counterfeit, damaged, tampered with, or expired; arranging for each
shipment of eligible prescription drugs to be tested by a qualifying
laboratory; and arranging for them to be relabeled with the FDA-
approved labeling, including the carton and container labels,
prescribing information, and any patient labeling, such as medication
guides, instruction for use documents, and patient package inserts. The
Importer is also responsible for facilitating the affixation or
imprinting of a product identifier at the same time that the eligible
prescription drugs are relabeled with the FDA-approved labeling.
    We propose that the screening conducted by the Importer would
include examination of the Canadian labeling of a sample of each
shipment of section 804 drugs to verify that the labeling is consistent
with that of an HPFB-approved drug and that the drugs have been
serialized as prescribed in the proposed rule, when finalized. The
screening could also include a visual comparison of a sample of the
section 804 drug to a sample of the HPFB-approved drug. We seek comment
on the feasibility and sufficiency of this screening, as well as on
what additional or alternative screenings that the Importer could do to
ensure that imported eligible prescription drugs are not adulterated,
counterfeit, damaged, tampered with, or expired.

    If an Importer will be relabeling the drug itself, the Importer
must also be registered with FDA under section 510(b) of the FD&C Act
and obtain a labeler code from FDA under Sec.  207.33(c) (21 CFR
207.33(c)). If the Importer chooses to contract with a separate entity
(e.g., a repackager or relabeler) to relabel the drug on its behalf,
the Importer will be a private label distributor, as that term is
defined in Sec.  207.1 (21 CFR 207.1), because it will be commercially
distributing under its own label drugs that it did not itself
manufacture, repackage, or relabel. As noted elsewhere in this proposed
rule, a repackager or relabeler acting on an Importer's behalf would
only repackage to the extent it is required to label the drug. As a
private label distributor, the Importer will not be required to
register with FDA, but it must obtain its own labeler code from FDA,
under Sec.  207.33(c). Under the proposed rule, the NDCs for the
section 804 drugs that are relabeled by an entity other than the
Importer would nonetheless incorporate the Importer's labeler code.
Among other requirements, before an eligible prescription drug can be
released into interstate commerce it will need a new NDC and will need
to be listed. We note that a drug imported under section 804 of the
FD&C Act will have a different NDC than its FDA-approved counterpart.
Under the requirements proposed in this rule, if the Importer is also a
repackager or relabeler, it will be the Importer's responsibility to
propose an NDC for assignment for each eligible prescription drug under
Sec.  207.33. Under these circumstances, the Importer will also be
responsible for listing each eligible prescription drug under Sec.
207.53 (21 CFR 207.53). If the Importer is a private label distributor,
it would be the Importer's responsibility to ensure that the entity
relabeling an eligible prescription drug on its behalf proposes an NDC
under Sec.  207.33 and lists each eligible prescription drug under
Sec.  207.53.
    The Importer, or authorized customs broker, would also be
responsible for filing an entry for consumption in ACE for the drugs to
be imported through a CBP port of entry designated in a SIP Proposal
authorized by FDA. In addition, Importers would be required to collect
and submit to FDA the information and documentation about the imported
drug that is set forth in section 804(d) of the FD&C Act as discussed
later. Importers also would have responsibilities related to adverse
event, medication error, field alert reports, and other reports, and
related to drug recalls.
    We seek comment on whether there are qualifications Importers
should be required to have, beyond being licensed as a pharmacist or
wholesaler, given their responsibilities.

F. Supply Chain Requirements

    When Congress enacted section 804 of the FD&C Act in 2003, FDA's
authority with respect to drug supply chain security was more limited
than it is today. In 2013, Congress enacted the DSCSA, which
strengthened FDA's authority to protect the security and integrity of
the drug supply chain. Specifically, section 582 of the FD&C Act, as
added by the DSCSA, establishes the product identification,
verification, and tracing requirements that manufacturers, wholesale
distributors, pharmacists, and other trading partners must adhere to
for covered transactions involving certain prescription drugs. Because
the DSCSA did not include an exemption for drugs imported under section
804 of the FD&C Act, such drugs are subject to the requirements in
section 582 of the FD&C Act. We recognize, however, that certain
requirements in section 582 may be difficult or impossible for such
drugs to meet. Accordingly, under the authority provided by section
582(a)(3)(A)(iii) of the FD&C Act, FDA proposes to exempt from section
582 certain transactions for drugs imported under section 804 of the
FD&C Act.
    Under section 804(c)(3), this proposed rule may contain ``any
additional provisions determined by the Secretary to be appropriate as
a safeguard to protect the public health or as a means to facilitate
the importation of prescription drugs.'' To ensure the proposed
exemptions from section 582 of the FD&C Act do not compromise the
security of the supply chain for drugs imported under section 804 of
the FD&C Act, this rule also proposes additional provisions to
safeguard the public health. These additional safeguards are necessary
for the Secretary to certify that implementation of section 804 of the
FD&C Act would pose no additional risk to the public's health and
safety.
    First, if an eligible prescription drug is manufactured outside of
Canada, it would need to be exported commercially into Canada by the
manufacturer and labeled for the Canadian market. It could not be
transshipped through Canada for sale in another country because this
could create opportunities for counterfeiting or other forms of fraud.
    Second, an eligible prescription drug would need to be sold by the
manufacturer directly to a Foreign Seller in Canada. FDA has determined
that this requirement is critical because FDA would generally not
possess information needed to trace drug products labeled for the
Canadian market back to the original manufacturer. As discussed further
in the ``Supply Chain Security Requirements'' section below, for
products and transactions that are subject to the DSCSA, supply chain
protections are in place to allow for tracing products up to the
manufacturer at the package and homogenous case level.
    Under FDA's general proposed approach, a Foreign Seller would then
ship the drug directly to the Importer in the United States. We
considered whether to propose allowing more than one Foreign Seller in
the Canadian supply chain but decided against this approach because we
do not believe it would be possible for a SIP Sponsor to demonstrate
that the same level of safety would be assured. For a SIP to pose no
additional risk, it would have to match the protections of the DSCSA
through other means. The short supply chain, coupled with this proposed
rule's other provisions like serialization and testing, would permit
control over and transparency into the supply chain to help ensure
comparable safety. Therefore, we propose to require that each Foreign
Seller buy the drug directly from the manufacturer and then sell it
directly to the Importer in the United States because this would
minimize supply chain security risks, including the risks posed by
increased opportunities for counterfeiting and other forms of fraud
that obscure the origin of drugs imported under section 804 of the FD&C
Act. As the number of entities outside the United States that handle
the drugs increases, the supply chain becomes progressively less
transparent and more vulnerable to risk. The proposed short supply
chains would also allow FDA and States to supervise the supply chain
participants more closely. This rule proposes additional safeguards on
tracing products through the pre-U.S. supply chain, which we believe
will result in a level of supply chain security that poses no
additional risk to the public's health and safety, but these proposed
provisions are premised on the presence of just one Foreign Seller per
supply chain. Allowing for additional Foreign Sellers in a supply chain
would undermine our ability to ensure that our proposed approach poses
no additional risk.
    Although we cannot foresee at this time how a longer supply chain
would not pose additional risk to the public's health and safety, we
seek comment on whether there actually are safeguards

that could be put in place that would enable FDA to authorize a SIP
with multiple Foreign Sellers in a single supply chain in Canada. Such
comments should provide specific details regarding the additional
safeguards and how they would provide the same level of protection to
the supply chain. If, in response to comments, we determine that FDA
could authorize a SIP with more than one Foreign Seller in a single
supply chain because we are able to adopt additional safeguards such
that the SIP would pose no additional risk to the public's health and
safety, we would consider having the final rule account for this
possibility. For example, we could revise Sec. Sec.  251.3,
251.14(a)(4), 251.19(c), and 251.19(d)(2), as follows.
     Section 251.3 could be revised to state that, in its
initial proposal, a SIP Sponsor must only designate one Foreign Seller
and one Importer that may engage in the distribution of any drug
specified in the proposal, unless the SIP Sponsor demonstrates that the
SIP will meet additional safeguards, which would be detailed in the
final rule, necessary to ensure that the inclusion of subsequent
specified Foreign Sellers would pose no additional risk to the public's
health and safety.
     Section 251.14(a)(4) could be revised to state: ``For each
drug imported under the SIP, the drug is only shipped by the entities
that are specified in the SIP.''
     Section 251.19(c) could be revised to state: ``The
Importer must also confirm that the eligible prescription drug was
bought directly from the manufacturer by a Foreign Seller, and that all
subsequent sales of that eligible prescription drug, up to and
including the sale to the Importer, were made only among Foreign
Sellers described in the SIP.''
     Section 251.19(d)(2) could be revised to state:
``documentation demonstrating that the eligible prescription drug was
only handled by the manufacturer and Foreign Seller(s) described in the
SIP before the Importer received the drug;''.
    In addition, among other potential revisions that may be necessary,
if the final rule were to permit longer supply chains, we would include
in the final rule those additional safeguards--submitted in comments
justifying an allowance for multiple Foreign Sellers in a single supply
chain--that would be applicable to most, and perhaps all, proposals
that include multiple Foreign Sellers. We note that other requirements
would apply as well that would need to be specified in the final rule,
including the testing requirements described in section
804(d)(1)(J)(ii).
    Under the proposed rule, following the shipment into the United
States, the Importer would be responsible for: (1) Sending FDA
information about the drug, including information it receives from the
Foreign Seller and the test results from the qualifying laboratory and
also for (2) ensuring that the drug is relabeled with the required U.S.
labeling and DSCSA product identifier. The Importer would then sell the
product to either another entity in the United States (if it is a
wholesaler) or dispense the product itself to patients (if it is a
pharmacist).
    We acknowledge that there are certain assurances regarding
authenticity and quality when a manufacturer manufactures drugs
intended for sale in the United States. We seek comment on the approach
in this proposed rule and whether it contains sufficient safeguards to
ensure that the proposed importation poses no additional risk to health
or safety.
1. Foreign Seller's Supply Chain Security Obligations
    Once the Foreign Seller receives product from a foreign
manufacturer, which would be entirely intended and labeled for sale in
the Canadian market, the Foreign Seller would need to separate the
portion of product it intends to sell to the Importer in the United
States under section 804, and maintain that portion in a separate area
in its facility from the portion intended for the Canadian market. We
anticipate that the volume of drug included in the portion intended for
the U.S. market will be agreed upon between the Foreign Seller and the
Importer to whom it will sell the drug, and that such volume will be
identified in a contract agreement and in records that the Importer is
obligated to send to FDA under section 804(d) of the FD&C Act.
    Under the proposed rule, for the portion of drug that will be
transacted between the Foreign Seller and the Importer under section
804, the Foreign Seller would need to assign an SSI to each package and
homogenous case of drug in that portion. The rule proposes that
``package'' means the smallest individual salable unit of product for
distribution that is intended by the Foreign Seller for sale to the
Importer located in the United States, and that ``individual saleable
unit'' means the smallest container of product sold by the Foreign
Seller to the Importer. The rule proposes that an ``SSI'' consists of a
unique alphanumeric serial number of up to 20 characters. Using a stamp
or adhesive sticker, the Foreign Seller would be required to place the
SSI on each package and homogenous case, but would not otherwise
repackage or relabel the drug. If the product already contained a
manufacturer-affixed DSCSA-compliant product identifier at the time the
Foreign Seller receives it, the Foreign Seller would not be required to
assign an SSI to the product before further engaging in a transaction
with the Importer.
    Under the proposed rule, the Foreign Seller would need to maintain
records identifying its process for serializing and affixing the SSI
onto each package and homogenous case, including an explanation of the
controls in place to ensure the stamp or adhesive sticker is properly
affixed. The Foreign Seller would also be required to adhere to all
applicable good manufacturing practice requirements in accordance with
section 501(a)(2)(B) of the FD&C Act and part 211. The SSI would need
to occupy blank space on the package and homogenous case, and not
obscure any other labeling information, including the manufacturer-
labeled Canadian DIN that was on the package and homogenous case at the
time the Foreign Seller received the product from the manufacturer.
Therefore, a drug without a DIN would not be an eligible prescription
drug that could be imported into the United States. Finally, the
Foreign Seller would need to maintain records associating the SSI with
the DIN and all the records it received from the manufacturer upon
receipt of the original shipment intended for the Canadian market.
    The rule also proposes that various verification requirements on a
Foreign Seller, that correspond, where applicable, with those
provisions pertaining to a ``manufacturer'' under the DSCSA in section
582(b)(4)(A) through (C) of the FD&C Act. Specifically, the Foreign
Seller would need to verify that a drug was not a suspect or
illegitimate foreign product and would need to send information to the
Importer about the purchase of the drug. ``Suspect foreign product''
and ``illegitimate foreign product'' are proposed in the rule as
defined terms relating to the product that the foreign seller purchases
from the manufacturer and align with the definitions of ``suspect
product'' and ``illegitimate product'' in DSCSA. In addition, the
Foreign Seller would need to be able to respond to requests for
verification from FDA or others within 24 hours or in other such
reasonable time as determined by FDA based on the circumstances of the
request. We seek comment on the scope of the foreign seller's proposed
verification

responsibilities, and the extent to which Foreign Sellers currently or
in the future may have systems or processes in place to meet such
requirements.
    Under the proposed rule, the Foreign Seller would not be engaged in
repackaging, only relabeling, and it would be receiving a product from
the original manufacturer that is not DSCSA-compliant, since that
product would have been intended and labeled entirely for the Canadian
market. To address potential risks, this rule proposes to impose
several requirements on Foreign Sellers. For example, as noted above,
the Foreign Seller would need to be registered with FDA under section
804 of the FD&C Act. Additionally, the rule proposes that, prior to or
at the time of each transaction with the Importer in which the Foreign
Seller transfers ownership of the product to the Importer, the Foreign
Seller would need to provide the Importer with a statement and
information that is comparable with transaction information and
transaction statement as defined in section 581(26) and (27) of the
FD&C Act, respectively. Specifically, the Foreign Seller would be
required to provide to the Importer:
     The proprietary or established name of the product;
     Strength and dosage form of the product;
     The container size;
     The number of containers;
     The lot number of the product;
     The date of the transaction;
     The date of the shipment, if more than 24 hours after the
date of the transaction;
     The business name and address of the person associated
with the Foreign Seller from whom ownership is being transferred;
     The business name and address of the person associated
with the Importer to whom ownership is being transferred;
     The SSI for each package and homogenous case of product;
and
     The Canadian DIN for each product transferred.
    These requirements would be in addition to the statutory
requirement under section 804(d)(1)(G) of the FD&C Act that the
Importer obtain from the Foreign Seller, and submit to FDA,
documentation specifying the original source of the prescription drug
(i.e., identifying the original foreign manufacturer) and the quantity
of each lot of the drug the Foreign Seller originally received from the
manufacturer. The rule also proposes that the Foreign Seller would be
required to send information to FDA and other officials as appropriate
and upon request. For example, upon a request by FDA, or other
appropriate Federal or State official, in the event of a recall or for
purpose of investigating a suspect product or an illegitimate product,
the Foreign Seller would need to promptly provide the official with the
information about the transaction with the Importer. This is comparable
to the requirement for repackagers under section 582(e)(1)(C) of the
FD&C Act; other DSCSA trading partners currently have similar
obligations.
    The required activities of the Foreign Seller proposed in this
rule, as described above, presume a single Foreign Seller between the
manufacturer and Importer in a particular supply chain. However, as
noted above, if in response to comments, we determine that additional
safeguards exist such that a SIP with a subsequent Foreign Seller or
Foreign Sellers in a supply chain could be proposed to ensure that the
longer supply chain would not pose additional risk to the public's
health and safety, we would consider having the final rule account for
this possibility. Our analysis of comments received will include a
consideration of how the requirements described above on the single
Foreign Seller (e.g., to place an SSI on products, send transaction
information to the Importer, verify products, and maintain records)
would be applied to subsequent Foreign Sellers in a supply chain.
    In sum, we have determined that a Foreign Seller would need to be
capable not only of registering with FDA per section 804(f) of the FD&C
Act and sharing relevant information and records with the Importer per
section 804(d)(1)(G) of the FD&C Act, but also of preserving supply
chain security and sending package-level information about the product
they are selling to the Importer in a format that enables
interoperability. This is consistent with section 804(c) of the FD&C
Act, which permits the Secretary to include any additional requirements
determined to be appropriate as a safeguard to protect the public
health. Without these requirements, the Secretary would not be able to
make the certification required under 804(l) that importation poses
``no additional risk to the public's health and safety.''
2. Importer's Supply Chain Security Obligations
    Under the proposed rule, when the Foreign Seller sends a shipment
of the product to the Importer, the product would need to include the
Foreign Seller-affixed SSI, and, as noted earlier, contain the original
Canadian labeling that the manufacturer had applied to the drug. The
Importer would be responsible for relabeling the product with the
required U.S. labeling.
    If the Importer intends to place the product into further
transactions in commerce, that relabeling would also need to include
placing or affixing a product identifier that is associated with the
SSI that the Foreign Seller assigned to the product prior to sending it
to the Importer. Therefore, as part of the relabeling, this rule
proposes that the Importer is responsible for affixing or placing a
product identifier, as that term is defined in section 581(14) of the
FD&C Act, on each package and homogenous case of product that it
receives from the Foreign Seller. If, however, the Importer intends to
directly administer the product to patients, as may be the case if the
Importer intends to dispense the drug as a pharmacist, a product
identifier would not be required to be affixed or imprinted on each
package and homogenous case of the eligible prescription drug.
    To avoid unnecessary steps in the supply chain, the product
identifier would need to be affixed or imprinted at the same time at
which the drug is being relabeled with the required U.S. labeling. As
proposed, the Importer may relabel the product itself, or may choose to
contract with a separate entity to relabel on its behalf. In either
case, the entity that relabels the product must be registered with FDA
as a relabeler, or a repackager if limited repackaging will occur as
permitted in this proposed rule, under section 510(b) of the FD&C Act,
in accordance with part 207, and also list the drug as required. We
note that an entity that is a ``repackager'' as defined in the DSCSA
under section 581(16) of the FD&C Act is likely to already have
facilities and capabilities in place to affix or imprint a product
identifier based on existing DSCSA requirements. A relabeler who
contracts with the Importer to affix a product identifier on the
Importer's behalf must, even if not engaged in a repackaging operation
with respect to the eligible prescription drug, have systems and
processes in place to meet applicable requirements of a ``repackager''
under section 582(e) of the FD&C Act for any transaction involving the
eligible prescription drug.
    Per section 581(14) of the FD&C Act, the product identifier must
include a standardized numerical identifier (SNI), as that term is
defined in section 581(20) of the FD&C Act, the lot number, and
expiration date of the product and be in human and machine-readable
form encoded in a 2-dimensional barcode. An SNI consists of an
alphanumeric serial number and

NDC under section 581(20). For a product imported under section 804 of
the FD&C Act, the Importer is responsible for obtaining an NDC for the
product (as described elsewhere in this proposed rule). With regard to
the serial number component of the SNI, the Importer may elect to use
the same serial number (i.e., the SSI) that the Foreign Seller had
previously assigned to the product, or it may elect to assign a new
serial number. Under the proposed rule, the Importer would need to
maintain records, for no less than 6 years, that allow the Importer to
associate the product identifier it affixed on each package and
homogenous case of product it received from the Foreign Seller, with
the SSI that had been assigned by the Foreign Seller, and the Canadian
DIN that was on the package when the Foreign Seller received the
product from the original manufacturer. This is analogous to the record
retention requirement in section 582(e)(2)(A)(iv) of the FD&C Act for a
repackager that associates a product identifier with a manufacturer-
affixed product identifier.
    In addition to the requirements proposed in the rule, the Importer
is required to comply with any applicable existing requirement of the
DSCSA for subsequent transactions to trading partners in the supply
chain once the product has been relabeled with the required U.S.
labeling (including the product identifier). For example, any Importer
of eligible drugs under a SIP who is a ``pharmacist'' as defined in
section 804(a)(2) of the FD&C Act (i.e., a person licensed by a State
to practice pharmacy, including the dispensing and selling of
prescription drugs), is also considered to be a ``dispenser'' under the
DSCSA, as defined in section 581(3) of the FD&C Act. Such dispenser
must be ``authorized'' under the DSCSA, i.e., have a valid license
under State law (as defined in section 581(2)(D) of the FD&C Act). Such
dispenser must also comply with all applicable requirements pertaining
to a dispenser under section 582(d) of the FD&C Act. Furthermore, any
Importer of eligible drugs under section 804 who is a ``wholesaler'' as
defined in section 804(a)(5)(A) of the FD&C Act, is also considered to
be a ``wholesale distributor'' under the DSCSA, as defined in section
581(29) of the FD&C Act. Such wholesale distributor must be
``authorized'' under the DSCSA, i.e., have a valid license under State
law or section 583, in accordance with section 582(a)(6) of the FD&C
Act, and otherwise meet the definition in section 581(2)(C) of the FD&C
Act. Such wholesale distributor must also comply with all applicable
requirements pertaining to a wholesale distributor under section 582(c)
of the FD&C Act.
3. Exemptions From Certain DSCSA Requirements
    We propose to exempt certain transactions from DSCSA requirements
in section 582 of the FD&C Act, as permitted by section 582(a)(3)(iii),
because they would be difficult or impossible for section 804 imported
drugs to meet, and the proposed rule includes other safeguards to
maintain supply chain security:
     Section 582(c)(1)(A) and (d)(1)(A): For an Importer that
is a wholesale distributor receiving the product from a Foreign Seller
in Canada, the proposed rule would exempt the Importer from the
requirement not to accept ownership unless the previous owner provides
the transaction history, transaction information, and a transaction
statement for the product. Similarly, if the Importer is a pharmacist
receiving the product from a Foreign Seller in Canada, the proposed
rule would exempt the Importer from the requirement on dispensers to
not accept ownership unless the previous owner provides the transaction
history, transaction information, and a transaction statement for the
product. Instead, as previously described, this rule proposes to
require the Foreign Seller to provide certain transaction-related
information to the Importer that is adequate to ensure no additional
risk to supply chain security.
     Section 582(c)(2) and (d)(2): The proposed rule would
exempt Importers that are wholesale distributors and dispensers from
the prohibition on receiving products that are not encoded with a
product identifier. Instead, as previously described, products received
from the Foreign Seller would be required to have an SSI. Wholesale
distributors and dispensers would otherwise be required to engage only
in transactions of products encoded with a product identifier, as
defined in DSCSA.
     Section 582(c)(3) and (d)(3): Importers that are wholesale
distributors and dispensers would be permitted to conduct transactions
with Foreign Sellers even though they are not ``authorized trading
partners'' under section 581. Wholesale distributors and dispensers
would otherwise be required to transact only with authorized trading
partners, as defined in the DSCSA.
     Section 582(c)(4)(A)(i)(II) and (d)(4)(A)(ii)(II): For
section 804 imported products, the proposed rule would exempt an
Importer from the requirement to verify that a product in the
Importer's possession or control contains a ``standardized numerical
identifier.'' Instead, the Importer would be required to verify that
the section 804 imported product at the package level includes the SSI
that the Foreign Seller had previously assigned to the product.
    Note that FDA would not consider a drug imported under section 804
to have been diverted solely as a result of being imported under a SIP.
A drug imported under section 804 may meet the definition of suspect or
illegitimate product for other reasons, however (e.g., counterfeit or
stolen products), and entities that are obligated to identify such
products under the DSCSA would be obligated to do so for drugs imported
under section 804 in the same manner as they would for any other drugs
subject to the same requirement.
    We welcome comments on whether FDA should include exemptions from
additional DSCSA requirements. We also note that manufacturers,
repackagers, wholesale distributors, or dispensers may request waivers
or exceptions at any time, under section 582(a)(3)(i) and (ii) of the
FD&C Act.
4. Manufacturer's Supply Chain Security Obligations
    Pursuant to section 804(d)(1) of the FD&C Act, this regulation,
once finalized, would require the Importer to submit to FDA certain
information and records about the imported drug. Under section
804(d)(1)(J) of the FD&C Act, such information would include the
results of testing for authenticity and degradation, to be done per
section 804(e) by either the Importer or the manufacturer. In the case
of testing that is done by the Importer, other parts of this regulation
specify information that the manufacturer is required to share in
confidence with the Importer in order for the testing to occur, but in
this section we further propose that the manufacturer would also need
to provide to the Importer information it has about the transaction of
the drug to the Foreign Seller located in Canada. Such information is
necessary, along with other testing and laboratory record information
specified elsewhere in this proposed rule, to ensure that the imported
drug is authentic, as required in section 804(d)(1)(J) of the FD&C Act.
Furthermore, under section 804(d)(1)(N) of the FD&C Act, we consider
such information pertaining to drug's transactions in the pre-U.S.
supply chain to be necessary to ensure the protection of public health.
    Manufacturers would also need to be able to provide sufficient
information to the Importer about the imported drug's movements in the
pre-U.S. supply chain. To this end, this rule proposes to

require, under section 804(e) of the FD&C Act, that the manufacturer
provide to the Importer all relevant documentation about the
transaction that it provided to the Foreign Seller, upon its transfer
of ownership of the product for the Canadian market. The rule does not
propose to require any additional information about this transaction
that is otherwise not maintained or submitted in accordance with
Canadian law, or in the normal course of business for products the
manufacturer intends to introduce to the Canadian market. The Importer
would be required to use this information obtained from manufacturers
under section 804(e) of the FD&C Act to help determine whether the
supply chain was intact, by comparing the information about the
transaction between the manufacturer and Foreign Seller to that
received by the Importer from the Foreign Seller, as required under
this rule.
    We seek comments on this approach, including whether different or
additional safeguards are necessary to ensure the integrity of the
supply chain with respect to drugs imported under section 804 of the
FD&C Act.

G. Requirements for Qualifying Laboratories

    Section 804 of the FD&C Act requires that imported drugs be tested
by a ``qualifying laboratory,'' which is defined as ``a laboratory in
the United States that has been approved by the Secretary for the
purposes of this section.'' As indicated earlier in this document, a
SIP Proposal would need to indicate which laboratory the SIP will use
to test the drugs it imports. The SIP Proposal would also need to
explain why that laboratory is qualified to do the testing and so
should be approved by FDA for use by a SIP.
    To be considered qualified, we propose that a laboratory would need
to comply with the applicable elements of the CGMP requirements,
including provisions regarding laboratory controls in 21 CFR 211.160
and regarding laboratory records in 21 CFR 211.194. In addition, a
laboratory would need to have ISO 17025 accreditation. Finally, we
propose that it also would need to have an FDA inspection history and
it would need to have satisfactorily addressed any objectionable
conditions or practices identified during its most recent FDA
inspection.
    We seek comment on whether there are other requirements that all
laboratories should meet before FDA approves them for use by a SIP. For
example, we seek comment on whether we should require accreditation
different from or in addition to ISO 17025.
    If the rule is finalized as proposed, FDA would approve qualifying
laboratories for use by a SIP on a case-by-case basis as part of its
review and authorization of a SIP Proposal. FDA would also consider
publishing a list of approved qualifying laboratories for the benefit
of States or other non-federal governmental entities and their co-
sponsors, if any, that may be developing a SIP Proposal.

H. Laboratory Testing Requirements

    Section 804(d)(1)(J)(i) of the FD&C Act sets forth testing
requirements for shipments of imported drugs that are shipped directly
to the Importer from the first foreign recipient of the prescription
drug from the manufacturer and section 804(d)(1)(J)(ii) sets forth
testing requirements for shipments that are not shipped directly to the
Importer from the first foreign recipient of the prescription drug from
the manufacturer. Because we are proposing to require that all
shipments under a SIP be shipped directly from the Foreign Seller,
which is the first foreign recipient of the prescription drug from the
manufacturer, to the Importer, this rule focuses on the testing
requirements in section 804(d)(1)(J)(i) and does not address the
requirements in section 804(d)(1)(J)(ii) of the FD&C Act. In addition,
section 804(d)(1)(L) of the FD&C Act requires that the Importer provide
laboratory records to FDA that include ``complete data derived from all
tests necessary to ensure that the prescription drug is in compliance
with established specifications and standards.''
    Section 804(d)(1)(J)(i) of the FD&C Act provides that, in the case
of an initial imported shipment, an Importer must provide documentation
to FDA demonstrating that the drug ``was received by the recipient from
the manufacturer and subsequently shipped by the first foreign
recipient to the importer,'' that ``the quantity being imported into
the United States is not more than the quantity that was received by
the first foreign recipient,'' and that ``each batch of the
prescription drug in the shipment was statistically sampled and tested
for authenticity and degradation.'' For any subsequent shipments from
the same batch of a drug, section 804(d)(1)(J)(i)(III)(bb) of the FD&C
Act allows for more limited testing, of ``a statistically valid sample
of the shipment.'' For an initial imported shipment, the testing would
have to be done on a statistical sample of ``each batch of the
prescription drug in the shipment.'' For example, if a shipment
contained drugs from two batches, Batch A and Batch B, the testing
would have to be done on a statistical sample of all of the drugs that
came from Batch A and on a separate statistical sample of all the drugs
that came from Batch B. For a subsequent shipment, the testing could be
done on a statistical sample of the shipment as a whole, unless, for
example, there are drugs from a third batch, Batch C, in the shipment.
In that case, the testing would need to be done on a statistical sample
of all the drugs that came from Batch A and Batch B, as a whole, and on
a separate statistical sample of all the drugs that came from Batch C.
    We propose to require that a statistical sample of a batch or
shipment of section 804 drugs be randomly selected from the batch or
shipment being tested or, in the alternative, that the sample be
representative of the batch or shipment. We seek comment on whether we
should specify a sampling method. We also seek comment on whether we
should require that sampling be done according to an established
standard such as those issued by the American National Standards
Institute (ANSI) or by ASTM International.
    Regarding the size of the sample, the number of packaged units in
the sample would need to be large enough to enable a statistically
valid statement to be made regarding the authenticity and stability of
the entire batch or entire shipment. We seek comment on whether we
should require that the sample size be determined using an established
standard such as ASTM International's E122-17 ``Standard Practice for
Calculating Sample Size to Estimate, With Specified Precision, the
Average for a Characteristic of a Lot or Process'' (Ref. 30).
    As noted previously, we propose that the testing done on the sample
of the batch or shipment be sufficiently thorough to establish, in
conjunction with data and information from the manufacturer, that the
batch or shipment is eligible for importation under a SIP. The proposed
rule would require the sample of the HPFB-approved drug to be tested to
confirm that the HPFB-approved drug meets the FDA-approved drug's
specifications, including the analytical procedures and methods and the
acceptance criteria. In addition, to meet the statutory requirement
that shipments be tested for degradation, a stability-indicating assay
provided by the manufacturer would be required to be conducted on the
sample of the drug that is proposed for import. Pursuant to section
804, the proposed rule would require all testing to be done

in a qualifying laboratory in the United States.
    The testing required under section 804(d)(1)(J) of the FD&C Act can
be conducted ``by the importer or by the manufacturer.'' If the
Importer conducts the testing, section 804(e)(2)(A) of the FD&C Act
requires the manufacturer to provide the Importer with the information
needed to authenticate the prescription drug. Under the proposed rule,
specifically, the manufacturer would be required to provide the
Importer with formulation information about the HPFB-approved drug and
the FDA-approved drug and any testing methodologies and protocols that
the manufacturer has developed that the Importer needs to conduct the
Statutory Testing.
    In addition, under the proposed rule, the manufacturer would be
required to provide an attestation to the Importer, or alternatively to
FDA if the manufacturer conducts the testing itself, to establish that,
but for the fact that it bore the HPFB-approved labeling, the drug that
the manufacturer sold to the Foreign Seller in fact met the conditions
in the FDA-approved NDA or ANDA. This would include any process-related
or other requirements for which compliance cannot be established
through laboratory testing. If the manufacturer does the testing, the
manufacturer would be required to provide the attestation to FDA under
the proposed rule. We propose that the attestation would need to
include confirmation that the HPFB-approved drug has the active
ingredient(s), active ingredient source(s) (including manufacturing
facility or facilities), inactive ingredient(s), dosage form,
strength(s), route(s) of administration, etc., described in the FDA-
approved drug's NDA or ANDA. The attestation would also need to confirm
that the HPFB-approved drug conforms to the specifications in the FDA-
approved drug's NDA or ANDA regarding the quality of the drug
substance(s), drug product, intermediates, raw materials, reagents,
components, in-process materials, container closure systems, and other
materials used in the production of the drug. In addition, the
attestation would need to confirm that the HPFB-approved drug was
manufactured in accordance with the specifications described in the
FDA-approved drug's NDA or ANDA, including with regard to the
facilities and manufacturing lines that are used, and in compliance
with CGMP requirements set forth in section 501(a)(2)(B) of the FD&C
Act and 21 CFR parts 4 (if a combination product), 210, and 211. The
attestation would also need to include the original date of manufacture
or whatever date was used in calculating the labeled expiration date
based on the HPFB-approved or scientifically validated expiration
period, the expiration period set forth in the FDA-approved drug's NDA
or ANDA, and any other information needed to label the drug with an
expiration date that meets the specifications of the FDA-approved
drug's NDA or ANDA.
    The attestation would also need to include information needed to
confirm that the labeling of the prescription drug complies with
labeling requirements of the FD&C Act. Finally, as discussed elsewhere
in this proposed rule, the attestation would need to include
information about the transaction of the eligible prescription drug to
the Foreign Seller.
    In addition to the attestation, the manufacturer would need to
provide the Importer with the executed batch record, including the
executed COA, for at least one recently manufactured, commercial-scale
batch of the HPFB-approved drug and for at least one recently
manufactured commercial-scale batch of the FDA-approved drug that was
produced for and released for distribution to the U.S. market under an
NDA or ANDA. The manufacturer would need to provide these analyses for
each manufacturing line that the manufacturer used to produce either or
both of the drugs.
    As discussed earlier in this document, section 804(e)(2)(B) of the
FD&C Act states that the information that a manufacturer provides to an
Importer under section 804(e)(2)(A) must be kept in strict confidence
and used only for purposes of testing or otherwise complying with this
Act.'' The statute goes on to state that the regulations implementing
section 804 of the FD&C Act can include provisions to provide for the
protection of trade secrets and commercial or financial information
that is privileged or confidential. We have proposed in Sec.  251.15(g)
and (h) additional provisions regarding the protection of information
that may be supplied by a manufacturer to an Importer under this rule.
We seek comment on whether any other provisions are needed to protect
the information that manufacturers would need to provide to Importers
under this rule. We note that instead of providing its proprietary test
methods to an Importer, a manufacturer can do the testing itself in a
qualifying laboratory in the United States.
    As discussed above, for subsequent shipments of drugs from a batch,
drugs from which have already been imported under a SIP, section
804(d)(1)(J)(i)(III)(bb) of the FD&C Act allows Importers to test a
statistically valid sample of each shipment, as opposed to a
statistically valid sample of each batch within a shipment. We seek
comment on whether a different approach to testing subsequent shipments
should be permitted. For example, it may be appropriate to use
vibrational spectroscopic tests to test drugs in subsequent shipments.
We note, however, that formulation-related physical stability and other
quality issues cannot be tested by using spectroscopy. For that reason,
a stability-indicating assay developed by USP or the manufacturer would
have to be conducted as well. We seek comment on what testing would be
appropriate at this stage.
    The obligations on manufacturers under section 804(e) of the FD&C
Act are enforceable under section 301(aa) of the FD&C Act, which
provides that, among other things, a violation of the regulations
implementing section 804 is a prohibited act. Furthermore, section
303(b)(6) of the FD&C Act sets forth penalties for manufacturers or
Importers that knowingly fail to comply with a requirement of section
804(e) of the FD&C Act. These requirements include that: (1) The
manufacturer or Importer conduct the Statutory Testing at a qualifying
laboratory; (2) if the Importer conducts the testing, the manufacturer
supply the information needed to authenticate the drug being tested and
to confirm that the labeling is in compliance with the FD&C Act in a
timely fashion, and (3) if the manufacturer supplies information to the
Importer, the Importer keep it in strict confidence and only use it for
testing and complying with the FD&C Act. A manufacturer or Importer
that fails to comply with these requirements can be imprisoned for not
more than 10 years under section 303(b)(6) of the FD&C Act, fined under
18 U.S.C.3571, or both.
    In the event that a manufacturer fails to provide information
required by this proposed rule in a timely fashion, including
information necessary for the Importer to conduct the Statutory
Testing, authenticate the drug being tested, or confirm that the
labeling is in compliance with the FD&C Act, FDA may provide such
information to an Importer if the information is contained in the
manufacturer's approved NDA or ANDA. We seek comment on what would be
considered a timely fashion that would provide the manufacturer
adequate time to provide the necessary information and that would not
create excessive difficulty for the Importer

who needs that information to import the drugs.

I. Listing and Labeling of Eligible Prescription Drugs

    Section 804(d)(1)(K)(ii) of the FD&C Act requires that a drug
covered by section 804 meets all labeling requirements of the FD&C Act.
Additionally, section 804(c) of the FD&C Act requires that each
prescription drug imported under this importation program comply with
sections 501, 502, and 505 of the FD&C Act. Under section 804(h) of the
FD&C Act, the manufacturer of a prescription drug is required to
provide the Importer with written authorization to use the drug's
approved labeling at no cost. If the manufacturer fails to do so in a
timely fashion, FDA will deem this authorization to have been given. In
addition, under the proposed rule, as required by section
804(e)(2)(A)(ii) of the FD&C Act, the manufacturer would need to supply
the Importer, in a timely fashion, with information needed to confirm
that the labeling of the prescription drug complies with the labeling
requirements of the FD&C Act. Furthermore, under the requirements
proposed by this rule, before a drug can be introduced into interstate
commerce under section 804 of the FD&C Act, it would be required to be
listed in accordance with part 207, and it would be relabeled so that
it bears certain information that is unique to the eligible
prescription drug. Specifically, the labeling will need to display an
NDC that is unique to the eligible prescription drug, and it will need
to provide information about the Importer. This section describes the
proposed requirements for obtaining an NDC, listing, and relabeling an
eligible prescription drug.
    The rule proposes that before an eligible prescription drug can be
sold it would need to bear a new NDC and be listed. We note that drugs
imported under section 804 will have the same name but will have a
different NDC than do their FDA-approved counterparts. As stated above,
the Importer of an eligible prescription drug would need to either: (1)
Propose an NDC for the drug, following the procedures in Sec.  207.33,
and it would need to list the drug, following the procedures in Sec.
207.53 or (2) if the Importer is a private label distributor, take
responsibility to ensure that the entity performing relabeling on its
behalf proposes an NDC and lists each eligible prescription drug in
accordance with the applicable requirements of part 207.
    Additionally, we propose to make the Importer responsible for
relabeling the drug, or arranging for it to be relabeled, to meet the
requirements of this proposed rule. The relabeling and associated
limited repackaging activities must meet applicable requirements,
including applicable CGMP requirements under parts 210 and 211. At the
time that an eligible prescription drug is sold or dispensed it would
need to have been relabeled to be consistent with the FDA-approved the
carton and container labels, prescribing information, and any patient
labeling, such as medication guides, instruction for use documents, and
patient package inserts. In addition, the eligible prescription drug
would need to have been assigned a product identifier in compliance
with section 582 of the FD&C Act. The relabeled eligible prescription
drug will be considered consistent if it varies from the FDA-approved
carton and container labels, prescribing information, and patient
labeling solely to the extent described in this rule.
    Except for repackaging that is necessary to perform the relabeling
described in this proposed rule, the proposed rule would not allow
further repackaging of drugs imported pursuant to a SIP. ``Repack'' or
``repackage'' is defined in Sec.  207.1 as ``the act of taking a
finished drug product or unfinished drug from the container in which it
was placed in commercial distribution and placing it into a different
container without manipulating, changing, or affecting the composition
or formulation of the drug.'' We believe that allowing repackaging that
breaches the immediate container closure system introduces unnecessary
risk of adulteration, degradation, and fraud for drugs subject to a
SIP. We also note that some container closure systems include a tamper-
evident seal, which would be disturbed if repackaging were allowed. In
addition, if a drug is repackaged from its immediate container closure,
the expiration period set forth in the NDA or ANDA may no longer be
valid because the expiration period in an approved NDA or ANDA is based
on stability studies involving the particular container closure system
into which a drug is placed without opening it to expose the contents
to the outside environment. Additional stability studies would
generally be required to establish a new expiration period.
    The proposed rule would require that the prescribing information of
an eligible prescription drug would need to include that drug's NDC in
the HOW SUPPLIED/STORAGE AND HANDLING section for products with
Physician Labeling Rule (PLR) labeling (see Sec.  201.57(c)(17)(iii)
(21 CFR 201.57(c)(17)(iii))) or the HOW SUPPLIED section for products
with ``old'' (non-PLR) format labeling (see Sec.  201.80(k)(3) (21 CFR
201.80(k)(3))) in place of any NDCs assigned to the FDA-approved U.S.
versions of the drug. The proposed rule would also require that the
eligible drug's new NDC be added to the container label and the carton
labeling. If applicable, the new NDC would replace any NDC otherwise
appearing on the label and carton labeling of the FDA-approved version
of the drug. We seek comment on whether having multiple otherwise
identical drugs in the marketplace with different NDCs will create any
issues, such as with pharmacy dispensing or otherwise, and, if so, if
there are steps that can be taken to mitigate such issues.
    In addition to the names and places of businesses of entities that
appear on the FDA-approved labeling, in this rule we propose to require
that the label and labeling of an eligible prescription drug also bear
conspicuously the name and place of business of the Importer. If the
FDA-approved labeling does not include the name and place of business
of the manufacturer, the name and place of business of the manufacturer
should be added as well.
    We also propose to require that the labeling on or within the
package from which the drug is dispensed include the following
statement: ``This drug was imported from Canada under the [Name of
State or Other Governmental Entity and of Its Co-Sponsors, If Any]
Section 804 Importation Program to reduce its cost to the American
consumer.'' If the SIP maintains a website, the statement could also
include the website address. To help avoid potential confusion between
products with the same name, we propose that this statement would be
included after the PATIENT COUNSELING INFORMATION section for products
subject to Sec.  201.56(d) (21 CFR 201.56(d)) and Sec.  201.57, or
after the HOW SUPPLIED section (or after the last section of labeling)
for products subject to Sec. Sec.  201.56(e) and 201.80. The statement
also would be included on the immediate container and outside package
to help pharmacists distinguish a section 804 product when selecting
the product on the pharmacy shelf. The statement would be sufficiently
prominent to help a pharmacist readily distinguish the eligible
prescription drug without obscuring required or recommended information
(e.g., information that will reduce the risk of medication errors and
ensure safe administration of the drug) (see FDA, 2013, ``Draft
Guidance for Industry: Safety Considerations for Container Labels and
Carton Labeling Design to

Minimize Medication Errors.'' Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/safety-considerations-container-labels-and-carton-labeling-design-minimize-medication-errors). The statement may also aid in pharmacovigilance by
increasing the likelihood that adverse event, medication error, field
alert, and other reports include the fact that the drug was imported
under a SIP. We seek comments on the content of the disclosure
statement, in particular whether such a statement is necessary, whether
it will be understandable and meaningful to prescribers, pharmacists,
and patients, and whether more or less information is needed. We seek
comment on whether it is necessary to provide the name of the SIP or
whether it would be sufficient to state that the drug was imported
under a SIP.
    If an eligible prescription drug's container is too small to fit
the additional information required by this proposed rule, FDA would
consider a proposal for supplementary labeling from the SIP Sponsor.
The container label would need to include at minimum the product's
proprietary and established name (if any); product strength; lot
number; and the name of the manufacturer and the Importer (see FDA,
2013, ``Draft Guidance for Industry: Safety Considerations for
Container Labels and Carton Labeling Design to Minimize Medication
Errors.'' Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/safety-considerations-container-labels-and-carton-labeling-design-minimize-medication-errors).
    In addition to the required statement on the labeling, the proposed
regulation also would require the SIP Sponsor to describe in the SIP
Proposal how it will educate pharmacists, healthcare providers, and
patients about its SIP. If pharmacists, healthcare providers, and
patients know that a drug was originally intended for sale in Canada,
they will have the ability to include this information if they
subsequently report any adverse events or quality concerns. It may also
help ensure that a recall is effective if healthcare providers and
patients have this knowledge.
    Among other things, a SIP could create and maintain a website that
would set forth the name and NDC number of each drug that it imports.
This would allow pharmacists, healthcare providers, and patients to use
the NDC number to determine at any time whether a drug was originally
intended for sale in Canada. The website could also include any
relevant adverse event, medication error, field alert reports, or other
reports or recall information. As stated earlier, the website address
could be included along with the disclosure statement in the labeling
of an eligible prescription drug.
    A SIP could also distribute a Dear Healthcare Provider letter to
physicians and pharmacists by United States mail, by email, by posting
the letter on the Importer's website, or by other effective means,
explaining that the drugs will have a different NDC because they were
originally intended for sale in Canada. The letter could recommend that
patients be counseled that the drugs were originally intended for sale
in Canada, that they have different NDCs than their FDA-approved
counterparts, and that they can use the NDCs to find out pertinent new
information regarding the HPFB-approved drug or its FDA-approved
counterpart, including information about recalls. A SIP could also
propose to distribute a Dear Consumer letter (similar to a Dear
Healthcare Provider letter) that pharmacists could dispense along with
eligible prescription drugs and that consumers could access on the
SIP's website.

J. Information and Records

    Section 804(d) of the FD&C Act lists information and documentation,
to be required in the regulations under section 804(b), that Importers
of eligible prescription drugs must submit to the Secretary. The rule
proposes that section 804(d) information would be submitted to FDA each
quarter by SIP Sponsors. SIP Sponsors would be required to submit a
report to FDA each quarter containing the information set forth in
section 804(d) of the FD&C Act, beginning after the SIP Sponsor files
an electronic import entry for consumption for its first shipment of
drugs.
    Consistent with the statute, the proposed rule would require that
Importers collect and submit to FDA the information listed here, but
also clarifies that the Importer's submission obligations are met if
the SIP sponsor submits a report to FDA as described above: (1) The
name, address, telephone number, and professional license number (if
any) of the Importer; (2) the name and quantity of the active
ingredient of the prescription drug; (3) a description of the dosage
form of the prescription drug; (4) the date on which the prescription
drug is shipped; (5) the quantity of the prescription drug that is
shipped; (6) the lot or control number assigned to the prescription
drug by the manufacturer of the prescription drug; (7) the point of
origin and destination of the prescription drug; and (8) the per unit
price paid by the Importer for the prescription drug in U.S. dollars,
as well as any other information that FDA determines is necessary to
ensure the protection of the public health. We propose to require that
Importers submit to FDA, in addition to the point of origin (i.e., the
manufacturer of the finished dosage form) and the destination (i.e.,
the wholesaler, pharmacy, or patient to whom the Importer sells or
dispenses the drug), information regarding the rest of the supply
chain, which this rule proposes would consist solely of the Foreign
Seller in Canada.
    Section 804(d) of the FD&C Act also requires the Importer to
collect and submit to FDA certain documentation, including: (1)
Documentation from the Foreign Seller specifying the original source of
the prescription drug (which under this rule would be the manufacturer
of the eligible prescription drug) and the quantity of each lot of the
prescription drug originally received by the seller from that source
and (2) in the case of a prescription drug that is shipped directly
from the first foreign recipient of the prescription drug from the
manufacturer (which, under this rule, would be the Foreign Seller),
documentation demonstrating that the prescription drug was received by
the first foreign recipient from the manufacturer and subsequently
shipped by the first foreign recipient to the Importer. The Importer
must also collect and submit documentation of the quantity of each lot
of the prescription drug received by the first foreign recipient
demonstrating that the quantity being imported into the United States
is not more than the quantity that was received by the first foreign
recipient. While the Importer does not need to submit records
associating the eligible prescription drugs' SSIs with their U.S.
product identifiers, the Importer would need to maintain such records
and make them available to FDA upon request. In the case of an initial
imported shipment, Importers would also need to submit documentation
demonstrating that each batch of the prescription drug in the shipment
was statistically sampled and tested for authenticity and degradation,
and in the case of any subsequent shipment, they would need to submit
documentation demonstrating that a statistically valid sample of the
shipment was tested for authenticity and degradation.
    Importers also would need to submit a certification from the
Importer or the manufacturer of an imported drug that the drug is
approved for marketing in the United States and is not adulterated or
misbranded, and meets all labeling

requirements under the FD&C Act. In this rule, we propose to require
that the certification include: (1) That there is an approved SIP; (2)
that the drug is covered by the SIP; (3) that the drug is an eligible
prescription drug as defined in this rule; (4) that the FDA-approved
counterpart of the drug is currently commercially marketed in the
United States; (5) that the drug is approved for marketing in Canada;
and (6) that the drug is not adulterated or misbranded and meets all
labeling requirements under the FD&C Act. Importers would need to
collect and submit laboratory records, including complete data derived
from all tests necessary to ensure that the prescription drug is in
compliance with established specifications and standards, and
documentation demonstrating that the Statutory Testing was conducted at
a qualifying laboratory, unless the manufacturer conducted the
Statutory Testing and submitted the relevant information directly to
FDA.
    In addition, SIP Sponsors would be required to provide FDA with
data and information on the SIP's cost savings to the American
consumer. We recognize a SIP's scope will influence the appropriate
cost savings calculation methodology. SIPs should, therefore, report
their total cost savings to consumers as well as the methodology used
to calculate this measure. Cost savings calculations should be based on
savings to the American consumer. Calculations should therefore rely,
to the greatest extent possible, on prices paid by the intended
consumer population. Average price measures by drug may be appropriate
if drugs are dispensed through multiple channels or if the imported
drugs' prices fluctuate throughout the reporting period. Calculation
methods should also account for factors that may influence cost savings
over time, such as changes in drug utilization, the price of domestic
drugs, and exchange rates. As mentioned above, we anticipate that some
SIP Sponsors may seek to import drugs to be used by patients in State-
run programs. In such cases, a SIP Sponsor could submit information
about whether cost-sharing expenses are reduced for the participants,
or whether the program will result in cost savings that are passed on
to consumers in other ways, such as increasing the number of people who
can be covered by a State program, or increasing the availability of
drugs covered by the program. We seek comments on these and other
factors relevant to the reporting of cost savings.

K. Post-Importation Requirements

    Under proposed Sec.  251.18, SIP Sponsors and Importers would be
required to take certain actions regarding eligible prescription drugs
if they are violative of an applicable requirement. Under the proposed
rule, the SIP Sponsor would be required to immediately stop importation
of eligible prescription drugs under a SIP if it determines that a drug
or entity in the supply chain does not meet all applicable requirements
of the FD&C Act, FDA regulations, and the authorized SIP. The Importer
must establish and maintain records and submit reports to FDA and to
the manufacturer of all domestic adverse events and medication errors
associated with the use of their imported eligible prescription drugs
about which they obtain or otherwise receive information. These reports
would be required to help inform whether there are safety concerns with
imported eligible prescription drugs, generally, and also specifically
in relation to the handling of these drugs. The Importer must also
develop written procedures for the surveillance, receipt, evaluation,
and reporting of adverse events and medication errors to FDA and to the
relevant manufacturer.
    The Importer must submit expedited reports on adverse events that
are both serious and unexpected to FDA and the manufacturer as soon as
possible but no later than 15 calendar days from initial receipt of the
information by the Importer. The Importer must also submit expedited
reports on medication errors to FDA and the manufacturer within the
same timeframe.
    The Importer must promptly investigate all adverse events and
medication errors that are the subject of these expedited reports and
must submit follow-up reports within 15 calendar days of receipt of new
information or as requested by FDA. If additional information is not
obtainable, the Importer should maintain records of the unsuccessful
steps taken to seek additional information. Furthermore, the Importer
must submit reports on adverse events that are both serious and
expected or that are nonserious, whether expected or unexpected, to FDA
and the manufacturer within a 90-calendar day timeline.
    FDA may require the Importer to submit certain adverse events
within 15 calendar days, even though the events do not meet the
criteria for expedited reporting. FDA will specify these adverse events
in advance and will provide the reason for requiring that they be
reported to the Agency on an expedited basis.
    While Sec.  314.80(c)(1)(iii) (21 CFR 314.80(c)(1)(iii)) gives
distributors of approved drugs the choice of submitting reports to
either FDA or the applicant, we propose to require that Importers of
section 804 drugs be required to submit reports to both FDA and the
manufacturer. This will aid the manufacturer in its pharmacovigilance
efforts, and it will provide FDA with information that may be relevant
to its review of SIP Proposals and Pre-Import Requests as well as to
its oversight of drugs imported under section 804 of the FD&C Act and
section 804 in general.
    FDA proposes to require submission of individual case safety
reports (ICSRs) and ICSR attachments in electronic format, as described
in Sec.  314.80(g)(1). Importers may request in writing a temporary
waiver of the electronic reporting requirements as described in Sec.
314.80(g)(2). Such waivers will be granted on a limited basis and for
good cause.
    The Importer would also be required to submit to the manufacturer
and to FDA field alert reports about the products it distributes. These
reports would need to be made when the Importer becomes aware of
information concerning any incident that causes the drug product or its
labeling to be mistaken for, or applied to, another article, or
information concerning any bacteriological contamination, or any
significant chemical, physical, or other change or deterioration in the
distributed drug product, or any failure of one or more distributed
batches of the drug product to meet the specification established for
it in the FDA-approved NDA or ANDA. If a SIP imports a drug-device
combination product, the Importer would also need to submit to the
manufacturer and to FDA the reports described in 21 CFR 4.102(c)(1) for
combination products containing a device constituent part, in the
manner and by the deadlines provided in part 4. The Importer would also
need to maintain the records described in 21 CFR 4.102(c)(1) and
4.105(b).
    An Importer should notify the Foreign Seller and the SIP Sponsor
any time it makes an adverse event, medication error, field alert
report, or other report to FDA and the manufacturer. Notification to
Health Canada would be done by the Foreign Seller in accordance with
Health Canada requirements. FDA would share adverse event, medication
error, field alert report, or other report information it receives with
Health Canada as appropriate.

    The SIP Sponsor would be required to establish a procedure to track
the public announcements of the manufacturer of each of the drugs that
they import and they must also monitor FDA's recall website at https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts, and Health
Canada's recall website at https://healthycanadians.gc.ca/recall-alert-rappel-avis/index-eng.php?cat=3, for any recall or market withdrawal
information relevant to the drugs that they import under section 804 of
the FD&C Act. The SIP Sponsor would have to explain in its SIP Proposal
how it will ensure that information about recalls or market withdrawals
will be shared among the SIP Sponsor, the Foreign Seller, the Importer,
and FDA and provided to the manufacturer.
    If FDA or a SIP Sponsor determines that a recall is necessary, the
SIP Sponsor must ensure that the recall is carried out effectively
based on the classification and depth determined by FDA or the SIP
Sponsor. A SIP must have a written recall plan that describes the
procedures to perform a recall of the product and specifies who will be
responsible for performing the procedures. The recall plan must cover
recalls initiated by FDA and recalls initiated by the SIP Sponsor, as
well as recalls in Canada or the United States initiated by a drug's
manufacturer that implicate a drug imported under a SIP, with which the
Foreign Seller and/or Importer must cooperate. The recall plan must
include sufficient procedures for the SIP Sponsor, Foreign Seller and/
or Importer to:
     Immediately cease distribution of the drugs affected by
the recall;
     directly notify consignees of the drug or drugs included
in the recall, including how to return or dispose of the recalled
drugs;
     specify the depth to which the recall will extend (e.g.,
wholesale, intermediate wholesale, retail, or consumer level);
     notify the public about any hazard or hazards presented by
the recalled drug when appropriate to protect the public health;
     conduct effectiveness checks to verify that all consignees
at the specified recall depth have received notification about the
recall and have taken appropriate action;
     appropriately dispose of recalled product; and
     notify FDA of the recall.
    In addition, in the event of a recall, Importers and Foreign
Sellers would be required, upon request by FDA, to provide the
transaction history, information, and statement, as those terms are
defined in sections 581(25), 581(26), and 581(27) of the FD&C Act,
respectively, of the FD&C Act. We seek comment on how a SIP Sponsor and
co-sponsor, if any, Foreign Seller, or Importer would effectuate a
recall in the United States, given that this will be a new
responsibility for these entities.

L. Severability

    Proposed Sec.  251.20 contains a severability provision clarifying
the Agency's intent regarding whether the provisions of part 251 are
severable from the rest of the regulation if one or more of the
provisions are stayed or determined to be invalid by a court. The
provisions of part 251 contain requirements that are either expressly
mandated by section 804 of the FD&C Act, or are otherwise necessary
pursuant to section 804(c)(3) because they have been determined by the
Secretary to be appropriate as a safeguard to protect the public health
or as a means to facilitate the importation of prescriptions drugs
under section 804. Each of the requirements that will be included in
the final rule will address significant potential safety concerns
associated with drugs imported under section 804 and would be necessary
to protect public health. If one or more of these provisions becomes
invalid, the rule, as a whole, would no longer adequately protect
public health and therefore should be invalid in its entirety.
    In addition, section 804 of the FD&C Act, and by extension, this
regulation, which is promulgated in part pursuant to that authority,
only becomes effective if the Secretary certifies to Congress that
implementation of section 804 will pose no additional risk to the
public's health and safety. This certification is contingent upon this
rule becoming effective with all the requirements that are included
when finalized. If one or more of the provisions in this rule becomes
invalid, in addition to the entire rule becoming invalid, the
certification would become null and void because the certification is
based on a finding that implementation of section 804 will pose no
additional risk to the public's health and safety, and that finding
would no longer be accurate because it would have been based on a final
rule that contains all the requirements that were included when
published.

VI. Proposed Effective and/or Compliance Dates

    FDA proposes that any final rule that issues based on this proposal
become effective 30 days after the final rule publishes in the Federal
Register.

VII. Preliminary Economic Analysis of Impacts

    We have examined the impacts of the proposed rule under Executive
Order 12866, Executive Order 13563, Executive Order 13771, the
Regulatory Flexibility Act (5 U.S.C. 601-612), and the Unfunded
Mandates Reform Act of 1995 (Pub. L. 104-4). Executive Orders 12866 and
13563 direct us 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). Executive Order 13771
requires that the costs associated with significant new regulations
``shall, to the extent permitted by law, be offset by the elimination
of existing costs associated with at least two prior regulations.'' We
believe that this proposed rule is a significant regulatory action as
defined by Executive Order 12866.
    The Regulatory Flexibility Act requires us to analyze regulatory
options that would minimize any significant impact of a rule on small
entities. We cannot anticipate if sponsors will contract with small
entities to implement their authorized SIP proposals and request
comment on the impact the proposed rule may have on small entities. We
also lack information to quantify the total impacts of the proposed
rule. Therefore, we propose to certify that the proposed rule will not
have a significant economic impact on a substantial number of small
entities.
    The Unfunded Mandates Reform Act of 1995 (section 202(a)) requires
us to prepare a written statement, which includes an assessment of
anticipated costs and benefits, before proposing ``any rule that
includes any Federal mandate that may result in the expenditure by
State, local, and tribal governments, in the aggregate, or by the
private sector, of $100,000,000 or more (adjusted annually for
inflation) in any one year.'' The current threshold after adjustment
for inflation is $154 million, using the most current (2018) Implicit
Price Deflator for the Gross Domestic Product. This proposed rule would
not result in an expenditure in any year that meets or exceeds this
amount.
1. Summary of Costs and Benefits
    The proposed rule, if finalized, would allow commercial importation
of certain prescription drugs from Canada through time-limited
programs, SIPs, sponsored by at least one non-federal governmental
entity with possible co-sponsorship by a

wholesaler or pharmacist. If such programs allow Importers to leverage
drug price differences between the United States and Canada, they will
result in cost savings for U.S. consumers.
    Expected costs of the proposed rule accrue to the Federal
Government, SIP Sponsors, Importers, and manufacturers of imported
drugs. The Federal Government would incur one-time fixed costs as well
as ongoing costs to implement the rule, if finalized, and to review SIP
Proposals and reports. SIP Sponsors would face costs to prepare
proposals, implement approved SIPs, and produce SIP reports and
records. SIPs may offer cost savings to consumers, as well as other
parties in the drug supply chain including participating wholesale drug
distributors, pharmacies, hospitals, and third-party payers. If their
drugs are imported into the United States from Canada, drug
manufacturers will have to provide importers with certain information.
As drug distributors realize savings in acquiring imported drugs and
pass some of these savings to consumers, it is possible that U.S. drug
manufacturers may experience a transfer in U.S. sales revenues to these
parties.
    We are unable to estimate the cost savings from this proposed rule,
as we lack information about the likely size and scope of SIP programs
and about the specific drug products that may become eligible for
importation, the degree to which imported drugs would be less expensive
than non-imported drugs available in the United States, and which SIP
eligible products are produced by U.S. drug manufacturers.
    Table 1 summarizes the benefits and costs of the proposed rule.

                                     Table 1--Summary of Benefits, Costs and Distributional Effects of Proposed Rule
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                Units
                                                                           ------------------------------------
               Category                   Primary       Low        High                               Period                      Notes
                                         estimate    estimate    estimate      Year      Discount     covered
                                                                              dollars    rate (%)     (years)
--------------------------------------------------------------------------------------------------------------------------------------------------------
Benefits:
    Annualized Monetized $millions/     ..........  ..........  ..........        2019           7          10  ........................................
     year.                                                                        2019           3          10
    Annualized Quantified.............  ..........  ..........  ..........        2019           7          10  ........................................
                                                                                2019           3          10
                                       -----------------------------------------------------------------------------------------------------------------
    Qualitative.......................  Potential cost savings to           ..........  ..........          10  ........................................
                                        consumers and third-party payers
                                        or entities
--------------------------------------------------------------------------------------------------------------------------------------------------------
Costs:
    Annualized Monetized $millions/     ..........  ..........  ..........        2019           7          10
     year.                                                                        2019           3          10
    Annualized Quantified.............  ..........  ..........  ..........        2019           7          10  ........................................
                                                                                2019           3          10
                                       -----------------------------------------------------------------------------------------------------------------
    Qualitative.......................  Potential costs to Federal          ..........  ..........          10  ........................................
                                        Government, SIP sponsors,
                                        importers, and manufacturers of
                                        imported drugs
--------------------------------------------------------------------------------------------------------------------------------------------------------
Transfers:
    Federal Annualized Monetized        ..........  ..........  ..........        2019           7          10  ........................................
     $millions/year.                                                              2019           3          10
                                       -----------------------------------------------------------------------------------------------------------------
    From/To...........................  ..........  From:
                                        To:
--------------------------------------------------------------------------------------------------------------------------------------------------------
    Other Annualized Monetized          ..........  ..........  ..........        2019           7          10  ........................................
     $millions/year.                                                              2019           3          10
                                       -----------------------------------------------------------------------------------------------------------------
    From/To...........................  From: U.S. drug manufacturers
                                        To: Importers and U.S. consumers           Not
                                                                            Quantified
                                                                                .
--------------------------------------------------------------------------------------------------------------------------------------------------------
Effects:
    State, Local or Tribal Government: Potential costs and cost savings to State, tribal, and territorial government entities from sponsoring SIPs......
    Small Business:.....................................................................................................................................
    Wages:..............................................................................................................................................
    Growth:.............................................................................................................................................
--------------------------------------------------------------------------------------------------------------------------------------------------------

    We lack information about the likely size and scope of SIP
programs, the specific drug products that may become eligible for
importation, the degree to which drugs imported under section 804 would
be less expensive than drugs not imported under section 804, and which
SIP eligible products are produced by U.S. drug manufacturers to
estimate the present and annualized values of the costs and cost
savings of the proposed rule over an infinite time horizon. The
designation under Executive Order 13771 of any final rule resulting
from this proposal will be informed by comments received and subsequent
analysis at the final rule stage. Thus, we exclude the Executive Order
13771 summary table from this analysis.
    We have developed a comprehensive Preliminary Economic Analysis of
Impacts that assesses the impacts of the proposed rule. The full
preliminary analysis of economic impacts is available in the docket for
this proposed rule (Ref. 31) and at http://www.fda.gov/AboutFDA/ReportsManualsForms/Reports/EconomicAnalyses/default.htm.

VIII. Analysis of Environmental Impact

    We have determined under 21 CFR 25.30(h) and 25.31(a) 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.

IX. Paperwork Reduction Act of 1995

    This proposed rule contains information collection provisions that
are subject to review by the Office of Management and Budget (OMB)
under the Paperwork Reduction Act of 1995

(44 U.S.C. 3501-3521). A description of these provisions is given below
under the Description heading with an estimate of the annual reporting,
recordkeeping, and third-party disclosure burden. Included in the
estimate is the time for reviewing instructions, searching existing
data sources, gathering and maintaining the data needed, and completing
and reviewing each collection of information.
    FDA invites comments on these topics: (1) Whether the proposed
collection of information is necessary for the proper performance of
FDA's functions, including whether the information will have practical
utility; (2) the accuracy of FDA's estimate of the burden of the
proposed collection of information, including the validity of the
methodology and assumptions used; (3) ways to enhance the quality,
utility, and clarity of the information to be collected; and (4) ways
to minimize the burden of the collection of information on respondents,
including through the use of automated collection techniques, when
appropriate, and other forms of information technology.
    Title: Section 804 Importation Program Proposals--21 CFR part 251.
    Description: The proposed regulations provide that a SIP Sponsor
that seeks to implement a SIP to import prescription drugs from Canada
must submit a proposal that includes, among other things, information
about the SIP Sponsor and the SIP Sponsor's importation plan. In
addition, SIP Sponsors must provide FDA with data and information on
the drugs the SIP imports and on the SIP's cost savings to the American
consumer. Importers would have a number of responsibilities related to
submitting a Pre-Import Request, screening eligible prescription drugs
and arranging for importation, testing, and relabeling. Manufacturers
would provide information needed to authenticate eligible prescription
drugs.
    Description of Respondents: Respondents would include SIP Sponsors
(State, tribal, or territorial governmental entities), Importers
(pharmacists or wholesalers), and manufacturers of eligible
prescription drugs.
    FDA anticipates submissions will be made through the Electronic
Submissions Gateway.
    FDA estimates that there will be 10 SIP Sponsors requiring 360
hours each to research, prepare, and administer requirements annually;
10 Pre-Import Requests requiring 24 hours each annually; and 20
manufacturers also requiring 24 hours each annually to participate in
the program. In addition, FDA estimates that a recordkeeping burden of
52 hours will be imposed annually on the 10 SIP Sponsors; and a
recordkeeping burden of 24 hours will be imposed annually on each of
the 10 Importers and the 20 manufacturers. The 20 manufacturers
anticipated to participate in the program will also incur an estimated
burden of 24 hours each for copying and providing records to SIP
Sponsors and Importers of foreign transactions.
    FDA estimates the burden of this collection of information as
follows:

                                                     Table 2--Estimated Annual Reporting Burden \1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                Number of
         Type of information collection activity/respondent             Number of      responses per     Total annual    Average burden    Total hours
                                                                       respondents       respondent       responses       per response
--------------------------------------------------------------------------------------------------------------------------------------------------------
SIP Sponsor 251.3; 251.8; 251.14--SIP Proposal Submission                         10                1               10              360            3,600
 Requirements; 251.18--Post-Importation Requirements; 251.19--
 Reports to FDA....................................................
Importer 251.5; 251.12; 251.13; 251.17--Pre-Import Request and                    10                1               10               24              240
 Importation Requirements..........................................
Manufacturer 251.16 Lab Testing Requirements.......................               20                1               20               24              480
                                                                    ------------------------------------------------------------------------------------
    Total..........................................................  ...............  ...............  ...............  ...............            4,320
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.

                                                   Table 3--Estimated Annual Recordkeeping Burden \1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                Number of                       Average burden
         Type of information collection activity/respondent             Number of       records per      Total annual         per          Total hours
                                                                      recordkeepers     recordkeeper       records       recordkeeping
--------------------------------------------------------------------------------------------------------------------------------------------------------
SIP sponsor 251.8--Modification or Extension of Authorized                        10                1               10               52              520
 Importation Programs..............................................
Importer 251.14(d)--Supply Chain Security Requirements; 251.17--                  10                1               10               24              240
 Importation Requirements; 251.18 Post-Importation Requirements....
Manufacturer 251.14(b)--Supply Chain Security Requirements.........               20                1               20               24              480
                                                                    ------------------------------------------------------------------------------------
    Total..........................................................  ...............  ...............  ...............  ...............            1,240
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.

                                               Table 4--Estimated Annual Third-Party Disclosure Burden \1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                               Number of
 Type of information collection activity/respondent        Number of        disclosures per      Total annual     Average burden per      Total hours
                                                          respondents         respondent          disclosures         disclosure
--------------------------------------------------------------------------------------------------------------------------------------------------------
Manufacturer 251.14(b)--Supply Chain Security                        20                   1                  20                  24                 480
 Requirements.......................................
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.

    To ensure that comments on information collection are received, OMB
recommends that written comments be faxed to the Office of Information
and Regulatory Affairs, OMB (see ADDRESSES). All comments should be
identified with the title of the information collection.
    In compliance with the Paperwork Reduction Act of 1995 (44 U.S.C.
3407(d)), we have submitted the information collection provisions of
this proposed rule to OMB for review. These information collection
requirements will not be effective until FDA publishes a final rule,
OMB approves the information collection requirements, and the rule goes
into effect. FDA will announce OMB approval of these requirements in
the Federal Register.

X. Federalism

    We have analyzed this proposed rule in accordance with the
principles set forth in Executive Order 13132. We have determined that
this proposed 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,
we conclude that the rule does not contain policies that have
federalism implications as defined in the Executive Order and,
consequently, a federalism summary impact statement is not required.

XI. Consultation and Coordination With Indian Tribal Governments

    We have analyzed this proposed rule in accordance with the
principles set forth in Executive Order 13175. We have tentatively
determined that the rule does not contain policies that would have a
substantial direct effect on one or more Indian Tribes, on the
relationship between the Federal Government and Indian Tribes, or on
the distribution of power and responsibilities between the Federal
Government and Indian Tribes. The Agency solicits comments from tribal
officials on any potential impact on Indian Tribes from this proposed
action.

XII. References

    The following references marked with an asterisk (*) are on display
at the Dockets Management Staff (see ADDRESSES) and are available for
viewing by interested persons between 9 a.m. and 4 p.m., Monday through
Friday; they also are available electronically at https://www.regulations.gov. References without asterisks are not on public
display at https://www.regulations.gov because they have copyright
restriction. Some may be available at the website address, if listed.
References without asterisks are available for viewing only at the
Dockets Management Staff. FDA has verified the website addresses, as of
the date this document publishes in the Federal Register, but websites
are subject to change over time.

*1. Donna Shalala, Secretary of Health and Human Services, 2000,
Letter to President Clinton, accessed September 27, 2019, https://www.congress.gov/congressional-record/2002/7/17/senate-section/article/s6906-2?q={%22search%22:[%22Shalala+\%22flaws+and+loopholes\%22%22]{time} &
s=1&r=3.
*2. Mark B. McClellan, FDA Commissioner, 2003, Letter to Senator
Thad Cochran, accessed September 27, 2019, https://www.congress.gov/congressional-record/2003/6/19/senate-section/article/s8202-2?r=73.
*3. Randall W. Lutter, Acting Associate Commissioner for Policy and
Planning, 2005, Letter to Theodore R. Kulongoski, Governor of
Oregon, Requested Waiver for Certification of Oregon's Pioneer
Prescription Drug Program, accessed September 27, 2019, https://wayback.archive-it.org/7993/20170112030500/http:/www.fda.gov/Drugs/DrugSafety/ucm179372.htm.
*4. Nomination of Robert Califf to Serve as FDA Commissioner, 2015,
Hearing Before the Committee on Health, Education, Labor and
Pensions, S Hrg 114-717 at 47, accessed September 27, 2019, https://www.govinfo.gov/content/pkg/CHRG-114shrg97694/pdf/CHRG-114shrg97694.pdf.
*5. HHS Task Force on Drug Importation, 2004, Report on Prescription
Drug Importation, accessed September 27, 2019, http://www.safemedicines.org/wp-content/uploads/2018/03/HHS-Report1220.pdf.
*6. United States Government Accountability Office (GAO), 2017,
``Fast Facts--Drug Industry: Profits, Research and Development
Spending, and Merger and Acquisition Deals,'' GAO-18-40, accessed
July 31, 2019, https://www.gao.gov/assets/690/688472.pdf.
*7. HHS, 2016, Office of The Assistant Secretary for Planning and
Evaluation (ASPE) Issue Brief: Observations on Trends in
Prescription Drug Spending, accessed July 31, 2019, https://aspe.hhs.gov/system/files/pdf/187586/Drugspending.pdf.
*8. Kaiser Family Foundation, 2019, Kaiser Family Foundation (KFF)
Health Tracking Poll--February 2019: Prescription Drugs, accessed
September 26, 2019, https://www.kff.org/health-costs/poll-finding/kff-health-tracking-poll-february-2019-prescription-drugs/view/footnotes/.
*9. Iuga, A.O. and M.J. McGuire, 2014, ``Adherence and Health Care
Costs,'' Risk Management and Healthcare Policy, 7:35-44, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3934668/pdf/rmhp-7-035.pdf.
*10. Jonel Aleccia, 2019, ``Lawmakers, Advocates Push To Extend
Medicare's Coverage of Kidney Transplant Drugs,'' National Public
Radio, accessed October 15, 2019, https://www.npr.org/sections/health-shots/2019/07/17/742349066/lawmakers-advocates-push-to-extend-medicares-coverage-of-kidney-transplant-drugs.
*11. Liz Szabo, 2017, ``As Drug Costs Soar, People Delay or Skip
Cancer Treatments,'' National Public Radio, accessed July 31, 2019,
https://www.npr.org/sections/health-shots/2017/03/15/520110742/as-drug-costs-soar-people-delay-or-skip-cancer-treatments.
*12. John R. Thomas, 2016, Congressional Research Service, ``Patents
and Prescription Drug Importation,'' accessed September 27, 2019,
https://fas.org/sgp/crs/misc/R44640.pdf.
*13. Ben Hirschler, 2015, ``How the U.S. Pays 3 Times More for
Drugs,'' Scientific American, accessed July 31, 2019, https://www.scientificamerican.com/article/how-the-u-s-pays-3-times-more-for-drugs/.
*14. Gagnon, M.-A. and S. Wolfe, 2015, ``Mirror, Mirror on the Wall:
Medicare Part D Pays Needlessly High Brand-Name Drug Prices Compared
with Other OECD Countries and with U.S. Government Programs,''
Carleton University, School of Public Policy and Administration,
accessed July 31, 2019, https://carleton.ca/sppa/wp-content/uploads/Mirror-Mirror-Medicare-Part-D-Released.pdf.
*15. Patented Medicine Prices Review Board (PMPRB), 2017, ``Annual
Report 2017: Regulating Prices of Patented Medicines: Continued
Vigilance Necessary, Bilateral Price Comparisons, Average Foreign-
to-Canadian Price Ratios, Bilateral Comparisons,'' accessed July 31,
2019, http://www.pmprb-cepmb.gc.ca/view.asp?ccid=1380⟨=en.
*16. PMPRB, 2018, ``About Us: Mandate and Jurisdiction,'' http://pmprb-cepmb.gc.ca/about-us/mandate-and-jurisdiction, accessed July
31, 2019.
*17. Rachel Bluth, 2016, ``Faced with Unaffordable Drug Prices, Tens
of Millions Buy Medicine Outside U.S.,'' Kaiser Health News,
accessed September 27, 2019, https://khn.org/news/faced-with-unaffordable-drug-prices-tens-of-millions-buy-medicine-outside-u-s/.
*18. Kaiser Family Foundation, 2016, ``Kaiser Health Tracking Poll--
November 2016,'' accessed September 27, 2019, http://files.kff.org/attachment/Kaiser-Health-Tracking-Poll-November-2016-Topline.
*19. FDA, 2018, ``FDA Launches Global Operation to Crack Down on
websites Selling Illegal, Potentially Dangerous Drugs; Including
Opioids,'' accessed September 3, 2019, https://www.fda.gov/news-events/press-announcements/fda-launches-global-operation-crack-down-websites-selling-illegal-potentially-dangerous-drugs.
*20. U.S. Department of Justice, 2017, ``September 25, 2017:
Millions of

Medicines Seized in Largest INTERPOL Operation Against Illicit
Online Pharmacies,'' accessed September 27, 2019, https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/press-releases/september-25-2017-millions-medicines-seized-largest-interpol-operation-against-illicit-online.
*21. U.S. Department of Justice, 2013, ``April 24, 2013: Paul Daniel
Bottomley Pleads Guilty in U.S. Federal Court,'' accessed August 19,
2019, https://wayback.archive-it.org/7993/20170723081601/https://www.fda.gov/ICECI/CriminalInvestigations/ucm349880.htm.
*22. U.S. Department of Justice, 2018, ``April 13, 2018: Canadian
Drug Firm Admits Selling. Counterfeit and Misbranded Prescription
Drugs Throughout the United States,'' accessed September 3, 2019,
https://wayback.archive-it.org/7993/20180725182130/https://www.fda.gov/ICECI/CriminalInvestigations/ucm605139.htm.
*23. FDA, 2012, FDA Warning Letter to Canadadrugs, accessed
September 27, 2019, https://wayback.archive-it.org/7993/20170723020703/ https://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2012/ucm321068.htm.
*24. FDA, 2005, ``FDA Operation Reveals Many Drugs Promoted as
`Canadian' Products Really Originate From Other Countries,''
accessed September 27, 2019, https://wayback.archive-it.org/7993/20170112030444/http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm108534.htm.
* 25. Ashley, D. D., 2017, ``Letter to the Editor: The Price of
Crossing the Border for Medications,'' New England Journal of
Medicine, October 26, 2017, 377:1699-1700, doi: 10.1056/NEJMc1711278
(referencing Fralick, M., J. Avorn, A.S. Kesselheim, 2017, ``The
Price of Crossing the Border for Medications,'' New England Journal
of Medicine, July 27, 2017, 377:311-313, doi: 10.1056/NEJMp1704489),
https://www.nejm.org/doi/full/10.1056/NEJMp1704489#article_letters.
* 26. Government of Canada, Archived, ``Consultation: Regulations
Amending the Food and Drug Regulations 1447-Good Manufacturing
Practices,'' accessed September 27, 2019, https://www.canada.ca/en/health-canada/services/drugs-health-products/public-involvement-consultations/compliance-enforcement/regulations-amending-food-drug-regulations-1447.html.
* 27. Government of Canada, Health Canada, ``GMP Drug Establishment
Good Manufacturing Practices Pre-Application Package: Importers,
Distributors and Wholesalers,'' accessed September 27, 2019, https://www.canada.ca/content/dam/hc-sc/migration/hc-sc/dhp-mps/alt_formats/pdf/compli-conform/gmp-bpf/docs/gmp-package-bpf-eng.pdf.
* 28. Government of Canada, Health Canada, 2019, ``Health Canada and
United States Food and Drug Administration Joint Public Consultation
on ICH Guidelines--Update,'' accessed December 10, 2019, https://www.canada.ca/en/health-canada/services/drugs-health-products/public-involvement-consultations/drug-products/notice-international-council-harmonisation-registration-pharmaceuticals-human-use-consultation-update.html.
29. Joanne S. Eglovitch, 2019, ``GS1 Standard Would Speed the Sale
of Returned Drugs After November Deadline,'' Pink Sheet, accessed
September 27, 2019, https://pink.pharmaintelligence.informa.com/PS140811/GS1-Standard-Would-Speed-The-Sale-Of-Returned-Drugs-After-November-Deadline.
30. ASTM E122-17, 2017, Standard Practice for Calculating Sample
Size to Estimate, With Specified Precision, the Average for a
Characteristic of a Lot or Process, www.astm.org.
* 31. FDA, Preliminary Regulatory Impact Analysis: Importation of
Prescription Drugs, http://www.fda.gov/AboutFDA/ReportsManualsForms/Reports/EconomicAnalyses/default.htm.

List of Subjects

21 CFR Part 1

    Cosmetics, Drugs, Exports, Food labeling, Imports, Labeling,
Reporting and recordkeeping requirements.

21 CFR Part 251

    Exports, Labeling, Packaging and containers, Prescription drugs,
Reporting and recordkeeping requirements.

    Therefore, under the Federal Food, Drug, and Cosmetic Act and under
authority delegated to the Commissioner of Food and Drugs, the Food and
Drug Administration proposes to amend 21 CFR chapter I as follows:

PART 1--GENERAL ENFORCEMENT REGULATIONS

0
1. The authority citation for part 1 continues to read as follow:

    Authority:  15 U.S.C. 1333, 1453, 1454, 1455, 4402; 19 U.S.C.
1490, 1491; 21 U.S.C. 321, 331, 332, 333, 334, 335a, 342, 343, 350c,
350d, 350e, 350j, 350k, 352, 355, 360b, 360ccc, 360ccc-1, 360ccc-2,
362, 371, 373, 374, 379j-31, 381, 382, 384a, 384b, 384d, 387, 387a,
387c, 393; 42 U.S.C. 216, 241, 243, 262, 264, 271; Pub. L. 107-188,
116 Stat. 594, 668-69; Pub. L. 111-353, 124 Stat. 3885, 3889.

0
2. Revise Sec.  1.74 to read as follows:

Sec.  1.74   Human drugs.

    In addition to the data required to be submitted in Sec.  1.72, an
ACE filer must submit the following information at the time of filing
entry in ACE for drugs, including biological products and eligible
prescription drugs as defined in Sec.  251.2 of this chapter that are
imported or offered for import under section 804 of the Federal Food,
Drug, and Cosmetic Act, intended for human use that are regulated by
the FDA Center for Drug Evaluation and Research.
    (a) For a drug intended for human use that is not an eligible
prescription drug covered under paragraph (b) of this section:
    (1) Registration and listing. The Drug Registration Number and the
Drug Listing Number if the foreign establishment where the human drug
was manufactured, prepared, propagated, compounded, or processed before
being imported or offered for import into the United States is required
to register and list the drug under part 207 of this chapter. For the
purposes of this section, the Drug Registration Number that must be
submitted at the time of entry in ACE is the unique facility identifier
of the foreign establishment where the human drug was manufactured,
prepared, propagated, compounded, or processed before being imported or
offered for import into the United States. The unique facility
identifier is the identifier submitted by a registrant in accordance
with the system specified under section 510(b) of the Federal Food,
Drug, and Cosmetic Act. For the purposes of this section, the Drug
Listing Number is the National Drug Code number of the human drug
article being imported or offered for import.
    (2) Drug application number. For a drug intended for human use that
is the subject of an approved application under section 505(b) or
505(j) of the Federal Food, Drug, and Cosmetic Act, the number of the
new drug application or abbreviated new drug application. For a
biological product regulated by the FDA Center for Drug Evaluation and
Research that is required to have an approved new drug application or
an approved biologics license application, the number of the applicable
application.
    (3) Investigational new drug application number. For a drug
intended for human use that is the subject of an investigational new
drug application under section 505(i) of the Federal Food, Drug, and
Cosmetic Act, the number of the investigational new drug application.
    (b) For an eligible prescription drug as defined in Sec.  251.2 of
this chapter that is imported or offered for import under section 804
of the Federal Food, Drug, and Cosmetic Act:
    (1) Registration and listing. The Drug Registration Number and the
Drug Listing Number. For the purposes of this section, the Drug
Registration Number that must be submitted in ACE is the unique
facility identifier of the Foreign

Seller. The unique facility identifier is the identifier submitted by a
Foreign Seller registrant under Sec.  251.5 of this chapter. For the
purposes of this section, the Drug Listing Number is the National Drug
Code that the Importer will use when relabeling the eligible
prescription drug as required in Sec.  251.13 of this chapter.
    (2) Drug application number. The number of the new drug application
or abbreviated new drug application for the corresponding FDA-approved
drug.
    (3) Lot or control number. The lot or control number assigned by
the manufacturer of the eligible prescription drug.
    (4) FDA Quantity. FDA Quantity, which is the quantity of each
eligible prescription drug in an import line delineated by packaging
level, including the type of package from the largest packaging unit to
the smallest packaging unit; the quantity of each packaging unit; and
the volume and/or weight of each of the smallest of the packaging
units.
    (5) Pre-Import Request number. The Pre-Import Request number
assigned by FDA.
0
3. Add part 251 to read as follows:

PART 251--SECTION 804 IMPORTATION PROGRAM PROPOSAL

Subpart A--General Provisions
Sec.
251.1 Scope of the part.
251.2 Definitions.
Subpart B--Section 804 Importation Program Proposals and Pre-Import
Requests
251.3 SIPproposal submission requirements.
251.4 Review and authorization of importation program proposals.
251.5 Pre-Import Request.
251.6 Limitations on authorized importation programs.
251.7 Suspension and revocation of authorized importation programs.
251.8 Modification or extension of authorized importation programs.
Subpart C--Certain Requirements for Section 804 Importation Programs
251.9 Registration of Foreign Sellers.
251.10 Reviewing and updating registration information for Foreign
Sellers.
251.11 Official contact and U.S. agent for Foreign Sellers.
251.12 Importer responsibilities.
251.13 Labeling of eligible prescription drugs.
251.14 Supply chain security requirements for eligible prescription
drugs.
251.15 Qualifying laboratory requirements.
251.16 Laboratory testing requirements.
251.17 Importation requirements.
251.18 Post-importation requirements.
251.19 Reports to FDA.
251.20 Severability.
251.21 Consequences for violations.

    Authority:  21 U.S.C. 351, 352, 353, 355, 371, 374, 381, 384.

Subpart A--General Provisions

Sec.  251.1   Scope of the part.

    (a) This part sets forth the procedures that Section 804
Importation Program sponsors (SIP Sponsors) must follow when submitting
plans to implement time-limited programs to begin importation of drugs
from Canada under section 804 of the Federal Food, Drug, and Cosmetic
Act. This part also sets forth certain requirements that are necessary
for such programs to be authorized by FDA. Additionally, this part sets
forth requirements for eligible prescription drugs and requirements for
entities that engage in importation of eligible prescription drugs.
    (b) This part includes provisions that exempt eligible prescription
drugs that meet certain requirements from section 502(f)(1) of the
Federal Food, Drug, and Cosmetic Act. It also includes provisions that
exempt certain transactions involving eligible prescription drugs from
certain requirements in section 582 of the Federal Food, Drug, and
Cosmetic Act.

Sec.  251.2   Definitions.

    The definitions of terms in section 804 of the Federal Food, Drug,
and Cosmetic Act apply to the terms used in this part, if not otherwise
defined in this section. The following definitions apply to this part:
    Active ingredient means any component that is intended to furnish
pharmacological activity or other direct effect in the diagnosis, cure,
mitigation, treatment, or prevention of disease, or to affect the
structure or any function of the body of man or other animals. The term
includes those components that may undergo chemical change in the
manufacture of the drug product and be present in the drug product in a
modified form intended to furnish the specified activity or effect.
    Adverse event means any untoward medical occurrence associated with
the use of a drug product in humans, whether or not it is considered
related to the drug product. An adverse event can occur in the course
of the use of a drug product; from overdose of a drug product, whether
accidental or intentional; from abuse of a drug product (e.g.,
physiological withdrawal); and includes any failure of expected
pharmacological action.
    Combination product has the meaning set forth in Sec.  3.2(e) of
this chapter.
    Constituent part has the meaning set forth in Sec.  4.2 of this
chapter.
    Disability means a substantial disruption of a person's ability to
conduct normal life functions.
    Eligible prescription drug means a drug subject to section 503(b)
of the Federal Food, Drug, and Cosmetic Act that has been approved and
has received a Notice of Compliance and a Drug Identification Number
(DIN) from the Health Products and Food Branch of Health Canada (HPFB)
and, but for the fact that it deviates from the required U.S. labeling,
also meets the conditions in an FDA-approved new drug application (NDA)
or abbreviated new drug application (ANDA) for a drug that is currently
marketed in the United States, including those relating to the drug
substance, drug product, production process, quality controls,
equipment, and facilities.
    Exclusion. The term eligible prescription drug does not include:
    (1) A controlled substance (as defined in section 102 of the
Controlled Substances Act (21 U.S.C. 802));
    (2) A biological product (as defined in section 351 of the Public
Health Service Act (42 U.S.C. 262));
    (3) An infused drug (including a peritoneal dialysis solution);
    (4) An intravenously injected drug;
    (5) A drug that is inhaled during surgery;
    (6) An intrathecally or intraocularly injected drug;
    (7) A drug that is subject to a risk evaluation and mitigation
strategy under section 505-1 of the Federal Food, Drug, and Cosmetic
Act;
    (8) A drug that is not a ``product'' for purposes of section 582 as
defined in section 581(13) of the Federal Food, Drug, and Cosmetic Act;
    Entry means the information or data filed electronically to the
Automated Commercial Environment (ACE) or any other U.S. Customs and
Border Protection (CBP)-authorized electronic data interchange system
to secure the release of imported merchandise from CBP, or the act of
filing that information or data.
    Foreign Seller means an establishment within Canada engaged in the
distribution of an eligible prescription drug that is imported or
offered for importation into the United States. A Foreign Seller must
have an active drug establishment license as a drug wholesaler by
Health Canada. A Foreign Seller must be registered with provincial
pharmacy regulatory authorities to distribute HPFB-approved drugs. A
Foreign Seller must not be licensed by a provincial pharmacy regulatory
authority with an international pharmacy license that allows it to
distribute drugs that are

approved by countries other than Canada and that are not HPFB-approved
for distribution in Canada. A Foreign Seller must also be registered
with FDA under section 804 of the Federal Food Drug and Cosmetic Act in
accordance with the requirements described in this part.
    Illegitimate foreign product means a drug purchased by a Foreign
Seller from a manufacturer, and intended for sale to the Importer in
the United States, where the Foreign Seller has credible evidence that
the product:
    (1) Is counterfeit, diverted, or stolen;
    (2) Is intentionally adulterated such that the product would result
in serious adverse health consequences or death to humans;
    (3) Is the subject of a fraudulent transaction; or
    (4) Appears otherwise unfit for distribution such that the product
would be reasonably likely to result in serious adverse health
consequences or death to humans.
    Importer means a pharmacist or wholesaler. An Importer must be a
State-licensed pharmacist, or a State or FDA-licensed wholesaler, who
is the U.S. owner of an eligible prescription drug at the time of entry
into the United States. An Importer's pharmacist or wholesaler license
must be in effect (i.e., not expired) and the Importer must be in good
standing with the licensor.
    Individual case safety report (ICSR) means a description of an
adverse event related to an individual patient or subject and/or a
description of a medication error.
    ICSR attachments means any document related to the adverse event or
medication error described in an ICSR, such as medical records,
hospital discharge summaries, or other documentation.
    Life-threatening adverse event means any adverse event that places
the patient, in the view of the initial reporter, at immediate risk of
death from the adverse event as it occurred, i.e., it does not include
an adverse event that, had it occurred in a more severe form, might
have caused death.
    Manufacturer means an applicant, as defined in Sec.  314.3 of this
chapter, or a person who owns or operates an establishment that
manufactures an eligible prescription drug. Manufacturer also means a
holder of a drug master file containing information necessary to
authenticate an eligible prescription drug.
    Medication error means any preventable event that may cause or lead
to inappropriate medication use or patient harm while the medication is
in the control of a healthcare professional, patient, or consumer. The
medication error may or may not result in an adverse event.
    Minimum data set for an adverse event means the minimum four
elements required for reporting an ICSR of an adverse event: An
identifiable patient, an identifiable reporter, a suspect drug product,
and an adverse event.
    Minimum data set for a medication error means the minimum three
elements required for reporting an ICSR of a medication error: An
identifiable reporter, a suspect drug product, and a medication error.
    Pre-Import Request means a request made to FDA by an Importer that
must be granted by FDA before the Importer can start importation under
a Section 804 Importation Program.
    Qualifying laboratory means a laboratory in the United States that
has been approved by FDA for the purposes of section 804 of the Federal
Food, Drug, and Cosmetic Act.
    Relabel has the meaning set forth in Sec.  207.1 of this chapter.
    Relabeler has the meaning set forth in Sec.  207.1 of this chapter.
    Repack or repackage has the meaning set forth in Sec.  207.1 of
this chapter.
    Section 804 Importation Program (``SIP'') means a program under
section 804 of the Federal Food, Drug, and Cosmetic Act that has been
authorized by FDA for the importation of eligible prescription drugs
from Canada.
    Section 804 Importation Program Sponsor (``SIP Sponsor''): (Option
1): Means a State, tribal, or territorial governmental entity that
regulates wholesale drug distribution and/or the practice of pharmacy,
and a co-sponsor or co-sponsors, if any, that submits a proposal to FDA
that describes a program to facilitate the importation of prescription
drugs from Canada under section 804 of the Federal Food, Drug, and
Cosmetic Act. A co-sponsor must be a State, tribal, or territorial
governmental entity, a pharmacist, or a wholesaler.
    Section 804 Importation Program Sponsor (``SIP Sponsor''): (Option
2): Means a State, tribal, or territorial governmental entity that
regulates wholesale drug distribution and/or the practice of pharmacy,
a wholesaler, or a pharmacist, and a co-sponsor or co-sponsors, if any,
that submits a proposal to FDA that describes a program to facilitate
the importation of prescription drugs from Canada under section 804 of
the Federal Food, Drug, and Cosmetic Act. A co-sponsor must be a State,
tribal, or territorial governmental entity, a wholesaler, or a
pharmacist.
    Section 804 Serial Identifier (``SSI'') means a unique alphanumeric
serial number of up to 20 characters that is assigned and affixed by
the Foreign Seller to each package and homogenous case of the product
that it intends to sell to the Importer. For purposes of the SSI,
``package'' means the smallest individual saleable unit of product for
distribution that is intended by the Foreign Seller for sale to the
Importer located in the United States, and ``individual saleable unit''
means the smallest container of product sold by the Foreign Seller to
the Importer.
    Serious adverse event. (1) An adverse event is considered
``serious'' if it results in any of the following outcomes:
    (i) Death;
    (ii) A life-threatening adverse event where the patient was at
immediate risk of death at the time of the event; it does not include
an adverse event that might have caused death had it occurred in a more
severe form;
    (iii) Inpatient hospitalization or prolongation of existing
hospitalization;
    (iv) A persistent or significant incapacity or substantial
disruption of the ability to conduct normal life functions; and/or
    (v) A congenital anomaly/birth defect.
    (2) Other events that may be considered serious adverse events:
Important medical events that may not result in one of the listed
outcomes in this definition may be considered serious adverse events
when, based upon appropriate medical judgment, they may jeopardize the
patient or study subject and may require medical or surgical
intervention to prevent one of the outcomes listed in this definition.
Examples include: Allergic bronchospasm requiring intensive treatment
in an emergency department or at home, blood dyscrasias, or convulsions
that do not result in inpatient hospitalization, or the development of
product dependency or product abuse.
    Statutory Testing means the testing of an eligible prescription
drug for authenticity, degradation, and to ensure that the prescription
drug is in compliance with established specifications and standards, as
required by section 804(d)(1)(J) and (L) of the Federal Food, Drug, and
Cosmetic Act.
    Suspect foreign product means a drug purchased by the Foreign
Seller from the manufacturer, and intended for sale to the Importer in
the United States, that the Foreign Seller has reason to believe is:
    (1) Potentially counterfeit, diverted, or stolen;

    (2) Potentially intentionally adulterated such that the product
would result in serious adverse health consequences or death to humans;
    (3) Is potentially the subject of a fraudulent transaction; or
    (4) Appears otherwise unfit for distribution such that the product
would result in serious adverse health consequences or death to humans.
    Transaction means the transfer of product between persons in which
a change of ownership occurs.
    Unexpected adverse event means an adverse event that is not
included in the current U.S. labeling for the drug product. Events that
may be symptomatically and pathophysiologically related to an adverse
event included in the labeling but differ from the labeled event
because of greater severity or specificity, would be considered
unexpected. ``Unexpected,'' as used in this definition, also refers to
adverse events that are mentioned in the product labeling as occurring
with a class of products or anticipated from the pharmacological
properties of the product but are not specifically mentioned as
occurring with the particular product.
    (1) Example of greater severity. Under this definition, hepatic
necrosis would be unexpected if the labeling referred only to elevated
hepatic enzymes or hepatitis.
    (2) Example of greater specificity. Cerebral thromboembolism and
cerebral hemorrhage would be unexpected if the labeling included only
cerebrovascular accidents.
    Unique facility identifier means the identifier required to be
submitted by the registrant for drug establishment registration under
section 510(b) of the Federal Food, Drug, and Cosmetic Act in
accordance with Sec.  207.25 of this chapter.
    Wholesaler means a person licensed as a wholesaler or distributor
of prescription drugs in the United States under section 503(e)(1) of
the Federal Food, Drug, and Cosmetic Act. The term ``wholesaler'' does
not include a person authorized to import drugs under section
801(d)(1).

Subpart B--Section 804 Importation Program Proposals and Pre-Import
Requests

Sec.  251.3   SIP proposal submission requirements.

    (a) A SIP Sponsor must only designate one Foreign Seller and one
Importer per initial proposal. Additional Foreign Sellers and Importers
may be added to an authorized SIP through a supplement under Sec.
251.8.
    (b) A SIP Sponsor that intends to implement a SIP under this part
must submit a proposal to FDA in electronic form to FDA's Electronic
Submissions Gateway (ESG) or to an alternative transmission point
identified by FDA. The proposal must include:
    (1) A cover sheet containing the following:
    (i) Name or names of SIP Sponsor and co-sponsors, if any; and
    (ii) Name and contact information for a person authorized to serve
as the point of contact with FDA during its review of the proposal;
    (2) A table of contents;
    (3) An introductory statement that includes an overview of the SIP
Sponsor's SIP Proposal; and
    (4) The SIP Sponsor's importation plan.
    (c) The overview of the SIP Proposal must include:
    (1) The name or names and address or addresses of the SIP Sponsor
and co-sponsors, if any;
    (2) The name and DIN of each eligible prescription drug that the
SIP Sponsor seeks to include in the SIP;
    (3) The name and address of the applicant that owns the approved
NDA or ANDA for each eligible prescription drug's FDA-approved
counterpart, and the approved NDA or ANDA number;
    (4) The name and address of the manufacturer of the finished dosage
form of the drug, if available;
    (5) The name and address of the manufacturer of the active
ingredient or ingredients of the drugs, if available;
    (6) The name and address of the Foreign Seller;
    (7) The name and address of the Importer;