Guidance for Industry 

Responding to Unsolicited Requests for 

Off-Label Information About 

Prescription Drugs and Medical Devices 

 
 
DRAFT GUIDANCE 

 
This guidance document is being distributed for comment purposes only. 
 
Comments and suggestions regarding this draft document should be submitted within 90 days of 
publication in the Federal Register of the notice announcing the availability of the draft guidance.  
Submit comments to Division of Dockets Management (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For questions regarding this draft guidance document, contact (CDER) Jean-Ah Kang at (301) 796-
1200; (CBER) Office of Communication, Outreach and Development at 800-835-4709 or 301-827-
1800; (CVM) Dorothy McAdams at (240) 276-9300; or (CDRH) Deborah Wolf at (301) 796-5732. 
 
 
 
 
U.S. Department of Health and Human Services 

Food and Drug Administration 

Center for Drug Evaluation and Research (CDER) 

Center for Biologics Evaluation Research (CBER) 

Center for Veterinary Medicine (CVM) 

Center for Devices and Radiological Health (CDRH) 

 
 
 
 
December 2011 

Procedural 

   
 
Guidance for Industry 

Responding to Unsolicited Requests for 

Off-Label Information About 

Prescription Drugs and Medical Devices 

 
Additional copies are available from: 
Office of Communications, Division of Drug  Communications Staff (CVM) 
Information  Center for Veterinary Medicine 
Center for Drug Evaluation and Research  Food and Drug Administration 
Food and Drug Administration  7519 Standish Place, HFV-12 
10903 New Hampshire Ave., Bldg. 51, rm. 2201  Rockville, MD 20855 
Silver Spring, MD 20993-0002  Tel: 240-276-9300; E-mail: AskCVM@fda.hhs.gov  
Tel: 301-796-3400; Fax: 301-847-8714; E-mail:  http://www.fda.gov/AnimalVeterinary/GuidanceCompli 
druginfo@fda.hhs.gov   anceEnforcement/GuidanceforIndustry/default.htm  
http://www.fda.gov/Drugs/GuidanceComplianceReg 
ulatoryInformation/Guidances/default.htm 
 
Office of Communication, Outreach and  Division of Small Manufacturers, International and 
Development (HFM-40)  Consumer Assistance (DSMICA) 
Center for Biologics Evaluation and Research  Office of Communication, Education and Radiation 
Food and Drug Administration  Programs 
1401 Rockville Pike, Suite 200N  Center for Devices and Radiological Health 
Rockville, MD 20852-1448  Food and Drug Administration 
Tel: 800-835-4709 or 301-827-1800; E-mail:  10903 New Hampshire Ave., Bldg. 66, rm. 4613 
ocod@fda.hhs.gov  Silver Spring, MD 20993-0002 
http://www.fda.gov/BiologicsBloodVaccines/Guidanc  Tel: 800-638-2041 or 301-796-7100; Fax: 301-847-
eComplianceRegulatoryInformation/default.htm   8149; E-mail: dsmica@fda.hhs.gov  
http://www.fda.gov/MedicalDevices/DeviceRegulationa 
ndGuidance/GuidanceDocuments/default.htm  
 
U.S. Department of Health and Human Services 

Food and Drug Administration 

Center for Drug Evaluation and Research (CDER) 

Center for Biologics Evaluation Research (CBER) 

Center for Veterinary Medicine (CVM) 

Center for Devices and Radiological Health (CDRH) 

 
 
December 2011 

Procedural 

 
 
   
 
TABLE OF CONTENTS 

 
I.   INTRODUCTION..........................................................................................1 
 
II.   BACKGROUND...........................................................................................2 
 
III.   DETERMINING WHETHER A REQUEST IS UNSOLICITED OR SOLICITED.........4 
 
IV.   OVERVIEW OF FDAS POLICY ON RESPONDING TO UNSOLICITED REQUESTS 
FOR OFF-LABEL INFORMATION.......................................................................................6 
 
V.   RESPONDING TO NON-PUBLIC UNSOLICITED REQUESTS FOR OFF-LABEL 
INFORMATION DIRECTED TO DRUG OR MEDICAL DEVICE FIRMS................7 
 
VI.   RESPONDING TO PUBLIC UNSOLICITED REQUESTS FOR OFF-LABEL 
INFORMATION, INCLUDING THOSE ENCOUNTERED THROUGH EMERGING 
ELECTRONIC MEDIA BY DRUG OR MEDICAL DEVICE FIRMS.......................10 
  Contains Nonbinding Recommendations 
Draft  Not for Implementation  
Guidance for Industry 
1   
 
2 
3  Responding to Unsolicited Requests for Off-Label Information About 
4  Prescription Drugs and Medical Devices  
5    
  
6 
7   
8  This draft guidance, when finalized, will represent the Food and Drug Administrations (FDA) 
9  current thinking on this topic. It does not create or confer any rights for or on any person and does 
10  not operate to bind FDA or the public.  You may use an alternative approach if the approach 
11  satisfies the requirements of the applicable statutes and regulations.  If you want to discuss an 
12  alternative approach, contact the FDA staff responsible for implementing this guidance.  If you 
13  cannot identify the appropriate FDA staff, call the appropriate number listed on the title pages of 
14  this guidance. 
15   
16   
17  I.  INTRODUCTION 
18   
19  This draft guidance is intended to describe the Food and Drug Administrations (FDA or Agency) 
20  current thinking about how manufacturers and distributors (firms) of prescription human and 
21  animal drug products (drugs) and medical devices (devices) can respond to unsolicited requests for 
22  information about unapproved or uncleared indications or conditions of use (off-label information) 
23  related to their FDA-approved or cleared products.1,2  This draft guidance updates and clarifies 
24  FDAs policies on unsolicited requests for off-label information, including those that firms may 
25  encounter through emerging electronic media. 
                                                 
1 This  draft  guidance has been prepared by the Office of Prescription Drug  Products (OPDP) in the Center for Drug  
Evaluation and Research (CDER) in consultation with the Center for Biologics Evaluation Research  (CBER), the  
Center for Devices and Radiological Health (CDRH), and the Center for Veterinary  Medicine (CVM). 
2 The recommendations in this draft  guidance also apply to  biological  products that are approved for marketing under 
section 351 of the Public Health Service Act (PHS Act).  Because each biological product also meets the definition of 
drug or device under the  Federal Food, Drug, and Cosmetic Act (FD&C Act), it is also subject to regulation under 
provisions of the FD&C Act applicable to  drugs or devices, as well as the regulations implementing these provisions, 
except that a biological product licensed  under section  351  of the PHS Act is not required to  have an approved  new 
drug application  under section 505 of the FD&C Act. (See PHS Act section  351(j), 42  U.S.C. 262(j).)  
 
In addition, the term approved  or cleared product in this draft guidance encompasses devices that are legally 
marketed for a  specific intended use without  an individual product approval or substantial equivalence determination 
(clearance). This includes class I and class  II devices marketed for uses  that make them  exempt from premarket 
notification, in accordance with sections 510(l) or (m) of the FD&C Act (21 U.S.C. 360(l) & (m)).  As a result, with 
regard to such  products, a request for off-label information refers to any request for information regarding a new use 
for which approval  or clearance would be required.  This  draft  guidance does not address devices solely intended for 
use in animals. 
 
  Contains Nonbinding Recommendations 
Draft  Not for Implementation  
 
 
26  This draft guidance does not address requests for information about approved or cleared 
27  indications or conditions of use (on-label information) for FDA-regulated medical products.  It 
28  also does not address requests for information about medical products that are not currently 
29  approved or cleared for any purpose. 
30   
31  FDAs guidance documents, including this draft guidance, do not establish legally enforceable 
32  rights or responsibilities. Instead, guidances describe the Agencys current thinking on a topic and 
33  should be viewed only as recommendations, unless specific regulatory or statutory requirements 
34  are cited. The use of the word should in Agency guidances means that something is suggested or 
35  recommended, but not required. 
36   
37   
38  II.  BACKGROUND 
39   
40  The Federal Food, Drug, and Cosmetic Act (FD&C Act) and FDA's implementing regulations 
41  prohibit manufacturers and distributors (firms) from introducing new drugs, new animal drugs, and 
42  most Class III medical devices into interstate commerce for any intended use that FDA has not 
43  determined to be safe and effective.  The FD&C Act and FDAs implementing regulations also 
44  prohibit device firms subject to premarket notification requirements under section 510(k), which 
45  includes most class II and some class I devices, from introducing such devices into interstate 
46  commerce for any intended use that is outside FDAs substantial equivalence determination 
47  (clearance) for such devices.3  Statements that promote a drug or medical device for uses other 
48  than those approved or cleared by FDA may be used as evidence of a new intended use.  
49  Introducing a product into commerce for such a new intended use without FDA approval or 
50  clearance would, under these requirements, generally violate the law.  However, once a drug or 
51  medical device has been approved or cleared by FDA, generally, health care professionals can 
52  lawfully use or prescribe that product for uses or treatment indications that are not included in the 
53  product's approved labeling4 (or, in the case of a medical device cleared under the 510(k) process, 
54  in the product's statement of intended uses).  FDA recognizes that these off-label uses or treatment 
55  regimens may be important therapeutic options and may even constitute a medically recognized 
56  standard of care. 
57   
58  Scientific or medical departments within drug or medical device firms often maintain a large body 
59  of information about their products.  This information typically includes data and other 
60  information consistent with the approved or cleared indications or conditions of use for their 
61  products, but may also include off-label information for their products.  As noted, although 
62  dissemination of off-label information can be used as evidence of new intended uses for products 
63  in distribution, such information may also be of use to individuals seeking information about a 
                                                 
3 See e.g., sections 505(a), 501(a),  301(d), 501(f)(1)(B) and  502(o)  of the FD&C Act; 21  U.S.C. 355(a), 351(a), 
331(d), 351(f)(1)(B)  and 352(o). 
4 See sections  512(a)(4) and  (a)(5) of the FD&C Act and this Agencys regulations at 21  CFR part 530 for specific 
provisions related to the off-label (or extra-label) use of approved animal and human drugs in animals. 
2 
  Contains Nonbinding Recommendations 
Draft  Not for Implementation  
 
 
64  medical product for themselves, patients, family members, or friends.  These individuals 
65  sometimes submit non-public requests for off-label information directly and privately to firms. 
66   
67  The rapid growth of the Internet, including social media tools and other emerging technologies, 
68  has made it easier for both consumers and health care professionals to quickly seek information 
69  about medical conditions and treatments.5  Many firms have also used emerging electronic media 
70  to disseminate product information.  As a result, firms may encounter requests for off-label 
71  information about their products through product websites, discussion boards, chat rooms, or other 
72  public electronic forums that they maintain and over which they have full control.  In addition, 
73  third-party sites (i.e., websites and other venues that are either entirely independent of a firms 
74  control and influence or not fully controlled by a firm) also may reveal questions about off-label 
75  uses of a firms products.  These questions about off-label uses are typically directed to users of 
76  the site at large, rather than directly and privately to firms.  Such posted information is likely to be 
77  available to a much broader audience than just the original requester, especially because 
78  communication threads (i.e., questions and replies) are often available for an indefinite period of 
79  time. 
80   
81  This draft guidance provides FDAs recommendations to firms wishing to respond to unsolicited 
82  requests for off-label information, including both requests made directly and privately to firms and 
83  requests made in public forums, including through emerging electronic media.  FDA recognizes 
84  that firms are capable of responding to requests about their own named products in a truthful, non-
85  misleading, and accurate manner.  Furthermore, as these firms are regulated by FDA and have 
86  robust and current information about their products, FDA recognizes that it can be in the best 
87  interest of public health for a firm to respond to unsolicited requests for information about off-label 
88  uses of the firms products that are addressed to a public forum, as other participants in the forum 
89  who offer responses may not provide or have access to the most accurate and up-to-date 
90  information about the firms products. 
91   
92  If a firm responds to unsolicited requests for off-label information in the manner described in this 
93  draft guidance, FDA does not intend to use such responses as evidence of the firms intent that the 
94  product be used for an unapproved or uncleared use.  Such responses would also not be expected 
95  to comply with the disclosure requirements related to promotional labeling and advertising.  Firms  
96  may choose to respond to unsolicited requests for information about off-label uses of their 
97  approved or cleared products in a manner other than that recommended in this draft guidance.  
98  Such activity would not constitute a per se violation of the law, but could potentially be introduced 
99  as evidence of a new intended use.6  
                                                 
5 For example, the public is able to  obtain information  on certain clinical trial results from  www.ClinicalTrials.gov. 
This may include information related to  off-label uses.  This information  may generate questions  directly to a firm. 
6 This draft guidance is not intended to suggest that receiving an  unsolicited request is the only circumstance in which 
a firm can disseminate information about  unapproved uses  of its FDA-regulated products without  such  dissemination 
being used as evidence of the firms intent that the product  be used for an  unapproved use.  For example, FDA has  
developed  separate guidance that addresses manufacturer-initiated distribution of reprints regarding  off-label uses.  
See Good Reprint Practices for the Distribution of  Medical  Journal Articles and Medical or  Scientific Reference 
3 
  Contains Nonbinding Recommendations 
Draft  Not for Implementation  
 
 
100  III.   DETERMINING WHETHER A REQUEST IS UNSOLICITED OR SOLICITED 
101   
102  This draft guidance addresses how to respond to unsolicited requests for off-label information 
103  about drugs and medical devices.  To illustrate the difference between unsolicited and solicited 
104  requests, this section describes these two categories of requests and presents a number of examples 
105  of both types of requests. 
106   
107    A.  Unsolicited Requests 
108   
109  Unsolicited requests are those initiated by persons or entities that are completely independent of 
110  the relevant firm.  (This may include many health care professionals, health care organizations, 
111  members of the academic community, and formulary committees, as well as consumers such as  
112  patients and caregivers).  Requests that are prompted in any way by a manufacturer or its 
113  representatives are not unsolicited requests.  Two types of unsolicited requests are addressed in this  
114  draft guidance: non-public unsolicited requests and public unsolicited requests.  Responses to 
115  unsolicited requests can likewise be non-public (private) or public. 
116   
117     Non-public unsolicited requests 
118   
119  A non-public unsolicited request is an unsolicited request that is directed privately to a firm using a 
120  one-on-one communication approach. 
121   
122  Example 1: An individual calls or e-mails the medical information staff at a firm seeking 
123  information about an off-label use.  In this case, neither the request nor the response would be 
124  visible to the public. 
125   
126     Public unsolicited requests 
127   
128  A public unsolicited request is an unsolicited request made in a public forum, whether directed to a 
129  firm specifically or to a forum at large. 
130   
131  Example 2:  During a live presentation, an individual asks a question, directed to a firms 
132  representative but heard by other attendees, regarding off-label use of a specific product.  This 
133  request is a public request. Similarly, a response by the firm that is conveyed to the same audience 
134  as the original question would be considered a public response. 
135   
136  Example 3: An individual posts a question about off-label use of a specific product on a firm-
137  controlled website (or a third-party discussion forum) that is visible to a broad audience.  The 
138  request could be directed to a firm specifically or posed to users of a discussion forum at large.  
                                                                                                                                                                
Publications on Unapproved New  Uses of  Approved Drugs  and  Approved of  Cleared Medical Devices, available at 
http://www.fda.gov/RegulatoryInformation/Guidances/ucm125126.htm. 
4   Contains Nonbinding Recommendations 
Draft  Not for Implementation  
 
 
139  This request is a public online request. Similarly, a response by the firm that is visible to the same  
140  audience as the original question would be considered a public online response.  
141   
142  B.  Solicited Requests 
143   
144  FDA considers requests for off-label information that are prompted in any way by a manufacturer 
145  or its representatives to be solicited.  Such solicited requests may be considered evidence of a 
146  firms intent that a drug or medical device be used for a use other than that specifically approved 
147  or cleared by FDA. Although not exhaustive, the following examples illustrate what FDA 
148  generally considers to be solicited requests for off-label information7: 
149   
150  Example 4:  If a firms sales representative mentions a use of a product that is not reflected in the 
151  products approved labeling and invites a health care professional to request more information, 
152  resulting requests would be considered solicited requests. 
153   
154  Example 5:  If a representative of a firm, such as a medical science liaison or paid speaker (e.g., 
155  key opinion leader), presents off-label use data at a company-sponsored promotional event (e.g., a 
156  dinner) and attendees then ask or submit requests for more information, these requests would be 
157  considered solicited requests. 
158   
159  Example 6:  If a firm issues to health care professionals business reply cards that are intended for 
160  use in requesting off-label information, presents statements or contact information in promotional 
161  pieces in a manner that solicits requests for off-label medical or scientific information (e.g., 
162  Product X continues to be evaluated in more than 50 trials in a broad range of conditions and 
163  patients and Call 1-800-... for more information), or displays a commercial exhibit panel 
164  suggesting a new indication (e.g., a sign that reads Coming Soon, a new use for Product X), 
165  requests made in response to these types of prompts would be considered solicited requests. 
166   
167  Example 7:  If a firm provides a phone number, e-mail address, uniform resource locator (URL), or 
168  username that is a word, alpha phrase, or alpha representation implying the availability of off-label 
169  information for its product, requests using this phone number, e-mail address, URL, or username  
170  would be considered solicited requests. 
171   
172  Example 8:  A firm asks or otherwise encourages users to post videos about their own uses of its 
173  product on third-party video-sharing sites (e.g., YouTube), which may result in video postings 
174  about an off-label use of its product.  If the firms initial request for posting of videos results in any 
175  questions about off-label uses, or if any off-label video posting made in response to the firms 
176  encouragement of video postings results in questions about the products off-label use, these 
177  questions would be considered solicited requests.  
                                                 
7 The focus of this draft guidance is unsolicited  requests for off-label information, not compliance with provisions of  
FDAs advertising and labeling  regulations for drugs. We note, however, that in some of the following examples, a 
firms activities that serve to  solicit the requests for off-label information  may themselves give rise to specific 
regulatory violations. 
5 
  Contains Nonbinding Recommendations 
Draft  Not for Implementation  
 
 
178  Example 9:  If a firm sends out packets of information to known bloggers or online consumer 
179  reviewers and encourages them to write about an off-label use of its product on third-party sites 
180  and this then provokes a discussion about that off-label use, any requests inquiring about the 
181  products off-label use as a result of these blogs, whether posted as comments to the third-party 
182  site or directed to the firm, would be considered solicited requests. 
183   
184  Example 10:  If a firm announces results of a study via a microblogging service (e.g., Twitter) and  
185  suggests that an off-label use of its product is safe and effective, any comments and requests 
186  received as a result of the original message about the off-label use would be considered solicited 
187  requests. 
188   
189  Example 11:  If a firm sets up a website that enables viewers to read prepared standard responses 
190  for the firms products that are generated from  prefixed pull-down menus naming various disease 
191  states, including any standard responses related to off-label uses for the firms product, resulting 
192  requests for off-label information would be considered solicited.  Moreover, if this website makes 
193  it possible to use search terms to generate standard responses that go beyond the scope of the 
194  product information being requested, including off-label use information, resulting requests for and 
195  responses to such a search would be considered solicited requests. 
196   
197   
198  IV.  OVERVIEW OF FDAS POLICY ON RESPONDING TO UNSOLICITED 
199  REQUESTS FOR OFF-LABEL INFORMATION 
200   
201  FDA has long taken the position that firms can respond to unsolicited requests for information 
202  about FDA-regulated medical products by providing truthful, balanced, non-misleading, and non-
203  promotional scientific or medical information that is responsive to the specific request, even if 
204  responding to the request requires a firm to provide information on unapproved or uncleared 
205  indications or conditions of use. If responses to unsolicited requests fall within these parameters, 
206  FDA has not expected those responses to meet regulatory requirements for promotional labeling or 
207  advertising and has not considered these responses as evidence of intended use.  This draft 
208  guidance sets forth FDAs current thinking on this topic, consistent with the Agencys past policy 
209  statements about responding to unsolicited requests.8,9  Regardless of whether the initial 
                                                 
8 This policy was articulated in a letter to industry in 1982 and has been restated on many occasions.  See  Position on  
the Concept of Solicited and Unsolicited  Requests (April 22, 1982) ("[T]he Division of  Drug Advertising and Labeling 
will not regulate as labeling any and all unsolicited requests received from outside the company for information about 
a drug manufactured,  distributed, or repacked  by the company.  These types of legitimate requests from  
scientists/individuals  for drug  information will be regarded  and treated as a personal communication between the 
requestor and firm."); 59 Fed. Reg. 59820, 59823  (November 18, 1994) (stating that manufacturers may respond to  
unsolicited  requests for information with "responsive, nonpromotional, balanced  scientific information, which may 
include information  on unapproved  uses, without subjecting their products to regulation  based  on the information").  
FDAs current  views (expressed in this  draft  guidance)  remain consistent  with these past policy statements. 
9 In addition, section  557(a) of the FD&C Act, which expired  on September 30, 2006, provided that "nothing in section  
551 [of the Act] shall be construed as prohibiting a manufacturer from disseminating information in response to an  
unsolicited  request from a health care practitioner."  21 U.S.C.360aaa-6  
6 
  Contains Nonbinding Recommendations 
Draft  Not for Implementation  
 
 
210  unsolicited request for off-label information was made in a non-public or public forum, a firm that 
211  chooses to respond should provide the final response containing the requested off-label 
212  information about its product only to the specific individual who requested the information as a 
213  private, one-on-one communication. 
214   
215  Section V explains in detail FDAs recommendations for firms that choose to respond to non-
216  public unsolicited requests for off-label information, and Section VI addresses FDAs 
217  recommendations for firms that choose to respond to public unsolicited requests for off-label 
218  information, including those that are encountered through emerging electronic media. 
219   
220   
221  V.  RESPONDING TO NON-PUBLIC UNSOLICITED REQUESTS FOR OFF-LABEL 
222  INFORMATION DIRECTED TO DRUG OR MEDICAL DEVICE FIRMS 
223   
224  This section of the draft guidance makes recommendations about responding to non-public 
225  unsolicited requests for off-label information about prescription human and animal drugs (drugs) 
226  and medical devices (devices) specifically directed to firms privately through one-on-one 
227  communications. For example, an individual might call or correspond directly with a firm  
228  concerning the use of its product for an unapproved or uncleared indication or condition of use.  
229  The firm could receive the request by mail, e-mail, telephone, or through a firm-controlled website 
230  that enables individuals to privately submit a request directly to the firm so that the request is not  
231  available to the public. 
232   
233  FDA makes the following recommendations to a firm that is responding to a non-public  
234  unsolicited request for off-label information about its product that was specifically directed to the 
235  firm privately through a one-on-one communication. 
236   
237  1.   Information distributed in response to an unsolicited request should be provided only to the 
238  individual making the request directly to the firm as a private, one-on-one communication. 
239   
240  2.   Information distributed in response to an unsolicited request should be tailored to answer only 
241  the specific question(s) asked. 
242   
243  A firm should ensure that all pertinent background data are obtained to be able to determine what 
244  information is being requested before providing a response.  If an unsolicited question is broad in 
245  nature, the firm should appropriately narrow the question.  In other words, the level of specificity 
246  of the question posed is important to ensure that the firms response is tailored to the request. 
247   
248  Example 12:  An individual requests information on the use of a drug or device for one particular 
249  disease or condition that is considered off-label for that drug or device (e.g., use of Drug X during 
250  pregnancy in patients with diabetes).  Generally, a firm should provide information pertaining only 
251  to that disease or condition (i.e., the firm should provide a response tailored only to the use of Drug 
252  X during pregnancy in patients with diabetes). 
7 
  Contains Nonbinding Recommendations 
Draft  Not for Implementation  
 
 
253  However, if there is information about known or suspected risks associated with other diseases or 
254  conditions that is also relevant to the disease or condition for which information was requested, the 
255  firm should provide such information to ensure a complete and accurate presentation of the risk 
256  issues associated with the requested use (e.g., Drug X is known to cause fetal harm when used in 
257  pregnant patients with arthritis, and this risk information should be disclosed as part of the 
258  response about use of Drug X during pregnancy in patients with diabetes). 
259   
260  3.   Information distributed in response to an unsolicited request should be truthful, non-
261  misleading, accurate, and balanced.10  
262   
263  A response should provide non-biased information or data relating to the particular off-label use 
264  that is the subject of the request, including applicable data that are not supportive or that cast doubt 
265  on the safety or efficacy of that use.  For example, when conclusions of articles or texts that are 
266  disseminated have been specifically called into question by other articles or texts, a firm should 
267  disseminate representative publications that reach contrary or different conclusions regarding the 
268  use at issue. The response should include complete copies of scientific reprints, technical 
269  literature, or other scientific and medical information responsive to the request, not just summary 
270  documents or abstracts prepared by the firm.  The response can include unpublished data on file if 
271  they are responsive to the specific request (either supporting or casting doubt on the safety or 
272  efficacy of the off-label use). However, to the greatest extent possible, a firm should rely on 
273  published peer-reviewed journal articles, medical texts, or data derived from independent sources.  
274  To the extent the response consists of published reprints from journals, those reprints should be 
275  from journals that have a publicly stated policy, to which the organization adheres, of full 
276  disclosure of any conflict of interest or biases for all authors, contributors, or editors associated 
277  with the journal or organization. 
278   
279  4.   Information distributed in response to an unsolicited request should be scientific in nature. 
280   
281  When responding to an unsolicited request for information, a firm should respond with material 
282  that is scientific in tone and presentation. The material should not be promotional in tone or 
283  presentation. Furthermore, the responsive material should not be distributed along with other 
284  material or information that is promotional in nature or tone. 
285   
286  5.   Responses to unsolicited requests for information should be generated by medical or scientific 
287  personnel independent from sales or marketing departments. 
288   
289  FDA recommends that questions or requests about off-label uses be referred to the firms medical 
290  or scientific representative or department.  FDA recommends  that medical or scientific personnel 
291  have specialized backgrounds in responding to unsolicited requests for information, including 
                                                 
10 Evaluating evidence of intended use may also involve considering  the context in which manufacturer  
communication about an  off-label use occurs.  For this reason, FDAs recommendations in this  draft  guidance for  
responding to  unsolicited requests  for information by third parties are not identical to its recommendations regarding 
the spontaneous manufacturer-initiated activity of  distributing reprints, as addressed in  other FDA guidance.  
8 
  Contains Nonbinding Recommendations 
Draft  Not for Implementation  
 
 
292  important training, such as appropriately narrowing questions, tailoring responses only to the 
293  specific questions being asked, providing unbiased responses, and properly documenting 
294  responses. 
295   
296  By contrast, because sales and marketing personnel are focused by training and experience on 
297  promoting a firms products, FDA recommends that sales and marketing personnel have no input 
298  on the content of responses to unsolicited questions or requests for off-label information. 
299   
300  6.   Information distributed in response to an unsolicited request should be accompanied by the 
301  following: 
302   
303     A copy of the FDA-required labeling, if any, for the product (e.g., FDA-approved package 
304  insert and, if the response is for a consumer, FDA-approved patient labeling or, for new 
305  animal drugs, FDA-approved client information sheet) 
306     A prominent statement notifying the recipient that FDA has not approved or cleared the 
307  product as safe and effective for the use addressed in the materials provided 
308     A prominent statement disclosing the indication(s) for which FDA has approved or cleared 
309  the product 
310     A prominent statement providing all important safety information including, if applicable, 
311  any boxed warning for the product 
312     A complete list of references for all of the information disseminated in the response (e.g., a 
313  bibliography of publications in peer-reviewed medical journals or in medical or scientific 
314  texts; citations for data on file, for summary documents, or for abstracts) 
315   
316  7.   A firm should maintain the following records: 
317   
318     The nature of the request for information, including the name, address, and affiliation 
319  of the requestor 
320     Records regarding the information provided to the requestor 
321     Any follow-up inquiries or questions from the requestor 
322   
323  If a firm responds to non-public unsolicited requests for off-label information in the manner 
324  described above, FDA does not intend to use such responses as evidence of the firms intent that 
325  its product be used for an unapproved or uncleared use.  Such responses also would not be 
326  expected to comply with the disclosure requirements related to promotional labeling and 
327  advertising. 
328   
329   
9 
  Contains Nonbinding Recommendations 
Draft  Not for Implementation  
 
 
330  VI.  RESPONDING TO PUBLIC UNSOLICITED REQUESTS FOR OFF-LABEL 
331  INFORMATION, INCLUDING THOSE ENCOUNTERED THROUGH 
332  EMERGING ELECTRONIC MEDIA BY DRUG OR MEDICAL DEVICE FIRMS 
333   
334  This section of the draft guidance makes recommendations about responding to public unsolicited 
335  requests for off-label information about prescription human and animal drugs (drugs) and medical 
336  devices (devices), including those that are encountered through emerging electronic media. 
337   
338  The Internet has revolutionized communication, information-sharing, information exchange among 
339  systems, and collaboration, enabling consumers to become more proactive about their health and 
340  safety. Consequently, the Internet has become a widely used medium for manufacturers and 
341  distributors of FDA-regulated medical products to disseminate information.  The Internet has also 
342  spawned a variety of social media tools that host online content primarily created and published by  
343  users other than the intellectual property owner or product manufacturer.  In some cases, this 
344  online content may not be accurate.  Because consumers increasingly use the Internet to search for 
345  information about medical conditions and treatments, firms may receive public requests for off-
346  label information about their products through, for example, product websites, discussion boards, 
347  chat rooms, or other public electronic forums that they maintain and over which they have full 
348  control.  Firms may also encounter requests for off-label information on third-party sites (i.e., 
349  websites and other venues that are either entirely independent of a firms control and influence or 
350  not fully controlled by a firm).  Questions about off-label use may be directed to the website users 
351  at large, rather than specifically to a firm. 
352   
353  As previously stated in Section II, FDA recognizes that firms are capable of responding to requests 
354  about their own named products in a truthful, non-misleading, and accurate manner.  Moreover, 
355  because firms usually have robust and current information about their products, it can be in the 
356  best interest of public health for a firm to respond to unsolicited requests for information about off-
357  label uses of the firms products that are made in public forums, especially since other responders 
358  may not provide or have access to the most accurate and up-to-date medical product information. 
359   
360  However, because product information posted on  websites and other public electronic forums is 
361  likely to be available to a broad audience and for an indefinite period of time, FDA is concerned 
362  that firms may post detailed public online responses to questions about off-label uses of their 
363  products in such a way that they are communicating unapproved or uncleared use information 
364  about FDA-regulated medical products to individuals who have not requested such information.  In 
365  this circumstance, communications to persons who have not requested information may promote a 
366  product for a use or condition for which FDA has not approved or cleared.  FDA is also concerned 
367  about the enduring nature of detailed public online responses to off-label questions because 
368  specific drug or device information may become  outdated (e.g., new risk information may become  
369  available). 
370   
10  
  Contains Nonbinding Recommendations 
Draft  Not for Implementation  
 
 
371  FDA makes the following recommendations to a firm that chooses to respond to public  unsolicited 
372  requests for off-label information about its product(s), including those encountered through 
373  emerging electronic media. 
374   
375  1.   If a firm chooses to respond to public unsolicited requests for off-label information, the firm  
376  should respond only when the request pertains specifically to its own named product (and is 
377  not solely about a competitors product). 
378   
379  The level of specificity of the question posed in a public forum is important in determining the 
380  appropriateness of a firm responding to the unsolicited request. 
381   
382  Example 13:  An individual poses the specific question Can Drug/Device X be used for Condition 
383  Y in a public forum (and this question is not prompted by or on behalf of the firm).  It may be 
384  appropriate for the firm to respond as outlined below because the question is unsolicited and 
385  specific to the firms named drug or device. 
386   
387  However, if an individual poses the non-specific question What drug/device can be used for 
388  Condition Y in a public communication thread and the firm manufactures or distributes 
389  Drug/Device X, which is not FDA-approved or cleared for Condition Y, the firm should not 
390  respond to the request because the question is not specific to Drug/Device X. 
391   
392  2.   A firms public response to public unsolicited requests for off-label information about its 
393  named product should be limited to providing the firms contact information and should not  
394  include any off-label information.  
395   
396     The firms public response should convey that the question pertains to an unapproved or 
397  uncleared use of the product and state that individuals can contact the medical/scientific 
398  representative or medical affairs department with the specific unsolicited request to obtain 
399  more information. 
400     The firms public response should provide specific contact information for the medical or 
401  scientific personnel or department (e.g., e-mail address, telephone number, facsimile) so 
402  that individuals can follow up independently with the firm to obtain specific information 
403  about the off-label use of the product through a non-public, one-on-one communication. 
404   
405  After an individual has privately contacted a firm  for more information regarding an off-label use 
406  of the firms product, the firm should provide a detailed response and maintain records following 
407  the parameters outlined in Section V of this draft guidance.  Therefore, any substantive 
408  communication about off-label uses for the product, in response to the original unsolicited off-
409  label question, should occur solely between the firm and the individual who made the request.  
410  Regardless of the fact that the original, unsolicited off-label question may have been available to a 
411  very broad audience, the firm should not make its detailed response with off-label information 
412  publicly available within the same forum.  For example, after the requestor has contacted the firm  
413  and provided a personal e-mail address to obtain an answer to the off-label question, the firms 
11  
  Contains Nonbinding Recommendations 
Draft  Not for Implementation  
 
 
414  detailed off-label response, within the parameters outlined in Section V of this draft guidance, 
415  should be e-mailed to the requestor since this resulting communication will occur solely between 
416  the firm and the specific individual making the unsolicited request for the off-label information. 
417   
418  3.   Representatives who provide public responses to unsolicited requests for off-label information 
419  should clearly disclose their involvement with a particular firm.  
420   
421  FDA recommends that a representative who responds to a public request clearly disclose in his/her 
422  public response that he/she is a particular firms representative and inform the requestor of the 
423  name of the firm representative or department to contact should the individual choose to follow up 
424  directly with the firm in a non-public forum for detailed information about the unsolicited request 
425  for off-label information.  
426   
427  4.   Public responses to public unsolicited requests for off-label information described in numbers 
428  2 and 3 should not be promotional in nature or tone. 
429   
430  In addition to a firms contact and disclosure information, a public response should include a 
431  mechanism for providing readily accessible current FDA-required labeling, if any, for the product 
432  (e.g., FDA-approved package insert and, if the response is for a consumer, FDA-approved patient 
433  labeling or, for new animal drugs, FDA-approved client information sheet).  The public response 
434  should not provide any promotional information.  For example, a public online response should 
435  include a direct link to the current FDA-required labeling, if any, but should not include links to 
436  any other information (e.g., product websites, product promotional materials, firm websites, third-
437  party websites). Furthermore, the uniform resource locator (URL) or web address where viewers 
438  are directed to obtain the FDA-required labeling, if any, should not itself be promotional in tone or 
439  content (e.g., should not be www.bestcancercure.com). 
440   
441  If a firm responds to public unsolicited requests for off-label information, including those 
442  encountered through emerging electronic media, in the manner described above, FDA does not 
443  intend to use such responses as evidence of the firms intent that its product be used for an 
444  unapproved or uncleared use. Such responses also would not be expected to comply with the 
445  disclosure requirements related to promotional labeling and advertising. 
1 2