Biosimilars and Interchangeable 

Biosimilars:  Licensure for Fewer Than 

All Conditions of Use for Which the 

Reference Product Has Been Licensed 

 
Guidance for Industry 

 
 
DRAFT GUIDANCE 

 
This guidance document is being distributed for comment purposes only. 
 
Comments and suggestions regarding this draft document should be submitted within 60 days of 
publication in the Federal Register of the notice announcing the availability of the draft 
guidance.  Submit electronic comments to https://www.regulations.gov. Submit written 
comments to the Dockets Management Staff (HFA-305), Food and Drug Administration, 5630 
Fishers Lane, Rm. 1061, Rockville, MD  20852.  All comments should be identified with the 
docket number listed in the notice of availability that publishes in the Federal Register. 
 
For questions regarding this draft document, contact (CDER) Sandra Benton 301-796-1042, or 
(CBER) Office of Communication, Outreach and Development, 800-835-4709 or 240-402-8010.  
 
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 

Food and Drug Administration 

Center for Drug Evaluation and Research (CDER)
	 
Center for Biologics Evaluation and Research (CBER)
	 
 
February 2020 

Biosimilars 

   
Biosimilars and Interchangeable 

Biosimilars:  Licensure for Fewer Than 

All Conditions of Use for Which the 

Reference Product Has Been Licensed 

 
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/guidance-compliance-regulatory-information/guidances-drugs 
  
 
and/or  
 
Office of Communication, Outreach and Development  

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Food and  Drug Administration 
 
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Phone:  800-835-4709 or 240-402-8010 

Email:  ocod@fda.hhs.gov  
 
https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics/biologics-
guidances 
 
 
 
 
 
U.S. Department of Health and Human Services 

Food and Drug Administration 

Center for Drug Evaluation and Research (CDER)
	 
Center for Biologics Evaluation and Research (CBER)
	 
 
 
February 2020 

Biosimilars 

  Contains Nonbinding Recommendations 
Draft  Not for Implementation  
TABLE OF CONTENTS  
 
 
I.	 	 INTRODUCTION............................................................................................................. 1
	 
II.	 	 BACKGROUND ............................................................................................................... 2
	 
A.		  The Biosimilar Pathway ................................................................................................................ 2
	 
B.		  Licensure of a Biosimilar or Interchangeable Biosimilar for Fewer Than All of the 

Reference Products Licensed Conditions of Use........................................................................ 3
	 
III. 		 RECOMMENDATIONS FOR APPLICANTS SEEKING LICENSURE OF A 

BIOSIMILAR OR INTERCHANGEABLE BIOSIMILAR FOR FEWER THAN 

ALL OF THE REFERENCE PRODUCTS LICENSED CONDITIONS OF USE ... 4	
 
A.		  Submission of Original 351(k) BLA or Supplement to a 351(k) BLA ....................................... 4
	 
1. 	  Submission of an Original 351(k) BLA for Licensure for Fewer Than All of the Reference 

Products Licensed Conditions of Use ...................................................................................... 4
  
2. 	  Submission of a Supplement to a 351(k) BLA Seeking Licensure of a Biosimilar or 

Interchangeable Biosimilar for an Additional Condition of Use Previously Licensed for the 

Reference Product ..................................................................................................................... 5
  
B.		  Development of Draft Labeling for a Proposed Biosimilar or Interchangeable Product for 

Fewer Than All of the Reference Products Licensed Conditions of Use ................................. 5
	 
1. 	  Content of Draft Labeling ......................................................................................................... 5
  
2. 	  Information to Support Draft Labeling for a Biosimilar or Interchangeable Product for 

Fewer Than All of the Reference Products Licensed Conditions of Use ................................. 6
  
C.		  Timing Considerations for Submission of a 351(k) BLA or Supplement to a 351(k) BLA ..... 6
	 
1. 	  Targeted Timelines for Review.................................................................................................. 7
  
2. 	  Unexpired Exclusivity................................................................................................................ 8
  
3.	   Circumstances Other Than Exclusivity, Including Patents ....................................................... 8
  
 
  Contains Nonbinding Recommendations 
DraftNot for Implementation 
Biosimilars and Interchangeable Biosimilars:  Licensure for Fewer 
1 
Than All Conditions of Use for Which the Reference Product Has 
2 
Been Licensed  
3 
Guidance for Industry1  
4 
5   
6   
7  This draft guidance, when finalized, will represent the current thinking of the Food and Drug 
8  Administration (FDA or Agency)  on this topic.  It does not establish any rights for any  person and is not 
9  binding on FDA or the public.  You can use an alternative approach if it satisfies the requirements of the 
10  applicable statutes and regulations.  To discuss an alternative approach, contact the FDA staff responsible 
11  for this guidance as listed on the title page.   
12   
13   
14   
15  I.   INTRODUCTION  
16   
17  This guidance provides recommendations to applicants seeking licensure under section 351(k) of 
18  the Public Health Service (PHS) Act of a proposed biosimilar or proposed interchangeable 
19  biosimilar2 for fewer than all of the reference products licensed conditions of use.  This 
20  guidance also provides recommendations on the submission of a supplement to a licensed 351(k) 
21  biologics license application (BLA) seeking to add a condition of use that previously has been 
22  licensed3 for the reference product to the labeling4 of a licensed biosimilar or interchangeable 
23  product, including considerations related to the timing of such submissions. 
24   
25  This guidance includes recommendations regarding the following specific issues: 
26   
27     Submission of an application seeking licensure of a proposed biosimilar or proposed 
28  interchangeable biosimilar for fewer than all of the reference products licensed conditions of 
29  use. 
                                                 
1  This  draft guidance  has been prepared  by the Center for Drug Evaluation and Research (CDER) and the Center for 
Biologics Evaluation and Research (CBER) at the Food and Drug Administration  (FDA or the Agency).   
2  In  this draft guidance,  the following  terms  are used to describe biological  products licensed under  section 351(k)  of  
the PHS Act:  (1)  biosimilar or biosimilar product  refers to  a product that  FDA has determined to be biosimilar to 
the reference product (see  sections 351(i)(2)  and 351(k)(2) of  the PHS Act); and  (2) interchangeable,  
interchangeable biosimilar, or interchangeable product refers to a biosimilar product  that FDA has also  determined  
to be interchangeable with the reference product (see sections 351(i)(3)  and  351(k)(4) of the PHS Act).  
Biosimilarity, interchangeability, and  related issues are discussed in more detail  in section II of this draft  guidance. 
3 As stated in FDAs guidance for industry Considerations in  Demonstrating Interchangeability With  a  Reference 
Product (May 2019), FDA expects that applicants seeking to demonstrate interchangeability will submit  data and  
information to  support a showing that the proposed interchangeable product can be expected to produce the same  
clinical result as the reference  product in all of the reference products licensed  conditions of use.  We update 
guidances periodically.  For the most recent  version of a guidance, check the FDA  Drugs  guidance  web page at  
https://www.fda.gov/regulatory-information/search-fda-guidance-documents.  
4 Unless otherwise specified, the terms  biosimilar product  labeling and labeling as used  in this  guidance address  
only the prescribing information as described in 21 CFR 201.56 and 201.57.  
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30     Development of proposed labeling when the applicant seeks licensure of a proposed 
31  biosimilar or proposed interchangeable product for fewer than all of the reference products 
32  licensed conditions of use. 
33     Submission of a supplement to an application for a biosimilar or interchangeable biosimilar 
34  to seek licensure for a condition of use previously licensed for the reference product.  This 
35  may occur, for example, when (1) the biosimilar or interchangeable product was initially 
36  licensed for fewer than all of the reference products licensed conditions of use, or (2) the 
37  reference product is licensed for a new condition of use after licensure of the biosimilar or 
38  interchangeable product. 
39     Timing for the submission of a 351(k) BLA or supplement to a licensed 351(k) BLA 
40  described above with the goal of obtaining licensure of a condition of use for a biosimilar or 
41  interchangeable product as soon as possible after the expiration of any relevant exclusivity or 
42  patents. 
43   
44  This guidance is one in a series of guidances that FDA is developing to implement the Biologics 
45  Price Competition and Innovation Act of 2009 (BPCI Act) and includes references to 
46  information from other FDA guidances, where appropriate. 
47   
48  In general, FDAs guidance documents do not establish legally enforceable responsibilities.  
49  Instead, guidances describe the Agencys current thinking on a topic and should be viewed only 
50  as recommendations, unless specific regulatory or statutory requirements are cited.  The use of 
51  the word should in Agency guidances means that something is suggested or recommended, but 
52  not required. 
53   
54   
55  II.   BACKGROUND 
56   
57  A.   The Biosimilar Pathway  
58   
59  Section 351(k) of the PHS Act (42 U.S.C. 262(k)), added by the BPCI Act, sets forth the 
60  requirements for the licensure of a biosimilar or interchangeable biosimilar.  Section 351(i) 
61  defines biosimilarity to mean that the biological product is highly similar to the reference 
62  product notwithstanding minor differences in clinically inactive components and that there are 
63  no clinically meaningful differences between the biological product and the reference product in 
64  terms of the safety, purity, and potency of the product (section 351(i)(2) of the PHS Act).  A 
65  BLA submitted under section 351(k) (a 351(k)  BLA) must contain, among other things, 
66  information demonstrating that the biological product is biosimilar to a reference product based 
67  upon data derived from  analytical studies, animal studies,5 and a clinical study or studies, unless 
68  FDA determines, in its discretion, that certain studies are unnecessary in a 351(k) BLA (see 
69  section 351(k)(2) of the PHS Act). 
70   
                                                 
5 We support the principles of the 3Rs, to reduce, refine, and replace animal use in testing when feasible.  We  
encourage sponsors to  consult with us if it they wish to use a non-animal testing method  they  believe is suitable, 
adequate, validated, and feasible.  We will consider if such an alternative method could  be assessed  for  equivalency  
to an animal test method. 
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	 Contains Nonbinding Recommendations 
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71  To meet the standard for interchangeability, an applicant must provide sufficient information 
72  to demonstrate biosimilarity to the reference product and also to demonstrate that the biological 
73  product can be expected to produce the same clinical result as the reference product in any given 
74  patient and, if the biological product is administered more than once to an individual, the risk in 
75  terms of safety or diminished efficacy of alternating or switching between the use of the 
76  biological product and the reference product is not greater than the risk of using the reference 
77  product without such alternation or switch (see section 351(k)(4) of the PHS Act).  
78  Interchangeable biosimilars may be substituted for the reference product without the intervention 
79  of the prescribing healthcare provider (see section 351(i)(3) of the PHS Act). 
80   
81  B.   Licensure of a Biosimilar or Interchangeable Biosimilar for Fewer Than All of the 
82  Reference Products Licensed Conditions of Use 
83   
84  A biosimilar or interchangeable biosimilar may be licensed only for conditions of use that have 
85  been previously licensed for the reference product.6  An applicant generally may obtain licensure 
86  of a biosimilar or interchangeable for fewer than all of the conditions of use for which the 
87  reference product is licensed.7  However, FDA recommends that an applicant seeking licensure 
88  for a proposed interchangeable product seek licensure for all of the reference products licensed 
89  conditions of use when possible.8  
90   
91  A variety of circumstances may lead an applicant to seek licensure of a proposed biosimilar or 
92  proposed interchangeable product for fewer than all of the conditions of use for which the 
93  reference product is licensed. Examples of these circumstances are described below. 
94   
95  Orphan-drug Exclusivity 
96   
97  The reference product may be licensed for one or more indications that are protected by orphan-
98  drug exclusivity.  In such cases, until the applicable exclusivity expires, FDA will not be able to 
99  license a biosimilar or interchangeable product for the protected indications.  However, assuming 
100  that the requirements for licensure are met, FDA may be able to license a biosimilar or  
101  interchangeable product for one or more indications of the reference product that are not 
102  protected by orphan-drug exclusivity.  In such circumstances, an applicant may choose to seek 
103  licensure of a biosimilar or interchangeable product for such indications.   
104   
105  After the applicable orphan-drug exclusivity expires, the applicant may, in a supplement to the 
106  licensed 351(k) BLA, seek licensure of the biosimilar or interchangeable biosimilar for a 
                                                 
6 Section  351(k)(2)(A)(i)(III) of the PHS Act. 
7  Notably,  section 351(k)(4)(A) of  the PHS Act provides, among other things, that an application  for an  
interchangeable product must  include information  sufficient to  show that  the proposed interchangeable product can 
be expected to produce  the same clinical result as the reference product  in any given patient.  FDA expects that 
applicants seeking  to demonstrate interchangeability will submit data and information  to support a showing that the  
proposed interchangeable  product  can be expected to produce the same clinical result as the reference product in all 
of the reference products licensed  conditions of use.  Guidance for industry  Considerations in  Demonstrating 
Interchangeability With a Reference Product (May 2019).   
8 Guidance for industry  Considerations in Demonstrating Interchangeability With  a Reference Product (May 2019).  
 
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107  previously protected indication, and FDA may license the biosimilar or interchangeable 
108  biosimilar for this indication if the requirements for licensure are met.9   
109   
110  Circumstances Other Than Exclusivity  
111   
112     Patent(s) covering a licensed condition of use of the reference product:  An applicant may 
113  conclude that a licensed condition of use of the reference product is protected by one or more 
114  patent(s).  As a result, the applicant may decide not to seek licensure of a proposed biosimilar 
115  or proposed interchangeable product for conditions of use that are protected by patent, 
116  according to  the applicants own assessment. 
117   
118     Other reasons:  Reasons other than patents or exclusivity may lead an applicant to choose to 
119  seek licensure for fewer than all conditions of use for which the reference product is licensed.   
120   
121  III.   RECOMMENDATIONS FOR APPLICANTS SEEKING LICENSURE OF A 
122  BIOSIMILAR OR INTERCHANGEABLE BIOSIMILAR FOR FEWER THAN 
123  ALL OF THE REFERENCE PRODUCTS LICENSED CONDITIONS OF USE  
124   
125  A.   Submission of Original 351(k) BLA or Supplement to a 351(k) BLA  
126   
127  1.   Submission of an Original 351(k) BLA for Licensure for Fewer Than All of the 
128  Reference Products Licensed Conditions of Use 
129   
130  As part of an original 351(k) BLA, an applicant is expected to submit draft labeling that includes 
131  the conditions of use for which the applicant is seeking licensure of the proposed biosimilar or 
132  proposed interchangeable product.10, 11  Additional considerations regarding draft labeling are 
133  described in section III.B in this guidance.  Applicants may contact the appropriate review 
134  division in FDA for more information about submitting a 351(k) BLA for licensure of a 
135  proposed biosimilar or proposed interchangeable biosimilar for fewer than all of the reference 
136  products licensed conditions of use.   
137   
                                                 
9 Similarly, as provided by section 351(m) of  the PHS  Act, an additional six-month period of exclusivity will attach  
to certain applicable periods of exclusivity if the sponsor conducts pediatric studies that  meet the requirements for 
pediatric exclusivity pursuant  to section  505A of the Federal Food, Drug, and Cosmetic Act (FD&C Act).  As with 
orphan-drug  exclusivity, during the  applicable period of pediatric exclusivity FDA may be able to license a 
biosimilar or interchangeable product for one or more indications of  the reference product  that are not protected by 
such exclusivity, and FDA may license the biosimilar or interchangeable biosimilar for a previously protected 
indication  after the applicable pediatric exclusivity expires. 
10 FDA  has issued draft  guidance regarding the submission of  data and information to support approval  of a 
proposed  biosimilar or interchangeable product for an  indication for which  the reference  product  has unexpired  
exclusivity.  See Q.I.24 in the draft guidance  for industry New and Revised Draft Q&As on Biosimilar Development 
and the BPCI Act (Revision 2) (December 2018).  When  finalized, this guidance will represent FDAs current 
thinking on this topic. 
11  See section  351(k)(2)(A)(i)(III) of  the PHS Act, which requires that a 351(k) application include information 
demonstrating  that the condition or conditions of use prescribed,  recommended, or suggested in  the labeling 
proposed  for the biological  product  have  been  previously  approved for  the  reference  product. 
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138  2.   Submission of a Supplement to a 351(k) BLA Seeking Licensure of a Biosimilar or 
139  Interchangeable Biosimilar for an Additional Condition of Use Previously Licensed 
140  for the Reference Product 
141   
142  The holder of a licensed 351(k) BLA may, in a supplement to the 351(k) BLA, seek licensure of 
143  its biosimilar or interchangeable biosimilar for an additional condition of use that has been 
144  previously licensed for the reference product and for which the applicant did not originally seek 
145  licensure.  A 351(k) BLA holder seeking licensure for an additional condition of use must submit 
146  a supplement in accordance with 21 CFR 601.12 seeking licensure of the proposed change.  See 
147  section III.C. 
148   
149  A supplement to a 351(k) BLA seeking licensure of a biosimilar or interchangeable biosimilar 
150  for an additional condition of use should contain all the data and information needed to support 
151  licensure of the biosimilar or interchangeable biosimilar for the proposed condition of use, which 
152  may include reference to data and information previously submitted to the 351(k) BLA with 
153  appropriate scientific justification.  Applicants may contact the appropriate clinical review 
154  division at FDA for more information about licensure of a biosimilar or interchangeable 
155  biosimilar in such circumstances. 
156   
157  B.   Development of Draft Labeling for a Proposed Biosimilar or Interchangeable 
158  Product for Fewer Than All of the Reference Products Licensed Conditions of Use 
159  FDAs guidance for industry Labeling for Biosimilar Products (Biosimilar Labeling  
160  Guidance), provides general recommendations on the development of draft labeling for 
161  proposed biosimilar products for submission in a 351(k) BLA.12  In the Biosimilar Labeling 
162  Guidance, FDA recommends that labeling for a biosimilar product incorporate relevant data and 
163  information from  the reference product labeling, with appropriate modifications.  The Biosimilar 
164  Labeling Guidance also explains that determining which data and information from  the reference 
165  product labeling should be incorporated into the proposed labeling for a biosimilar will depend 
166  on whether the applicant is seeking licensure for allor fewer than allof the conditions of use 
167  licensed for the reference product. 
168   
169  1.   Content of Draft Labeling 
170   
171  The applicant should develop draft labeling for the proposed biosimilar or proposed 
172  interchangeable biosimilar that includes information from  the  reference product labeling that is 
173  relevant to the proposed conditions of use for the proposed biosimilar or interchangeable, with 
174  appropriate modifications.  In preparing such draft labeling, the applicant should carefully 
175  scrutinize the content of all sections of the labeling to ensure that relevant information is 
                                                 
12 See guidance  for  industry  Labeling for Biosimilar Products (July 2018), which  states that it does not provide 
specific labeling recommendations for interchangeable products and that any specific recommendations for 
interchangeable products will be provided  in future guidance.   
 
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176  included, based on the proposed conditions of use for the proposed biosimilar or interchangeable 
177  product.13  
178   
179  FDA will evaluate the labeling to determine whether it complies with applicable requirements.14   
180  For example, the labeling must summarize the essential scientific information needed for the safe 
181  and effective use of the product.15  FDA regulations also require that prescription drug labeling 
182  contain:   
183   
184  adequate information ... including indications, effects, dosages, routes, methods, 
185  and frequency and duration of administration and any relevant warnings, hazards, 
186  contraindications, side effects, and precautions, under which practitioners licensed 
187  by law to administer the drug can use the drug safely and for the purposes for 
188  which it is intended ...16  
189   
190  2.   Information to Support Draft Labeling for a Biosimilar or Interchangeable Product 
191  for Fewer Than All of the Reference Products Licensed Conditions of Use 
192   
193  In general, FDA does not expect an applicant to submit a justification for the applicants decision 
194  not to seek licensure of a biosimilar for all of the reference products licensed conditions of use.  
195  FDA does not consider the applicability of patents to a proposed biosimilar product (e.g., the 
196  validity or enforceability of patents or potential infringement) in its review of a 351(k) BLA or 
197  supplement to a 351(k) BLA.17  An applicant seeking licensure of a biosimilar or interchangeable 
198  biosimilar for fewer than all of the reference products licensed conditions of use may, in a 
199  351(k) BLA or a supplement to a 351(k) BLA, submit information that is intended to  inform  
200  FDAs review of the draft labeling.  For example, an applicant may submit a justification as to 
201  why, in the applicants view, the draft labeling meets the requirements for approval, considering 
202  the conditions of use for which the applicant is seeking licensure. 
203   
204  C.   Timing Considerations for Submission of a 351(k) BLA or Supplement to a 351(k) 
205  BLA 
206   
207  The recommendations in this section are intended  to facilitate submission of a 351(k) BLA or 
208  supplement to a licensed 351(k) BLA with the goal of obtaining licensure of a biosimilar or 
209  interchangeable biosimilar soon after expiration of any relevant exclusivity or expiration of a 
                                                 
13 For example, as noted  in the guidance  for  industry  Labeling for Biosimilar Products  (July 2018), in certain 
circumstances it  may  be necessary to  include information in the biosimilar product  labeling relating to an 
indication(s)  for which the biosimilar product is not  licensed, in order to help ensure safe use ...  Additionally, 
although  biosimilar labeling need not  be identical to reference  product  labeling,  deviations should  be  carefully  
considered to  ensure that the condition or conditions of use prescribed, recommended, or suggested in the draft 
labeling for the  proposed  biosimilar product  have  been  previously approved for the  reference product (see section  
351(k)(2)(A)(i)(III) of the PHS Act). 
14 See, e.g., 21 CFR 201.56 and 21 CFR 201.57.  
15 See 21 CFR 201.100 and 201.56(a)(1).  
16 See 21 CFR  201.100(d)(1) (emphasis added).  
17 For more information  about the exchange of confidential information for purposes of  determining whether a claim  
of patent  infringement could reasonably  be asserted against  a 351(k) applicant, refer to section  351(l) of the PHS Act 
(42 U.S.C. 262(l)).  
 
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210  patent that, in the 351(k) applicants assessment, protects a licensed condition of use of the 
211  reference product. These recommendations also are applicable to a supplement to a licensed 
212  351(k) BLA that seeks licensure of a biosimilar or interchangeable biosimilar for an additional 
213  condition of use for which the applicant did not originally seek licensure but that has since been 
214  licensed for the reference product. 
215   
216  1.   Targeted Timelines for Review  
217   
218  Original 351(k) BLA 
219  As described in the Biosimilar User Fee Act (BsUFA) II Goals Letter, FDA is committed to 
220  reviewing and acting on original 351(k) BLAs within 10 months of the 60-day filing date.18    
221   
222  Supplements to a Licensed 351(k) BLA 
223  In the BsUFA II Goals Letter, FDA also committed to reviewing and acting on original 351(k) 
224  BLA supplements with clinical data within 10 months of receipt.19  In light of the anticipated 
225  FDA review burden (among other considerations), FDA anticipates that it will review and act on 
226  many supplements seeking licensure for additional conditions of use for a licensed biosimilar or 
227  interchangeable product before the BsUFA goal date.  To the extent practicable, FDA intends 
228  that a supplement to a licensed 351(k) BLA seeking licensure of the biosimilar or 
229  interchangeable product for an additional condition of use that has been previously licensed for 
230  the reference product will be reviewed and acted upon in a 6-month timeframe, without regard to 
231  whether the biosimilar or interchangeable product was initially licensed for fewer than all of the 
232  reference products licensed conditions of use or the reference product is licensed for a new 
233  condition of use after licensure of the biosimilar or interchangeable product.  
234   
235  FDA recognizes that targeting a 6-month timeline for such supplements may surpass, in many 
236  cases, the performance goal commitment FDA made in the BsUFA II Goals Letter.  Supplements 
237  seeking licensure for additional conditions of use for a licensed biosimilar or interchangeable 
238  product likely will include clinical data or reference clinical data submitted previously to the 
239  351(k) BLA. As noted, the BsUFA II Goals Letter describes a 10-month goal date for original 
240  351(k) BLA supplements with clinical data.  However, at this time, FDA believes that a review 
241  timeframe of 6 months will generally be appropriate for a supplement to a licensed 351(k) BLA 
242  seeking licensure of the biosimilar or interchangeable product for an additional condition of use 
243  that has been previously licensed for the reference product, assuming the supplement does not 
244  raise novel review issues. Among other considerations, this is based on the anticipated FDA 
245  review burden associated with these types of supplements.  FDA intends to notify applicants in 
246  an acknowledgement letter if it believes that the 10-month review timeline described in the 
247  BsUFA II Goals Letter is more appropriate for any such supplement.  
248   
249     
                                                 
18 See Biosimilar Biological Product Reauthorization Performance Goals and Procedures  Fiscal Years 2018
  
through 2022 (BsUFA II Goals Letter) at https://www.fda.gov/media/100573/download. 

19 See BsUFA II Goals Letter.  

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250  2.   Unexpired Exclusivity 
251   
252  The Agency cannot license a biosimilar or interchangeable product for an indication protected by 
253  orphan-drug exclusivity or pediatric exclusivity until the expiration of that exclusivity.20  If an 
254  applicants proposed labeling includes conditions of use that are protected by unexpired orphan-
255  drug exclusivity or unexpired pediatric exclusivity, the Agency may communicate this issue to 
256  the applicant in the Day 74 letter.21  In these circumstances, an applicant may seek to time the 
257  submission of a 351(k) BLA or supplement to a 351(k) BLA with the goal of obtaining licensure 
258  after a specific date, such as the expiration of orphan-drug or  pediatric exclusivity.  
259   
260  3.   Circumstances Other Than Exclusivity, Including Patents 
261   
262  As described above, an applicant may choose to seek licensure of a proposed biosimilar or 
263  interchangeable biosimilar for fewer than all of the reference products licensed conditions of use 
264  based on an assessment by the applicant that one or more of the reference products licensed 
265  conditions of use is protected by patent.  In these circumstances, an applicant may seek to time 
266  the submission of a 351(k) BLA or supplement to a 351(k) BLA with the goal of obtaining 
267  licensure after a specific date, such as the expiration of a patent.  Other nonpatent reasons may 
268  also lead an applicant to take this approach.   
269   
270  In contrast to orphan-drug and pediatric exclusivity, the BPCI Act does not limit FDAs ability to 
271  license a 351(k) BLA or a supplement to a 351(k) BLA where a biosimilar seeks licensure for a 
272  condition of use which may be subject to one or more patents.  FDA may therefore license the 
273  product for such condition of use if FDA determines that the requirements for licensure have 
274  been met. 
275   
276  Applicants should be aware that FDA may review and act on (i.e., license or issue a complete 
277  response letter to)22 a 351(k) BLA or supplement to a 351(k) BLA before any applicable BsUFA 
278  goal date or 6-month targeted review timeline.  If an applicant does not want FDA to take action 
279  on a 351(k) BLA or supplement to a 351(k) BLA before a specified date, the applicant should 
280  request that the Agency refrain from  acting on the BLA or supplement before the specified date, 
281  so long as that date falls on or before the applicable BsUFA goal date. 
282   
283  To request that FDA not take action on a 351(k) BLA or supplement to a 351(k) BLA before a 
284  specified date, the applicant should include the following language on the cover letter of their 
285  BLA or supplement, in bold typeface and prominently placed above the body of the cover letter: 
286   
287  351(k) BLA action timing request: [Applicant Name] requests that FDA not 
288  take action on this [application/supplement] before [specified date].  
289   
290  If the applicant requests that FDA refrain from  taking action on the 351(k) BLA or a supplement 
291  to a 351(k) BLA until a specified date that is on or before any applicable BsUFA goal date, the 
                                                 
20 See section 527 of the FD&C Act; section  351(m) of the PHS Act; 21 CFR 316.31.  
21 See BsUFA II Goals Letter, p.  10. 
22 See BsUFA II  Goals Letter,  p. 32  (defining  review and act  on to mean the issuance of a complete action letter 
after complete review of a filed  complete application). 
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292  Agency intends to honor the applicants request, where appropriate.  Applicants should take 
293  BsUFA goal dates into consideration before making such requests.  If the requested date extends 
294  beyond any applicable BsUFA goal date, the Agency does not intend to honor the applicants 
295  request. 
296   
297  Upon receipt of the 351(k) BLA or supplement to a 351(k) BLA containing a request not to act 
298  before any applicable BsUFA goal date (or another specified date prior to a BsUFA goal date), 
299  FDA intends to acknowledge the applicants request along with the date of receipt of the 351(k) 
300  BLA or supplement to a 351(k) BLA through an acknowledgment letter.   
301   
302  Applicants may contact the appropriate review division in FDA with specific questions about the 
303  timing of submission for a 351(k) BLA or supplement to a 351(k) BLA.  
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