Promotional Labeling and 
Advertising Considerations for 
Prescription Biological Reference 
and Biosimilar Products 
Questions and Answers 
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DRAFT GUIDANCE
 
 
  This guidance document is being distributed for comment purposes only.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publication in the Federal Register of the notice announcing the availability of the draft 
guidance.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) Elizabeth Pepinsky, 301-796-1200, 
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 
Advertising 
 
10307676dft.docx 
01/30/20 
   
Promotional Labeling and Advertising 
Considerations for Prescription 
Biological Reference and  
Biosimilar Products 
Questions and Answers 
 
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) 
 
February 2020 
Advertising 
 
 
  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
TABLE OF CONTENTS 
 
 
 
I.  INTRODUCTION............................................................................................................. 1 
II.  BACKGROUND ............................................................................................................... 2 
III.  QUESTIONS AND ANSWERS ....................................................................................... 3 
  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
1  Promotional Labeling and Advertising Considerations for 
2  Prescription Biological Reference and Biosimilar Products 
3  Questions and Answers 
4  Guidance for Industry1 
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 addresses questions firms2 may have when developing FDA-regulated 
18  promotional labeling and advertisements (promotional materials)3,4 for prescription reference 
19  products5 licensed under 351(a) of the Public Health Service Act (PHS Act) (42 U.S.C. 262(a)) 
                                                 
1 This guidance has been prepared by the Office of Prescription Drug Promotion in consultation with the Office of 
Therapeutic Biologics and Biosimilars in the Center for Drug Evaluation and Research in cooperation with the 
Center for Biologics Evaluation and Research at the Food and Drug Administration.  
 
2 In this guidance, the term firms refers to manufacturers, packers, and distributors, including representatives of 
these entities, of biological products licensed under section 351(a) or (k) of the Public Health Service Act (PHS Act) 
(42 U.S.C. 262(a) or (k)). 
 
3 Under the Federal Food, Drug, and Cosmetic Act (FD&C Act), FDAs authority includes provisions addressing 
labeling for all drugs and advertisements for prescription drugs.  See, e.g., section 502(a), (f), and (n) (21 U.S.C. 
352(a), (f), and (n)); see also section 201(m) (21 U.S.C. 321(m) (defining labeling).  If a biological product meets 
the definition of drug under section 201(g) of the FD&C Act (21 U.S.C. 321), it is subject to these provisions to the 
same extent as any other drug.  See section 351(j) of the PHS Act (42 U.S.C. 262(j)). 
 
4 Promotional labeling is generally any labeling other than FDA-required labeling that is devised for promotion of 
the product.  Promotional labeling may also have other functions in addition to promotion.  Such promotional 
labeling can include printed, audio, or visual matter descriptive of a drug for which the labeling is disseminated by 
or on behalf of a drugs manufacturer, packer, or distributor (21 CFR 202.1(l)(2)).  The FD&C Act does not define 
what constitutes an advertisement for a prescription drug, but FDA regulations provide several examples, including 
advertisements in published journals, magazines, other periodicals, and newspapers, and advertisements broadcast 
through media such as radio, television, and telephone communication systems (21 CFR 202.1(l)(1)). 
 
5 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 an application submitted under section 351(k) of the PHS Act 
(section 351(i)(4) of the PHS Act (42 U.S.C. 262(i)(4))).  
 
 
  1  Contains Nonbinding Recommendations 
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20  and prescription biosimilar products6 licensed under section 351(k) of the PHS Act (42 U.S.C. 
21  262(k)).  The guidance discusses considerations for presenting data and information about 
22  reference or biosimilar products in these promotional materials in a truthful and non-misleading 
23  way.  Although the guidance covers promotional issues involving both reference and biosimilar 
24  products, some questions and answers are focused on only biosimilar product promotional 
25  materials.  This guidance  does not discuss considerations unique to promotional materials for 
26  interchangeable biosimilars.7              
27      
28  In general, FDAs guidance documents do not establish legally enforceable responsibilities.  
29  Instead, guidances describe the Agencys current thinking on a topic and should be viewed only 
30  as recommendations, unless specific regulatory or statutory requirements are cited.  The use of 
31  the word should in Agency guidances means that something is suggested or recommended, but 
32  not required.  
33   
34   
35  II.  BACKGROUND 
36   
37  Section 351(k) of the PHS Act, added by the Biologics Price Competition and Innovation Act of 
38  2009 (BPCI Act), outlines an abbreviated licensure pathway for biological products shown to be 
39  biosimilar to or interchangeable with an FDA-licensed reference product.  A biosimilar is a 
40  biological product that is highly similar to the reference product notwithstanding minor 
41  differences in clinically inactive components and for which there are no clinically meaningful 
42  differences between the biological product and the reference product in terms of safety, purity, or 
43  potency.8,9   
44   
45  To meet the standard for interchangeability, an applicant must (1) provide sufficient information 
46  to demonstrate biosimilarity to the reference product and (2) demonstrate that the biological 
47  product can be expected to produce the same clinical result as the reference product in any given 
48  patient and, if the biological product is administered more than once to an individual, the risk in 
49  terms of safety or diminished efficacy of alternating or switching between the use of the 
50  biological product and the reference product is not greater than the risk of using the reference 
51  product without such alternation or switch.10   
52   
                                                 
6 In this guidance, the terms biosimilar and biosimilar product refer to a biological product that FDA has licensed as 
biosimilar to a reference product (see sections 351(i)(2) and (k)(2) of the PHS Act (42 U.S.C. 262(i)(2) and (k)(2))).   
 
7 In this guidance, the terms interchangeable biosimilar and interchangeable product refer to a biosimilar product 
that FDA has determined to be interchangeable with the reference product (see sections 351(i)(3) and (k)(4) of the 
PHS Act (42 U.S.C. 262(i)(3) and (k)(4))).    
 
8 See section 351(i)(2) of the PHS Act (42 U.S.C. 262(i)(2)).  
 
9 See 21 CFR 600.3(s).  The standard for licensure of a biological product as potent under section 351(a) of the PHS 
Act has long been interpreted to include effectiveness. 
 
10 See section 351(k)(4) of the PHS Act (42 U.S.C. 262(k)(4)).  
 
 
  2  Contains Nonbinding Recommendations 
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53  Once FDA licenses a biosimilar or interchangeable product, providers and patients can be 
54  assured of the safety and effectiveness of a biosimilar or an interchangeable product, just as they 
55  would be for the reference product. 
56     
57  As the number of licensed biosimilar products increases, FDA expects an increase in promotion 
58  involving reference and biosimilar products.  FDA is providing this guidance to address 
59  questions firms may have when developing FDA-regulated promotional materials for reference 
60  products or biosimilar products.  The guidance discusses considerations for presenting data and 
61  information about reference or biosimilar products in these promotional materials to help ensure 
62  that they are accurate, truthful, and non-misleading as required under the Federal Food, Drug, 
63  and Cosmetic (FD&C) Act and FDAs implementing regulations.11   
64   
65   
66  III.  QUESTIONS AND ANSWERS   
67   
68  Q1.  What are the general requirements for the content of FDA-regulated promotional 
69  materials for reference products and biosimilar products?  
70   
71  Prescription drugs, including those that are reference products or biosimilar products, are subject 
72  to the FD&C Act and FDAs implementing regulations, including misbranding provisions that 
73  address advertisements and promotional labeling for prescription drugs issued by or on behalf of 
74  manufacturers, packers, or distributors.    
75   
76  Under the FD&C Act and FDAs implementing regulations, prescription drug promotional 
77  labeling and advertising must be truthful and non-misleading, convey information about a drugs 
78  efficacy and its risks in a balanced manner, and reveal material facts about the drug.12  Whether a 
79  promotional presentation is truthful and non-misleading involves a fact-specific determination 
80  that takes into account such factors as how the information is presented, the type and quality of 
81  the data relied on to support the presentation, and contextual and disclosure considerations.  FDA 
82  regulations also require that firms promptly revise promotional labeling and advertising for their 
83  biological products upon certain labeling changes, including labeling changes to risk 
84  information.13   
85   
86  Q2.  How should firms identify reference products and biosimilar products in 
87  promotional materials?    
88   
89  Depending on the context, biological products, including reference and biosimilar products, may 
90  be identified by their proprietary name, nonproprietary or proper name, or core name.  As used in 
                                                 
11 See sections 201(n) and 502(a) and (n) of the FD&C Act (21 U.S.C. 321(n), 352(a) and (n)); 21 CFR 1.21(a) and 
202.1(e)(5).   
 
12 Ibid.  
 
13 21 CFR 601.12(a)(4).   
 
 
  3  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
91  this guidance, a biological products proprietary name means the trademark or brand name.14  A 
92  biological products proper name is the nonproprietary name designated by FDA in the license 
93  for a biological product licensed under the PHS Act.15,16  A biological products core name is the 
94  component shared among a reference product and any related biological product, biosimilar 
95  product, or interchangeable product as part of the proper names of those products.17  
96   
97  Firms should carefully evaluate the information presented in promotional materials for reference 
98  products or biosimilar products to ensure that in each instance where the promotional materials 
99  address a product or products, the materials correctly and specifically identify the product or 
100  products to which the information applies (e.g., the reference product, the biosimilar product, or 
101  both the reference product and the biosimilar).18  For instance, if a biosimilar products FDA-
102  approved labeling uses the core name of the reference product followed by the word products 
103  to convey that a risk applies to both the biosimilar and the reference product,19 it would also be 
104  appropriate for similar presentations about this risk in promotional materials for the biosimilar to  
105  use this nomenclature.   Firms should also ensure that if promotional materials describe studies in 
106  which non-U.S.-licensed comparator biological products were used (or if promotional materials 
107  otherwise mention such products), the promotional materials accurately identify the non-U.S.-
108  licensed comparator biological products.   
109   
110  Clearly and correctly identifying the relevant biological product or products in promotional 
111  materials can help prevent presentations that are inaccurate because they attribute data or 
112  information to the wrong product.  It can also help the audience identify which product or 
113  products are the subject of a particular promotional presentation.  
114      
                                                 
14 See the guidance for industry Nonproprietary Naming of Biological Products (January 2017).  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.  
 
15 See section 351(a)(1)(B)(i) of the PHS Act (42 U.S.C. 262(a)(1)(B)(i)) and 21 CFR 600.3(k)). 
 
16 See the guidance for industry Nonproprietary Naming of Biological Products. 
 
17 Ibid. 
 
18 Firms should also consider the requirements related to the placement, size, prominence, and frequency of the 
proprietary name and established name in prescription drug labeling and advertisements (see 21 CFR 201.10(g); 
202.1(b) through (d)).  For biological products, these requirements pertain to the placement, size, prominence, and 
frequency of the proprietary name and proper name of the product.   
 
19 See the guidance for industry Labeling for Biosimilar Products (July 2018).  The guidance recommends that in 
labeling sections where the risk applies to both the biosimilar product and the reference product, it would be 
appropriate to use the core name of the reference product followed by the word products to convey, for instance, 
that a risk or other information necessary for the safe use of the product applies to both the biosimilar product and 
the reference product.  The guidance also explains, among other things, that the biosimilar products proprietary 
name (or if a proprietary name is not available, the biosimilar products proper name) should be used when 
providing directive statements and recommendations for preventing, monitoring, managing, or mitigating risks.   
 
  4  Contains Nonbinding Recommendations 
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115  Q3.  When developing promotional materials for biosimilars, what should firms consider 
116  if presenting information from the studies conducted to support licensure of the 
117  reference product when the information is included in the FDA-approved labeling 
118  of both the reference and the biosimilar products?          
119   
120  When developing promotional materials for a biosimilar product that include information from 
121  the studies conducted to support licensure of the reference product that are reflected in both the 
122  reference products FDA-approved labeling and the biosimilars FDA-approved labeling, firms 
123  should refer to the biosimilar products FDA-approved labeling.  FDA has recommended that a 
124  biosimilar products FDA-approved labeling incorporate relevant data and information from the 
125  reference products FDA-approved labeling, including clinical data that supported FDAs finding 
126  of safety and effectiveness of the reference product.20   
127   
128  For instance, if a biosimilar product is licensed for fewer than all conditions of use for which the 
129  reference product is licensed, the biosimilars FDA-approved labeling generally contains the data 
130  and information from the reference products FDA-approved labeling that is relevant to the 
131  licensed conditions of use of the biosimilar product.21  In general, a biosimilar products FDA-
132  approved labeling contains data and information from the CLINICAL STUDIES section of the 
133  reference products FDA-approved labeling for the conditions of use for which the biosimilar 
134  product is licensed and also generally includes data from the reference products FDA-approved 
135  labeling regarding clinical pharmacology studies, immunogenicity, and toxicity, among other 
136  information.    
137      
138  Q4.  When developing promotional materials for biosimilars, what should firms consider 
139  if presenting data or information from studies conducted to support a 
140  demonstration of biosimilarity when the data or information is not included in the 
141  FDA-approved labeling for their biosimilar product? 
142   
143  If biosimilar promotional materials present data and information from studies that were  
144  conducted to support a demonstration of biosimilarity between the biosimilar product and the 
145  reference product but are not included in the biosimilar products FDA-approved labeling, those 
146  presentations should be consistent with the biosimilars FDA-approved labeling and be truthful 
147  and non-misleading, as described in the guidance for industry Medical Product Communications 
148  That Are Consistent With the FDA-Required Labeling  Questions and Answers (June 2018) 
149  (CFL guidance).   
150   
151  FDA has recommended that the FDA-approved labeling for a biosimilar product generally not 
152  include data and information from studies conducted to support a demonstration of biosimilarity 
                                                 
20 See the guidance for industry Labeling for Biosimilar Products. 
 
21 In certain circumstances it may have been 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 (e.g., 
when safety information in the reference product labeling is related to use of the product and is not specific to a 
particular licensed indication(s) or when information specific to only the biosimilar products indication(s) cannot be 
easily extracted).  See the guidance for industry Labeling for Biosimilar Products.   
 
 
  5  Contains Nonbinding Recommendations 
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153  between the reference product and the biosimilar product.22  However, firms developing 
154  promotional materials for their biosimilar products have expressed interest in communicating 
155  this information to health care providers or other interested parties.  FDA encourages these firms 
156  to apply the principles outlined in the CFL guidance if the promotional materials for their 
157  biosimilar products include data or information from studies that supported the demonstration of 
158  biosimilarity between the biosimilar and the reference product, which generally will not be 
159  included in the biosimilar products FDA-approved labeling.  
160   
161  Q5.  What should firms consider when comparing reference products and biosimilar 
162  products in their promotional materials?  
163   
164  FDAs licensure of a biosimilar product means that the Agency has determined that the 
165  biosimilar is highly similar to the reference product notwithstanding minor differences in 
166  clinically inactive components and that there are no clinically meaningful differences in terms of 
167  safety purity, or potency.  Although assessment of each promotional presentation involves a fact-
168  specific determination, representations or suggestions that create an impression that there are 
169  clinically meaningful differences between the reference product and its biosimilar, such as 
170  promotional presentations representing or suggesting that a reference product is safer or more 
171  effective than its biosimilar product, or that a biosimilar is safer or more effective than its 
172  reference product are likely to be false or misleading.23  Similarly, representations or suggestions 
173  that create an impression that a biosimilar is not highly similar to its reference product are likely 
174  to be false or misleading.    
175   
176  Accordingly, FDA recommends that firms carefully evaluate presentations that compare a 
177  reference product and a biosimilar product and avoid presentations that represent or suggest that 
178  a licensed biosimilar is not highly similar to the reference product or that a clinically meaningful 
179  difference in terms of safety, purity, or potency exists between the reference product and 
180  biosimilar.  
181   
182  For example,24 a firm generates promotional materials for a biosimilar product and the materials 
183  present data and information on response rates in patients treated with the reference product 
184  alone, response rates in patients initially started on the biosimilar product, and response rates in 
185  patients transitioned from the reference product to the biosimilar product from a study supporting 
186  a demonstration of biosimilarity.  The presentation includes a header that the biosimilar is just as 
187  effective as the reference product.   
188   
                                                 
22 See footnote 20. 
 
23 False or misleading presentations about the safety or effectiveness of a prescription drug in its labeling or 
advertisements misbrand the product and thus cause its distribution in interstate commerce, among other actions, to 
be prohibited.  See sections 201(n), 301(a), and 502(a) and (n) of the FD&C Act (21 U.S.C 321(n), 331(a), 352(a) 
and (n)); 21 CFR 1.21(a) and 202.1(e)(5).   
 
24 See the response for Q7 for additional explanation of the use of examples in this guidance. 
   
 
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189  This presentation would not create a misleading impression that there is a clinically meaningful 
190  difference between the reference product and the biosimilar so long as appropriate context is 
191  provided in the presentation.25, 26  By contrast, the same data and information presented with a 
192  header that claims greater efficacy for the biosimilar product would be misleading.   
193   
194  Similarly, representations or suggestions that a biosimilar product is superior to its reference 
195  product based on a difference that is not clinically meaningful between the rates of occurrence of 
196  a particular adverse reaction from a study that supported a demonstration of biosimilarity 
197  between the reference product and biosimilar would be misleading.  Representations or 
198  suggestions that the reference product is less safe or less effective than its biosimilar based on 
199  this study also would be misleading.   
200   
201  In some cases, individual statements of accurate information about a reference product or  
202  about a biosimilar product could contribute to a misleading presentation when provided in a 
203  comparative context.   For example, presentations in promotional materials for a reference 
204  product comparing the number of indications for which the reference product is licensed to the 
205  number of indications for which the biosimilar is licensed in a manner that creates the net 
206  impression that the biosimilar product is in general less safe or less effective than the reference 
207  product simply because the biosimilar is licensed for fewer indications than the reference product 
208  would be misleading.   
209   
210  Where a biosimilar has not been directly studied in a particular indication (i.e., the biosimilars 
211  licensure for the indication is based in part on extrapolation), representations or suggestions in 
212  promotional materials for the reference product that the biosimilar is less safe or less effective 
213  than the reference product in that indication because licensure for that indication was based in 
214  part on extrapolation also would be misleading.       
215        
216  Q6.  What else should firms consider when developing promotional materials for  
217  reference products or biosimilar products?     
218   
219  Promotional presentations about a products licensure as biosimilar to a reference product should 
220  accurately describe the biosimilar product.  For instance, promotional materials for a biosimilar 
221  product that FDA has not licensed as interchangeable with the reference product should avoid 
222  creating an impression that the biosimilar has been licensed as interchangeable with the reference 
223  product, because this would not be accurate.  Also, promotional materials for a reference product 
224  should avoid representing or suggesting that a biosimilar product is less safe or effective than its 
225  reference product because it has not been licensed as interchangeable with the reference product.   
226   
227  FDA also reminds firms that a biosimilar product is not required to be identical to the reference 
228  product in order to be licensed; rather, licensure means the biosimilar product has been found to 
                                                 
25 For a discussion of contextual considerations, refer to the CFL guidance. 
 
26 See the guidance for industry Scientific Considerations in Demonstrating Biosimilarity to a Reference Product 
(April 2015) (explains that [c]linically meaningful differences could include a difference in the expected range of 
safety, purity, or potency of the proposed product and the reference product.  By contrast, slight differences in rates 
of occurrence of certain adverse  reactions between the two products ordinarily would not be considered clinically 
meaningful differences). 
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229  be highly similar to the reference product notwithstanding minor differences in clinically inactive 
230  components and that there are no clinically meaningful differences between the biosimilar and 
231  the reference product in terms of safety, purity, and potency.  Accordingly, promotional 
232  materials for a biosimilar product that represent or suggest that a finding of biosimilarity means 
233  that FDA determined that the reference product and biosimilar product are identical to one 
234  another generally would not be accurate.  Additionally, FDA recommends that promotional 
235  materials for reference products avoid presentations that represent or suggest that the licensed 
236  biosimilar is not as safe and as effective as the reference product because it is not or may not be 
237  identical to the reference product.     
238       
239  Q7.  What are some examples of applying the considerations in this guidance to 
240  promotional presentations?  
241   
242  The following examples are intended to illustrate some of the general considerations outlined in 
243  this guidance.  The examples in this guidance contain hypothetical scenarios for illustrative 
244  purposes only and focus on the topics addressed by this guidance; they do not describe every 
245  aspect of the promotional material that would be necessary to satisfy all applicable requirements.  
246  As noted in Q1, whether a promotional presentation is truthful and non-misleading involves a 
247  fact-specific determination that takes into account such factors as how the information is 
248  presented, the type and quality of the data relied on to support the presentation, and contextual 
249  and disclosure considerations.   
250   
251  The examples that follow use a fictional reference product JUNEXANT (replicamab-hjxf) and a 
252  fictional biosimilar to JUNEXANT, a product named NEXSYMEO (replicamab-cznm).   
253      
254  Examples 1 and 2 illustrate scenarios where FDA would not expect to object to the presentations 
255  described.  
256   
257  Example 1:  A firm is developing promotional materials for its biosimilar, NEXSYMEO.   
258  In the materials, the firm includes the route of administration, dosage form, and strength 
259  described in NEXSYMEOs labeling and a claim that NEXSYMEO has the same route 
260  of administration, dosage form, and strength as JUNEXANT in the conditions of use for 
261  which both products are licensed.  The claim is supported by NEXSYMEOs licensure as 
262  biosimilar to JUNEXANT given that NEXSYMEOs licensure is based, in part, on 
263  information showing that the route of administration, dosage form, and strength of 
264  NEXSYMEO are the same as those of JUNEXANT.27   
265   
266  Additionally, the materials include a claim that NEXSYMEO can be considered for 
267  patients who are new to replicamab product therapy for the treatment of a licensed 
268  indication and for patients currently being treated with JUNEXANT for the same 
269  indication.  This claim is supported by data and information submitted as part of 
270  NEXSYMEOs application for licensure as biosimilar to JUNEXANT, including data 
271  from a comparative clinical study that included patients who underwent a single 
272  transition from JUNEXANT to NEXSYMEO and patients who were new to replicamab 
                                                 
27 See section 351(k)(2) of the PHS Act (42 U.S.C. 262(k)(2)).  
 
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273  product therapy, which supported a demonstration of no clinically meaningful differences 
274  between NEXSYMEO and JUNEXANT in terms of safety, purity, and potency.   
275    
276  Example 2:  As part of NEXSYMEOs application for licensure as biosimilar to  
277  JUNEXANT, FDA evaluated a comparative clinical study that included patients treated 
278  with a non-U.S.-licensed comparator product to support a demonstration of no clinically 
279  meaningful differences between NEXSYMEO and JUNEXANT.   
280   
281  NEXSYMEOs firm wants to present data and information describing outcomes observed 
282  in this study in promotional materials for NEXSYMEO.  Data from this study is not 
283  included in the FDA-approved labeling for NEXSYMEO.    
284   
285  The firm develops a presentation consistent with the CFL guidance, including the 
286  recommendations in the CFL guidance regarding appropriate scientific and statistical 
287  support for the outcome information presented.  The firm clearly and prominently 
288  provides contextual information about the study design and methodology, the role the 
289  study played in the biosimilarity evaluation, relevant data from NEXSYMEOs FDA-
290  approved labeling, and any material limitations of the data.  The firm also accurately 
291  describes the comparator used in the study as non-U.S.-licensed.    
292   
293  Example 3 illustrates promotional materials that FDA would consider misleading.      
294   
295  Example 3:  Promotional materials for JUNEXANT state that in a clinical study, patients 
296  on JUNEXANT experienced a numerically higher overall response rate than patients on 
297  NEXSYMEO.  The basis for the statement is a comparative clinical study that supported 
298  a demonstration of no clinically meaningful differences in terms of safety, purity, and 
299  potency between JUNEXANT and NEXSYMEO.   
300   
301  Although this statement accurately conveys the reference products higher numeric 
302  overall response rates observed in the study, the materials do not disclose that this 
303  difference in response rates was not statistically significant, and they do not describe the 
304  study design or include other appropriate context.  By focusing on the numerical 
305  difference in response rates, which was not statistically significant, the presentation 
306  misleadingly implies that JUNEXANT is superior to NEXSYMEO.  It also misleadingly 
307  implies that there is a clinically meaningful difference between the products when the 
308  data presented in the promotional materials do not support this conclusion. 
309   
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310  Q8.   How can firms request FDA review of draft promotional materials for reference 
311  products and biosimilar products before their dissemination?  
312   
313  Firms voluntarily seeking FDA feedback on promotional materials for reference products or 
314  biosimilar products before their dissemination should follow the current process for submitting 
315  draft promotional materials for comment.28  
316   
317  Furthermore, FDA reminds firms that they are subject to the postmarketing reporting 
318  requirements for submitting promotional materials to FDA (Form FDA 2253 submissions for 
319  prescription drugs and biologics).29, 30  In addition to the considerations specifically outlined in 
320  this guidance, firms should ensure that their FDA-regulated promotional materials otherwise 
321  satisfy the applicable requirements of the FD&C Act and FDAs implementing regulations.31  
322  Firms should also ensure that they comply with the provisions obligating them to update the 
323  FDA-approved labeling for their products to ensure that the labeling is not false or misleading or 
324  for other reasons.32   
325   
                                                 
28 See 21 CFR 202.1(j)(4).  See also the guidance for industry Providing Regulatory Submissions in Electronic and 
Non-Electronic FormatPromotional Labeling and Advertising Materials for Human Prescription Drugs (June 
2019) and the draft guidance for industry Fulfilling Regulatory Requirements for Postmarketing Submissions of 
Interactive Promotional Media for Prescription Human and Animal Drugs and Biologics (July 2014).  When final, 
this guidance will represent FDAs current thinking on this topic. 
 
29 See 21 CFR 601.12(f)(4)), section 745A(a) of the FD&C Act (21 U.S.C. 379k-1).    
 
30 For additional guidance on electronic submission of these materials, see footnote 29. 
 
31 See, e.g., sections 502(a) and (n) of the FD&C Act (21 U.S.C. 352(a) and (n)); 21 CFR 1.21(a) and 202.1(e)(5). 
 
32 See, e.g., 21 CFR 201.56(a)(2) (referring to labeling updates in accordance with 21 CFR 601.12); sections 502(a), 
(f), and (j) (21 U.S.C. 352(a), (f), and (j)).  
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