Federal Register / Vol. 77, No. 31 / Wednesday, February 15, 2012 / Notices 8883 

1 In section 7002(b)(3) of the Patient Protection 

and Affordable Care Act (Affordable Care Act), 

Public Law 111–148, ‘‘biosimilar’’ or 

‘‘biosimilarity’’ means ‘‘that the biological product 

is highly similar to the reference product 

notwithstanding minor differences in clinically 

inactive components,’’ and that ‘‘there are no 

clinically meaningful differences between the 

biological product and the reference product in 

terms of the safety, purity, and potency of the 

product.’’ 

2Section 7002(a)(2) of the Affordable Care Act, 

adding section 351(k)(3) of the PHS Act (citing 

section 351(a)(2)(C) of the PHS Act). 

TABLE 1—ESTIMATED ANNUAL REPORTING BURDEN 1—Continued 

351(k) Application for biosimilars (42 U.S.C. 262(k)) Number of 

respondents 

Number of 

responses per 

respondent 

Total annual 

responses 

Average 

burden per 

response 

Total hours 

351(l)(6)(C) ........................................................................... 2 1 2 2 4 

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

Dated: February 9, 2012. 

Leslie Kux, 

Acting Assistant Commissioner for Policy. 

[FR Doc. 2012–3548 Filed 2–14–12; 8:45 am] 

BILLING CODE 4160–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2011–D–0605] 

Draft Guidance for Industry on 

Scientific Considerations in 

Demonstrating Biosimilarity to a 

Reference Product; Availability 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA) is announcing the 

availability of a draft guidance for 

industry entitled ‘‘Scientific 

Considerations in Demonstrating 

Biosimilarity to a Reference Product.’’ 

This draft guidance is intended to assist 

sponsors in demonstrating that a 

proposed therapeutic protein product is 

biosimilar to a reference product for the 

purpose of submitting a marketing 

application through an abbreviated 

licensure pathway. This draft guidance 

gives an overview of FDA’s approach to 

determining biosimilarity. 

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 April 16, 2012. 

ADDRESSES: Submit written requests for 

single copies of the draft 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 (HFM–40), Center for 

Biologics Evaluation and Research, 

Food and Drug Administration, 1401 

Rockville Pike, Suite 200N, Rockville, 

MD 20852–1448. Send one selfaddressed adhesive label to assist that 

office in processing your requests. See 

the SUPPLEMENTARY INFORMATION section 

for electronic access to the draft 

guidance document. 

Submit electronic comments on the 

draft 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: 

Sandra Benton, Center for Drug 

Evaluation and Research, Food and 

Drug Administration, 10903 New 

Hampshire Ave., Bldg. 51, Rm. 6340, 

Silver Spring, MD 20993–0002, 301– 

796–1042; or Stephen Ripley, Center for 

Biologics Evaluation and Research 

(HFM–17), Food and Drug 

Administration, 1401 Rockville Pike, 

Suite 200N, Rockville, MD 20852–1448, 

301–827–6210. 

SUPPLEMENTARY INFORMATION: 

I. Background 

FDA is announcing the availability of 

a draft guidance for industry entitled 

‘‘Scientific Considerations in 

Demonstrating Biosimilarity to a 

Reference Product.’’ This draft guidance 

is intended to assist sponsors in 

demonstrating that a proposed 

therapeutic protein product is 

‘‘biosimilar’’ 1 to a reference product for 

the purpose of submitting a marketing 

application through the abbreviated 

licensure pathway under section 351(k) 

of the Public Health Service Act (PHS 

Act) (42 U.S.C. 262(k)). 

The Biologics Price Competition and 

Innovation Act of 2009, enacted as part 

of the Affordable Care Act (Pub. L. 111– 

148) on March 23, 2010, created an 

abbreviated licensure pathway under 

section 351(k) of the PHS Act for 

biological products demonstrated to be 

biosimilar to, or interchangeable with, a 

reference product. Under this 

abbreviated licensure pathway, FDA 

will license a proposed biological 

product submitted under section 351(k) 

of the PHS Act if FDA ‘‘determines that 

the information submitted in the 

application * * * is sufficient to show 

that the biological product is biosimilar 

to the reference product * * *’’ and the 

351(k) applicant (or other appropriate 

person) consents to an inspection of the 

facility that is the subject of the 

application (i.e., a facility in which the 

proposed biological product is 

manufactured, processed, packed, or 

held).2 The draft guidance gives an 

overview of FDA’s approach to 

determining biosimilarity. FDA intends 

to consider the totality of the evidence 

submitted in a 351(k) application and is 

recommending that sponsors use a 

stepwise approach in their development 

of biosimilar products. The draft 

guidance discusses important scientific 

considerations in demonstrating 

biosimilarity, including: 

• A stepwise approach to 

demonstrating biosimilarity, which can 

include a comparison of the proposed 

therapeutic protein product and the 

reference product with respect to 

structure, function, animal toxicity, 

human pharmacokinetics and 

pharmacodynamics, clinical 

immunogenicity, and clinical safety and 

effectiveness; 

• The totality-of-the-evidence 

approach that FDA will use to review 

applications for biosimilar products; 

and 

• General scientific principles in 

conducting comparative structural and 

functional analysis, animal testing, 

human pharmacokinetics and 

pharmacodynamics studies, clinical 

immunogenicity assessment, and 

clinical safety and effectiveness studies 

(including clinical study design issues). 

This draft guidance is being issued 

consistent with FDA’s good guidance 

practices regulation (21 CFR 10.115). 

The draft guidance, when finalized, will 

represent the Agency’s current thinking 

on scientific considerations in 

demonstrating biosimilarity to a 

reference product. It does not create or 

confer any rights for or on any person 


sroberts on DSK5SPTVN1PROD with NOTICES
8884 Federal Register / Vol. 77, No. 31 / Wednesday, February 15, 2012 / Notices 

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 to the 

Division of Dockets Management (see 

ADDRESSES) either electronic or written 

comments regarding this document. 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. 

III. The Paperwork Reduction Act 

This draft guidance describes 

information collection provisions that 

are subject to review by the Office of 

Management and Budget (OMB) under 

the Paperwork Reduction Act of 1995 

(the PRA) (44 U.S.C. 3501–3520). In 

particular, the draft guidance refers to 

information collections related to the 

submission of 351(k) application. In 

accordance with the PRA, FDA is 

soliciting public comment, in a separate 

document published elsewhere in this 

issue of the Federal Register (see 

‘‘Agency Information Collection 

Activities: Proposed Collection; 

Comment Request; General Licensing 

Provisions; Section 351(k) Biosimilar 

Applications’’) on the information 

collection associated with the 

submission of a 351(k) application. FDA 

will also seek OMB approval for this 

information collection. 

In addition, this draft guidance 

references other information collections 

that are already approved by OMB and 

are not expected to change as a result of 

the draft guidance. This includes 

information collections related to the 

submission of (1) an investigational new 

drug application, which is covered 

under 21 CFR part 312 and approved 

under OMB control number 0910–0014; 

(2) a new drug application, which is 

covered under 21 CFR 314.50 and 

approved under OMB control number 

0910–0001; (3) a biologics license 

application, which is covered under 21 

CFR part 601 and approved under OMB 

control number 0910–0338; and (4) 

labeling, which is covered under 21 CFR 

201.57 and approved under OMB 

control number 0910–0572. 

IV. Electronic Access 

Persons with access to the Internet 

may obtain the document at either 

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

GuidanceCompliance

RegulatoryInformation/Guidances/

default.htm, http://www.fda.gov/ 

BiologicsBloodVaccines/

GuidanceComplianceRegulatory

Information/default.htm, or http:// 

www.regulations.gov. 

Dated: February 9, 2012. 

Leslie Kux, 

Acting Assistant Commissioner for Policy. 

[FR Doc. 2012–3552 Filed 2–14–12; 8:45 am] 

BILLING CODE 4160–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2011–D–0602] 

Draft Guidance for Industry on Quality 

Considerations in Demonstrating 

Biosimilarity to a Reference Protein 

Product; Availability 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA) is announcing the 

availability of a draft guidance for 

industry entitled ‘‘Quality 

Considerations in Demonstrating 

Biosimilarity to a Reference Protein 

Product.’’ This draft guidance is 

intended to provide sponsors with an 

overview of analytical factors to 

consider when assessing biosimilarity 

between a proposed protein product and 

a reference product for the purpose of 

submitting a marketing application 

through an abbreviated licensure 

pathway. This draft guidance provides 

an overview of FDA’s approach to 

quality considerations in determining 

biosimilarity. 

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 comments 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 April 16, 2012. 

ADDRESSES: Submit written requests for 

single copies of the draft 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 Office 

of Communication, Outreach, and 

Development (HFM–40), Center for 

Biologics Evaluation and Research, 

Food and Drug Administration, 1401 

Rockville Pike, Suite 200N, Rockville, 

MD 20852–1448. Send one selfaddressed adhesive label to assist that 

office in processing your requests. See 

the SUPPLEMENTARY INFORMATION section 

for electronic access to the draft 

guidance document. 

Submit electronic comments on the 

draft 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: 

Sandra Benton, Center for Drug 

Evaluation and Research, Food and 

Drug Administration, 10903 New 

Hampshire Ave., Bldg. 51, Rm. 6340, 

Silver Spring, MD 20993–0002, 301– 

796–1042, or Stephen Ripley, Center for 

Biologics Evaluation and Research 

(HFM–17), Food and Drug 

Administration, 1401 Rockville Pike, 

Suite 200N, Rockville, MD 20852–1448, 

301–827–6210. 

SUPPLEMENTARY INFORMATION: 

I. Background 

FDA is announcing the availability of 

a draft guidance for industry entitled 

‘‘Quality Considerations in 

Demonstrating Biosimilarity to a 

Reference Protein Product.’’ This draft 

guidance is intended to provide 

sponsors with an overview of analytical 

factors to consider when assessing 

biosimilarity between a proposed 

protein product and a reference product 

for the purpose of submitting a 

marketing application through the 

abbreviated licensure pathway under 

section 351(k) of the Public Health 

Service Act (PHS Act) (42 U.S.C. 

262(k)). Although the 351(k) pathway 

applies generally to biological products, 

this draft guidance focuses on 

therapeutic protein products. 

The Biologics Price Competition and 

Innovation Act of 2009, enacted as part 

of the Patient Protection and Affordable 

Care Act (Affordable Care Act) (Pub. L. 

111–148) on March 23, 2010, created an 

abbreviated licensure pathway under 

section 351(k) of the PHS Act for 

biological products demonstrated to be 

biosimilar to, or interchangeable with, a 

reference product. Under this 

abbreviated licensure pathway, FDA 

will license a proposed biological 

product submitted under section 351(k) 

of the PHS Act if FDA ‘‘determines that 

the information submitted in the 

application * * * is sufficient to show 

that the biological product is biosimilar 

to the reference product * * *’’ and the 

351(k) applicant (or other appropriate 

person) consents to an inspection of the 

facility that is the subject of the 

application (i.e., a facility in which the 

proposed biological product is 


sroberts on DSK5SPTVN1PROD with NOTICES