Naming of Drug 
Products Containing 
Salt Drug Substances  
 
 
Guidance for Industry 
 
 
 
 
   
 
.  
 
 
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
 
 
 
June 2015 
Labeling
 
   
Naming of Drug 
Products Containing 
Salt Drug Substances 
 
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  
Phone: 855-543-3784 or 301-796-3400; Fax: 301-431-6353 
druginfo@fda.hhs.gov  
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
 
 
June 2015 
Labeling
 
  Contains Nonbinding Recommendations 
 
TABLE OF CONTENTS 
 
 
 
I.  INTRODUCTION............................................................................................................. 2 
II.  DISCUSSION .................................................................................................................... 2 
A.  USP Salt Policy Overview ............................................................................................................. 3 
B.  How CDER is Applying the USP Salt Policy ............................................................................... 3 
C.  How CDER is Applying Exceptions ............................................................................................. 4 
III.  HOW TO IMPLEMENT THE USP SALT POLICY ................................................... 5 
A.  Product Development .................................................................................................................... 5 
B.  Labels and Labeling Information ................................................................................................. 5 
C.  USP Salt Policy Does not Impact Statutory or Regulatory Requirements Related to Active 
Ingredients ...................................................................................................................................... 6 
IV.  PRODUCTS THAT FAIL TO FOLLOW THE USP SALT POLICY RISK BEING 
MISBRANDED ................................................................................................................. 7 
V.  REFERENCES .................................................................................................................. 7 
VI.  DEFINITION .................................................................................................................... 7 
APPENDIX 1:  Monograph Naming Policy for Salt Drug Substances in Drug Products 
and Compounded Preparations ................................................................... 8 
APPENDIX 2:  Sample Labels with Equivalency Statement Language and Formatting 
for Prescription Drug Products .................................................................... 9 
 
    Contains Nonbinding Recommendations 
1  Naming of Drug Products Containing Salt Drug Substances 
1
2  Guidance for Industry  
3   
4   
5  This guidance represents the current thinking of the Food and Drug Administration (FDA or Agency) on 
6  this topic.  It does not create any rights for any person and is not binding on FDA or the public.  You can 
7  use an alternative approach if it satisfies the requirements of the applicable statutes and regulations.  To 
8  discuss an alternative approach, contact the FDA staff responsible for this guidance as listed on the title 
9  page.   
10   
11   
12   
13   
14  I.  INTRODUCTION 
15   
16  This guidance for industry is intended to help you, the sponsor, understand how products with 
17  active ingredients that are salts may be affected by CDERs implementation of the United States 
18  Pharmacopeia (USP) policy entitled, Monograph Naming Policy for Salt Drug Substances in 
19  Drug Products and Compounded Preparations2 (the USP Salt Policy).  Your involvement with 
20  the implementation of this policy helps to ensure drug product naming that is consistent with the 
21  USP Salt Policy, which became effective on May 1, 2013.  
22   
23  This guidance addresses prescription drug products approved under the Federal Food, Drug, and 
24  Cosmetic Act (FD&C Act).3  This guidance does not address implementation of the USP Salt 
25  Policy for nonprescription drug products4 or biological products licensed under the Public Health 
26  Service Act (PHS Act).5   
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  II.  DISCUSSION 
35   
36  The USP Salt Policy is a naming and labeling policy applicable to drug products that contain an 
37  active ingredient that is a salt. The policy stipulates that USP will use the name of the active 
38  moiety, instead of the name of the salt, for such a drug product when creating a drug product 
                                                           
1 This guidance has been prepared by the Center for Drug Evaluation and Research (CDER) at the Food and Drug 
Administration.  
2 The Monograph Naming Policy for Salt Drug Substances in Drug Products and Compounded Preparations is 
published in USP General Chapter <1121> Nomenclature.  Please see Appendix 1. 
3 See section 505 of the FD&C Act. This guidance does not address naming and labeling of compounded 
preparations. 
4 See 21 CFR 201.66.  
5 See section 351 of the PHS Act. 
  2 
 
 
  Contains Nonbinding Recommendations 
39  monograph title. The USP Salt Policy also states that USP will base the strength of the product 
40  on the active moiety. The policy allows for exceptions under specified circumstances. 
41   
42  The USP Salt Policy became effective on May 1, 2013, and USP is now applying it to all new 
43  drug product monographs for products that contain an active ingredient that is a salt. It affects 
44  the development of new drug products, because a USP monograph title for a new drug product, 
45  in most instances, serves as the nonproprietary or established name of the related drug 
46  product.6  A drug product with a label or labeling that contains a name that is inconsistent with 
47  the applicable monograph title risks being misbranded.7   
48   
49  The USP Salt Policy only applies to the monograph titles for drug products. The policy will not 
50  apply to the titles of monographs for drug substances (active ingredients). Accordingly, the 
51  names of active ingredients (e.g., salts) will not be affected.  
52   
53  A.  USP Salt Policy Overview8  
54   
55  The USP Salt Policy provides the following: 
56     
57  1.  When an active ingredient in a drug product is a salt, the drug product monograph title will 
58  contain the name of the active moiety (or neutral form), and not the name of the salt (e.g., 
59  newdrug tablets instead of newdrug hydrochloride tablets).  
60   
61  2.  The strength also will be expressed in terms of the active moiety (e.g., 100 mg newdrug) 
62  rather than the salt strength equivalent (e.g., 123.7 mg newdrug hydrochloride).  
63   
64  3.  If the name and strength of a drug product are expressed in terms of the active moiety, the 
65  full name and full strength (or proportion, if CDER has determined proportion is more 
66  appropriate) of the active ingredient (e.g., salt), will appear elsewhere on the drug product 
67  label and labeling.9  
68   
69  4.  The USP Salt Policy provides for exceptions to the active moiety naming approach, when 
70  the name of the salt conveys vital information from a clinical perspective.  In these cases, the 
71  drug product monograph title will include the name of the salt, and the strength of the drug 
72  product also is expressed in terms of the salt form (active ingredient).   
73   
74  5.  USP does not anticipate changing existing monograph titles, unless necessary for safety.  
75  USP and CDER have agreed to coordinate regarding any necessary retrospective name 
76  changes.   
77   
78  B.  How CDER is Applying the USP Salt Policy 
79   
80  We are applying the USP Salt Policy to prescription drug products under development for which 
81  approval is sought under section 505 of the FD&C Act.   
82   
                                                           
6 See section 502(e)(3) of the FD&C Act.    
7 See section 502(e)(1)(A)(i) of the FD&C Act. 
8 See USP General Chapter <1121> Nomenclature. 
9 See section III.B. for additional information related to the labeling of products that are salts. 
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  Contains Nonbinding Recommendations 
83  CDERs application of the USP Salt Policy should help avoid medication errors that could result 
84  from a mismatch of established name and strength (e.g., the name includes the salt but the 
85  strength is based on active moiety).  In addition, we anticipate that the policy will make it easier 
86  for healthcare practitioners to calculate an equivalent dose when transferring patients from one 
87  dosage form to another (e.g., calculating dose from an injection to a tablet), even if the products 
88  contain active ingredients that are different salts, because the strengths and names both will be 
89  based on the active moiety.  
90   
91  We recommend you consistently use the established name of the drug product as determined 
92  under the USP Salt Policy in all contexts in which a products established name is used. 
93     
94  C.  How CDER is Applying Exceptions 
95   
96  We anticipate that most drug products containing active ingredients that are salts will be named 
97  using the active moiety, in accordance with the USP Salt Policy. To facilitate implementation of 
98  the policy and its exceptions, we have developed the procedures described below that we 
99  generally intend to follow when considering whether an exception to the USP Salt Policy is 
100  appropriate. To help determine if your product meets one of the exceptions listed below, contact 
101  the review division for your specific drug product and request a meeting. Early communication 
102  for a potential exception (at Pre-IND or Phase I) is important because it could affect how the 
103  product could be developed so that the name and dosing is based on the active moiety or the salt. 
104  The Agency, not the sponsor, will determine whether USP Salt Policy exceptions apply, and 
105  early discussions will help us decide. As we apply the USP Salt Policy, we may identify 
106  additional grounds for exceptions. 
107   
108  1.  The name of the salt could be retained if any of the following conditions are met:  
109   
110  a.  The active ingredient is a relatively simple salt and administration of the entire salt is 
111  therapeutically important. Examples include: lithium carbonate; iron sulfate, and 
112  other oral and intravenous iron salts; calcium gluconate and other calcium salts; 
113  potassium chloride; magnesium sulfate; sodium or potassium phosphate; and sodium 
114  citrate. 
115   
116  b.  Scientific evidence demonstrates the salt form affects the absorption, distribution, 
117  metabolism, and/or excretion (ADME) of the drug in a manner that influences the 
118  clinicians product selection. 
119   
120  c.  Clinically significant amounts of cations (e.g., sodium, potassium, magnesium or 
121  calcium) accompany the active moiety of a drug product. Clinical significance may 
122  be related to the recommended maximum daily amount of an electrolyte intake in 
123  special patient populations. Examples include: recommended daily intake of sodium 
124  in patients with congestive heart failure or recommended daily intake of potassium in 
125  patients with chronic kidney disease. 
126   
127  d.  There is a significant evidence-based safety concern that the counter-ion part of the 
128  salt could cause acid-base disturbances, hepatic, renal or other organ damage, or 
129  hypersensitivity reactions. 
130   
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  Contains Nonbinding Recommendations 
131  2.  The name of the salt could be retained if any of the following safety or historical conditions 
132  are met:   
133   
134  a.  The name of the salt is necessary to maintain consistency with other dosage forms of 
135  the same active ingredient (salt).  For example, if a tablet dosage form that was 
136  approved before May 1, 2013 included the salt in its established name and the drug 
137  products strength is based on the salt form, the naming convention would not change 
138  for a new capsule dosage form with the same active ingredient (salt) that is approved 
139  after the effective date. 
140   
141  b.  We identify that the USP Salt Policy should not be applied because there are relevant, 
142  documented safety reasons (e.g., documented medication errors related to name or 
143  strength) in a closely related product.  
144   
145  c.  If we name a drug product according to the USP Salt Policy (e.g., the name and 
146  strength of the product are based on the active moiety) and, postapproval, there are 
147  safety concerns, we will consider whether a retrospective name change is appropriate.  
148  CDER and USP have agreed to coordinate any retrospective name changes. 
149   
150  III.  HOW TO IMPLEMENT THE USP SALT POLICY  
151   
152   A.  Product Development 
153     
154  When developing a drug product that may be affected by the USP Salt Policy, we encourage you 
155  to do the following: 
156   
157  1.  Consider whether the USP Salt Policy applies to your product. Does your product contain an 
158  active ingredient that is a salt?  
159   
160  2.  If you think your product qualifies for an exception, contact CDER for preliminary feedback 
161  on whether the USP Salt Policy or one of its exceptions applies to your product. You should 
162  provide data to support your position. 
163   
164  3.  Develop your product so the name and strength match and are defined in accordance with the 
165  USP policy or CDER feedback.  
166   
167  B.  Labels and Labeling Information 
168   
169  Application of the USP Salt Policy does not affect existing statutory and regulatory requirements 
170  for drug products.    
171     
172  1.  You should create labels and labeling with the following in mind: 
173   
174  a.  The name of the active ingredient in a drug product is not subject to or affected by 
175  application of the USP Salt Policy. This means that the established name of the drug 
176  product may be different than the established name of the active ingredient (e.g., the 
177  active ingredient in new drug tablets will remain newdrug hydrochloride). The name 
178  and the amount of the active ingredient (salt) should appear on the container label, carton 
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  Contains Nonbinding Recommendations 
179  labeling, and other labeling as required by statute and regulation even when the active 
180  moiety is used in the established name and strength of the drug product.10 
181   
182  b.  Products that use the active moiety in the name and strength should include an 
183  equivalency statement to indicate the amount of active moiety related to the amount of 
184  active ingredient (salt). This equivalency statement should appear on the container label, 
185  carton labeling, and other labeling.11  
186   
187  c.  Products that include the name of the active ingredient (salt) in the established name of 
188  the drug product, because they qualify for an exception, also should include an 
189  equivalency statement indicating the strength in terms of the active moiety. The 
190  equivalency statement should appear on the container label, carton labeling, and other 
191  labeling.12   
192   
193  d.  The established name of the drug product and the active ingredient should be correctly 
194  displayed throughout the labeling.  
195   
196  2.  You should pay careful attention to the language used in the following locations in the 
197  prescribing information:  
1 98 
199  a.  Confirm that the product title in the Highlights section of the Prescribing Information13 is 
200  accurate. 
201   
202  b.  Confirm that the Dosage Forms and Strengths section14 clearly states the product contents 
203  in a manner that allows the reader to understand whether the strength is based on the 
204  active moiety or active ingredient (salt). 
205   
206  c.  Confirm that the Description section15 for drug products containing an active ingredient 
207  that is a salt clearly identifies the active ingredient (salt), the active moiety, and the 
208  strengths of each. This can be accomplished with the use of an equivalency statement. 
209   
210  C.  USP Salt Policy Does not Impact Statutory or Regulatory Requirements 
211  Related to Active Ingredients 
212   
213  Using the name of the active moiety in the established name and in the expression of strength 
214  does not implicate or change other statutory and regulatory requirements related to active 
215  ingredient.  For example, an applicant for an abbreviated new drug application will still have to 
216  demonstrate that the companys proposed generic product has the same active ingredient as the 
217  reference listed drug.16  The Orange Book: Approved Drug Products with Therapeutic 
218  Equivalence Evaluations will continue to provide listings based on the active ingredient.   
                                                           
10 See section 502(e)(1)(A)(ii) of the FD&C Act. 
11 See Appendix 2, Example 1. 
12 See Appendix 2, Example 2. 
13 See 21 CFR 201.57(a)(2). 
14 See 21 CFR 201.57(a)(8), and 21 CFR 201.57(c)(4). 
15 See 21 CFR 201.57(c)(12)(i).  
16 See sections 505(j)(2)(A)(ii) and 505(j)(4)(C) of the FD&C Act.   
  6 
 
 
  Contains Nonbinding Recommendations 
219   
220  IV.  PRODUCTS THAT FAIL TO FOLLOW THE USP SALT POLICY RISK 
221  BEING MISBRANDED 
222   
223  The USP Salt Policy became effective on May 1, 2013.  After that date, we anticipate that titles 
224  for new USP drug product monographs17 will not include the active ingredient (salt) unless an 
225  exception applies. A product with a name that is inconsistent with a USP monograph title18 risks 
226  being misbranded under the FD&C Act.19   
227   
228  V.  REFERENCES 
229   
230  Section 502 of the FD&C Act: Misbranded Drugs and Devices 
231   
232  Section 505 of the FD&C Act: New Drugs 
233   
234  Section 751 of the FD&C Act: National Uniformity for Nonprescription Drugs 
235   
236  21 CFR 201.10: Drugs; Statement of Ingredients 
237   
238  21 CFR 201.57: Specific Requirements on Content and Format of Labeling for Human 
239  Prescription Drug and Biological Products Described in Section 201.56(b)(1) 
240   
241  21 CFR 314.108(a): New Drug Product Exclusivity; Definitions  
242   
243  Monograph Naming Policy for Salt Drug Substances in Drug Products and Compounded 
244  Preparations: The USP Salt Policy is published in General Chapter <1121> Nomenclature.   
245   
246  Section 351 of the PHS Act; Regulation of Biological Products 
247   
248  VI.  DEFINITION 
249    
250  Active moiety - The molecule or ion, excluding those appended portions of the molecule that 
251  cause the drug to be an ester,20 salt (including a salt with hydrogen or coordination bonds), or 
252  other noncovalent derivative (such as a complex, chelate, or clathrate) of the molecule, 
253  responsible for the physiological or pharmacological action of the drug substance.21     
254   
255     
                                                           
17 After May 1, 2013, the date the USP Salt Policy became effective, the names of already published drug product 
monograph titles should not change unless necessary for safety reasons.   
18 USP uses the following as the general format when creating a drug product monograph title: [DRUG][ROUTE OF 
ADMINISTRATION][DOSAGE FORM]. See USP General Chapter <1121> Nomenclature.  CDER will generally 
follow this naming structure for products approved before the creation of a USP monograph title. 
19 See section 502(e)(1)(A)(i) of FD&C Act.  
20 The USP Salt Policy definition of an active moiety does not include esters.  See USP General Chapter <1121> 
Nomenclature. Consequently, esters should be named as the entire existing covalent entity. 
21 See 21 CFR 314.108(a). 
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  Contains Nonbinding Recommendations 
256  APPENDIX 1:  Monograph Naming Policy for Salt Drug Substances in 
257  Drug Products and Compounded Preparations22 
258   
259  The titles of USP monographs for drug products and compounded preparations formulated with a 
260  salt of an acid or base use the name of the active moiety, as defined below.  The strength of the 
261  product or preparation is also expressed in terms of the active moiety. 
262   
263  An active moiety is the molecule or ion, excluding those appended portions of the molecule that 
264  cause the drug to be a salt (including a salt with hydrogen or coordination bonds), or other 
265  noncovalent derivative (such as a complex, chelate, or clathrate) of the molecule.  The active 
266  moiety is responsible for the physiological or pharmacological action of the drug substance, 
267  without regard to the actual charged state of the molecule in vivo.  For example, the active 
268  moiety of a hydrochloride salt of a base is the free base and not the protonated form of the base.  
269  The active moiety of a metal salt of an acid is the free acid. 
270   
271  This policy is followed by USP in naming drug products and compounded preparations that are 
272  newly recognized in the USP.  Revising existing monographs to conform to this policy is not 
273  intended, except where the USP Council of Experts determines that, for reasons such as safety, a 
274  nomenclature change is warranted. 
275   
276  Labeling: The labeling clearly states the specific salt form of the active moiety that is present in 
277  the product or preparation because this information may be useful to practitioners and patients.  
278  The names and strengths of both the active moiety and specific salt form (when applicable) are 
279  provided in the labeling. 
280   
281  Exceptions: In rare cases in which the use of the specific salt form of the active moiety in the 
282  title provides vital information from a clinical perspective, an exception to this policy may be 
283  considered.  In such cases, when the monograph title contains the specific salt form of the active 
284  moiety, the strength of the product or preparation also is expressed in terms of the specific salt 
285  form. 
286     
                                                           
22 See USP General Chapter <1121>. 
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  Contains Nonbinding Recommendations 
287   
288  APPENDIX 2:  Sample Labels with Equivalency Statement Language and 
289  Formatting for Prescription Drug Products23 
290   
291  Weve created the following examples to help you design labels for products subject to the USP 
292  Salt Policy.  
293   
294  Example 1: Label with name and strength based on active moiety. The information about the 
295  salt is included on the side panel.24  
296   
297  The new language adds the information about the salt in parentheses with equivalent to. 
298   
299  Each capsule contains:  
300  New Drug.....10 mg 
301  (equivalent to 10.5 mg New Drug Hydrochloride USP) 
302   
303   
 
 
  Each capsule contains:  
New Drug........10 mg  
(equivalent to 10.5 mg New Drug 
Hydrochloride USP) 
Usual Adult Dose: See package insert. 
NDC 12345-678-90 
Trade Name  Dispense in a tight, light-resistant container as defined    A
in the USP, with a child-resistant closure.  1-  
Keep tightly closed.  9-0
(new drug) Capsules USP   Store at 25C (77F): excursions permitted to 15 to 30 90-C7     
C (59 to 86F). [See USP controlled room  78-
10 mg  6
temperature.]   -
 
   
Pharmacist: Dispense the accompanying Medication    14 
Guide to each patient.   Manufactured by: ( F  o  r m   u  l a  tAioBnC D Livimisiiotend)   xp  07/
Rx only                                                                   100 CAPSULES  Distributed by: BABnBAy pnwayhwcekaraeyg,,  iUUngSS AAse  53rv43i33c23e13s    737363       E           
304   
 
305 
306 
                                                           
23 The sample labels are included to only show the addition of an equivalency statement and changes to the name 
and strength that are necessary to implement the USP Salt Policy and its exceptions.   
24 Certain products with small container labels may be exempt from certain label requirements under 21 CFR 
201.10(h)(2). To find out if your product is exempt from this regulation, you should contact the agency to discuss 
appropriate labeling that satisfies the USP Salt Policy. 
 
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  Contains Nonbinding Recommendations 
307  Example 2: Label with name and strength based on active ingredient (palmitate salt). The 
308  information about the active moiety is included on the side panel. 25  
309   
310  The new language adds the information about the active moiety in parentheses with equivalent 
311  to. 
312   
313  Each capsule contains:  
314  New Drug Palmitate USP.....10 mg 
315  (equivalent to 8.72 mg New Drug) 
316   
317   
318   
   
  Each capsule contains:  
New Drug Palmitate USP ........10 mg  
(equivalent to 8.72 mg New Drug)  
Usual Adult Dose: See package insert. 
NDC 12345-678-90 
Dispense in a tight, light-resistant container as defined in   
Trade Name 
the USP, with a child-resistant closure. 
Keep tightly closed.  01-A   
(new drug palmitate) Capsules USP   Store at 25C (77F): excursions permitted to 15 to 30C  90-C79-     
10 mg  ( 59 to 86F). [See USP controlled room temperature.]   -678-
 
   
 
Pharmacist: Dispense the accompanying Medication    14 
Guide to each patient.    07/
   Manufactured by: ( F  o  r m   u  l a  tAioBnC D Livimisiiotend)   Exp  
Rx only                                                                   100 CAPSULES  Distributed by: BABnBAy pnwayhwcekaraeyg,,  iUUngSS AAse  53rv43i33c23e13s    737363                  
319   
320   
321   
322   
323   
324   
                                                           
25  See footnote 24.  
  10