Reporting - Radiopharmaceutical Compounding and Repackaging by Outsourcing Facilities GFI, Repackaging GFI

Human Drug Compounding, Repackaging, and Related Activities Regarding Sections 503A and 503B of the Federal Food, Drug, and Cosmetic Act

CompoundingandRepackagingofRadiopharmaceuticalsbyOF (2024)

Reporting - Radiopharmaceutical Compounding and Repackaging by Outsourcing Facilities GFI, Repackaging GFI

OMB: 0910-0858

Document [pdf]

Download: pdf | pdf

Compounding and Repackaging
of Radiopharmaceuticals by
Outsourcing Facilities
Guidance for Industry

U.S. Department of Health and Human Services
Food and Drug Administration
Center for Drug Evaluation and Research (CDER)

September 2018
Compounding and Related Documents

Compounding and Repackaging
of Radiopharmaceuticals by
Outsourcing Facilities
Guidance for Industry
Additional copies are available from:
Office of Communications, Division of Drug Information
Center for Drug Evaluation and Research
Food and Drug Administration
10001 New Hampshire Ave., Hillandale Bldg., 4th Floor
Silver Spring, MD 20993-0002
Phone: 855-543-3784 or 301-796-3400; Fax: 301-431-6353
Email: druginfo@fda.hhs.gov
https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm

U.S. Department of Health and Human Services
Food and Drug Administration
Center for Drug Evaluation and Research (CDER)
September 2018
Compounding and Related Documents

Contains Nonbinding Recommendations
TABLE OF CONTENTS

INTRODUCTION AND SCOPE .................................................................................... 1

II.

BACKGROUND ............................................................................................................... 2

Radiopharmaceuticals, Generally ................................................................................................ 2

Compounding, Generally .............................................................................................................. 3

III.

POLICY ............................................................................................................................. 5

Compounding ................................................................................................................................. 5

Repackaging of Radiopharmaceuticals........................................................................................ 7

Establishment Registration and Drug Listing ........................................................................... 10

Contains Nonbinding Recommendations

Compounding and Repackaging of Radiopharmaceuticals by
Outsourcing Facilities
Guidance for Industry1
This guidance represents the current thinking of the Food and Drug Administration (FDA or Agency) on
this topic. It does not establish any rights for any person and is not binding on FDA or the public. You can
use an alternative approach if it satisfies the requirements of the applicable statutes and regulations. To
discuss an alternative approach, contact the FDA staff responsible for this guidance as listed on the title
page.

INTRODUCTION AND SCOPE

This guidance sets forth the FDA’s policy regarding compounding and repackaging of
radiopharmaceuticals for human use by entities that are registered with FDA as outsourcing
facilities under section 503B of the Federal Food, Drug, and Cosmetic Act (FD&C Act or the
Act). This guidance describes how FDA generally intends to apply section 503B of the FD&C
Act to radiopharmaceuticals compounded by outsourcing facilities. It also describes the
conditions under which FDA generally does not intend to take action for violations of sections
505 and 502(f)(1) of the FD&C Act when an outsourcing facility repackages
radiopharmaceuticals.
This guidance does not address the following:
•
•
•
•
•

Mixing, reconstituting, combining, diluting, or repackaging of a radiopharmaceutical, or
other such acts, performed in accordance with directions contained in the FDA-approved
labeling
Positron emission tomography (PET) drugs
Drug products that are not radiopharmaceuticals2
Radioactive biological products that are subject to licensure under section 351 of the
Public Health Service (PHS) Act
Radiopharmaceuticals for use in animals

This guidance has been prepared by multiple offices in the Center for Drug Evaluation and Research (CDER) and
in consultation with the Office of Regulatory Affairs at the Food and Drug Administration.
2

FDA has issued several guidance documents concerning its policies for compounding drug products that are not
radiopharmaceuticals under sections 503B of the FD&C Act. See, for example, Guidance For Entities Considering
Whether to Register As Outsourcing Facilities Under Section 503B of the Federal Food, Drug, and Cosmetic Act.
All FDA guidances are available on the FDA guidance web page. FDA updates guidances regularly. To make sure
you have the most recent version of a guidance, always consult the guidance web page at
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm.

Contains Nonbinding Recommendations
•

Compounding or repackaging of radiopharmaceuticals by entities that are not registered
with FDA as outsourcing facilities. See FDA guidance o Compounding and Repackaging
of Radiopharmaceuticals by State-Licensed Nuclear Pharmacies, Federal Facilities, and
Certain Other Entities

This guidance does not alter FDA’s current guidances addressing investigational new drugs.
In general, FDA’s guidance documents do not establish legally enforceable responsibilities.
Instead, guidances describe the Agency’s current thinking on a topic and should be viewed as
recommendations, unless specific regulatory or statutory requirements are cited. The use of the
word should in Agency guidances means that something is suggested or recommended, but not
required.
II.

BACKGROUND
A.

Radiopharmaceuticals, Generally

Radiopharmaceuticals are radioactive3 sterile and non-sterile drugs that are used to diagnose,
monitor, and treat diseases. Radiopharmaceuticals are used in diagnostic procedures and for
therapeutic purposes. For example, during diagnostic procedures involving
radiopharmaceuticals, the body is exposed to small amounts of radiation to observe organ
function. Radiopharmaceuticals used for therapeutic purposes are generally administered in
larger amounts to ensure that therapeutic doses of radiation are delivered to specific disease sites.
Some radiopharmaceuticals are produced by a conventional manufacturer and shipped in hot
(radioactive) multi-dose containers directly to an imaging center or hospital for patient
administration. The imaging center’s “hot lab” or hospital’s nuclear pharmacy transfers the
radiopharmaceuticals from the multi-dose containers into unit-dose, patient-ready containers, and
sometimes manipulates the radiopharmaceuticals in other ways, such as by diluting or pooling
them. Other radiopharmaceuticals are produced at the nuclear pharmacy by combining
radioactive materials eluted from a radionuclide generator with non-radioactive “cold kits.” The
nuclear pharmacy prepares the radiopharmaceutical product using the components of the kit and
by adding radioactive material eluted from a radionuclide generator for eventual administration
to a patient.

As used in this guidance, radiopharmaceutical and radioactive drug have the same meaning and refer to a drug
that meets the definition in 21 CFR 310.3(n): “any substance defined as a drug in section 201(g)(1) of the Federal
Food, Drug, and Cosmetic Act which exhibits spontaneous disintegration of unstable nuclei with the emission of
nuclear particles or photons and includes any nonradioactive reagent kit or nuclide generator which is intended to be
used in the preparation of any such substance but does not include drugs such as carbon-containing compounds or
potassium-containing salts which contain trace quantities of naturally occurring radionuclides. The term ‘radioactive
drug’ includes a ‘radioactive biological product’ as defined in 600.3(ee) of this chapter.” Radioactive biological
product is defined in 21 CFR 600.3(ee) as “a biological product which is labeled with a radionuclide or intended
solely to be labeled with a radionuclide.” As stated previously, this guidance does not apply to radioactive biological
products.

Contains Nonbinding Recommendations
Because radioactive drugs generally have short half-lives (e.g., hours, a few days), they must
reach the patient for administration soon after they are produced. Therefore, hospitals and
imaging centers often place orders with a nuclear pharmacy for delivery of radiopharmaceutical
unit-doses for procedures scheduled for the following day or in anticipation of unscheduled
nuclear medicine procedures that might take place during the evening or weekend when the
nuclear pharmacy is closed.
There are legal restrictions as to who is permitted to obtain, transport, manipulate, and use
radioactive drugs. At the federal level, the Nuclear Regulatory Commission (NRC) has
established rules to protect the general public, patients, and radiation workers from
unnecessary exposure to radiation. 4 The NRC and those states that have entered into certain
agreements with the NRC (Agreement States) 5 issue radioactive materials (RAM) licenses
to authorize possession of specific types of radioactive materials and who may use the
material under the license.6 Transport of radioactive materials is regulated by the NRC or
the Agreement State and the U.S. Department of Transportation.7
Separate from the RAM licenses issued by the NRC or an Agreement State, state boards of
pharmacy may issue pharmacy permits to holders that receive, prepare, repackage, or dispense
radioactive drugs. Certain states specifically recognize a separate category of pharmacists who
practice as nuclear pharmacists and issue credentials specific for this practice.
B.

Compounding, Generally
1.

Compounding of Radiopharmaceuticals By an Outsourcing Facility

In 2013, the Drug Quality and Security Act added a new section 503B to the FD&C Act, which
describes a new category of compounders called outsourcing facilities.8 Section 503B of the
FD&C Act describes the conditions that must be satisfied for human drug products compounded
by or under the direct supervision of a licensed pharmacist in an outsourcing facility to qualify
for exemptions from the following three sections of the FD&C Act:
•
•
•

Section 502(f)(1) (concerning labeling with adequate directions for use)
Section 505 (concerning drug approval requirements)
Section 582 (concerning drug supply chain security requirements)9

See 10 CFR parts 19, 20, and 35.

The NRC defines an Agreement State in part as one that has entered into an agreement with the NRC under section
274 of the Atomic Energy Act of 1954 (42 U.S.C. 2021).
6

See 10 CFR 35.2

See 10 CFR 71.5, 49 CFR parts 107, 171 through 180, and 390 through 397.

See Pub..L. 113-54, §102(a), 127 Stat. 587, 587-588 (2013).

In addition to the exemption in section 503B, the definition of product in section 581(13) of the FD&C Act
excludes radioactive drugs from the drug supply chain security requirements of the FD&C Act, including section
582.

Contains Nonbinding Recommendations
A complete list of the conditions that must be met for a drug product to qualify for the
exemptions in section 503B appears in the Appendix to this guidance document.
In contrast to drug products compounded under section 503A of the FD&C Act, drug products
compounded by outsourcing facilities under section 503B cannot qualify for exemption from
current good manufacturing practice (CGMP) requirements in section 501(a)(2)(B) of the FD&C
Act. Outsourcing facilities are also subject to FDA inspections according to a risk-based
schedule, specific adverse event reporting requirements, and other conditions that help to
mitigate the risks associated with the drug products they compound.
Section 503B of the FD&C Act defines compounding as including “the combining, admixing,
mixing, diluting, pooling, reconstituting, or otherwise altering of a drug or bulk drug substance to
create a drug.”10 In contrast to section 503A of the FD&C Act, section 503B does not expressly
exclude radiopharmaceuticals, so the conditions of section 503B of the FD&C Act apply to
radiopharmaceuticals compounded by an entity that is registered with FDA as an outsourcing
facility.
Because section 503B applies to the compounding of radiopharmaceuticals, an entity is eligible
to become an outsourcing facility if some or all of its operations consist of compounding
radiopharmaceuticals for human use, provided that the entity otherwise meets the definition of an
outsourcing facility in section 503B(d)(4) of the FD&C Act (e.g., the entity must engage in the
compounding of at least some sterile products (radiopharmaceuticals or nonradiopharmaceuticals)).11
2.

Repackaging

FDA regards repackaging of radiopharmaceuticals as the act of removing an FDA-approved
radiopharmaceutical from the container in which it was distributed by the original manufacturer
and placing it into a different container without further manipulation of the drug. Repackaging
also includes the act of placing the contents of multiple containers (e.g., vials) of the same
finished drug product into one container, as long as the container does not include other
ingredients. If a radiopharmaceutical is manipulated in any other way, including if it is
reconstituted, diluted, mixed, or combined with another ingredient, that act is not considered
repackaging under this guidance.
Drugs that are repackaged are not subject to section 503B of the FD&C Act. Therefore,
repackaged radiopharmaceuticals are not eligible for the exemptions under section 503B.
Additionally, an entity that only repackages drugs, including radiopharmaceuticals, does not
meet the definition of an outsourcing facility in section 503B(d)(4) of the FD&C Act. However,
if an entity that meets the definition of an outsourcing facility in section 503B(d)(4) also
10

See section 503B(d)(1).

See Section 503Bf(d)(4)A)(i). Section 503B(d)(4) defines an outsourcing facility as a facility at one geographic
location or address that is engaged in the compounding of sterile drugs; has elected to register as an outsourcing
facility; and complies with all of the requirements of Section 503B. An outsourcing facility is not required to be a
licensed pharmacy and may or may not obtain prescriptions for identified individual patients.

Contains Nonbinding Recommendations
repackages radiopharmaceuticals, FDA generally does not intend to take action for violations of
sections 505 and 502(f)(1) of the FD&C Act when the outsourcing facility repackages
radiopharmaceuticals in accordance with the conditions described below and any other
applicable requirements. Further, the outsourcing facility’s compounded drugs would be eligible
for the exemptions in section 503B if they meet the conditions in that section. We describe our
policies with respect to repackaged and compounded radiopharmaceuticals in section III of this
guidance document.
III.

POLICY
A.

Compounding of Radiopharmaceuticals By an Outsourcing Facility
1.

Compounding

Outsourcing facilities that compound radiopharmaceuticals must do so in accordance with the
conditions of section 503B of the FD&C Act (see the Appendix to this guidance document). If an
outsourcing facility fails to compound a drug in accordance with a condition of section 503B,
none of the outsourcing facility’s compounded drugs, including radiopharmaceuticals and nonradiopharmaceuticals, would qualify for the exemptions in section 503B.12
In general, FDA’s policies regarding section 503B apply to the compounding of
radiopharmaceutical drug products by outsourcing facilities. However, we have developed the
following specific policies, applicable only to the compounding of radiopharmaceuticals by
outsourcing facilities:
•
•

Bulk drug substances used in compounding radiopharmaceuticals under section 503B
(see section III.A.2)
Compounding radiopharmaceuticals that are essentially copies of approved drugs
under section 503B when such compounding is limited to minor deviations, as
defined below (see section III.A.3).
2.

Bulk Drug Substances Used to Compound Radiopharmaceuticals Under
Section 503B of the FD&C Act13

One of the conditions that must be met for a drug product compounded by an outsourcing facility
to qualify for the exemptions provided by 503B is that the outsourcing facility does not
compound drug products using a bulk drug substance unless: (1) the bulk drug substance appears
on a list developed by FDA of bulk drug substances for which there is a clinical need (503B

See sections 503B(a)(11) and 503B(d)(4) of the FD&C Act.

FDA considers cold kits to be finished drug products. Therefore, preparation of a radiopharmaceutical from the
components of a cold kit according to FDA approved labeling is not compounding. However, if an ingredient is
added, or if the cold kit is otherwise manipulated in a manner not considered a minor deviation, it would be
considered compounding under this guidance.

Contains Nonbinding Recommendations
bulks list);14 or (2) the drug compounded from such bulk drug substance appears on the drug
shortage list in effect under section 506E of the FD&C Act (the FDA’s drug shortage list) at the
time of compounding, distribution,15 and dispensing.16
FDA solicited nominations for bulk drug substances for inclusion on the 503B bulks list;
however, FDA’s request for nominations for the 503B bulks list reserved the question of
compounded radiopharmaceutical products, and only one radiopharmaceutical was nominated
for the 503B bulks list.17
At this time, interested parties can nominate substances for inclusion on the 503B bulks list,18
and they will be evaluated as described in the FDA guidance for industry Interim Policy on
Compounding Using Bulk Drug Substances Under Section 503B of the Federal Food, Drug, and
Cosmetic Act. FDA has also published draft guidance for industry Evaluation of Bulk Drug
Substances Nominated for Use in Compounding Under Section 503B of the Federal Food, Drug,
and Cosmetic Act. This guidance, when finalized, will set forth the Agency’s interpretation of
bulk drug substances for which there is a clinical need and the statutory standard for including a
bulk drug substance on the 503B bulks list, including radiopharmaceuticals.
3.

Compounded Radiopharmaceuticals That Are Essentially Copies of
Approved Drugs

Under section 503B(a)(5) of the FD&C Act, a compounded drug that is essentially a copy of one
or more approved drugs is not eligible for the exemptions under section 503B of the FD&C Act.
In some cases, an outsourcing facility might receive a prescription or order for a
radiopharmaceutical compounded from an FDA-approved radiopharmaceutical, with one or
more minor deviations (see below) that are necessary to accommodate circumstances not
contemplated in the FDA-approved labeling, such as the rate of radioactive decay or
geographical distance from the patient.
For purposes of this guidance, FDA regards a minor deviation as a change from the approved
labeling in radioactivity, volume, and/or the step-by-step procedures that does not adversely
affect the quality of the product made when compounding the radiopharmaceutical from an
FDA-approved drug product in a patient-ready dose. If the deviation adversely impacts product
quality, then such change would not be minor. Examples of minor deviations include:

See section 503B(a)(2)(A)(i) of the FD&C Act.

Distribution means that the compounded or repackaged radiopharmaceutical has left the facility in which it was
compounded or repackaged.
16

See Section 503B(a)(2)(A)(ii).

See the guidance, Interim Policy on Compounding Using Bulk Drug Substances Under Section 503B of the
Federal Food, Drug, and Cosmetic Act.
18

Nominations of bulk drug substances to be used in compounding radiopharmaceuticals should be submitted to
Docket No. FDA-2015-N-3469. See 80 FR 65770 and the guidance, Interim Policy on Compounding Using Bulk
Drug Substances Under Section 503B of the Federal Food, Drug, and Cosmetic Act.

Contains Nonbinding Recommendations
•
•

•
•

The addition of a supplemental amount of Tc-99m sodium pertechnetate to an FDAapproved kit, so that the radiopharmaceutical can be provided to a patient with a later
use time.
The use of an additional quantity of normal saline to reduce the concentration of the
radiopharmaceutical in cases in which a supplemental amount of Tc-99m sodium
pertechnetate has been added, as described above. In such cases, the additional
radioactivity may necessitate a corresponding increase in volume so that the quantity
of the radiopharmaceutical to be drawn up into a unit-dose syringe can be more
precisely measured.
A minor deviation in the step-by-step procedures for preparation that may result in
the same finished radiopharmaceutical, but incorporates improvements in technology
or decreased radiation exposure to pharmacy personnel.
The use of enhanced quality control procedures that have been shown to be
equivalent or superior to the recommended procedures.

A compounded radiopharmaceutical that is prepared with minor deviations from the directions
contained in FDA-approved labeling provided by the product’s manufacturer may meet the
definition of essentially a copy of an approved drug under section 503B(d)(2).19 However, FDA
recognizes that for practical reasons radiopharmaceuticals might be compounded with minor
deviations from an approved radiopharmaceutical, including for the reasons listed above. After
considering the risks associated with these practices we generally do not intend to focus
enforcement on such compounding. Specifically, FDA generally does not intend to take action
against an outsourcing facility for compounding a radiopharmaceutical that is essentially a copy
of an approved drug and, thus, does not meet the condition of section 503B(a)(5) of the FD&C
Act, provided that the outsourcing facility:
•
•
•

Compounds the radiopharmaceutical from FDA-approved radiopharmaceuticals, and
not using bulk drug substances;
Makes minor deviations from the approved product labeling, as defined above; and
Compounds all of its drugs in accordance with all of the other conditions of section
503B and all other applicable statutory and regulatory requirements.
Repackaging of Radiopharmaceuticals

Outsourcing facilities sometimes receive a prescription or order for a radiopharmaceutical
product that differs from an approved radiopharmaceutical only in that it has been repackaged.
As discussed above, repackaged drug products are not eligible for the exemptions provided under
section 503B of the FD&C Act. In addition, repackaged radiopharmaceuticals are generally not
exempt from any of the provisions of the FD&C Act related to the production of drugs, including

See FDA guidance for industry Compounded Drug Products That Are Essentially Copies of Approved Drug
Products Under Section 503B of the Federal Food, Drug, and Cosmetic Act. This guidance describes FDA’s current
thinking on compounding drug products that are essentially copies of approved drugs under section 503B.

Contains Nonbinding Recommendations
the premarket approval, misbranding, and adulteration provisions of the FD&C Act, including
sections 505,20 502(f)(1), and 501(a)(2)(B).
Below, FDA describes the conditions under which it generally does not intend to take action
regarding violations of certain requirements of the FD&C Act, in the context of
radiopharmaceutical repackaging. Specifically, FDA generally does not intend to take action for
violations of sections 505 and 502(f)(1)21 if an outsourcing facility repackages
radiopharmaceuticals in accordance with the conditions described below, and any applicable
requirements other than sections 505, 502(f)(1) of the FD&C Act.22 The Agency may take other
factors into consideration when determining whether enforcement is appropriate in a particular
case.
Conditions:
1. The radiopharmaceutical that is being repackaged is a drug product approved under
section 505 of the FD&C Act.
2. The radiopharmaceutical is repackaged by or under the direct supervision of a
licensed, authorized nuclear pharmacist23 in an outsourcing facility that holds a RAM
license issued by the NRC or by an Agreement State.
3. The radiopharmaceutical is repackaged in accordance with applicable CGMP
requirements.24
4. The radiopharmaceutical is stored and shipped in a way that consistent with approved
drug product labeling.
5. The radiopharmaceutical being repackaged does not appear on a list of drug products
that have been withdrawn or removed from the market for reasons of safety or
effectiveness.25

However, see U.S. v. Kaybel, 430 F.2d 1346 (3d Cir. 1970), holding that repackaging of approved Enovid
(estrogen) tablets from large bottles into small bottles did not require pre-approval under Section 505 of the FD&C
Act.
21

See footnote 8.

Applicable requirements include, for example, the requirement that manufacturers not adulterate a drug product
by preparing, packing, or holding the drug product under insanitary conditions. See Section 501(a)(2)(A) of the
FD&C Act.
23

See definition of an authorized nuclear pharmacist at 10 CFR § 35.2.

See FDA draft guidance for industry Current Good Manufacturing Practice — Interim Guidance for Human Drug
Compounding Outsourcing Facilities Under Section 503B of the FD&C Act. Once final, this guidance will describe
FDA’s expectations regarding outsourcing facilities and the CGMP requirements in 21 CFR parts 210 and 211 until
more specific CGMP regulations for outsourcing facilities are promulgated.
24

See 21 CFR 216.24.

Contains Nonbinding Recommendations
6. The repackaged radiopharmaceutical is not sold or transferred by an entity other than
the entity that repackaged such radiopharmaceutical. For purposes of this condition, a
sale or transfer does not include administration of a repackaged radiopharmaceutical
in a health care setting.
7. The repackaged radiopharmaceutical is distributed only in states in which the
production of the radiopharmaceutical meets all applicable state requirements.
8. The radiopharmaceutical is repackaged in accordance with all applicable
requirements of the NRC or Agreement State (e.g., labeling requirements26) by a
facility that meets all applicable requirements of the NRC or Agreement State, and
the authorized nuclear pharmacist who repackages or supervises the repackaging of
the radiopharmaceutical meets all applicable NRC or Agreement State requirements.
9. The label on the immediate container (primary packaging) of the repackaged
radiopharmaceutical includes the following:
a. The statement “This radiopharmaceutical was repackaged by [name of
outsourcing facility].”
b. The address and phone number of the outsourcing facility that repackaged the
radiopharmaceutical.
c. The established name of the original, approved radiopharmaceutical that was
repackaged.
d. The lot or batch number of the repackaged radiopharmaceutical.
e. The dosage form and radioactive dose of the repackaged radiopharmaceutical.
f. A statement of either the quantity or volume of the repackaged
radiopharmaceutical, whichever is appropriate.
g. The date the radiopharmaceutical was repackaged.
h. The beyond use date (BUD) of the repackaged radiopharmaceutical.
i. Storage and handling instructions for the repackaged radiopharmaceutical.
j. The National Drug Code (NDC) number of the repackaged
radiopharmaceutical, if available.27

See 10 CFR 20.1904.

The NDC number of the original approved drug product should not be placed on the repackaged drug product.

Contains Nonbinding Recommendations
k. The statement “Not for resale” and, if the repackaged radiopharmaceutical is
distributed by an outsourcing facility other than pursuant to a prescription for
an individual identified patient, the statement “Office Use Only.”
l. A list of the active and inactive ingredients, unless such information is
included on the label for the container from which the individual units are
removed, as described below in condition 9.a.
10. The label on the container from which the individual units are removed for
administration (secondary packaging (e.g., the bag, box, or other package in which
the repackaged products are distributed)) includes:
a. The active and inactive ingredients, if the immediate drug product label is too
small to include this information
b. Directions for use, including, as appropriate, radioactive dosage and
administration, and the following information to facilitate adverse event
reporting: www.fda.gov/medwatch and 1-800-FDA-1088.
11. The radiopharmaceutical is included on a report submitted to FDA each June and
December identifying the drug products repackaged by the outsourcing facility during
the previous 6-month period, and providing the active ingredient(s); source of the
active ingredient(s); NDC number of the source ingredient(s), if available; the dosage
form and route of administration; the package description; the number of individual
units produced; and the NDC number of the final product, if assigned.28
12. The outsourcing facility reports serious adverse events to FDA that may be associated
with its repackaged radiopharmaceuticals.29
C.

Establishment Registration and Drug Listing

Under section 510(b)(1) of the FD&C Act, between October 1 and December 31 of each year,
every person who owns or operates any establishment in any state engaged in the manufacture,
preparation, propagation, compounding, or processing of a drug or drugs is required to register
with FDA, and under section 510(j) of the FD&C Act, every person who registers with FDA
28

FDA has issued guidance for industry Electronic Drug Product Reporting for Human Drug Compounding
Outsourcing Facilities Under Section 503B of the Federal Food, Drug, and Cosmetic Act, which describes how
outsourcing facilities are to submit drug product reports to FDA. Once finalized, that guidance will represent the
Agency’s current thinking on that topic. Although that guidance addresses reporting of compounded drug products,
outsourcing facilities should follow the same procedure to electronically report the radiopharmaceuticals they
repackaged.
29

FDA has issued guidance for industry Adverse Event Reporting for Outsourcing Facilities Under Section 503B of
the Federal Food, Drug, and Cosmetic Act, which describes how outsourcing facilities are to submit adverse event
reports to FDA and the content and format of the reports that they are required to submit. Although that guidance
addresses reporting of adverse events associated with compounded drug products, outsourcing facilities should
follow the same procedure to electronically report adverse events associated with the radiopharmaceuticals they
repackaged.

Contains Nonbinding Recommendations
under section 510(b) must list its drugs with the Agency. Outsourcing facilities that are statelicensed pharmacies that compound or repackage radiopharmaceuticals may qualify for an
exemption from registration and thus also not be required to list their drugs with FDA.
Specifically, under section 510(g)(1), the registration and listing requirements do not apply to:
pharmacies which maintain establishments in conformance with any applicable local laws
regulating the practice of pharmacy and medicine and which are regularly engaged in
dispensing prescription drugs or devices, upon prescriptions of practitioners licensed to
administer such drugs or devices to patients under the care of such practitioners in the
course of their professional practice, and which do not manufacture, prepare, propagate,
compound, or process drugs or devices for sale other than in the regular course of their
business of dispensing or selling drugs or devices at retail.

With respect to outsourcing facilities that do not qualify for the exemptions from registration
under section 510 of the FD&C Act,30 FDA generally does not intend to take action under
section 502(o) of the FD&C Act for failure to register and list radiopharmaceuticals that are
compounded or repackaged in accordance with this guidance.

File Type	application/pdf
File Title	Compounding and Repackaging of Radiopharmaceuticals by Outsourcing Facilities Guidance for Industry
Subject	Compounding and Repackaging of Radiopharmaceuticals by Outsourcing Facilities, Guidance for Industry
Author	FDA/CDER/"Dohm, Julie"
File Modified	2018-09-25
File Created	2018-09-25