresponding
changes in part 807 whenever a provision referred to a form by its
designation.
(Response) FDA has or will address issues regarding its
registration and listing forms as part of the process of seeking
approval, under the Paperwork Reduction Act of 1995, for the revised
information collection requirements in those forms.
(Comment 53) One comment said that FDA must amend Sec. 807.65,
``Exemptions for device establishments,'' so that certain exemptions
would not apply for foreign establishments. The comment said that the
following exemptions should not apply to foreign establishments:
1. Section 807.65(d) for licensed practitioners;
2. Section 807.65(e) for pharmacies, surgical supply outlets, or
other similar retail establishments making final deliveries or sales to
the ultimate user;
3. Section 807.65(f) for persons who manufacture, prepare,
propagate, compound, or process devices solely for use in research,
teaching, or analysis and do not introduce such devices into commercial
distribution; and
4. Section 807.65(i) for persons who dispense devices to the
ultimate consumer or whose major responsibility is to render a service
necessary to provide the consumer with a device or the benefits to be
derived from the use of a device.
The comment explained that amending Sec. 807.65 in this manner would be
similar to the limitations on exemptions in proposed Secs. 207.10 and
607.65.
(Response) FDA agrees with the comment and has amended Sec. 807.65
accordingly. Section 510(g)(5) of the act gives FDA discretion to
decide whether to exempt a class of persons from the registration
requirements. Here, in the case of Sec. 807.65(d) and (e), the
exemptions are expressly or implicitly dependent on a person's
compliance with Federal, State, or local laws, and so FDA has
insufficient information to make a finding, under section 510(g)(5) of
the act, to justify an exemption for foreign practitioners, pharmacies,
surgical supply outlets, and other similar establishments.
For Sec. 807.65(f) and (i), FDA, again, has insufficient
information to make a finding, under section 510(g)(5) of the act, to
justify an exemption for foreign establishments engaged in those
practices. Consequently, the exemptions in Sec. 807.65(d), (e), (f),
and (i) will apply only to domestic persons or establishments.
F. Registration Schedules
The preamble to the proposed rule indicated that FDA would develop
a staggered schedule for foreign establishment registration for foreign
establishments subject to part 207. FDA explained that a staggered
schedule might be needed because part 207 applies to human drugs,
animal drugs, and biologics. The preamble to the proposed rule also
stated that FDA did not intend to develop any special registration
schedules for parts 607 and 807 because, compared to part 207, fewer
foreign manufacturers are subject to the registration requirements in
parts 607 and 807.
After the proposed rule had appeared in the Federal Register, FDA
began efforts to create an electronic registration program for all
establishments subject to part 207. Thus, for foreign human drug,
animal drug, and biologics establishments subject to part 207, a
staggered registration schedule is no longer necessary. Foreign
establishments subject to part 207 should register by May 28, 2002.
For foreign blood and blood product establishments subject to part
607, no special registration schedules are necessary. FDA has
determined that the foreign establishments subject to part 607 have
previously submitted information that fulfills the registration
requirement (with the exception of the United States agent
requirement), and CBER will contact those manufacturers to obtain
information regarding the United States agent for each establishment.
For foreign device establishments, FDA will begin enforcing the
requirements in part 807 beginning on April 26, 2002.
III. Analysis of Impacts
FDA has examined the impacts of the final rule under Executive
Order 12866 and the Regulatory Flexibility Act (5 U.S.C. 601-612) (as
amended by subtitle D of the Small Business Regulatory Fairness Act of
1996 (Public Law 104-121)), and the Unfunded Mandates Reform Act of
1995 (Public Law 104-4). 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). Under the Regulatory Flexibility Act, if a rule has a
significant impact on a substantial number of small entities, an agency
must analyze regulatory options that would minimize any significant
impact of the rule on small entities. Title II of the Unfunded Mandates
Reform Act requires that agencies prepare a written assessment and
economic analysis before proposing any rule that may result in an
expenditure in any one year by State, local, and tribal governments, in
the aggregate, or by the private sector,
[[Page 59154]]
of $100 million (adjusted annually for inflation).
The final rule is consistent with the principles set out in the
Executive order and in these two statutes. As explained below, FDA
finds that the final rule does not require a Regulatory Flexibility
Analysis. Also, because the rule does not impose any mandates on State,
local, or tribal governments, or the private sector, that will result
in an expenditure in any 1 year of $100 million or more, FDA is not
required to perform a cost-benefit analysis according to the Unfunded
Mandates Reform Act.
The new economic burdens imposed by the rule will involve broader
requirements for foreign firms with respect to the registration of
establishments and to the designation of United States agents. First,
some foreign manufacturers will have to register their establishment
before importing drugs, biological products, or devices into the United
States. As stated earlier, before FDAMA amended section 510 of the act
to require foreign establishment registration, many foreign
establishments voluntarily registered their establishments, but all
foreign establishments that imported or offered for import drugs, blood
and blood products, and devices into the United States were required to
list their products. The registration and listing activities used forms
prepared by FDA.
FDA is able to estimate the rule's economic impact by using time
and hourly wage estimates for registration. FDA estimates the labor
costs associated with establishment registration are small, ranging
from $25 per hour for device establishments, $20 per hour for blood and
blood product establishments, and $100 per hour for drug
establishments. These costs are based on information obtained primarily
from domestic establishments, and FDA assumes that the average costs
for foreign establishments will be similar. FDA also estimates that
completing an establishment registration form will range from 15
minutes to 1 hour (depending on the form used). These estimates are
derived from the estimated registration costs for domestic
establishments and foreign establishments that voluntarily registered
before FDAMA's enactment.
For devices subject to part 807, the agency's device establishment
data base presently includes about 8,200 foreign establishments, of
which almost 3,000 are unregistered establishments with listed
products. FDA's paperwork officials estimate that registration
activities would take about 15 minutes at a cost of about $6.25 per
facility. Thus, the one-time cost to register these foreign device
establishments would be about $18,750 (3,000 x 15 minutes x $25 per
hour). For the remaining device firms, the paperwork costs would be
minimal, consisting of the time required to name a United States agent.
For blood and blood products subject to part 607, FDA records
suggests there are 98 foreign establishments and that all have
voluntarily registered with FDA. Therefore, the cost to register these
foreign establishments should be minimal and consist of the time
required to name a United States agent.
For drugs and biological products subject to part 207, FDA records
suggest there are 5,630 foreign establishments, but the number of
foreign establishments that have already registered cannot easily be
determined. Thus, even if all of these foreign establishments must
register, the one-time cost to register would be about $281,500 (5,630
x 30 minutes x $100 per hour).
(Comment 54) Several comments, almost all from medical device
companies, criticized the proposed rule as not estimating the economic
impact of the United States agent requirement. One comment declared
that the United States agent requirement would ``easily'' exceed $100
million, but did not explain how it arrived at that conclusion. Another
comment stated that the Regulatory Flexibility Act requires U. S.
agencies to analyze regulatory options that would minimize any
significant impact on small entities and claimed that FDA failed to
conduct that analysis. Other comments said FDA must consider the
insurance costs for a United States agent, retainer fees, office costs,
hourly rates, and/or daily rates. One comment implied that the rule was
intended to lower FDA's operating costs while transferring more
responsibilities and costs to foreign establishments. Another comment
sought more time to determine the rule's economic impact.
(Response) FDA disagrees with the comments. The comments did not
provide any evidence to support their claims that the United States
agent requirement would result in costs exceeding $100 million. In
response to the comments, FDA examined the costs of retaining a United
States agent. Several persons have contacted FDA to express an interest
in becoming a United States agent, and their fees have ranged between
$750 and $2,000 annually.
FDA does not have a precise estimate of the number of foreign
device firms that would need to develop an arrangement with a United
States agent, but the agency's establishment data base identifies about
6,400 foreign device establishments that show only a foreign address
for their ``official correspondent.'' If each of these 6,400 device
establishments incurred costs of $1,000 to obtain a United States
agent, the total industry annual cost would be about $6,400,000.
Similarly, FDA does not know the precise number of drug
establishments that would incur costs to retain a United States agent.
The agency believes, however, that the added costs for most
pharmaceutical firms would be minimal, because under current rules (21
CFR 314.50(a)), all applications and supplements to approved
applications must already ``contain the name and address of, and be
countersigned by, an attorney, agent, or other authorized official who
resides or maintains a place of business within the United States.''
Bulk drug establishments not holding an approved application could
generally rely on the primary purchaser of their product to serve as
their United States agent. Thus, while many foreign drug establishments
would incur some additional paperwork costs, the additional costs would
be minimal.
(Comment 55) One comment said FDA failed to offer exemptions from
the United States agent requirement to small- and medium-sized Canadian
firms as required under the Regulatory Flexibility Act.
(Response) The agency examined, but rejected, alternatives to the
proposed rule. The registration information required by FDA is minimal,
consisting largely of the establishment's address, names of owners or
responsible officials, and additional identifying information on the
establishment (such as type of establishment, types of products at the
establishment, type of ownership). Similarly, identification of the
United States agent requires minimal information (name, address, phone
number). An alternative that required less information from foreign
establishments would not provide sufficient information to identify the
foreign establishment's location, a responsible person at the foreign
establishment, or the type of establishment, thereby complicating any
effort to locate or contact the foreign establishment or to determine
whether the foreign establishment complied with the appropriate
statutory and regulatory requirements. FDA also rejected an alternative
that would eliminate the United States agent requirement for small- and
medium-sized firms; section 510(i) of the act expressly requires
foreign establishment to have a United States agent and does not
provide for
[[Page 59155]]
exemptions from the United States agent requirement.
Moreover, as stated earlier, FDA does not object to having multiple
firms use the same United States agent. Neither the act nor these
regulations require a foreign establishment to enter an exclusive
arrangement with its United States agent. In other words, several
foreign establishments could use the same agent or ``share'' an agent,
so long as the foreign establishments and the United States agent meet
their regulatory obligations. This may reduce the United States agent's
cost for small- and medium-sized firms.
Finally, the agency is not required to prepare a Regulatory Impact
Analysis under the Regulatory Flexibility Act, because the rule will
not have a significant economic effect on a substantial number of small
entities. The term ``small entity'' is defined (5 U.S.C. 601(6)) to
include the term ``small business,'' which, in turn, is defined (5
U.S.C. 601(3)) to have the ``same meaning as the term small business
concern.'' The term ``business concern'' is defined by the Small
Business Administration (SBA), at 13 CFR 121.105(a), in relevant part,
as a business entity ``with a place of business located in the United
States or which makes a significant contribution to the U.S. economy
through payment of taxes or use of American products, materials or
labor.'' Although some foreign firms would meet the SBA definition of a
``business concern'' because of their significant contribution to the
United States economy (even though they do not operate primarily in the
United States), it is unlikely that a substantial number that do not
already have a U. S. presence that could act as a United States agent
would be significantly impacted by this rule.
The Unfunded Mandates Reform Act (Public Law 104-114) requires that
agencies prepare an assessment of anticipated costs and benefits before
proposing any rule that may result in an expenditure in any one year by
State, local, and tribal governments, in the aggregate, or by the
private sector, of $100 million or more (adjusted annually for
inflation). Because the total expenditures under the final rule will
not result in a 1-year expenditure of $100 million or more, FDA is not
required to perform a cost-benefit analysis under the Unfunded Mandates
Reform Act.
IV. Environmental Impact
The agency has determined under 21 CFR 25.30(h) 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.
V. Paperwork Reduction Act of 1995
This final rule contains information collection provisions 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.
Title: Foreign Establishment Registration and Listing
Description: The final rule requires foreign establishments that
import or offer to import human drugs, animal drugs, biologics, blood
products, and devices into the United States to register and to name a
United States agent. This information is required by section 510(i)(1)
of the act, as amended by section 417 of FDAMA.
Although section 510(i)(2) of the act also requires foreign
establishments to list their products at FDA, the final rule does not
include such a requirement because FDA's existing regulations already
require foreign manufacturers to submit such lists, and the agency has
already obtained OMB approval for the information collection burden
associated with product listing for parts 207 and 607 (for part 207,
the OMB approval number is 0910-0045 and expires on April 30, 2001; for
part 607, the OMB approval number is 0910-0052 and expires on February
28, 2003). Through this notice, FDA is also seeking approval for the
device listing requirements insofar as they will be applied to foreign
establishments.
Description of Respondents: Persons and businesses, including small
businesses.
FDA estimates the burden of this collection of information as
follows:
Table 1.--Estimated Annual Reporting Burden\1\
----------------------------------------------------------------------------------------------------------------
No. of No. of Responses Total Annual Hours per
21 CFR Section Respondents perRespondent Responses Response Total Hours
----------------------------------------------------------------------------------------------------------------
207.21(a) 2,463 1 2,463 0.5 1,231.5
207.22(a) and 207.40 5,630 1 5,630 0.5 2,815
207.25(b) 53 4.3 228 0.5 114
607.22(a) and 607.40 98 1 98 1 98
607.26 1 1 1 0.5 0.5
607.31 1 1 1 10 10
807.22(a) and 807.40 7,200 1 7,200 0.25 1,800
807.22(b) 27,720 1 27,720 0.5 13,860
807.31(c) 7 1 7 0.5 3.5
-----------------
Total 19,932.5
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
information.
Table 2.--Estimated Annual Recordkeeping Burden\1\
----------------------------------------------------------------------------------------------------------------
No. of No. of Responses Total Annual Hours per
21 CFR Section Respondents perRespondent Responses Response Total Hours
----------------------------------------------------------------------------------------------------------------
807.31 6,480 10 64,800 0.5 32,400
-----------------
[[Page 59156]]
Total 32,400
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
information.
The above estimates were based on the number of foreign
establishments that currently list drugs or devices (as required by
existing FDA regulations), the annual average number of new foreign
establishments that voluntarily registered or began importing devices,
and comparable burden hour estimates for registration by domestic
establishments.
For device listing by foreign establishments, the above estimates
are based on the number of foreign establishments that currently list
devices and comparable burden hour estimates and annual frequency per
response estimates for domestic firms. FDA has also made a correction
to the total hour figure for Sec. 807.31(e) to change 4 hours to 3.5
hours; the correction represents the accurate figure resulting from the
mathematical calculation of 7 annual responses multiplied by 0.5 hours
per response.
The estimated recordkeeping burden for Sec. 807.31 is based on
FDA's experience with foreign device establishments. FDA's experience
suggests that, for foreign device establishments, there are
approximately 9 owners or operators for every 10 foreign device
establishments. Therefore, because FDA records indicate that there are
7,200 foreign device establishments, the estimated number of
recordkeepers required to maintain the initial historical files is
6,480 (7,200 x 0.90 = 6,480).
The information collection provisions of this final rule have been
submitted to OMB for review.
Prior to the effective date of this final rule, FDA will publish a
notice in the Federal Register announcing OMB's decision to approve,
modify, or disapprove the information collection provisions in this
final rule. An agency may not conduct or sponsor, and a person is not
required to respond to, a collection of information unless it displays
a currently valid OMB control number.
VI. Federalism
FDA has analyzed this final rule in accordance with the principles
set forth in Executive Order 13132. FDA has determined that the rule
does not contain policies that have substantial direct effects on the
States, on the relationship between the National Government and the
States, or on the distribution of power and responsibilities among the
various levels of government. Accordingly, the agency has concluded
that the rule does not contain policies that have federalism
implications as defined in the order and, consequently, a federalism
summary impact statement is not required.
List of Subjects
21 CFR Part 207
Drugs, Reporting and recordkeeping requirements.
21 CFR Part 607
Blood.
21 CFR Part 807
Confidential business information, Imports, Medical devices,
Reporting and recordkeeping requirements.
Therefore, under the Federal Food, Drug, and Cosmetic Act and under
the authority delegated to the Commissioner of Food and Drugs, Title 21
of the Code of Federal Regulations is amended as follows:
PART 207--REGISTRATION OF PRODUCERS OF DRUGS AND LISTING OF DRUGS
IN COMMERCIAL DISTRIBUTION
1. The authority citation for part 207 is revised to read as
follows:
Authority: 21 U.S.C. 321, 331, 351, 352, 355, 360, 360b, 371,
374, 381, 393; 42 U.S.C. 262, 264, 271.
2. Section 207.3 is amended by revising paragraph (a)(5) and by
adding paragraph (a)(11) to read as follows:
Sec. 207.3 Definitions.
(a) * * *
(5) Commercial distribution means any distribution of a human drug
except for investigational use under part 312 of this chapter, and any
distribution of an animal drug or animal feed bearing or containing an
animal drug for noninvestigational uses, but the term does not include
internal or interplant transfer of a bulk drug substance between
registered establishments within the same parent, subsidiary, and/or
affiliate company. For foreign establishments, the term ``commercial
distribution'' shall have the same meaning except that the term shall
not include distribution of any drug that is neither imported nor
offered for import into the United States.
* * * * *
(11) United States agent means a person residing or maintaining a
place of business in the United States whom a foreign establishment
designates as its agent. This definition excludes mailboxes, answering
machines or services, or other places where an individual acting as the
foreign establishment's agent is not physically present.
* * * * *
3. Section 207.7 is amended by revising paragraph (a) to read as
follows:
Sec. 207.7 Establishment registration and product listing for human
blood and blood products and for medical devices.
(a) Owners and operators of human blood and blood product
establishments shall register and list their products with the Center
for Biologics Evaluation and Research (HFM-375), 1401 Rockville Pike,
suite 200N, Rockville, MD 20852-1448, on Form FDA-2830 (Blood
Establishment Registration and Product Listing), in accordance with
part 607 of this chapter. Such owners and operators who also
manufacture or process other drug products at the same establishment
shall, in addition, register and list all such other drug products with
the Drug Listing Branch in accordance with this part.
* * * * *
4. Section 207.10 is amended by revising the section heading and
the introductory text to read as follows:
Sec. 207.10 Exemptions for establishments.
The following classes of persons are exempt from registration and
drug listing in accordance with this part under section 510(g)(1),
(g)(2), and (g)(3) of the act, or because FDA has found, under section
510(g)(5) of the act, that their registration is not necessary for the
protection of the public health. The exemptions in paragraphs (a) and
(b) of this section are limited to pharmacies, hospitals, clinics, and
public health agencies located in any State as defined in section
201(a)(1) of the act.
* * * * *
[[Page 59157]]
5. Section 207.20 is amended by revising paragraphs (a) and (c) to
read as follows:
Sec. 207.20 Who must register and submit a drug list.
(a) Owners or operators of all drug establishments, not exempt
under section 510(g) of the act or subpart B of this part 207, that
engage in the manufacture, preparation, propagation, compounding, or
processing of a drug or drugs shall register and submit a list of every
drug in commercial distribution (except that registration and listing
information may be submitted by the parent, subsidiary, and/or
affiliate company for all establishments when operations are conducted
at more than one establishment and there exists joint ownership and
control among all the establishments). Drug listing is not required for
the manufacturing, preparation, propagation, compounding, or processing
of an animal feed bearing or containing an animal drug (i.e., a Type B
or Type C medicated feed), nor is drug listing required for
establishments engaged in drug product salvaging. Drug products
manufactured, prepared, propagated, compounded, or processed in any
State as defined in section 201(a)(1) of the act must be listed whether
or not the output of such establishments or any particular drug so
listed enters interstate commerce. No owner or operator may register an
establishment if any part of the establishment is registered by any
other owner or operator.
* * * * *
(c) Before beginning manufacture or processing of a drug subject to
one of the following applications, an owner or operator of an
establishment is required to register before the agency approves it: A
new drug application, an abbreviated new drug application, a new animal
drug application, an abbreviated new animal drug application, a
medicated feed mill license application, or a biologics license
application.
* * * * *
6. Section 207.21 is amended by revising paragraph (a) to read as
follows:
Sec. 207.21 Times for registration and drug listing.
(a) The owner or operator of an establishment entering into the
manufacture or processing of a drug or drugs shall register the
establishment within 5 days after the beginning of the operation and
shall submit a list of every drug in commercial distribution at that
time. If the owner or operator of the establishment has not previously
entered into such an operation, the owner or operator shall register
within 5 days after submitting a new drug application, abbreviated new
drug application, new animal drug application, abbreviated new animal
drug application, medicated feed mill license application, or a
biologics license application. Owners or operators shall renew their
registration information annually.
* * * * *
Sec. 207.25 [Amended]
7. Section 207.25 Information required in registration and drug
listing is amended in paragraph (b)(2) by removing ``or new animal drug
application number'' and by adding in its place the phrase ``new animal
drug application number, or abbreviated new animal drug application
number''.
8. Section 207.37 is amended by revising the introductory text of
paragraph (a) and by revising paragraph (b) to read as follows:
Sec. 207.37 Inspection of registrations and drug listings.
(a) A copy of the Form FDA-2656 (Registration of Drug
Establishment) filed by the registrant will be available for inspection
in accordance with section 510(f) of the act, at the Division of
Labeling and Non-Prescription Drug Compliance (HFD-310), Office of
Compliance, Center for Drug Evaluation and Research, Food and Drug
Administration, 7520 Standish Pl., Rockville, MD 20855. In addition,
copies of these forms for establishments located within a particular
geographic area are available for inspection at FDA district offices
responsible for that geographical area. Copies of forms submitted by
foreign drug establishments are available for inspection at the Foreign
Inspection Team (HFD-322), Office of Compliance, Center for Drug
Evaluation and Research, 7520 Standish Pl., Rockville, MD 20855. Upon
request and receipt of a stamped, self-addressed envelope, the Division
of Labeling and Non-Prescription Drug Compliance, the Foreign
Inspection Team, or the appropriate FDA district office will verify
registration numbers or provide the location of a registered
establishment.
* * * * *
(b) Requests for information about registrations and drug listings
of an establishment should be directed to the Information Management
Team (HFD-095), Office of Information Technology, Center for Drug
Evaluation and Research, Food and Drug Administration, 5600 Fishers
Lane, Rockville, MD 20857 or, with respect to the information described
in paragraph (a) of this section, to the FDA district office
responsible for the geographic area in which the establishment is
located.
9. Section 207.40 is revised to read as follows:
Sec. 207.40 Establishment registration and drug listing requirements
for foreign establishments.
(a) Foreign drug establishments whose drugs are imported or offered
for import into the United States shall comply with the establishment
registration and drug listing requirements in subpart C of this part,
unless exempt under subpart B of this part or unless the drugs enter a
foreign trade zone and are re-exported from that foreign trade zone
without having entered U. S. commerce.
(b) No drug may be imported or offered for import into the United
States unless it is listed as required in subpart C of this part and
manufactured, prepared, propagated, compounded, or processed at a
registered foreign drug establishment; however, this restriction does
not apply to a drug imported or offered for import under the
investigational use provisions in part 312 of this chapter, or the
investigational new animal drug use provisions in part 511 of this
chapter, or to a component of a drug imported under section 801(d)(3)
of the act. Foreign drug establishments shall submit all listing
information, including labels and labeling, and registration
information in the English language.
(c) Each foreign drug establishment required to register under
paragraph (a) of this section shall submit the name, address, and phone
number of its United States agent as part of its initial and updated
registration information in accordance with subpart C of this part.
Each foreign drug establishment shall designate only one United States
agent.
(1) The United States agent shall reside or maintain a place of
business in the United States.
(2) Upon request from FDA, the United States agent shall assist FDA
in communications with the foreign drug establishment, respond to
questions concerning the foreign drug establishment's products that are
imported or offered for import into the United States, and assist FDA
in scheduling inspections of the foreign drug establishment. If the
agency is unable to contact the foreign drug establishment directly or
expeditiously, FDA may provide information or documents to the United
States agent, and such an action shall be considered to be equivalent
to providing the same information or documents to the foreign drug
establishment.
[[Page 59158]]
(3) The foreign drug establishment or the United States agent shall
report changes in the United States agent's name, address, or phone
number to FDA within 10-business days of the change.
PART 607--ESTABLISHMENT REGISTRATION AND PRODUCT LISTING FOR
MANUFACTURERS OF HUMAN BLOOD AND BLOOD PRODUCTS
10. The authority citation for part 607 is revised to read as
follows:
Authority: 21 U.S.C. 321, 331, 351, 352, 355, 360, 371, 374,
381, 393; 42 U.S.C. 262, 264, 271.
11. Section 607.3 is amended by revising paragraphs (b) and (e) and
by adding paragraph (j) to read as follows:
Sec. 607.3 Definitions.
* * * * *
(b) Blood and blood product means a drug which consists of human
whole blood, plasma, or serum or any product derived from human whole
blood, plasma, or serum, hereinafter referred to as ``blood product.''
For the purposes of this part only, blood and blood product also means
those products that meet the definition of a device under the Federal
Food, Drug, and Cosmetic Act and that are licensed under section 351 of
the Public Health Service Act.
* * * * *
(e) Commercial distribution means any distribution of a blood
product except under the investigational use provisions of part 312 of
this chapter, but does not include internal or interplant transfer of a
bulk product substance between registered establishments within the
same parent, subsidiary, and/or affiliate company. For foreign
establishments, the term ``commercial distribution'' shall have the
same meaning except that the term shall not include distribution of any
blood or blood product that is neither imported nor offered for import
into the United States.
* * * * *
(j) United States agent means a person residing or maintaining a
place of business in the United States whom a foreign establishment
designates as its agent. This definition excludes mailboxes, answering
machines or services, or other places where an individual acting as the
foreign establishment's agent is not physically present.
12. Section 607.7 is amended by revising paragraphs (b) and (c) to
read as follows:
Sec. 607.7 Establishment registration and product listing of blood
banks and other firms manufacturing human blood and blood products.
* * * * *
(b) Forms for registration of an establishment are obtainable on
request from the Center for Biologics Evaluation and Research (HFM-
375), 1401 Rockville Pike, suite 200N, Rockville, MD 20852-1448, or at
any of the Food and Drug Administration district offices.
(c) The completed form should be mailed to the Center for Biologics
Evaluation and Research (HFM-375), 1401 Rockville Pike, suite 200N,
Rockville, MD 20852-1448.
13. Section 607.20 is amended by revising paragraph (a) to read as
follows:
Sec. 607.20 Who must register and submit a blood product list.
(a) Owners or operators of all establishments, not exempt under
section 510(g) of the act or subpart D of this part, that engage in the
manufacture of blood products shall register and submit a list of every
blood product in commercial distribution (except that registration and
listing information may be submitted by the parent, subsidiary, and/or
affiliate company for all establishments when operations are conducted
at more than one establishment and there exists joint ownership and
control among all the establishments). Blood products manufactured,
prepared, propagated, compounded, or processed in any State as defined
in section 201(a)(1) of the act must be listed whether or not the
output of such blood product establishment or any particular blood
product so listed enters interstate commerce.
* * * * *
14. Section 607.22 is revised to read as follows:
Sec. 607.22 How and where to register establishments and list blood
products.
(a) The first registration of an establishment shall be on Form FD-
2830 (Blood Establishment Registration and Product Listing) obtainable
on request from the Department of Health and Human Services, Food and
Drug Administration, Center for Biologics Evaluation and Research (HFM-
375), 1401 Rockville Pike, suite 200N, Rockville, MD 20852-1448, or
from Food and Drug Administration district offices. Subsequent annual
registration shall also be accomplished on Form FD-2830, which will be
furnished by the Food and Drug Administration before November 15 of
each year to establishments whose product registration for that year
was validated under Sec. 607.35. The completed form shall be mailed to
the preceding address before December 31 of that year.
(b) The first list of blood products and subsequent June and
December updatings shall be on Form FD-2830, obtainable upon request as
described in paragraph (a) of this section.
15. Section 607.25 is amended in the second sentence in paragraph
(a) by removing the word ``ZIP'', and by revising paragraph (b)(3) to
read as follows:
Sec. 607.25 Information required for establishment registration and
blood product listing.
* * * * *
(b) * * *
(3) For each blood product listed, the registration number of the
parent establishment. An establishment not owned, operated, or
controlled by another firm or establishment is its own parent
establishment.
16. Section 607.26 is amended by revising the first sentence to
read as follows:
Sec. 607.26 Amendments to establishment registration.
Changes in individual ownership, corporate or partnership
structure, location, or blood-product handling activity shall be
submitted on Form FDA-2830 (Blood Establishment Registration and
Product Listing) as an amendment to registration within 5 days of such
changes. * * *
17. Section 607.31 is revised to read as follows:
Sec. 607.31 Additional blood product listing information.
(a) In addition to the information routinely required by
Secs. 607.25 and 607.30, the Director of the Center for Biologics
Evaluation and Research may require submission of the following
information by letter or by Federal Register notice:
(1) For a particular blood product so listed, upon request made by
the Director of the Center for Biologics Evaluation and Research for
good cause, a copy of all advertisements.
(2) For a particular blood product so listed, upon a finding by the
Director of the Center for Biologics Evaluation and Research that it is
necessary to carry out the purposes of the act, a quantitative listing
of all ingredients.
(3) For each registrant, upon a finding by the Director of the
Center for Biologics Evaluation and Research that it is necessary to
carry out the purposes of the act, a list of each listed blood product
containing a particular ingredient.
(b) [Reserved]
[[Page 59159]]
18. Section 607.35 is amended by revising paragraph (a) to read as
follows:
Sec. 607.35 Notification of registrant; blood product establishment
registration number and NDC Labeler Code.
(a) The Director of the Center for Biologics Evaluation and
Research will provide to the registrant a validated copy of Form FD-
2830 (Blood Establishment Registration and Product Listing) as evidence
of registration. This validated copy will be sent to the location shown
for the registering establishment, and a copy will be sent to the
reporting official if at another address. A permanent registration
number will be assigned to each blood product establishment registered
in accordance with these regulations.
* * * * *
19. Section 607.37 is amended by revising the introductory text of
paragraph (a) and by revising paragraph (b) to read as follows:
Sec. 607.37 Inspection of establishment registrations and blood
product listings.
(a) A copy of the Form FD-2830 (Blood Establishment Registration
and Product Listing) filed by the registrant will be available for
inspection under section 510(f) of the act, at the Department of Health
and Human Services, Food and Drug Administration, Office of
Communication, Training and Manufacturers' Assistance (HFM-40), Center
for Biologics Evaluation and Research, 1401 Rockville Pike, suite 200N,
Rockville, MD 20852-1448. In addition, for domestic firms, the same
information will be available for inspection at each of the Food and
Drug Administration district offices for firms within the geographical
area of such district office. Upon request and receipt of a self-
addressed stamped envelope, verification of registration number, or
location of registered establishment will be provided. The following
information submitted under the blood product listing requirements is
illustrative of the type of information that will be available for
public disclosure when it is compiled:
* * * * *
(b) Requests for information regarding blood establishment
registrations and blood product listings should be directed to the
Department of Health and Human Services, Food and Drug Administration,
Office of Communication, Training and Manufacturers' Assistance (HFM-
40), Center for Biologics Evaluation and Research, 1401 Rockville Pike,
suite 200N, Rockville, MD 20852-1448.
20. Section 607.40 is revised to read as follows:
Sec. 607.40 Establishment registration and blood product listing
requirements for foreign blood product establishments.
(a) Every foreign establishment shall comply with the establishment
registration and blood product listing requirements contained in
subpart B of this part, unless exempt under subpart D of this part or
unless the blood product enters a foreign trade zone and is re-exported
from that foreign trade zone without having entered U. S. commerce.
(b) No blood product may be imported or offered for import into the
United States unless it is the subject of a blood product listing as
required under subpart B of this part and is manufactured, prepared,
propagated, compounded, or processed at a registered foreign
establishment; however, this restriction does not apply to a blood
product imported or offered for import under the investigational use
provisions of part 312 of this chapter or to a blood product imported
under section 801(d)(4) of the act. The establishment registration and
blood product listing information shall be in the English language.
(c) Each foreign establishment required to register under paragraph
(a) of this section shall, as part of the establishment registration
and blood product listing, submit the name and address of the
establishment and the name of the individual responsible for submitting
establishment registration and blood product listing information. Any
changes in this information shall be reported to the Food and Drug
Administration at the intervals specified for updating establishment
registration information in Sec. 607.26 and blood product listing
information in Sec. 607.30(a).
(d) Each foreign establishment required to register under paragraph
(a) of this section shall submit the name, address, and phone number of
its United States agent as part of its initial and updated registration
information in accordance with subpart B of this part. Each foreign
establishment shall designate only one United States agent.
(1) The United States agent shall reside or maintain a place of
business in the United States.
(2) Upon request from FDA, the United States agent shall assist FDA
in communications with the foreign establishment, respond to questions
concerning the foreign establishment's products that are imported or
offered for import into the United States, and assist FDA in scheduling
inspections of the foreign establishment. If the agency is unable to
contact the foreign establishment directly or expeditiously, FDA may
provide information or documents to the United States agent, and such
an action shall be considered to be equivalent to providing the same
information or documents to the foreign establishment.
(3) The foreign establishment or the United States agent shall
report changes in the United States agent's name, address, or phone
number to FDA within 10-business days of the change.
21. Section 607.65 is amended by revising the introductory text to
read as follows:
Sec. 607.65 Exemptions for blood product establishments.
The following classes of persons are exempt from registration and
blood product listing in accordance with this part 607 under the
provisions of section 510(g)(1), (g)(2), and (g)(3) of the act, or
because the Commissioner of Food and Drugs has found, under section
510(g)(5), that such registration is not necessary for the protection
of the public health. The exemptions in paragraphs (a), (b), (f), and
(g) of this section are limited to those classes of persons located in
any State as defined in section 201(a)(1) of the act.
* * * * *
PART 807--ESTABLISHMENT REGISTRATION AND DEVICE LISTING FOR
MANUFACTURERS AND INITIAL IMPORTERS OF DEVICES
22. The authority citation for part 807 is revised to read as
follows:
Authority: 21 U.S.C. 321, 331, 351, 352, 360, 360c, 360e, 360i,
360j, 371, 374, 381, 393; 42 U.S.C. 264, 271.
23. Section 807.3 is amended by revising paragraphs (b) and (r) to
read as follows:
Sec. 807.3 Definitions.
* * * * *
(b) Commercial distribution means any distribution of a device
intended for human use which is held or offered for sale but does not
include the following:
(1) Internal or interplant transfer of a device between
establishments within the same parent, subsidiary, and/or affiliate
company;
(2) Any distribution of a device intended for human use which has
in effect an approved exemption for investigational use under section
520(g) of the act and part 812 of this chapter;
(3) Any distribution of a device, before the effective date of part
812 of this chapter, that was not introduced or delivered for
introduction into interstate
[[Page 59160]]
commerce for commercial distribution before May 28, 1976, and that is
classified into class III under section 513(f) of the act: Provided,
That the device is intended solely for investigational use, and under
section 501(f)(2)(A) of the act the device is not required to have an
approved premarket approval application as provided in section 515 of
the act; or
(4) For foreign establishments, the distribution of any device that
is neither imported nor offered for import into the United States.
* * * * *
(r) United States agent means a person residing or maintaining a
place of business in the United States whom a foreign establishment
designates as its agent. This definition excludes mailboxes, answering
machines or services, or other places where an individual acting as the
foreign establishment's agent is not physically present.
* * * * *
Subpart B [Amended]
24. The heading for subpart B of this part is revised to read as
follows:
Subpart B--Procedures for Device Establishments
25. Section 807.20 is amended by revising paragraph (a) to read as
follows:
Sec. 807.20 Who must register and submit a device list.
(a) An owner or operator of an establishment not exempt under
section 510(g) of the act or subpart D of this part who is engaged in
the manufacture, preparation, propagation, compounding, assembly, or
processing of a device intended for human use shall register and submit
listing information for those devices in commercial distribution,
except that registration and listing information may be submitted by
the parent, subsidiary, or affiliate company for all the domestic or
foreign establishments under the control of one of these organizations
when operations are conducted at more than one establishment and there
exists joint ownership and control among all the establishments. The
term ``device'' includes all in vitro diagnostic products and in vitro
diagnostic biological products not subject to licensing under section
351 of the Public Health Service Act. An owner or operator of an
establishment located in any State as defined in section 201(a)(1) of
the act shall register its name, places of business, and all
establishments and list the devices whether or not the output of the
establishments or any particular device so listed enters interstate
commerce. The registration and listing requirements shall pertain to
any person who:
(1) Initiates or develops specifications for a device that is to be
manufactured by a second party for commercial distribution by the
person initiating specifications;
(2) Manufactures for commercial distribution a device either for
itself or for another person. However, a person who only manufactures
devices according to another person's specifications, for commercial
distribution by the person initiating specifications, is not required
to list those devices.
(3) Repackages or relabels a device;
(4) Acts as an initial importer; or
(5) Manufactures components or accessories which are ready to be
used for any intended health-related purpose and are packaged or
labeled for commercial distribution for such health-related purpose,
e.g., blood filters, hemodialysis tubing, or devices which of necessity
must be further processed by a licensed practitioner or other qualified
person to meet the needs of a particular patient, e.g., a manufacturer
of ophthalmic lens blanks.
* * * * *
Sec. 807.25 [Amended]
26. Section 807.25 Information required or requested for
establishment registration and device listing is amended in the last
sentence of paragraph (a) by removing the word ``ZIP''.
27. Section 807.40 is revised to read as follows:
Sec. 807.40 Establishment registration and device listing for foreign
establishments importing or offering for import devices into the United
States.
(a) Any establishment within any foreign country engaged in the
manufacture, preparation, propagation, compounding, or processing of a
device that is imported or offered for import into the United States
shall register and list such devices in conformance with the
requirements in subpart B of this part unless the device enters a
foreign trade zone and is re-exported from that foreign trade zone
without having entered U. S. commerce. The official correspondent for
the foreign establishment shall facilitate communication between the
foreign establishment's management and representatives of the Food and
Drug Administration for matters relating to the registration of device
establishments and the listing of device products.
(b) Each foreign establishment required to register under paragraph
(a) of this section shall submit the name, address, and phone number of
its United States agent as part of its initial and updated registration
information in accordance with subpart B of this part. Each foreign
establishment shall designate only one United States agent and may
designate the United States agent to act as its official correspondent.
(1) The United States agent shall reside or maintain a place of
business in the United States.
(2) Upon request from FDA, the United States agent shall assist FDA
in communications with the foreign establishment, respond to questions
concerning the foreign establishment's products that are imported or
offered for import into the United States, and assist FDA in scheduling
inspections of the foreign establishment. If the agency is unable to
contact the foreign establishment directly or expeditiously, FDA may
provide information or documents to the United States agent, and such
an action shall be considered to be equivalent to providing the same
information or documents to the foreign establishment.
(3) The foreign establishment or the United States agent shall
report changes in the United States agent's name, address, or phone
number to FDA within 10-business days of the change.
(c) No device may be imported or offered for import into the United
States unless it is the subject of a device listing as required under
subpart B of this part and is manufactured, prepared, propagated,
compounded, or processed at a registered foreign establishment;
however, this restriction does not apply to devices imported or offered
for import under the investigational use provisions of part 812 of this
chapter or to a component, part, or accessory of a device or other
article of a device imported under section 801(d)(3) of the act. The
establishment registration and device listing information shall be in
the English language.
28. Section 807.65 is amended by revising the introductory text to
read as follows:
Sec. 807.65 Exemptions for device establishments.
The following classes of persons are exempt from registration in
accordance with Sec. 807.20 under the provisions of section 510(g)(1),
(g)(2), and (g)(3) of the act, or because the Commissioner of Food and
Drugs has found, under section 510(g)(5) of the act, that such
registration is not necessary for the protection of the public health.
The exemptions in paragraphs (d), (e), (f), and (i) of this section are
limited to those classes of persons located in any
[[Page 59161]]
State as defined in section 201(a)(1) of the act.
* * * * *
Dated: November 15, 2001.
Margaret M. Dotzel,
Associate Commissioner for Policy.
[FR Doc. 01-29393 Filed 11-26-01; 8:45 am]
BILLING CODE 4160-01-S