Federal Register / Vol. 80, No. 33 / Thursday, February 19, 2015 / Notices 8881 

TABLE 2—ESTIMATED ANNUAL RECORDKEEPING BURDEN 1

Compounding MOU between FDA and States Number of 

recordkeepers 

Number of 

records per 

recordkeeper 

Total annual 

records 

Average burden per recordkeeping 

(in Hours) 

Total Hours 

State recordkeeping for 3 years of compounding complaints ............................................................................. 25 15 375 1 375 

Total ............................................................................ 25 15 375 1 375 

1There are no capital costs or operating and maintenance costs associated with this collection of information. 

TABLE 3—ESTIMATED ANNUAL THIRD-PARTY DISCLOSURE BURDEN 1

Compounding MOU between FDA and States Number of 

respondents 

Number of 

disclosures 

per 

respondent 

Total annual 

disclosures 

Average burden per disclosure 

(in Hours) 

Total hours 

State notification to pharmacists, pharmacies, and physicians that its participation in the MOU has been terminated by FDA ................................................................... 1 1 1 1 1 

Total .............................................................................. 1 1 1 1 1 

1There are no capital costs or operating and maintenance costs associated with this collection of information. 

VII. Request for Comments 

FDA invites comments from 

interested persons on the new draft 

standard MOU that would establish an 

agreement between the signatory States 

and FDA regarding the appropriate 

investigation by such States of 

complaints relating to compounded 

human drug products distributed 

outside the State, and the distribution of 

inordinate amounts of compounded 

human drug products interstate. The 

Agency is providing a 120-day comment 

period. 

After considering any comments on 

the new draft standard MOU submitted 

to this docket, FDA intends to finalize 

the standard MOU and make it available 

for signature by individual States. FDA 

will determine at the time of publication 

of the final MOU how long it will allow 

States to consider whether to sign the 

MOU before FDA begins to enforce the 

5 percent limit in those States that have 

not signed an MOU. 

Interested persons may submit either 

electronic comments regarding this 

document to http://www.regulations.gov 

or written comments to the Division of 

Dockets Management (see ADDRESSES). It 

is only necessary to send one set 

comments. Identify comments with the 

docket number found in brackets in the 

heading of this document. Received 

comments may be seen in the Division 

of Dockets Management between 9 a.m. 

and 4 p.m., Monday through Friday, and 

will be posted to the docket at http://

www.regulations.gov. 

VIII. Electronic Access 

Persons with access to the Internet 

may obtain the draft standard MOU at 

http://www.regulations.gov. 

Dated: February 12, 2015. 

Leslie Kux, 

Associate Commissioner for Policy. 

[FR Doc. 2015–03420 Filed 2–18–15; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2014–D–1525] 

Mixing, Diluting, or Repackaging 

Biological Products Outside the Scope 

of an Approved Biologics License 

Application; Draft Guidance for 

Industry; Availability 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA or the Agency) is 

announcing the availability of a draft 

guidance for industry entitled ‘‘Mixing, 

Diluting, or Repackaging Biological 

Products Outside the Scope of an 

Approved Biologics License 

Application.’’ This draft guidance 

describes the conditions under which 

FDA does not intend to take action 

against a state-licensed pharmacy, a 

Federal facility, or outsourcing facility 

that mixes, dilutes, or repackages 

certain biological products without 

obtaining an approved biologics license 

application (BLA). 

DATES: Although you can comment on 

any guidance at any time (see 21 CFR 

10.115(g)(5)), to ensure that the Agency 

considers your comment on this draft 

guidance before it begins work on the 

final version of the guidance, submit 

either electronic or written comments 

on the draft guidance by May 20, 2015. 

ADDRESSES: Submit written requests for 

single copies of this guidance to the 

Division of Drug Information, Center for 

Drug Evaluation and Research, Food 

and Drug Administration, 10903 New 

Hampshire Ave., Bldg. 51, Rm. 2201, 

Silver Spring, MD 20993–0002; or the 

Office of Communication, Outreach and 

Development, Center for Biologics 

Evaluation and Research (CBER), Food 

and Drug Administration, 10903 New 

Hampshire Avenue, Bldg. 71, Rm. 3128, 

Silver Spring, MD 20993–0002. Send 

one self-addressed adhesive label to 

assist that office in processing your 

requests. See the SUPPLEMENTARY

INFORMATION section for electronic 

access to the guidance document. 

Submit electronic comments on the 

guidance to http://www.regulations.gov. 

Submit written comments to the 

Division of Dockets Management (HFA– 

305), Food and Drug Administration, 

5630 Fishers Lane, Rm. 1061, Rockville, 

MD 20852. 

FOR FURTHER INFORMATION CONTACT: 

Leah Christl, Center for Drugs 

Evaluation and Research, Food and 

Drug Administration, 10903 New 

Hampshire Ave., Bldg. 22, Rm. 6426, 

Silver Spring, MD 20903, 301–796– 

0869; or Stephen Ripley, Center for 

Biologics Evaluation and Research, 

Food and Drug Administration, 10903 


emcdonald on DSK67QTVN1PROD with NOTICES
8882 Federal Register / Vol. 80, No. 33 / Thursday, February 19, 2015 / Notices 

New Hampshire Ave., Bldg. 71, Rm. 

7301, Silver Spring, MD 20993–0002, 

240–402–7911. 

SUPPLEMENTARY INFORMATION: 

I. Background 

FDA is announcing the availability of 

a draft guidance for industry entitled 

‘‘Mixing, Diluting, or Repackaging of 

Biological Products Outside the Scope 

of an Approved Biologics License 

Application.’’ Certain licensed 

biological products may need to be 

mixed, diluted, or repackaged in a way 

not described in the approved labeling 

for the product to meet the needs of a 

specific patient. For example, for some 

biological products there is no licensed 

pediatric strength and/or dosage form. 

In addition, there may be certain 

circumstances when a person would 

remove a licensed biological product 

from its original container and place it 

into a different container(s) (repackage 

it), in a manner that is not within the 

scope of the approved labeling for the 

product. As described in the draft 

guidance, mixed, diluted, or repackaged 

biological products are not eligible for 

the statutory exemptions available to 

certain compounded drugs under 

sections 503A and 503B of the Federal 

Food, Drug, and Cosmetic Act (FD&C 

Act) (21 U.S.C. 353A and 353B). In 

addition, a biological product that is 

mixed, diluted, or repackaged outside 

the scope of an approved BLA is 

considered an unlicensed biological 

product under section 351 of the Public 

Health Service (PHS) Act (21 U.S.C. 

262). 

This draft guidance describes the 

conditions under which FDA does not 

intend to take action for violations of 

section 351 of the PHS Act and section 

502(f)(1) (21 U.S.C. 352(f)(1) and where 

specified, section 501(a)(2)(B) (21 U.S.C. 

351(a)(2)(B) of the FD&C Act, when a 

state-licensed pharmacy, a Federal 

facility, or an outsourcing facility 

dilutes, mixes, or repackages certain 

biological products without obtaining 

an approved BLA. 

Elsewhere in this issue of the Federal 

Register, the Agency is making available 

for comment a draft guidance entitled 

‘‘Repackaging of Certain Human Drug 

Products by Pharmacies and 

Outsourcing Facilities.’’ When these two 

guidances become final, they will 

address and clarify the Agency’s policy 

regarding hospital pharmacies 

repackaging and safely transferring 

repackaged drug, including biological 

products, to other hospitals within the 

same health system during a drug 

shortage. Therefore, under section 

506F(d) of the FD&C Act (21 U.S.C. 

356f(d), when FDA issues these as final 

guidances, section 506F will no longer 

apply. 

This draft guidance is being issued 

consistent with FDA’s good guidance 

practices regulation (21 CFR 10.115). 

This guidance, when finalized, will 

represent FDA’s current thinking on 

mixing, diluting, and repackaging of 

biological products not within the scope 

of the product’s approved BLA as 

described in the approved labeling for 

the product. It does not create or confer 

any rights for or on any person and does 

not operate to bind FDA or the public. 

An alternative approach may be used if 

such approach satisfies the 

requirements of the applicable statutes 

and regulations. 

II. Comments 

Interested persons may submit either 

electronic comments regarding this 

document to http://www.regulations.gov 

or written comments to the Division of 

Dockets Management (see ADDRESSES). It 

is only necessary to send one set of 

comments. Identify comments with the 

docket number found in brackets in the 

heading of this document. Received 

comments may be seen in the Division 

of Dockets Management between 9 a.m. 

and 4 p.m., Monday through Friday, and 

will be posted to the docket at http://

www.regulations.gov. 

III. Paperwork Reduction Act of 1995 

This draft guidance contains 

information collection provisions that 

are subject to review by OMB under the 

Paperwork Reduction Act of 1995 (44 

U.S.C. 3501–3520). The title, 

description, and respondent description 

of the information collection are given 

under this section with an estimate of 

the annual reporting and recordkeeping 

burdens. Included in the estimate is the 

time for reviewing instructions, 

searching existing data sources, 

gathering and maintaining the data 

needed, and completing and reviewing 

the collection of information. 

We invite 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: Draft Guidance for Industry: 

Mixing, Diluting, or Repackaging of 

Biological Products Outside the Scope 

of an Approved Biologics License 

Application. 

Description: The draft guidance 

describes FDA’s policy with respect to 

the mixing, diluting, and repackaging of 

certain types of biological products that 

have been licensed under section 351 of 

the PHS Act when such activities are 

not within the scope of the product’s 

approved BLA as described in the 

approved labeling for the product. The 

draft guidance describes the conditions 

under which FDA does not intend to 

take action for violations of section 351 

of the PHS Act and section 502(f)(1) and 

where specified, section 501(a)(2)(B) of 

the FD&C Act, when a state-licensed 

pharmacy, a Federal facility, or an 

outsourcing facility mixes, dilutes, or 

repackages certain biological products 

without obtaining an approved BLA. 

The draft guidance includes the 

following collection of information 

under the PRA. 

One condition described in the draft 

guidance is that, if the biological 

product is mixed, diluted, or repackaged 

by an outsourcing facility, the label on 

the immediate container (primary 

packaging, e.g., the syringe) of the 

mixed, diluted, or repackaged product 

includes the following information: 

• The statement ‘‘This product was 

mixed or diluted by [name of 

outsourcing facility],’’ or ‘‘This product 

was repackaged by [name of outsourcing 

facility]’’ whichever statement is 

appropriate; 

• the address and phone number of 

the outsourcing facility that mixed, 

diluted, or repackaged the biological 

product; 

• the proper name of the original 

biological product that was mixed, 

diluted, or repackaged; 

• the lot or batch number of the 

mixed, diluted, or repackaged biological 

product; 

• the dosage form and strength; 

• a statement of either the quantity or 

the volume of the mixed, diluted, or 

repackaged biological product, 

whichever is appropriate; 

• the date the biological product was 

mixed, diluted, or repackaged; 

• the beyond-use-date (BUD) of the 

mixed, diluted, or repackaged biological 

product; 

• storage and handling instructions 

for the mixed, diluted, or repackaged 

biological product; 

• the National Drug Code (NDC) 

number of the mixed, diluted, or 


emcdonald on DSK67QTVN1PROD with NOTICES
Federal Register / Vol. 80, No. 33 / Thursday, February 19, 2015 / Notices 8883 

1The NDC number of the original licensed 

biological product should not be placed on the 

mixed, diluted, or repackaged biological product. 

repackaged biological product, if 

available; 1

• The statement ‘‘Not for resale,’’ and, 

if the biological product is distributed 

by an outsourcing facility other than 

pursuant to a prescription for an 

individual identified patient, the 

statement ‘‘Office Use Only’’; and 

• If included on the label of the FDAlicensed product from which the 

biological product is being mixed, 

diluted, or repackaged, a list of the 

active and inactive ingredients; and if 

the ingredients are listed because they 

were listed on the original product, the 

label of the mixed, diluted, or 

repackaged product should include any 

additional ingredients that appear in the 

mixed, diluted, or repackaged product. 

Another condition in the draft 

guidance is that, if the immediate 

product label is too small or the mixed, 

diluted, or repackaged product is 

otherwise unable to accommodate a 

label with sufficient space to bear the 

active and inactive ingredients, such 

information should be included on the 

label of the container from which the 

individual units are removed for 

administration (secondary packaging, 

e.g., the bag, box, or other package in 

which the mixed, diluted, or repackaged 

biological products are distributed). 

In addition, the draft guidance 

describes the conditions that the 

container label include directions for 

use, including, as appropriate, dosage 

and administration, and the following 

information to facilitate adverse event 

reporting: http://www.fda.gov/

medwatch and 1–800–FDA–1088. 

Another condition in the draft guidance 

is that each mixed, diluted, or 

repackaged biological product is also 

accompanied by a copy of the 

prescribing information that 

accompanied the original licensed 

biological product that was mixed, 

diluted, or repackaged. 

We estimate that annually a total of 

approximately five registered 

outsourcing facilities that mix, dilute, or 

repackage biological products (‘‘Number 

of Respondents’’ in table 1, row 1) will 

each design, test, and produce 

approximately five different labels 

(‘‘Frequency per Disclosure’’ in table 1, 

row 1), for a total of 25 labels that 

include the information set forth in 

section III.B of the draft guidance 

(including directions for use) (‘‘Total 

Disclosures’’ in table 1, row 1). We also 

estimate that designing, testing, and 

producing each label will take 

approximately 0.5 hours (‘‘Hours per 

Disclosure’’ in table 1, row 1). The 

provision to add http://www.fda.gov/

medwatch and 1–800–FDA–1088 is not 

included in this burden estimate 

because it is not considered a collection 

of information under the PRA because 

the information is ‘‘originally supplied 

by the Federal Government to the 

recipient for the purpose of disclosure 

to the public’’ (5 CFR 1320.3(c)(2)). 

Section III.C of the draft guidance 

discusses the preparation of 

prescription sets (i.e., licensed 

allergenic extracts that are combined to 

provide subcutaneous immunotherapy 

to an individual patient) by a physician, 

state-licensed pharmacy, a Federal 

facility, or outsourcing facility. Under 

the draft guidance, if the prescription 

set is mixed or diluted by an 

outsourcing facility, the label on the 

immediate container of the prescription 

set (primary packaging) includes: 

• The patient’s name as identified on 

the prescription; 

• the statement ‘‘This prescription set 

was prepared by [name of outsourcing 

facility]’’; 

• the address and phone number of 

the outsourcing facility that prepared 

the prescription set; 

• the identity of each allergenic 

extract in the prescription set and the 

quantity of each; 

• the dilution of each dilution vial; 

• the lot or batch number of the 

prescription set; 

• the date the prescription set was 

prepared; 

• the BUD of the prescription set; 

• storage and handling instructions 

for the prescription set; and 

• the statement ‘‘Not for resale’’. 

In addition, under the draft guidance, 

the label of the container from which 

the individual units of the prescription 

set are removed for administration 

(secondary packaging) includes the 

following information to facilitate 

adverse event reporting: http://

www.fda.gov/medwatch and 1–800– 

FDA–1088. Each prescription set 

prepared is also accompanied by 

instructions for use and the FDA 

approved package insert for each 

allergenic extract. 

We estimate that annually a total of 

approximately five outsourcing facilities 

that prepare prescription sets (‘‘Number 

of Respondents’’ in table 2, row 1) will 

each include the information set forth in 

section III.C of the draft guidance 

(including directions for use) on the 

labels, packages, and/or containers of 

approximately 300 prescription sets 

(‘‘Frequency per Disclosure’’ in table 2, 

row 1) for a total of 1500 disclosures 

(‘‘Total Disclosures’’ in table 2, row 1). 

We also estimate that the initial process 

of designing, testing, and producing, 

and attaching each label, package, and/ 

or container to each prescription set will 

take approximately 0.5 hours (‘‘Hours 

per Disclosure’’ in table 2, row 1). The 

provision to add the statement http://

www.fda.gov/medwatch and 1–800– 

FDA–1088 is not included in this 

burden estimate because it is not 

considered a collection of information 

under the PRA because the information 

is ‘‘originally supplied by the Federal 

Government to the recipient for the 

purpose of disclosure to the public’’ (5 

CFR 1320.3(c)(2)). 

We also estimate that a total of 

approximately five outsourcing facilities 

(‘‘Number of Respondents’’ in table 2, 

row 2) will each design, test, and 

produce the instructions for use and a 

copy of prescribing information, as set 

forth in section III.C of the draft 

guidance, for approximately 300 

prescription sets (‘‘Frequency per 

Disclosure’’ in table 2, row 2) for a total 

of 1500 disclosures (total disclosures’’ 

in table 2, row 2), which we estimate 

will take approximately 1 hour for each 

prescription set (‘‘Hours per Disclosure’’ 

in table 2, row 2). The provision to 

include http://www.fda.gov/medwatch 

and 1–800–FDA–1088 is not included in 

this burden estimate because they are 

not considered a collection of 

information under the PRA because the 

information is ‘‘originally supplied by 

the Federal Government to the recipient 

for the purpose of disclosure to the 

public’’ (5 CFR 1320.3(c)(2)). 

The total estimated third-party 

disclosure burden resulting from the 

draft guidance is as follows: 


emcdonald on DSK67QTVN1PROD with NOTICES
8884 Federal Register / Vol. 80, No. 33 / Thursday, February 19, 2015 / Notices 

TABLE 1—ESTIMATED ANNUAL THIRD-PARTY DISCLOSURE BURDEN 1

Biological product mixing, diluting, and repackaging Number of 

respondents 

Frequency per 

disclosure 

Total 

disclosures 

Hours per 

disclosure Total hours 

Designing, testing, and producing the label, container, 

packages, and/or outer containers for each mixed, diluted, or repackaged biological product ......................... 5 5 25 0.5 12 .5 

Prescribing information labeling accompanying each 

mixed, diluted, or repackaged drug product .................. 5 5 25 1 25 

Total ............................................................................ ........................ ........................ ........................ ........................ 37 .5 

1There are no capital costs or operating and maintenance costs associated with this collection of information. 

*(30 minutes) 

TABLE 2—ESTIMATED ANNUAL THIRD-PARTY DISCLOSURE BURDEN 1

Preparation of prescription sets Number of 

respondents 

Frequency per 

disclosure 

Total 

disclosures 

Hours per 

disclosure Total hours 

Designing, testing, and producing each label on immediate containers, packages, and/or outer containers ..... 5 300 1500 0.5 750 

Including instructions for use labeling and the original 

package insert(s) for each prescription set .................... 5 300 1500 1 1500 

Total ............................................................................ ........................ ........................ ........................ ........................ 2250 

1There are no capital costs or operating and maintenance costs associated with this collection of information. 

*(30 minutes) 

The draft guidance also references 

registration, product reporting, current 

good manufacturing practice (CGMP) 

requirements, and the payment of 

certain fees by human drug 

compounding outsourcing facilities. In 

the Federal Register of December 4, 

2013 (78 FR 72899), FDA estimated the 

burden resulting from outsourcing 

facility registration. In the Federal 

Register of December 4, 2013 (78 FR 

72897), FDA estimated the burden 

resulting from outsourcing facility 

interim product reporting. In the 

Federal Register of April 1, 2014 (79 FR 

18297), FDA estimated the burden 

resulting from the payment of certain 

fees by outsourcing facilities. In the 

Federal Register of July 2, 2014 (79 FR 

37743), FDA estimated the burden 

resulting from outsourcing facility 

compliance with CGMP requirements. 

IV. Electronic Access 

Persons with access to the Internet 

can obtain the document at either 

http://www.fda.gov/Drugs/Guidance

ComplianceRegulatoryInformation/

Guidances/default.htm, http://

www.fda.gov/BiologicsBloodVaccines/

GuidanceComplianceRegulatory

Information/default.htm or http://

www.regulations.gov. 

Dated: February 11, 2015. 

Leslie Kux, 

Associate Commissioner for Policy. 

[FR Doc. 2015–03418 Filed 2–18–15; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2014–D–1524] 

Repackaging of Certain Human Drug 

Products by Pharmacies and 

Outsourcing Facilities; Draft Guidance 

for Industry; Availability 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice of availability. 

SUMMARY: The Food and Drug 

Administration (FDA or the Agency) is 

announcing the availability of a draft 

guidance for industry entitled 

‘‘Repackaging of Certain Human Drug 

Products by Pharmacies and 

Outsourcing Facilities.’’ This guidance 

describes the conditions under which 

FDA does not intend to take action for 

violations of the Federal Food, Drug, 

and Cosmetic Act (the FD&C Act), when 

a state-licensed pharmacy, a Federal 

facility, or an outsourcing facility 

repackages human drug products. 

When this guidance becomes final, 

the Agency may also consider 

withdrawing or revising other guidance 

documents that address human drug 

repackaging, including section 446.100 

of the Compliance Program Guidance 

(CPG) Manual, entitled ‘‘Regulatory 

Action Regarding Approved New Drugs 

and Antibiotic Drug Products Subjected 

to Additional Processing or other 

Manipulations,’’ which was issued in 

January 1991, and section 460.100 of the 

CPG Manual, entitled ‘‘Hospital 

Pharmacies—Status as Drug 

Manufacturer,’’ which was issued in 

October 1980. 

DATES: Although you can comment on 

any guidance at any time (see 21 CFR 

10.115(g)(5)), to ensure that the Agency 

considers your comment on this draft 

guidance before it begins work on the 

final version of the guidance, submit 

either electronic or written comments 

on the draft guidance by May 20, 2015. 

ADDRESSES: Submit written requests for 

single copies of this guidance to the 

Division of Drug Information, Center for 

Drug Evaluation and Research, Food 

and Drug Administration, 10903 New 

Hampshire Ave., Bldg. 51, Rm. 2201, 

Silver Spring, MD 20993–0002. Send 

one self-addressed adhesive label to 

assist that office in processing your 

requests. See the SUPPLEMENTARY

INFORMATION section for electronic 

access to the guidance document. 

Submit electronic comments on the 

guidance to http://www.regulations.gov. 

Submit written comments to the 

Division of Dockets Management (HFA– 

305), Food and Drug Administration, 

5630 Fishers Lane, Rm. 1061, Rockville, 

MD 20852. 

FOR FURTHER INFORMATION CONTACT: Gail 

Bormel, Food and Drug Administration, 

10001 New Hampshire Ave., Silver 

Spring, MD 20903, 301–796–3110. 

SUPPLEMENTARY INFORMATION: 

I. Announcement of Draft Guidance 

FDA is announcing the availability of 

a draft guidance for industry entitled 


emcdonald on DSK67QTVN1PROD with NOTICES