Classification Categories for 
Certain Supplements Under 
BsUFA III 
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DRAFT GUIDANCE 
 
  This guidance document is being distributed for comment purposes only.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publication in the Federal Register of the notice announcing the availability of the draft 
guidance.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 at 301-796-1042 or 
(CBER) Office of Communication, Outreach and Development, at 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) 
 
August 2023  
Biosimilars 
   
Classification Categories for 
Certain Supplements Under 
BsUFA III 
 
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  
Center for Biologics Evaluation and Research 
 Food and Drug Administration 
10903 New Hampshire Ave., Bldg. 71, Room 3128 
Silver Spring, MD 20993-0002 
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) 
 
August 2023 
Biosimilars 
  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
TABLE OF CONTENTS 
 
 
 
I.  INTRODUCTION............................................................................................................. 1 
II.  BACKGROUND ............................................................................................................... 3 
III.  DISCUSSION .................................................................................................................... 3 
A.  General Considerations ................................................................................................................. 3 
1. How to Submit .................................................................................................................................. 4 
2. Performance Goals .......................................................................................................................... 5 
B.  Classification Categories ............................................................................................................... 6 
1. Category A  Safety Information ..................................................................................................... 6 
2. Category B  Additional Indication(s) Without New Data Sets ....................................................... 7 
3. Category C  Removal of Indication(s) ........................................................................................... 8 
4. Category D  Additional Indication(s) With New Data Sets or Without New Data ........................ 9 
Sets But Subject To Section 505B(a) of the FD&C Act and Does Not Contain An Up-To-Date 
Agreed iPSP ......................................................................................................................................... 9 
5. Category E  Additional Indication(s) With Efficacy Data Sets ...................................................... 9 
6. Category F  Interchangeability .................................................................................................... 10 
  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
1  Classification Categories for Certain Supplements Under BsUFA III 
2  Guidance for Industry 1 
3   
4   
5   
6  This draft guidance, when finalized, will represent the current thinking of the Food and Drug 
7  Administration (FDA or Agency) on this topic.  It does not establish any rights for any person and is not 
8  binding on FDA or the public.  You can use an alternative approach if it satisfies the requirements of the 
9  applicable statutes and regulations.  To discuss an alternative approach, contact the FDA staff responsible 
10  for this guidance as listed on the title page.   
11   
12   
13   
14  I.  INTRODUCTION  
15   
16  This guidance provides recommendations for applicants and FDA review staff on classification 
17  categories A, B, C, D, E, and F for original and resubmitted prior approval supplements 
18  (hereafter referred to as PAS or supplements) submitted to approved applications under section 
19  351(k) of the Public Health Service Act (PHS Act) (42 U.S.C. 262(k)).2 The commitment letter 
20  associated with the Biosimilar User Fee Amendments of 2022 (BsUFA III) sets forth these 
21  supplement classification categories and their associated review performance goals (refer to 
22  Section I.A. of the BsUFA III commitment letter).3 This guidance is intended to help applicants 
23  identify the appropriate classification category and review goal date of the supplement being 
24  submitted.     
25   
26  The classification categories pertain to supplements for biosimilar and interchangeable 
27  biosimilar4 products for applicants seeking the following: 
28   
 
1 This 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). 
 
2 In this guidance, supplement refers to a request to FDA to approve a change in a biosimilar biological product 
application which has been approved, including a supplement requesting that FDA determine that the biosimilar 
biological product meets the standards for interchangeability. See section 744G(14) of the Federal Food, Drug, and 
Cosmetic Act (FD&C Act). The term biosimilar biological product application is defined in section 744G(4) of the 
FD&C Act, and applications under section 351(k) of the PHS Act discussed in this guidance are limited to those 
applications that meet the definition of biosimilar biological product application in section 744G(4). 
 
3 See the BsUFA III commitment letter titled Biosimilar Biological Product Reauthorization Performance Goals 
and Procedures Fiscal Years 2023 Through 2027 available on the FDA website at 
https://www.fda.gov/media/152279/download  
 
4 In this 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 biological product that FDA has determined to be 
biosimilar to the reference product (see sections 351(i)(2) and (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 (k)(4) of the PHS Act). 
  1  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
29    To update Prescribing Information and, if applicable, FDA-approved patient labeling 
30  (e.g., Patient Package Insert, Medication Guide, Instructions for Use)5 with safety 
31  information that has been updated in the reference product6 labeling and is applicable to 
32  one or more indications for which the biosimilar or interchangeable biosimilar product is 
33  licensed  
34   
35    To receive licensure for an additional indication 
36   
37    To remove an approved indication 
38   
39    To receive an initial determination of interchangeability 
40   
41  Supplements to approved 351(k) biologics license applications (BLAs) that do not meet the 
42  criteria under Categories A through F are outside the scope of this guidance and will not be 
43  addressed here. 
44   
45  When submitting supplements seeking to update labeling information, applicants should note 
46  that biosimilar and interchangeable biosimilar product labeling must meet the content and format 
47  requirements of the physician labeling rule7 as described in 21 CFR 201.56(d) and 201.57.8 
48  Additionally, applicants should consider all relevant FDA guidance documents for 
49  recommendations on the information that should be submitted to support a given change. If, after 
50  consulting the relevant guidances, an applicant has additional questions, such as whether the 
51  supplement classification categories described in this guidance apply to a supplement, or what 
52  information should be submitted in a supplement to support a particular labeling change, the 
53  applicant can consult the appropriate FDA review staff for advice. 
54   
55  In general, FDAs guidance documents do not establish legally enforceable responsibilities. 
56  Instead, guidances describe the Agencys current thinking on a topic and should be viewed only 
57  as recommendations, unless specific regulatory or statutory requirements are cited. The use of 
58  the word should in Agency guidances means that something is suggested or recommended, but 
59  not required.  
60   
 
 
5 Unless otherwise specified, the term labeling as used in this guidance refers only to the Prescribing Information as 
described in 21 CFR 201.56 and 201.57 and FDA-approved patient labeling (e.g., Patient Information, Medication 
Guide, and Instructions for Use). 
 
6 The term reference product means the single biological product licensed under section 351(a) of the PHS Act 
against which a biological product is evaluated in a 351(k) application (section 351(i)(4) of the PHS Act). 
 
7 See the final rule Requirements on Content and Format of Labeling for Human Prescription Drug and Biological 
Products (71 FR 3922, January 24, 2006). This rule is commonly referred to as the physician labeling rule because 
it addresses prescription drug labeling that is used by prescribing physicians and other health care providers. 
 
8 21 CFR 201.56(c)(1). See the guidance for industry Labeling for Biosimilar Products (July 2018). We update 
guidances periodically. For the most recent version of a guidance, check the FDA guidance web page at 
https://www.fda.gov/regulatory-information/search-fda-guidance-documents.  
 
  2  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
61  II.  BACKGROUND 
62   
63  Section 351(k) of the PHS Act provides an abbreviated licensure pathway for biological products 
64  shown to be biosimilar to, or interchangeable with, an FDA-licensed reference product (hereafter 
65  referred to as 351(k) BLA). Several circumstances may lead the applicant of an approved 351(k) 
66  BLA to seek to amend its labeling. One circumstance could be when the holder of a licensed 
67  351(k) BLA seeks to include safety labeling updates following revisions to the approved labeling 
68  of the reference product, where the revisions are applicable to one or more conditions of use for 
69  which the biosimilar or interchangeable biosimilar product is licensed. Another circumstance 
70  could be that following approval, an applicant may choose to remove from the Prescribing 
71  Information an indication for which the applicant sought and received licensure. Additionally, an 
72  applicant of an approved biosimilar or interchangeable biosimilar product may submit a 
73  supplement to seek licensure for an additional indication previously licensed for the reference 
74  product. This may occur, for example, when (1) the biosimilar or interchangeable biosimilar 
75  product was initially licensed for fewer than all of the reference products licensed conditions of 
76  use9 or (2) the reference product is licensed for a new condition of use after licensure of the 
77  biosimilar or interchangeable biosimilar product. Furthermore, after receiving licensure initially 
78  as only a biosimilar product, an applicant may submit a supplement to seek licensure as an 
79  interchangeable biosimilar. 
80   
81  In previous authorizations of BsUFA, FDAs review performance goals did not include 
82  commitments specifically related to various types of labeling changes. For BsUFA III, the 
83  commitment letter sets forth specific categories (categories A, B, C, D, E, and F) for supplements 
84  seeking to update biosimilar and interchangeable biosimilar product labeling, and FDA 
85  committed to specific review performance goals associated with those categories. FDA is 
86  committed to continuing to ensure effective scientific coordination and review consistency, as 
87  well as efficient governance and operations across the biosimilar product review program. These 
88  supplement categories will help to ensure consistent processes for reviewing these supplements 
89  across review divisions.  
90   
91  III.  DISCUSSION 
92   
93  A.  General Considerations 
94   
95  Generally, only one 351(k) BLA supplement classification category will be assigned to a 
96  submission. Applicants should submit separate supplements using the appropriate classification 
97  categories if multiple types of labeling changes are being requested that fall within different 
98  classification categories.   
99   
 
9 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). 
  3  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
100  FDA will confirm the appropriateness of the classification proposed by the applicant after receipt 
101  of the submission and will also assign the appropriate review timeline. If FDA disagrees with the 
102  applicants proposed classification, additional information may be requested by FDA, and FDA 
103  intends to notify the applicant of the appropriate classification category.   
104   
105  FDAs goal is to issue a letter to the applicant for original Category A through D supplements 
106  within 60 calendar days of receipt. The letter will acknowledge receipt of the submission and 
107  provide the date for FDA to take action on the supplement. FDAs goal is to issue a filing letter 
108  to the applicant for original Category E and F supplements within 74 calendar days of receipt. 
109  Consistent with the underlying principles articulated in the Good Review Management Principles 
110  and Practices (GRMP) guidance, the letter will acknowledge receipt of the submission and 
111  inform the applicant of the planned review timeline and whether substantive review issues were 
112  identified. If no substantive review issues were identified during the filing review, FDA will so 
113  notify the applicant. 
114   
115  Applicants may refer to the Section I.A. of the BsUFA III commitment letter, which provides 
116  more information about these goals and sets forth the associated review performance goals for 
117  these supplement classification categories.10 
118   
119  If an applicant would like to propose further updates to its biosimilar or interchangeable 
120  biosimilar product labeling during the intervening period between the submission of a PAS and 
121  before action is taken by FDA, FDA generally recommends that the 351(k) applicant submit a 
122  new PAS proposing such additional changes instead of adding such changes to the pending PAS 
123  and note the appropriate classification category.  
124   
125  1.  How to Submit 
126   
127  a.  FDA form 
128   
129  When applicants submit a supplement for one of the categories described in this guidance, FDA 
130  recommends that applicants select other when completing Form FDA 356h, Application to 
131  Market a New or Abbreviated New Drug or Biologic for Human Use, and fill in biosimilar 
132  supplement category [X] in line 21 of the application information block. This will allow rapid 
133  identification and processing of the submitted supplements. 
134   
135  b.  Cover letter considerations  
136   
137  Applicants should prominently identify the submission with the following wording in bold 
138  capital letters at the top of the first page of the submission, as appropriate: 
139    
 
10 See the BsUFA III commitment letter titled Biosimilar Biological Product Reauthorization Performance Goals 
and Procedures Fiscal Years 2023 Through 2027 available on the FDA website at 
https://www.fda.gov/media/152279/download  
  4  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
140  NEW SUPPLEMENT FOR BLA ###### 
141  PRIOR APPROVAL SUPPLEMENT  BIOSIMILAR CATEGORY [X] or 
142  RESUBMITTED SUPPLEMENT FOR BLA ######/S-XXX -  
143  PRIOR APPROVAL SUPPLEMENT  BIOSIMILAR CATEGORY [X]  
144   
145  Applicants should clearly and briefly state the basis for the proposed supplement category in the 
146  supplement submission. 
147   
148  Applicants should be aware that FDA may review and act on (i.e., license or issue a complete 
149  response letter to) a supplement to a 351(k) BLA before any applicable BsUFA goal date. If an 
150  applicant does not want FDA to take action on a supplement to a 351(k) BLA before a specified 
151  date, the applicant should request that FDA refrain from acting on the supplement before the 
152  specified date, as long as that date falls on or before the applicable BsUFA goal date.11 To 
153  request that FDA not take action on a supplement to a 351(k) BLA before a specified date, the 
154  applicant should include the following language prominently on the cover page of the 
155  supplement above the body of the cover letter using the bold typeface as shown below: 
156   
157  351(k) BLA action timing request: [Applicant Name] requests that FDA not take action 
158  on this supplement before [specified date]. 
159   
160  c.  Labeling submission 
161   
162  The applicant is required to describe the proposed change(s) in the labeling and include the 
163  information necessary to support the proposed change(s).12 , For recommendations regarding 
164  how to submit initial and revised labeling, please refer to the guidance for industry Labeling for 
165  Biosimilar Products (July 2018).13 
166   
167  2.  Performance Goals 
168   
169  The following table summarizes the BsUFA III performance goals for review of 351(k) BLA 
170  supplement Categories A through F.14 
171   
 
11 See also the timing considerations for submission of a 351(k) BLA or supplement to a 351(k) BLA in the draft 
guidance for industry Biosimilars and Interchangeable Biosimilars: Licensure for Fewer Than All Conditions of Use 
for Which the Reference Product Has Been Licensed (February 2020). When final, this guidance will represent the 
FDAs current thinking on this topic.   
 
12 21 CFR 601.12(f)(1). 
 
13 See the guidance for industry Labeling for Biosimilar Products (July 2018). See also Q.I.27 in the draft guidance 
for industry, Biosimilarity and Interchangeability: Additional Draft Q&As on Biosimilar Development and the BPCI 
Act (November 2020); when final, this guidance will represent the FDAs current thinking on this topic. 
 
14 See the BsUFA III commitment letter titled Biosimilar Biological Product Reauthorization Performance Goals 
and Procedures Fiscal Years 2023 Through 2027 available on the FDA website at: 
https://www.fda.gov/media/152279/download. 
 
  5  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
172  Table 1: BsUFA III Performance Goals 
173   
Category  Category   Acknowledgement  Action Timelines: 
Description  or Filing Letter  Original Submission / 
Timeline  Resubmission 
A  Safety Information  Acknowledgement  3 months / 3 months 
within 60 calendar 
B  Additional  4 months / 4 months 
days of receipt 
Indication(s) Without 
New Data Sets 
C  Removal of 
Indication(s) 
D  Additional  6 months / 6 months 
Indication(s) With 
New Data Sets or 
Without New Data 
Sets But Subject To 
Section 505B(a) of 
the FD&C Act and 
Does Not Contain An 
Up-To-Date Agreed 
iPSP 
E  Additional  Filing letter within  10 months / 6 months 
Indication(s) With  74 calendar days of 
Efficacy Data Sets  receipt 
F  Initial Determination 
of Interchangeability 
174   
175  B.  Classification Categories 
176   
177  1.  Category A  Safety Information  
178   
179  Category A is for a 351(k) BLA supplement seeking to update the labeling for a licensed 
180  biosimilar or interchangeable biosimilar product with safety information that has been updated in 
181  the reference product labeling and is applicable to one or more indications for which the 
182  biosimilar or interchangeable biosimilar product is licensed. For purposes of this classification 
183  category, FDA considers safety information to have been updated in the reference product 
184  labeling after FDA has approved a supplement for the reference products labeling change. 
185  Biosimilar and interchangeable biosimilar product labeling should incorporate relevant data and 
186  information from the reference product labeling, with appropriate modifications.15  When new 
187  information becomes available that causes information in labeling to be inaccurate, false, or 
188  misleading, the application holder must take steps to change the content of its product labeling, 
 
15 See the guidance for industry Labeling for Biosimilar Products (July 2018). See also Q.I.27 in the draft guidance 
for industry, Biosimilarity and Interchangeability: Additional Draft Q&As on Biosimilar Development and the BPCI 
Act (November 2020); when final, this guidance will represent the FDAs current thinking on this topic. 
 
  6  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
189  in accordance with 21 CFR 601.12. 16 All holders of marketing applications for biological 
190  products have an ongoing obligation to ensure their labeling is accurate and up-to-date.17   
191   
192  FDA anticipates Category A supplements to be straightforward changes incorporating safety 
193  labeling updates approved for the reference product labeling that also apply to the biosimilar or 
194  interchangeable biosimilar product labeling. If additional changes beyond safety information are 
195  proposed to the biosimilar or interchangeable biosimilar product labeling, then Category A 
196  would not be considered the appropriate supplement category.   
197   
198  In the occasional circumstance where safety information (approved in the reference product 
199  labeling)18 being updated in the biosimilar or interchangeable biosimilar product labeling 
200  includes related changes to container label(s) and carton labeling, FDA generally intends to 
201  review the revised container label(s) and carton labeling in the same Category A supplement.  
202   
203  2.  Category B  Additional Indication(s) Without New Data Sets  
204   
205  Category B is for a 351(k) BLA supplement seeking licensure for an additional indication for a 
206  licensed biosimilar or interchangeable biosimilar product when the submission does not include 
207  new data sets (other than analytical in vitro data obtained by use of physical, chemical and/or 
208  biological function assays, if needed to support the scientific justification for extrapolation), 
209  provided that:  
210   
211    The supplement does not seek a new route of administration, dosage form, dosage 
212  strength, formulation, or presentation; and  
213   
214    The supplement contains an up-to-date agreed initial pediatric study plan (iPSP) if the 
215  supplement is subject to section 505B(a) of the Federal Food, Drug, and Cosmetic Act 
216  (FD&C Act). For purposes of this commitment, FDA considers an up-to-date agreed 
217  iPSP to be an agreed iPSP that addresses Pediatric Research Equity Act (PREA) 
218  requirements for the additional indication proposed for licensure.19 
219   
220  For example, an applicant may have previously submitted data and information to support 
221  approval of a proposed biosimilar or interchangeable biosimilar product for one or more 
222  indications for which the reference product had unexpired orphan or pediatric exclusivity or was 
 
16 See e.g., 21 CFR 201.56(a)(2): In accordance with . . . [21 CFR 601.12], the labeling must be updated when new 
information becomes available that causes the labeling to become inaccurate, false, or misleading. 
 
17 Id. 
 
18 For more information about safety information on container labels and carton labeling see the guidance for 
industry Safety Considerations for Container Labels and Carton Labeling Design to Minimize Medication Errors 
(May 2022). 
 
19 FDA has issued final guidance about how a proposed biosimilar applicant can fulfill the requirement for pediatric 
assessments or investigations under PREA. See Q.I.16 in the guidance for industry Questions and Answers on 
Biosimilar Development and the BPCI Act (September 2021). 
 
  7  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
223  protected by a patent at the time of the submission. If the applicant subsequently submits a 
224  supplement seeking licensure for the previously protected indications after the applicable 
225  exclusivities or patent protections expire,20 such supplement would be appropriately categorized 
226  as a Category B, subject to the limitations described in the two bullets above. 
227   
228  The inclusion in a 351(k) BLA supplement of scientific justifications to support the extrapolation 
229  of data and information in the application to support licensure for the indication(s) being added 
230  in the supplement, or where applicable, the inclusion of a cross-reference to a prior submission to 
231  the BLA where such scientific justification was previously included, would be consistent with 
232  classification of the supplement as Category B. 
233   
234  A supplement subject to PREA would be categorized as Category B only if it includes an up-to-
235  date agreed iPSP. For purposes of this commitment, FDA generally considers a supplement to 
236  include an agreed iPSP if it cross references a prior submission to the application that includes 
237  such agreed iPSP. As noted, an agreed iPSP is considered up-to-date for purposes of this 
238  commitment if it addresses PREA requirements for the additional indication(s) proposed for 
239  licensure in the supplement.   
240   
241    If the supplement would otherwise fall under Category B, but FDA has not confirmed 
242  agreement on the iPSP, the supplement should be submitted as a Category D supplement 
243  (see Category D below).  
244   
245  As a general reminder, as noted in the guidance for industry Pediatric Study Plans: Content of 
246  and Process for Submitting Initial Pediatric Study Plans and Amended Initial Pediatric Study 
247  Plans (July 2020), a sponsor should not submit a marketing application or supplement that is 
248  subject to PREA until FDA confirms agreement on the iPSP. 
249   
250  3.  Category C  Removal of Indication(s) 
251   
252  Category C is for 351(k) BLA supplements seeking to remove an approved indication for a 
253  licensed biosimilar or interchangeable biosimilar product. 
254   
255  The applicant seeking removal of a previously licensed indication must submit in a supplement 
256  information necessary to support the labeling change.21    
257   
258  Applicants are encouraged to include supporting labeling documentation in their supplement 
259  describing how removing indication(s) affects other sections of the labeling, and whether these 
260  sections need revisions, based on the proposed removal of indication(s), and how revisions to 
261  any related data have been approached.   
 
20 FDA has issued 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 orphan 
exclusivity. See Q.I.24 in the guidance for industry Questions and Answers on Biosimilar Development and the 
BPCI Act (September 2021). 
 
21 21 CFR 601.12(f)(1). 
 
  8  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
262   
263  4.  Category D  Additional Indication(s) With New Data Sets or Without New Data  
264  Sets But Subject To Section 505B(a) of the FD&C Act and Does Not Contain An 
265  Up-To-Date Agreed iPSP 
266   
267  Category D is for 351(k) BLA supplements seeking licensure for an additional indication for a 
268  licensed biosimilar or interchangeable biosimilar product when the submission either: 
269   
270    Contains new data sets other than 1) efficacy data, 2) data to support a supplement 
271  seeking an initial determination of interchangeability, or 3) only analytical in vitro data 
272  obtained by use of physical, chemical, and/or biological function assays. Examples of 
273  datasets consistent with this supplement type include those from studies supporting a new 
274  presentation associated with an added indication, such as a comparative human factors 
275  study or comparative PK studies. 
276    Or, 
277    Does not contain new data sets with the exception of analytical in vitro data obtained by 
278  use of physical, chemical, and/or biological function assays but is subject to section 
279  505B(a) of the FD&C Act, and the supplement does not contain an up-to-date agreed 
280  iPSP that addresses PREA requirements for the additional indication(s) proposed for 
281  licensure.  
282   
283  A supplement to an approved 351(k) BLA that triggers PREA would not be eligible for Category 
284  B but may be eligible for Category D if the applicant does not have an up-to-date agreed iPSP 
285  addressing the additional indication(s) being sought. One such Category D scenario is as follows: 
286  If an applicant submits a supplement before FDA has confirmed agreement on the iPSP, then the 
287  supplement would not be eligible for Category B but could be eligible for Category D, regardless 
288  of whether the applicant submits a pediatric assessment in the supplement.  
289   
290  5.  Category E  Additional Indication(s) With Efficacy Data Sets 
291   
292  Category E is for 351(k) BLA supplements for a licensed biosimilar or interchangeable 
293  biosimilar product seeking licensure for an additional indication that has been previously 
294  approved for the reference product and where the submission contains efficacy data sets.  
295  A Category E supplement may be appropriate in the unlikely scenario where, subsequent to an 
296  initial 351(k) BLA approval, an additional indication is being sought which was approved for the 
297  reference product after the initial 351(k) BLA approval and uses a novel mechanism of action, 
298  for which a comparative clinical study is necessary. Given that, in general, the mechanism(s) of 
299  action of a product are known and the discovery of novel mechanism(s) of action unlikely, FDA 
300  expects these supplements to be exceedingly rare. 
301   
302  Applicants are strongly encouraged to discuss any planned Category E submissions with FDA in 
303  an appropriate Biosimilar Biological Product Development (BPD) meeting before submission of 
304  the supplement.22 
 
22 See the draft guidance for industry Formal Meetings Between the FDA and Sponsors or Applicants of BsUFA 
Products (Rev 1) (August 2023). When final, this guidance will represent the FDAs current thinking on this topic. 
 
  9  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
305   
306  6.  Category F  Interchangeability 
307   
308  Category F is for 351(k) BLA supplements seeking an initial determination of interchangeability.  
309   
310  For a product first licensed as a biosimilar to the reference product, the applicant may later seek 
311  licensure of the biosimilar product as an interchangeable biosimilar product in a supplement.23    
312   
313  Category F supplements may include, for example, a clinical study report for a switching study 
314  or a scientific justification for not needing such data as part of the demonstration of 
315  interchangeability in the submission. 
316   
317   
 
23 See the guidance for industry Considerations in Demonstrating Interchangeability With a Reference Product 
(May 2019). See also the draft guidance for industry Biosimilarity and Interchangeability: Additional Draft Q&As 
on Biosimilar Development and the BPCI Act (November 2020), which when final, will represent the FDAs current 
thinking on this topic.   
 
  10