Certification Process for 
Designated Medical Gases 
 
 
 
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DRAFT GUIDANCE
 
 
  This guidance document is being distributed for comment purposes only.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publication in the Federal Register of the notice announcing the availability of the draft 
guidance.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 comments to the 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 document contact Michael Folkendt at 301-796-1900.  
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
Center for Veterinary Medicine (CVM) 
 
November 2015 
Procedural 
 
 
Revision 1 
   
Certification Process for 
Designated Medical Gases 
 
 
 
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  
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) 
Center for Veterinary Medicine (CVM) 
 
 
 
 
November 2015 
Procedural 
 
 
Revision 1 
  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
TABLE OF CONTENTS 
 
 
I.  INTRODUCTION............................................................................................................. 1 
II.  THE STATUTORY CERTIFICATION PROCESS ..................................................... 2 
III.  THE CURRENT LIST OF DESIGNATED MEDICAL GASES ................................. 3 
IV.  REQUESTING A CERTIFICATION ............................................................................ 5 
A.  Who should submit a request for certification? .......................................................................... 5 
B.  What information should be submitted? ..................................................................................... 7 
1. Requestor information ..................................................................................................................... 7 
2. Type of Submission .......................................................................................................................... 7 
3. Description of Medical Gas ............................................................................................................. 7 
4. Facility Information ......................................................................................................................... 7 
C.  How should a requestor submit the certification request?......................................................... 8 
D.  How should information in a certification request be updated/corrected? .............................. 8 
V.  EVALUATING A CERTIFICATION REQUEST ........................................................ 9 
A.  Review of Request for Certification ............................................................................................. 9 
B.  Communication with the Requestor ............................................................................................. 9 
C.  Revocation of Certification; Withdrawal or Suspension of Approval .................................... 10 
VI.  ENFORCEMENT OF CERTIFICATION REQUIREMENT ................................... 10 
 
ATTACHMENT:  Request for Certification of Medical Gas 
 
  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
1  Certification Process for Designated Medical Gases 
1
2  Guidance for Industry  
3   
4   
5   
6  This draft guidance, when finalized, will represent the current thinking of the Food and Drug 
7  Administration (FDA or Agency) on this topic.  It does not establish any rights for any person and is not 
8  binding on FDA or the public.  You can use an alternative approach if it satisfies the requirements of the 
9  applicable statutes and regulations.  To discuss an alternative approach, contact the FDA staff responsible 
10  for this guidance as listed on the title page.   
11   
12   
13   
14  I.  INTRODUCTION  
15   
16  Title XI, Subtitle B of the Food and Drug Administration Safety and Innovation Act (FDASIA)2 
17  added sections 575 and 576 to the Federal Food, Drug, and Cosmetic Act (FD&C Act), creating 
18  a new certification process for approval of designated medical gases.  Section 575 defines 
19  designated medical gas to include oxygen, nitrogen, nitrous oxide, carbon dioxide, helium, 
20  carbon monoxide, and medical air that meet the standards set forth in an official compendium.  
21  Section 576 permits any person to file a request for certification of a medical gas as a designated 
22  medical gas for certain indications specified in the statute.  A designated medical gas for which a 
23  certification is granted is deemed to have in effect an approved marketing application  under 
24  Section 505 of the FD&C Act (human drugs), Section 512 of the FD&C Act (animal drugs), or 
25  both, depending on the type of certification requested and granted.  This guidance explains how 
26  the Food and Drug Administration (FDA) administers the certification process.  Specifically, the 
27  guidance discusses what products qualify as designated medical gases, who should submit a 
28  certification request, what information should be submitted, how FDA will evaluate and act on 
29  the request, and how FDA plans to enforce these new medical gas provisions.  
30   
31  Until a certification has been granted, anyone marketing a medical gas for human or animal drug 
32  use without an approved application under section 505 or 512 of the FD&C Act is marketing an 
33  unapproved new drug.3  See sections 505(a) and 512(a)(1)(A) of the FD&C Act.  FDA expects 
34  that persons or entities wishing to market designated medical gases for the indication or 
35  indications specified in section 576(a)(3)(A)(i) will request certification from FDA, or ensure 
                                                 
1 This guidance has been prepared by the Office of Regulatory Policy, the Office of Pharmaceutical Quality, and the 
Office of Compliance in the Center for Drug Evaluation and Research (CDER) and the Office of New Animal Drug 
Evaluation in the Center for Veterinary Medicine (CVM) at the Food and Drug Administration. 
2 Public Law 112-144, 126 Stat. 993 (July 9, 2012). 
3 See section IV below regarding who should request a certification and section VI below regarding the marketing of 
carbon monoxide for use in lung diffusion testing. 
 
  1  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
36  that the gases they receive and distribute are certified (i.e., are covered by a granted 
37  certification).4  Gases not intended for human or animal drug use, e.g., gases intended for 
38  industrial applications or non-drug medical applications (such as calibration gases), do not fall 
39  within the definition of medical gas provided in section 575(2) of the FD&C Act, and are not 
40  subject to the certification process described in this guidance. 
41   
42  To facilitate the process of requesting certifications, FDA has developed a form that requestors 
43  should complete when making their requests (see attachment).     
44   
45  This guidance does not discuss how FDA plans to implement its new authority to designate gases 
46  in addition to those listed above5 or to expand the indications for use for designated medical 
47  gases beyond those specified at section 576(a)(3)(A)(i) of the FD&C Act.  This document also 
48  does not discuss any of the other new authorities and obligations related to medical gases added 
49  to the FD&C Act by FDASIA (e.g., section 577 of the FD&C Act and sections 1112 and 1113 of 
50  FDASIA).   
51   
52  In general, FDAs guidance documents do not establish legally enforceable responsibilities.  
53  Instead, guidances describe the Agencys current thinking on a topic and should be viewed only 
54  as recommendations, unless specific regulatory or statutory requirements are cited.  The use of 
55  the word should in FDA guidances means that something is suggested or recommended, but not 
56  required. 
57   
58  II.  THE CERTIFICATION PROCESS  
59   
60  Any person may file a request for certification of a medical gas as a designated medical gas.  A 
61  certification request must contain a description of the medical gas for which the certification is 
62  sought, the name and address of the sponsor, the name and address of the facility or facilities 
63  where the medical gas is or will be manufactured, and any other information deemed appropriate 
64  by FDA to determine whether the medical gas is a designated medical gas (see section 576(a)(1) 
65  of the FD&C Act).  A certification request is deemed to be granted unless, within 60 days of 
66  filing, FDA finds that (1) the medical gas for which the certification is requested is not a 
67  designated medical gas, (2) the request lacks the information required by section 576(a)(1) noted 
68  at the outset of this paragraph or otherwise lacks sufficient information to permit FDA to 
69  determine that the medical gas is a designated medical gas, or (3) denying the request is 
70  necessary to protect the public health (see section 576(a)(2) of the FD&C Act). 
71   
72  A designated medical gas for which a certification is granted is deemed to have in effect an 
73  approved application under section 505 (for gases intended for human use) or 512 (for gases 
                                                 
4 Those seeking to market any other medical gas, or seeking to market a designated medical gas (alone or in 
combination with one or more other medical gases, designated or otherwise) for an indication that is neither 
specified in 576(a)(3)(A)(i) of the FD&C Act for that designated medical gas or later added by FDA under its 
authority at section 576(a)(3)(A)(i)(VIII), cannot obtain approval to do so through the certification process and must 
obtain approval by a different pathway (e.g., a new drug application (NDA) or a new animal drug application 
(NADA)).  See Part IV.A of this draft guidance. 
5 See section 575(1)(H) of the FD&C Act. 
  2  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
74  intended for animal use) of the FD&C Act (or both) for the indications listed below and is 
75  subject to all applicable post-approval requirements (see section 576(a)(3)(A)(i)).  The approval 
76  applies to the  designated medical gas alone or in combination, as medically appropriate, with 
77  one or more other designated medical gases for which certifications have been granted (see 
78  section 576(a)(3)(A)(i)). 
79   
80  Under section 576, at this time the designated medical gases may be certified only for the 
81  following indications: 
82   
83    Oxygen: for treatment or prevention of hypoxemia or hypoxia. 
84    Nitrogen: for use in hypoxic challenge testing. 
85    Nitrous oxide: for analgesia. 
86    Carbon dioxide: for use in extracorporeal membrane oxygenation therapy or respiratory 
87  stimulation. 
88    Helium: for treatment of upper airway obstruction or increased airway resistance.  
89    Medical air: to reduce the risk of hyperoxia.  
90    Carbon monoxide: for use in lung diffusion testing.  
91   
92  Section 576(a)(3)(A)(ii) of the FD&C Act provides that the labeling requirements at sections 
93  503(b)(4) and 502(f) are deemed to have been met for a designated medical gas if the labeling on 
94  final use containers for the medical gas bears--(I) the information required by section 503(b)(4); 
95  (II) a warning statement concerning the use of the medical gas as determined by the Secretary by 
96  regulation; and (III) appropriate directions and warnings concerning storage and handling.  
97  With regard to the warning statement referred to at section 576(a)(3)(A)(ii)(II), a warning 
98  statement applicable to carbon dioxide, helium, and nitrous oxide can be found at 21 CFR 
99  201.161(a).  However, no regulation sets forth warning statements for the other designated 
100  medical gases or for combinations of designated medical gases.  Until such time as FDA 
101  promulgates relevant final regulations, FDA recommends that the labeling for final use 
102  containers containing nitrogen, medical air, carbon monoxide, or any medically appropriate 
103  combination of designated medical gases bear the warning statement set forth at 21 CFR 
104  201.161(a).  FDA further recommends that labeling for final use containers containing oxygen 
105  should convey that uninterrupted use of high concentrations of oxygen over a long duration, 
106  without monitoring its effect on oxygen content of arterial blood, may be harmful, and that 
107  oxygen should not be used on patients who have stopped breathing unless used in conjunction 
108  with resuscitative equipment.   
109   
110  Section 576 further provides that, in the case of oxygen provided for certain uses specified at 
111  576(b)(2)(B), the requirements of section 503(b)(4) shall be deemed to have been met if the 
112  labeling bears a warning that oxygen can be used for emergency use only, and that for all other 
113  medical applications a prescription is required.  Accordingly, FDA recommends that labeling for 
114  final use containers containing oxygen that may be provided without a prescription for the uses 
115  listed at section 576(b)(2)(A) of the Act bear a warning statement in accord with section 
116  576(b)(2)(B).   
117   
118   
  3  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
119  III.  THE CURRENT LIST OF DESIGNATED MEDICAL GASES 
120   
121  Section 575(1) of the FD&C Act provides that oxygen, nitrogen, nitrous oxide, carbon dioxide, 
122  helium, medical air, and carbon monoxide are designated medical gases if they meet the 
123  standards set forth in an official compendium.  Section 201(j) of the FD&C Act defines official 
124  compendium to include the official United States Pharmacopoeia (USP), the official 
125  Homeopathic Pharmacopeia of the United States (HPUS), the official National Formulary (NF), 
126  or any supplement to any of them. 
127   
128  Based on the statutory language and the current language in these official compendia,6 FDA 
129  considers the following to be the current list of the gases that constitute designated medical gases 
130  for which a certification can be sought:7 
131   
132  Oxygen.  The product must conform to the requirements and standards set forth in the USP 
133  monograph entitled Oxygen and all applicable requirements and standards contained in the 
134  USP General Notices (see section 575(1)(A) of the Act).   
135   
136  Note:  The USP monograph entitled Oxygen states that Oxygen contains not less than 
137  99.0 percent, by volume, of O2.  There is another USP monograph entitled Oxygen 93 
138  Percent that describes a product that is Oxygen ... [that] contains not less than 90.0 
139  percent and not more than 96.0 percent, by volume of O2, the remainder consisting mostly 
140  of argon and nitrogen. Oxygen 93 Percent is different from Oxygen and does not fall 
141  within the meaning of 575(1)(A).  Thus, FDA considers only products that conform to the 
142  Oxygen monograph (and not the Oxygen 93 Percent monograph) to be oxygen, that 
143  meets the standards set forth in an official compendium (section 575(1)(A)). 
144   
145  Nitrogen.  The product must conform to the requirements and standards set forth in the NF 
146  monograph entitled Nitrogen and all applicable requirements and standards contained in the 
147  USP General Notices (see section 575(1)(B) of the Act).  
148    
149  Note:  The NF monograph entitled Nitrogen states that Nitrogen contains not less than 
150  99.0 percent, by volume, of N .  The NF also contains a monograph entitled Nitrogen 97 
2
151  Percent.  FDA considers only products that conform to the Nitrogen monograph to be 
152  nitrogen, that meets the standards set forth in an official compendium (section 575(1)(B)); 
153  conformance with the Nitrogen 97 monograph is not sufficient.  
154   
155  Nitrous Oxide.  The product must conform to the requirements and standards set forth in the USP 
156  monograph entitled Nitrous Oxide and all applicable requirements and standards contained in 
157  the USP General Notices (see section 575(1)(C) of the Act).8 
                                                 
6 Should a monograph in an official compendium for one of the designated gases change, persons or entities 
marketing that gas must comply with those changes.   
7 Section 575(1)(H) authorizes the Secretary to add other gases to the list of designated medical gases.  The 
Secretary has not taken any such action at this time.  As noted in the Introduction, this guidance does not discuss 
how FDA plans to implement this authority.     
  4  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
158   
159  Carbon dioxide.  The product must conform to the requirements and standards set forth in the 
160  USP monograph entitled Carbon Dioxide and all applicable requirements and standards 
161  contained in the USP General Notices (see section 575(1)(D) of the Act). 
162   
163  Helium.  The product must conform to the requirements and standards set forth in the USP 
164  monograph entitled Helium and all applicable requirements and standards contained in the 
165  USP General Notices (see section 575(1)(E) of the Act). 
166   
167  Medical air.  The product must conform to the requirements and standards set forth in the USP 
168  monograph entitled Medical Air and all applicable requirements and standards contained in the 
169  USP General Notices (see section 575(1)(G) of the Act). 
170   
171  Carbon monoxide.  There is currently no monograph in the USP or the NF for Carbon 
172  Monoxide.  Therefore, FDA does not plan to grant certification requests for this medical gas.9  
173  FDA does not intend to object to the marketing of this medical gas for use in lung diffusion 
174  testing pending its inclusion in the USP or NF, as discussed in Part VI of this guidance.  If a 
175  monograph for Carbon Monoxide is added to the USP or NF at a later date, FDA would expect 
176  persons or entities marketing carbon monoxide for use in lung diffusion testing to request a 
177  certification.  In addition, future requestors must conform to the requirements and standards set 
178  forth in such a monograph as well as all applicable requirements and standards contained in the 
179  USP General Notices, for the product to be considered a designated medical gas (see section 
180  575(1)(F) of the Act). 
181   
182  IV.  REQUESTING A CERTIFICATION 
183   
184  FDA expects all persons or entities that initially introduce or deliver for introduction a 
185  designated medical gas into interstate commerce to obtain a granted certification.10  To facilitate 
186  the certification process, FDA has developed the attached Request for Certification of 
187  Designated Medical Gas form.  FDA strongly encourages requestors to use this form, and to 
188  closely follow the instructions attached to that form.  
189   
190  A.  Who should submit a request for certification? 
191   
192  Only the first person or entity that initially introduces or delivers for introduction a designated 
193  medical gas into interstate commerce should request a certification.  In most cases, this will be 
                                                                                                                                                             
8 The HPUS also includes a monograph for nitrous oxide.  However section 501(b) of the FD&C Act states that 
[w]henever a drug is mentioned in both the USP and the HPUS it shall be subject to the requirements of the USP 
unless it is labeled and offered for sale as a homeopathic drug.  See also FDAs Compliance Policy Guide 400.400, 
Conditions Under Which Homeopathic Drugs May be Marketed, available at 
http://www.fda.gov/ICECI/ComplianceManuals/CompliancePolicyGuidanceManual/ucm074360.htm.      
9 While there is a HPUS monograph for carbon monoxide, it is inapplicable when the designated medical gas is not 
labeled as a homeopathic.  See FDAs Compliance Policy Guide 400.400. 
10 See generally section 505(a) of the FD&C Act for human drugs and sections 501(a)(5) and 512(a)(1)(A) and of 
the FD&C Act for animal drugs. 
  5  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
194  the original manufacturer of the gas, that is, the person or entity that initially produces the gas by 
195  chemical reaction, physical separation, compression of atmospheric air, or other means.  In some 
196  instances, original manufacturers may produce gases solely for industrial or other non-medical 
197  uses.  Such manufacturers are not subject to the certification requirements in the FD&C Act.  
198  However, if a person or entity downstream is the first to market that gas as a medical gas (e.g., 
199  after re-processing an industrial gas into a medical gas for human or animal use), that person or 
200  entity must obtain a certification to lawfully market the designated medical gas.   
201   
202  A person or entity that markets a medical gas but is neither the original manufacturer nor the 
203  original marketer of that gas should not submit a certification request, even if that person or 
204  entity is the first to market the gas in containers conforming to the requirements for labeling at 
205  576(a)(3)(A)(ii).11  Such downstream persons or entities should, however, verify and document 
206  that the gas or gases they receive are from a source or sources that have a granted certification 
207  for the gas (see Part VI below).      
208   
209  Requestors should submit separate certification requests for each designated medical gas they 
210  produce (e.g., one request for oxygen, another for nitrous oxide), but need only submit a single 
211  request for each gas regardless of whether the gas is manufactured in multiple facilities or by 
212  multiple methods. 
213   
214  The certification process is the same for designated medical gases intended for human drug use 
215  and animal drug use.  The attached form has a box for requestors to indicate whether they wish 
216  to market their gas for human use, animal use, or both.  Upon grant of a certification, FDA will 
217  issue the requestor an NDA number, a NADA number, or both.   
218   
219  Persons or entities that wish to market a medical gas that is a combination of one or more 
220  designated medical gases need not, and should not, seek certification for the combination of the 
221  two designated medical gases.  Rather, they may lawfully market medically appropriate 
222  combinations of designated medical gases under the certification process so long as each 
223  designated medical gas is covered by a granted certification (see section 576(a)(3)(A)(i) of  the 
224  FD&C Act). 
225   
226  The certification process only applies to designated medical gases and only for the indications 
227  specified in section 576 of the FD&C Act.12  A person or entity seeking to market a medical gas 
                                                 
11 We note that such downstream persons or entities commonly perform certain manufacturing or processing 
operations (e.g., combining gases or transfilling a gas from one container to another).  Such persons or entities must 
comply with all applicable current good manufacturing practices (CGMPs) (see 21 CFR Parts 210 and 211) as well 
as all applicable drug registration and listing requirements (see section 510 of the FD&C Act and 21 CFR Part 207).  
In addition, should such downstream manufacturing or processing operations cause the product to fall outside the 
scope of the certification scheme (e.g., should they result in a single gas product that no longer meets the applicable 
compendial standard or a combination gas product that is not a medically appropriate combination of certified 
designated medical gases), the resulting product will not be considered to be covered by any upstream certification 
or certifications, and would have to be separately approved under the FD&C Act.  See footnote 14 and 
accompanying text.   
12 See section 576(a)(3)(A)(i) of the FD&C Act.   
  6  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
228  or combination of medical gases that falls outside the scope of this certification process should 
229  obtain approval of that medical gas or combination of medical gases under a different approval 
230  pathway (e.g., an NDA or a NADA under sections 505 and 512 of the FD&C Act along with the 
231  implementing regulations at 21 CFR Part 314 and 21 CFR Part 514).13   
232   
233  B.  What information should be submitted? 
234   
235  This section is organized to follow the format in the attached form. 
236   
237  1.  Requestor Information 
238   
239  Section 576(a)(1)(B) requires the certification request to include the name and address of the 
240  sponsor.  FDA also requests additional contact information for the person or entity requesting the 
241  certification (email address and phone number), along with the name, address, and other contact 
242  information of an authorized U.S. agent if applicable.  FDA will use this information to 
243  communicate with the requestor as necessary. 
244   
245  2.  Type of Submission 
246   
247  The requestor should indicate the type of submission as one of the following:  Original 
248  Certification Request (for either new human or animal drugs, or both), Amendment to a Pending 
249  Certification Request, Resubmission, or Other.14  For submissions other than original 
250  certification requests, the requestor should briefly describe the purpose of the submission (e.g., 
251  an amendment to supply additional information regarding manufacturing facilities).  Following 
252  receipt of an original certification request, FDA plans to provide the requestor an NDA and/or 
253  NADA number in an acknowledgment letter.  The requestor should include their NDA and/or 
254  NADA number in all further submissions related to the gas to which that certification request 
255  applies. 
256   
257  3.  Description of Medical Gas    
258   
259  Section 576(a)(1)(A) requires that the certification request include a description of the medical 
260  gas.  This description must include the name of the gas and information sufficient to support that 
261  the gas meets the standards set forth in an official compendium (see section 575(1)). 
262   
263  4.  Facility Information 
264   
                                                 
13 The following products and/or indications fall outside the scope of the certification process: (1) any designated 
medical gas for any indication other than the indications listed in section 576(a)(3)(A)(i) or later added in 
accordance with section 576(a)(3)(A)(i)(VIII), (2) any other medical gas for any indication, or (3) any combination 
of medical gases other than medically appropriate combinations of certified designated medical gases for one or 
more of the indications specified at 576(a)(3)(A)(i) or later added in accordance with section 576(a)(3)(A)(i)(VIII). 
14 The Other category is intended as a catch-all for any submissions that do not fit into one of the other provided 
categories.  For example, a sponsor would check Other to submit information concerning a new manufacturing 
facility in connection with a previously-granted certification. 
  7  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
265  Section 576(a)(1)(C) requires that the certification request include the name and address of the 
266  facility or facilities where the medical gas is or will be manufactured.  FDA requests that contact 
267  information be included for each facility involved in original manufacturing or processing of the 
268  designated medical gas.  When the requestor is not the original manufacturer of the gas (if, for 
269  example, the original manufacturer produced the gas for industrial use), the requestor need only 
270  list the facilities involved in re-processing the gas into a designated medical gas.  FDA also asks 
271  that the requestor briefly describe the manufacturing or processing activities performed at each 
272  facility so that FDA understands the role each plays in manufacturing or processing the gas.   
273   
274  The requestor should include the Data Universal Numbering System (D-U-N-S) number for each 
275  facility, along with the facilitys FDA Establishment Identifier (FEI) if one exists.  If a D-U-N-S 
276  number has not been assigned, the facility may obtain one directly from Dun & Bradstreet 
277  (http://www.dnb.com) at no cost. 
278   
279    5. Additional Information 
280   
281  The requestor should affirm (by checking the appropriate box on the attached form) that the 
282  requestors methods, facilities, and controls used for the manufacture, processing, and handling 
283  of the gas, as applicable, are adequate to ensure its identity, strength, quality, and purity (see 
284  sections 501(a)(2)(B) and 505(d) of the FD&C Act, and 21 CFR Parts 210 and 211).  Pursuant to 
285  Section 576(a)(1)(D), the requestor must also provide any other information which the Secretary 
286  may, in the future, deem appropriate to determine whether the medical gas is a designated 
287  medical gas.   
288   
289  C.  How should a requestor submit the certification request? 
290   
291  FDA asks the requestor to submit the certification request by following the instructions on the 
292  attached form.  As previously noted, the attached form should be used to indicate whether the 
293  requestor expects to market the designated medical gas for human use, animal use, or both. 
294   
295  D.  How should information in a certification request be updated or corrected? 
296   
297  If the original information submitted in connection with a certification request becomes 
298  incomplete or inaccurate at any time, including after the request has been granted, the requestor 
299  should resubmit its certification request, submitting both a complete new form and a cover letter 
300  clearly explaining the purpose of the submission and highlighting the updated or corrected 
301  information.  Updated or corrected information to the information originally submitted on this 
302  form other than adding a new manufacturing facility can be submitted in this manner.  If the 
303  update or change involves adding a new manufacturing facility requestors should notify the FDA 
304  of the change by submitting a changes being effected supplement under 21 CFR 314.70(c) or 
305  21 CFR 514.8(b)(3).15  All other submissions must be made in accordance with 21 CFR 314.70 
306  or 21 CFR 514.8 as appropriate.  The requestor should also update its registration and listing data 
307  as appropriate.   
                                                 
15 See 21 CFR 314.70(a)(3) and 21 CFR 514.8(b)(1)(iii). 
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Draft  Not for Implementation 
308     
309  V.  EVALUATING A CERTIFICATION REQUEST 
310   
311  A.  Review of Request for Certification  
312   
313  As provided in section 576(a)(2) of the FD&C Act, a certification request is deemed to be 
314  granted unless, within 60 days of filing, FDA finds that (1) the gas to which the request applies is 
315  not a designated medical gas, (2) the request does not contain the information required by section 
316  576(a)(1) or otherwise lacks sufficient information to permit FDA to determine whether the gas 
317  is a designated medical gas, or (3) denying the request is necessary to protect the public health.  
318   
319  If the medical gas does not meet the applicable official compendial standards (e.g., the requestor 
320  fails to affirm that the medical gas meets the applicable compendial standards), FDA will not 
321  grant a certification request for such gas.  FDA may find that it lacks sufficient information to 
322  determine whether the gas for which certification is sought is a designated medical gas if the 
323  available information, including the information submitted with the request, is insufficient to 
324  assure FDA that the gas meets the applicable compendial standards and that the requestors 
325  methods, facilities, and controls used for the manufacture, processing, and handling of the gas, as 
326  applicable, are adequate to ensure its identity, strength, quality, and purity.  FDA will not grant a 
327  certification request if it cannot determine whether the gas is a designated medical gas.    Finally, 
328  FDA may conclude that denying the request is necessary to protect the public health.   
329   
330  In determining whether a request should be denied, FDA will consider information submitted 
331  with the request along with any other available, relevant information, including information 
332  obtained from state or federal officials, FDA inspection reports, or any other source. 
333   
334  B.  Communication with the Requestor 
335   
336  FDA plans to send an acknowledgement letter to the requestor after receipt of a certification 
337  request.    
338   
339  FDA may contact the requestor to request additional information.  If required information is not 
340  included in the request, and if FDA is not able to contact the requestor to obtain and evaluate the 
341  information within the 60 day review period, FDA may find that the request lacks sufficient 
342  information to permit a determination that the gas is a designated medical gas (see section 
343  576(a)(2)(B) of the FD&C Act). 
344   
345  Unless, within 60 days of filing, FDA makes a finding that the certification request should not be 
346  granted, the certification request is deemed to be granted.  See section 575(a)(2) of the FD&C 
347  Act.  In this case, the designated medical gas will be granted a certification, and will have in 
348  effect an approved application under sections 505, 512, or both, as applicable, for the indications 
349  for use specified in 576(a)(3) of the FD&C Act, subject to all applicable post-approval 
350  requirements.  FDA plans to issue a second letter to the requestor stating that the certification 
351  request has been granted.  This letter will include an NDA and/or NADA number which the 
352  sponsor should include in all further submissions to the Agency. 
353   
  9  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
354  If FDA makes one of the findings listed at section 576(a)(2) of the FD&C Act, however, FDA 
355  will notify the requestor within 60 days of filing that the certification request has not been 
356  granted.  In such an instance, FDA plans to issue a letter explaining its determination to the 
357  requestor.  If the requestor chooses to re-submit its certification request, it should provide a 
358  written response to the deficiencies identified in FDAs letter, along with the attached form.   
359   
360  C.  Revocation of Certification; Withdrawal or Suspension of Approval 
361   
362  Section 576(a)(4)(A) of the FD&C Act states that FDA may withdraw or suspend approval of a 
363  drug product, including a designated medical gas deemed under section 576 to have in effect an 
364  approved application under section 505 or 512 of the FD&C Act.  In addition, FDA may revoke 
365  the grant of a certification if it determines that the certification request contained any material 
366  omission or falsification.  See section 576(a)(4)(B) of the FD&C Act.   
367   
368  VI.  ENFORCEMENT OF CERTIFICATION REQUIREMENT 
369   
370  All medical gases intended for human or animal drug use that are not certified or do not 
371  otherwise have an approved marketing application will be considered unapproved new drugs or 
372  unapproved new animal drugs and may be subject to enforcement action.   This includes 
373  designated medical gases marketed for any indication other than those listed at section 
374  576(a)(3)(A)(i) of the FD&C Act  
375   
376  Sections 575 and 576 of the FD&C Act provide a streamlined mechanism for obtaining approval, 
377  and FDA expects original manufacturers or marketers of designated medical gases eligible for 
378  certification to obtain approvals for such gases through this certification process. 
379  As noted in Part IV.A, a person or entity that markets a medical gas but is neither the original 
380  manufacturer nor the original marketer should not obtain a granted certification but should verify 
381  and document that the gas or gases they receive are from a certified source or sources. 
382  Documentation should include the name of the original manufacturer(s) or marketer(s) as well 
383  the applicable new drug application number or numbers associated with the gas, and should be 
384  verified by reference to the FDA database Drugs@FDA, a searchable database available at 
385  http://www.accessdata.fda.gov/scripts/cder/drugsatfda/ that contains a record of all granted 
386  certifications. Each downstream customer should obtain documentation from their immediate 
387  supplier.  Proper certification by a supplier or suppliers should be verified initially for existing 
388  suppliers and for new suppliers as part of a vendor qualification process.  Once a new vendor or 
389  existing supplier has been qualified initially and the certification of the gas or gases confirmed, 
390  this documentation can consist of an annual letter from the immediate supplier attesting or 
391  certifying that the gas was originally manufactured at one or more firms with granted 
392  certifications.  The letter should contain the above-mentioned items of information for each 
393  certified original source.  We recommend that this statement of certified original sources be 
394  updated to reflect any changes with each annual renewal.   
395   
396  FDA does not plan to grant certification requests for carbon monoxide until a monograph for that 
397  medical gas is added to the USP or the NF.  FDA does not intend to object to the marketing of 
398  carbon monoxide for use in lung diffusion testing as long as the product conforms to an 
  10  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
399  acceptable alternative compendial standard.16  If and when a monograph entitled Carbon 
400  Monoxide is added to the USP or NF, original manufacturers and/or marketers of carbon 
401  monoxide should promptly submit a certification request. 
                                                 
16 See FDAs Manual of Policies and Procedures, MAPP 5310.7, Acceptability of Standards from Alternative 
Compendia, available at 
http://www.fda.gov/downloads/AboutFDA/CentersOffices/CDER/ManualofPoliciesProcedures/ucm079841.pdf. 
  11  DEPARTMENT OF HEALTH AND HUMAN SERVICES  Form Approved: OMB No. xxxx-xxxx 
Food and Drug Administration  Expiration Date: Xxxxxxx xx, 201x 
See PRA Statement on last numbered  
Request for Certification of Designated Medical Gas 
page. 
1. Requestor Information 
Requestor Name* 
Requestor Address* 
Address 1 
Address 2 (if applicable) 
City  State/Province/Region  ZIP or Postal Code 
Country (If not United States please provide contact information for authorized U.S. agent in Contact Information field below.) 
Contact Information (Enter address only if different from above.) 
Name 
Title 
Address 1 
F
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Address 2 (if applicable) 
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City  State/Province/Region  ZIP or Postal Code 
Country (if applicable) 
Telephone Number  Email Address  Fax Number 
2. Type of Submission (Select only one.) 
Original Certification Request to  Original Certification Request to  Original Certification Request to Market 
Market Gas for Human Drug Use  Market Gas for Animal Drug Use  Gas for Human and Animal Drug Use 
Amendment to Pending Certification Request  Resubmission 
Other (specify): 
NDA or NADA Number (Does not apply to original certification request.): 
Reason for Submission (Does not apply to original certification request.) 
3. Description of Medical Gas* 
Select the medical gas to which this request applies (select only one). By checking one of the following boxes you 
indicate that the gas to which this request applies satisfies the compendial standard listed in connection with the gas. 
Oxygen, USP  Nitrogen, NF  Nitrous oxide, USP  Carbon dioxide, USP 
Medical Air, USP  Helium, USP 
FORM FDA 3864 (12/12)  Page 1 of 3  * Required information 
PSC Publishing Services (301) 443-6740  EF  4. Facility Information 
Provide the following information regarding each facility involved in the manufacture and processing of the medical gas to which this 
request applies. 
Name of Facility* 
Facility Address* 
Address 1 
Address 2 (if applicable) 
City  State/Province/Region  ZIP or Postal Code 
Country (if applicable) 
Other Facility Information 
Facility D-U-N-S Number  Facility FEI Number 
Briefly describe the manufacturing or processing performed at the above facility in connection with the gas to which this request applies. 
 
F
O
O Add additional facility 
R
5. Additional Information  P
Check the following box to indicate that your methods, facilities, and controls used for the 
manufacture, processing, and handling of the gas to which this request applies are adequate 
to ensure its identity, strength, quality, and purity. 
Provide any other information you believe will assist FDA in evaluating your request. 
6. Signature(s) 
By my signature I hereby certify that the data and information in this submission have been reviewed and, to the best of my 
knowledge, are true and accurate. WARNING: A willfully false statement is a criminal offense, U.S. Code, title 18, section 1001. 
Applicant 
Name and Title 
Signature of Applicant  Date of Request (mm/dd/yyyy) 
Authorized U.S. Agent (if applicable) 
Name and Title  Telephone Number 
Signature of Authorized U.S. Agent  Date (mm/dd/yyyy) 
FORM FDA 3864 (12/12)  Page 2 of 3  * Required information  This section applies only to requirements of the Paperwork Reduction Act of 1995. 
DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF ADDRESS BELOW. 
The burden time for this collection of information is estimated to average 2 hours per response, including 
the time to review instructions, search existing data sources, gather and maintain the data needed and 
complete and review the collection of information. Send comments regarding this burden estimate or any 
other aspect of this information collection, including suggestions for reducing this burden, to: 
Department of Health and Human Services 
Food and Drug Administration 
Offi ce of Chief Information Officer 
Paperwork Reduction Act (PRA) Staff 
1350 Piccard Drive, Room 400 
Rockville, MD 20850 
An agency may not conduct or sponsor, and a person is not required to respond to, a collection of 
information unless it displays a currently valid OMB number. 
 
F
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FORM FDA 3864 (12/12)  Page 3 of 3  Instructions for Submitting Request for Certification of
 
Designated Medical Gas Using Form FDA 3864
 
1. REQUESTOR INFORMATION:  The name and contact information of the legal person or entity submitting 
the certification request should be provided in the indicated areas. For non-U.S. requestors the name and 
contact information of the legal person or entity authorized to represent the requestor should be entered in the 
Contact Information field. 
2. TYPE OF SUBMISSION: The submission type should be indicated by checking the appropriate box. If 
any box other than one of the three original certification request boxes is checked an explanation should be 
provided in the Reason for Submission block (e.g., Response to 02/15/13 Information Request Letter or 
Amendment to Supply Additional Information Regarding Manufacturing Facilities). The NDA and/or NADA  
number should also be provided if known. 
Original Certification Request  A certification request submitted by a person or entity to market a 
particular medical gas for human use, animal use, or both. 
Amendment to a Pending Certification Request  Any submission to a pending certification request, 
including responses to Information Request Letters. 
Resubmission  Any complete certification request submitted by a person or entity for a particular 
medical gas that has been previously denied certification. 
Other  Any submission that does not fit in one of the other categories. 
3. DESCRIPTION OF MEDICAL GAS: The requestor should affFirm  that the medical gas to which the request 
applies meets the applicable compendial standard.  O
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4. FACILITY  INFORMATION: Only a brief dePscription sufficient to enable FDA to understand the role of each 
facility involved in the manufacture and processing of the gas to which the certification request applies need 
be provided in this section. For example, production of [gas] by physical separation or production of [gas] by 
purification. If the D-U-N-S Number for a facility has not been assigned, one may be obtained for no cost 
directly from Dun & Bradstreet (http://www.dnb.com). If an FDA Establishment Identifier (FEI) exists for the 
facility it should be included. 
5. ADDITIONAL  INFORMATION: The requestor should affirm that its methods, facilities, and controls used 
for the manufacture, processing, and handling of the gas, as applicable, are adequate to preserve the identity, 
strength, quality, and purity of the gas. If the requestor believes any other information would be useful for FDA  
to consider, it may provide that information in this section as well. 
6. SIGNATURE(S): The form must be signed and dated. Ordinarily only one person should sign the form: 
the requestor, or the requestors attorney, agent, or other authorized official. However, if the person signing 
the request does not reside or have a place of business within the United States, the request should be 
countersigned by an attorney, agent, or other authorized official who resides or maintains a place of business 
within the United States. 
SUBMISSION: Send three copies of the completed, signed Form FDA 3864 with three copies of a cover letter 
to: Central Document Room, 5901B Ammendale Road, Beltsville, MD 20705. The cover letter should clearly 
identify the nature of the submission (for example, Original Certification Request to Market Gas for Human and 
Animal Drug Use). The cover letter should also provide the NDA and/or NADA number if known. 
FORM FDA 3864 (12/12)  FORM INSTRUCTIONS