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 
 
 
 
I.  INTRODUCTION AND SCOPE .................................................................................... 1 
II.  BACKGROUND ............................................................................................................... 2 
A.  Radiopharmaceuticals, Generally ................................................................................................ 2 
B.  Compounding, Generally .............................................................................................................. 3 
III.  POLICY ............................................................................................................................. 5 
A.   Compounding ................................................................................................................................. 5 
B.   Repackaging of Radiopharmaceuticals ........................................................................................ 7 
C.   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.  
 
 
 
 
I.  INTRODUCTION AND SCOPE  
 
This guidance sets forth the FDAs 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 
                                                 
1 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. 
1       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 FDAs current guidances addressing investigational new drugs. 
 
In general, FDAs guidance documents do not establish legally enforceable responsibilities. 
Instead, guidances describe the Agencys 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 centers hot lab or hospitals 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.  
 
                                                 
3 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. 
 
2       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  
 
                                                 
4 See 10 CFR parts 19, 20, and 35. 
 
5 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 
 
7 See 10 CFR 71.5, 49 CFR parts 107, 171 through 180, and 390 through 397.  
8 See Pub..L. 113-54, 102(a), 127 Stat. 587, 587-588 (2013). 
 
9 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. 
3       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 non-
radiopharmaceuticals)).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). 
11 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. 
4       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 facilitys 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 facilitys compounded drugs, including radiopharmaceuticals and non-
radiopharmaceuticals, would qualify for the exemptions in section 503B.12  
 
In general, FDAs 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 
                                                 
12 See sections 503B(a)(11) and 503B(d)(4) of the FD&C Act. 
13 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. 
 
5       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 FDAs 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, FDAs 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 Agencys 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:  
 
                                                 
14 See section 503B(a)(2)(A)(i) of the FD&C Act. 
15 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). 
17 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.  
6       Contains Nonbinding Recommendations 
  The addition of a supplemental amount of Tc-99m sodium pertechnetate to an FDA-
approved 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 products 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. 
 
B.  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 
                                                 
19 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 FDAs current 
thinking on compounding drug products that are essentially copies of approved drugs under section 503B. 
 
7       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  
 
                                                 
20 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. 
22 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. 
24 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 
FDAs 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.  
 
25 See 21 CFR 216.24. 
 
8       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 
 
                                                 
26 See 10 CFR 20.1904. 
27 The NDC number of the original approved drug product should not be placed on the repackaged drug product. 
 
9       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 
Agencys 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. 
10       Contains Nonbinding Recommendations 
under section 510(b) must list its drugs with the Agency. Outsourcing facilities that are state-
licensed 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. 
   
                                                 
30 See also 21 CFR 207.10. 
11       Contains Nonbinding Recommendations 
APPENDIX 
 
SUMMARY OF STATUTORY CONDITIONS IN SECTION 503B OF THE FD&C ACT 
 
The following are the statutory conditions contained in section 503B that must be met for a 
compounded drug, including a compounded radiopharmaceutical, to qualify for the exemptions 
in section 503B of the FD&C Act: 
 
1.  The outsourcing facility is in compliance with the registration and reporting 
requirements of section 503B(b). This includes submitting twice yearly reports 
regarding the drugs compounded by the outsourcing facility and submitting 
adverse event reports in accordance with section 503B(b)(5).31,32  
 
2.  If the outsourcing facility compounds drugs using one or more bulk drug 
substances, the bulk drug substances meet the requirements of 503B(a)(2). See the 
policy described in section II.A.2 of this guidance document. 
 
3.  If the outsourcing facility compounds using ingredients other than bulk drug 
substances, those ingredients must meet certain requirements.33  
 
4.  The outsourcing facility does not compound drugs that appear on a list published 
by FDA of drugs that have been withdrawn or removed from the market because 
the drugs or components of such drugs have been found to be unsafe or not 
effective.34,35 
 
5.  The outsourcing facility does not compound drugs that are essentially a copy of 
one or more approved drugs.36 See the policy described in section II.A.3 of this 
guidance document. 
 
                                                 
31 See section 301(ccc)(3) of the FD&C Act, which makes it a prohibited act for an entity that is registered in 
accordance with section 503B(b) to fail to report drugs or adverse events as required. 
32 See sections 503B(a)(1) and (b); FDA final guidance for industry Registration of Human Drug Compounding 
Outsourcing Facilities Under Section 503B of the FD&C Act, Adverse Event Reporting for Outsourcing Facilities 
Under Section 503B of the Federal Food, Drug, and Cosmetic Act, and Electronic Drug Product Reporting for 
Human Drug Compounding Outsourcing Facilities Under Section 503B of the Federal Food, Drug, and Cosmetic 
Act. 
33 See section 503B(a)(3). 
34 See section 503B(a)(4). 
35 The list of drugs that have been withdrawn or removed from the market because such drugs or components of 
such drugs have been found to be unsafe or not effective (the withdrawn-or-removed list) can be found at 21 CFR 
216.24.  
36 See section 503B(a)(5) and 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. 
 
12       Contains Nonbinding Recommendations 
6.  The outsourcing facility does not compound drugs that appear on a list published 
by FDA of drugs that present demonstrable difficulties for compounding.37 
 
7.  If the outsourcing facility compounds a drug that is the subject of a risk evaluation 
and mitigation strategy (REMS) approved with elements to assure safe use 
pursuant to section 505-1, or from a bulk drug substance that is a component of 
such drug, the outsourcing facility must demonstrate to FDA before beginning to 
compound that it will use controls comparable to the controls applicable under the 
REMS.38  
 
8.  The outsourcing facilitys compounded drugs will not be sold or transferred by an 
entity other than that outsourcing facility.39 
 
9.  The outsourcing facility has paid all applicable establishment and reinspection 
fees owed under section 744(k).40,41 
 
10.  The outsourcing facility includes on the labels and labeling of its compounded 
drug products the information required under section 503B(a)(10).42  
 
11.  All of the outsourcing facilitys compounded drugs are compounded in 
accordance with section 503B.43,44  
 
 
 
                                                 
37 See section 503B(a)(6). This list has not yet been developed. 
38 See section 503B(a)(7). 
39 See section 503B(a)(8). 
40 See section 503B(a)(9). 
41 See also sections 744J and 744K of the FD&C Act and FDA guidance for industry Fees for Human Drug 
Compounding Outsourcing Facilities Under Sections 503B and 744K of the FD&C Act.  
42 See section 503B(a)(10). 
43 See section 503B(a)(11). 
44 See FDA guidances for industry For Entities Considering Whether to Register as Outsourcing Facilities Under 
Section 503B of the Federal Food, Drug, and Cosmetic Act and Facility Definition Under Section 503B of the 
Federal Food, Drug, and Cosmetic Act. 
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