Type V DMFs for CDER-Led 
Combination Products Using 
Device Constituent Parts With 
Electronics or Software 
Guidance for Industry 
 
 
 
 
 
 
DRAFT GUIDANCE
 
 
  This guidance document is being distributed for comment purposes only. 
 
Comments and suggestions regarding this draft document should be submitted within 60 days of 
publication in the Federal Register of the notice announcing the availability of the draft 
guidance. Submit electronic comments to https://www.regulations.gov. Submit written 
comments to the Dockets Management Staff (HFA-305), Food and Drug Administration, 5630 
Fishers Lane, Rm. 1061, Rockville, MD 20852. All comments should be identified with the 
docket number listed in the notice of availability that publishes in the Federal Register. 
 
For questions regarding this draft document, contact (CDER) Kimberly Peters, 301-796-6350, 
Kimberly.Peters@fda.hhs.gov. 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
 
October 2019 
Pharmaceutical Quality/CMC 
 
   
Type V DMFs for CDER-Led 
Combination Products Using 
Device Constituent Parts With 
Electronics or Software 
Guidance for Industry 
 
 
Additional copies are available from: 
Office of Communications, Division of Drug Information  
Center for Drug Evaluation and Research 
Food and Drug Administration 
10001 New Hampshire Ave., Hillandale Bldg., 4th Floor  
Silver Spring, MD 20993-0002  
Phone: 855-543-3784 or 301-796-3400; Fax: 301-431-6353 
Email: druginfo@fda.hhs.gov  
https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
 
 October 2019 
Pharmaceutical Quality/CMC 
  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
TABLE OF CONTENTS 
 
 
 
I.  INTRODUCTION............................................................................................................. 1 
II.  BACKGROUND ............................................................................................................... 2 
III.  SCOPE ............................................................................................................................... 3 
IV.  ADMINISTRATIVE PROCEDURES FOR A TYPE V DMF ..................................... 4 
A.  Letter of Intent ............................................................................................................................... 4 
B.  Submission ...................................................................................................................................... 5 
C.  Administrative Review Process .................................................................................................... 5 
D.  Technical Review Process .............................................................................................................. 6 
V.  CONTENT RECOMMENDATIONS FOR TYPE V DMF SUBMISSIONS ............. 6 
A.  Cover Letter ................................................................................................................................... 7 
B.  Administrative Information .......................................................................................................... 7 
1.  DMF Holders Information ............................................................................................................. 7 
2. Reviewers Guide ............................................................................................................................. 7 
3. Communication Granting Permission for Type V DMF Submission ............................................... 8 
4. Letter of Authorization ..................................................................................................................... 8 
5. Reference to Other Applications ...................................................................................................... 8 
C.  Technical Information ................................................................................................................... 9 
VI.  CONTENT RECOMMENDATIONS FOR TYPE V DMF AMENDMENTS ........... 9 
A.  Cover Letter and Administrative Information ......................................................................... 10 
1.  Cover Letter ................................................................................................................................... 10 
2. Letter of Authorization ................................................................................................................... 10 
B.  Technical Information ................................................................................................................. 10 
VII.  CONTENT RECOMMENDATIONS FOR TYPE V DMF ANNUAL REPORTS .. 11 
VIII.  GLOSSARY..................................................................................................................... 11 
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Draft  Not for Implementation 
1  Type V DMFs for CDER-Led Combination Products Using Device 
2  Constituent Parts With Electronics or Software 
3  Guidance for Industry1 
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   
15  I.  INTRODUCTION  
16   
17  A drug master file (DMF) is a voluntary submission to FDA that may be used to provide 
18  confidential detailed information about facilities, processes, or articles used in the 
19  manufacturing, processing, packaging, and storing of one or more human drugs. The draft 
20  guidance for industry Drug Master Files (October 2019) (hereinafter DMF guidance)2 and the 
21  DMF web page3 identify the types of DMFs that may be submitted. A Type V DMF is intended 
22  for the submission of FDA-accepted reference information and supporting data that are not 
23  covered by DMF Types IIIV.  
24   
25  This guidance explains when a Type V DMF may be used to submit information regarding a 
26  combination product4 for which the Center for Drug Evaluation and Research (CDER) has 
27  primary jurisdiction5 (i.e., CDER-led combination product) and which features a device 
28  constituent part with electronics and/or software that is planned to be used as a platform, that is, 
29  may be used in multiple CDER-led combination products. The guidance also describes the 
30  administrative process and outlines the recommended content for these Type V DMF 
                                                 
1 This guidance has been prepared by the Office of Pharmaceutical Quality in the Center for Drug Evaluation and 
Research at the Food and Drug Administration in consultation with the Center for Devices and Radiological Health 
and the Office of Combination Products.  
2 When final, this guidance will represent FDAs current thinking on this topic. For the most recent version of a 
guidance, check the FDA guidance web page at https://www.fda.gov/regulatory-information/search-fda-guidance-
documents. 
3 See https://www.fda.gov/drugs/forms-submission-requirements/drug-master-files-dmfs. 
4 As defined in 21 CFR part 3. 
5 Based on the combination product primary mode of action (PMOA). The PMOA of a combination product is the 
single mode of action (drug, device, or biological product) expected to make the greatest contribution to the overall 
intended therapeutic effects of the combination product. See section 503(g)(1)(C) of the Federal Food, Drug, and 
Cosmetic Act; see also 21 CFR 3.2(k), which defines mode of action and therapeutic, and (m), which presents a 
definition for PMOA now codified in section 503(g). 
 
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31  submissions and amendments. Alternatively, applicants may also choose to incorporate by 
32  reference device constituent part information available in other submission types, such as a 
33  premarket notification submission (510(k)); premarket approval application (PMA); request for 
34  classification submitted under section 513(f)(2) of the Federal Food, Drug, and Cosmetic Act 
35  (FD&C Act) (De Novo request); or device master file (MAF). 
36   
37  This guidance does not address information about device constituent parts that are also container 
38  closure systems, which may be submitted as a Type III DMF. For a Type V DMF that is used for 
39  a shared system risk evaluation and mitigation strategy (REMS) submission, see draft guidance 
40  for industry Use of a Drug Master File for Shared System REMS Submissions (November 
41  2017).6  
42   
43  In general, FDAs guidance documents do not establish legally enforceable responsibilities. 
44  Instead, guidances describe the Agencys current thinking on a topic and should be viewed only 
45  as recommendations, unless specific regulatory or statutory requirements are cited. The use of 
46  the word should in Agency guidances means that something is suggested or recommended, but 
47  not required.  
48   
49   
50  II.  BACKGROUND 
51   
52  Some CDER-led combination products feature a device constituent part with electronics and/or 
53  software that may be used as a platform across multiple products. An application for such a 
54  combination product may necessitate review7 by multiple centers, offices, and divisions within 
55  FDA.8 In addition, because the device constituent part may be used as a platform in multiple 
56  CDER-led combination products, the same device information may be applicable to and used to 
57  support multiple CDER submissions, including an investigational new drug application (IND), a 
58  new drug application (NDA), an abbreviated new drug application (ANDA), a biologics license 
59  application (BLA), amendments and supplements to these applications, or another DMF. For 
60  such combination products, a Type V DMF can be an efficient mechanism to provide 
61  information regarding the device constituent part when the same information is applicable to 
62  several CDER applications.  
63   
64  Further, because of rapid advances in technology, the device constituent part in these types of 
65  combination products could be modified frequently. Knowledge of these modifications is 
66  important in determining whether they have any impact on the safety and effectiveness of the 
                                                 
6 When final, this guidance will represent FDAs current thinking on this topic. 
7 In this guidance, the term review also means assessment, which is the term that CDERs Office of Pharmaceutical 
Quality and Office of Generic Drugs will generally use in place of review. Assessment means the process of both 
evaluating and analyzing submitted data and information to determine whether the application meets the 
requirements for approval and documenting that determination. 
8 Cross-center collaboration and/or consultation is important for combination product review. Although CDER is the 
primary contact for combination products as described in this guidance, CDER consults with other centers as 
described in FDAs Staff Manual Guide 4101, Inter-Center Consult Request Process, available at 
https://www.fda.gov/media/81927/download. 
 
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67  combination product or its indications for use. As stated in 21 CFR 314.420(c), the DMF holder 
68  must submit any change, addition, or deletion of information to the DMF and must notify each 
69  person authorized to reference the information. Therefore, an amendment to a Type V DMF may 
70  be used to submit information regarding modifications to the device constituent part. 
71  Amendments provide a regulatory pathway for the DMF holder to report device modifications 
72  and for FDA to review device modifications, including those that may not warrant postapproval 
73  reporting by applicants whose applications incorporate the Type V DMF by reference.9  
74   
75  A DMF is neither approved nor disapproved. Its technical content is typically reviewed in 
76  connection with the review of an IND, NDA, ANDA, or BLA. A DMF is not a substitute for an 
77  application (e.g., if the device is also to be marketed alone). 
78   
79  Once FDA reviews the Type V DMF device information for one CDER application, its review 
80  may be applicable to other CDER applications if the device information remains unchanged and 
81  is pertinent to products in other CDER applications that also incorporate the DMF by reference. 
82  FDAs ability to use previously completed scientific reviews for a DMF can contribute to an 
83  efficient FDA review process and help ensure consistency across CDER applications referencing 
84  the same information. 
85   
86   
87  III.  SCOPE 
88   
89  This guidance applies to Type V DMF submissions as described above for CDER-led 
90  combination products. Specifically, the information in the guidance may be appropriate for 
91  device constituent parts with electronics and/or software that meet the statutory definition of a 
92  device and perform functions such as the following: 
93   
94    Facilitate drug delivery in a manner that may include patient input or analysis (e.g., an 
95  electromechanically driven pen injector with software that allows input of patient or 
96  dosing information or that analyzes dosing or device use information). 
97   
98    Provide information that is used in making a decision regarding treatment, therapy, or 
99  drug delivery.10 
100   
101    Interface with other devices or systems to provide patient use or other information to the 
102  user or health care provider (e.g., physiological parameters).11 
                                                 
9 When a DMF holder amends a DMF, he or she must notify each person (i.e., applicant) authorized to reference the 
DMF (21 CFR 314.420). It is the responsibility of each applicant to then determine whether a submission to an 
approved or pending application is necessary. 
10 Section 520(o)(1)(E) of the FD&C Act generally excludes software from the definition of a device if the software 
supports or provides treatment recommendations to health care professionals and enables them to independently 
review the basis for the recommendations so that it is not the intent that health care professionals rely primarily on 
such recommendations. 
11 Section 520(o)(1)(D) of the FD&C Act generally excludes software from the definition of a device if the software 
is only intended to display or transfer patient data or other medical information. 
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103   
104    Control or drive the features of the user interface. 
105   
106  This guidance addresses process and general content expectations for Type V DMFs for such 
107  device constituent parts. It does not address FDA premarket review standards or expectations for 
108  such constituent parts or the combination products that include them. This guidance is also not 
109  intended to suggest that a Type V DMF should be submitted to CDER if the sponsor has rights of 
110  reference to an MAF located in another center containing the same information. 
111   
112   
113  IV.  ADMINISTRATIVE PROCEDURES FOR A TYPE V DMF  
114   
115  A.  Letter of Intent 
116   
117  As specified in 21 CFR 314.420(a) and noted in the DMF guidance, if a prospective DMF holder 
118  intends to submit a Type V DMF, he or she must first email a letter of intent to the DMF staff 
119  (dmfquestion@cder.fda.gov). The subject field should clearly state Letter of Intent for Type V 
120  DMF.  
121   
122  The letter of intent should include the following information: 
123   
124    Name, title, address, and contact information for the prospective DMF holder and a 
125  contact for FDA correspondence. 
126   
127    Name of the CDER-led combination product and the name, title, address, and contact 
128  information for the combination product applicant. 
129   
130    Identification and brief description of the device constituent part that is the subject of the 
131  DMF. 
132   
133    Brief description of how the device constituent part in the DMF is used or how it 
134  functions in the combination product, if known. 
135   
136    Purpose and rationale for submitting the Type V DMF, which should explain why the 
137  information is not being submitted in an IND, NDA, ANDA, or BLA or amendments and 
138  supplements to these applications (e.g., intent to use the device constituent part with more 
139  than one drug product, submission of confidential or proprietary information that is not 
140  available to the applicant). 
141   
142  If there are any questions, or if additional information is necessary regarding the letter of intent 
143  or proposed submission, FDA will contact the prospective DMF holder to discuss and resolve 
144  these issues. Once all issues have been resolved or if there are no issues regarding the letter of 
145  intent or proposed submission, FDA will provide confirmation to the prospective DMF holder 
146  that the Type V DMF may be submitted. 
147   
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148  Before submitting a DMF, however, the prospective DMF holder should request a pre-assigned 
149  application number. For more information, see Requesting a Pre-Assigned Application Number 
150  at https://www.fda.gov/drugs/electronic-regulatory-submission-and-review/requesting-pre-
151  assigned-application-number. 
152   
153  B.  Submission  
154   
155  Once FDA provides confirmation that the proposed submission is appropriate for a Type V DMF 
156  and a pre-assigned number is obtained, the prospective DMF holder may submit the Type V 
157  DMF to CDER. 
158   
159  DMF submissions are subject to the electronic submission requirements as set forth in guidance 
160  implementing section 745A of the FD&C Act, including the guidance for industry Providing 
161  Regulatory Submissions in Electronic FormatCertain Human Pharmaceutical Product 
162  Applications and Related Submissions Using the eCTD Specifications (Rev. 6, January 2019) 
163  (Providing Regulatory Submissions guidance).12 This guidanceType V DMFs for CDER-Led 
164  Combination Products Using Device Constituent Parts With Electronics or Softwareis not 
165  issued under section 745A of the FD&C Act and does not establish legally enforceable 
166  responsibilities. To the extent it discusses binding requirements for DMFs, such requirements 
167  have been promulgated in previously issued guidance under section 745A and FDA regulations.  
168   
169  Unless otherwise stipulated in the Providing Regulatory Submissions guidance or successor 
170  guidance under section 745A, paper submissions for Type V DMFs are no longer being 
171  accepted.13 All Type V submissions, whether new DMFs or documents submitted to existing 
172  DMFs, must have a DMF number and must be submitted in electronic common technical 
173  document (eCTD) format.  
174   
175  For general information and suggestions regarding DMF submissionsincluding format, 
176  content, and processsee the DMF guidance. For information about the eCTD format, see the 
177  Providing Regulatory Submissions guidance and the eCTD Technical Conformance Guide.14 For 
178  content recommendations specific to Type V DMFs for combination products as described in 
179  this guidance, see sections VVII.  
180   
181  C.  Administrative Review Process  
182   
183  Upon receipt of a DMF, the Central Document Room (CDR) and DMF staff will complete an 
184  administrative review. DMF staff will convey any issues or questions identified during the 
185  administrative review to the DMF holder, and if there are administrative issues, the submission 
186  will be identified as incomplete. Once the administrative issues are adequately addressed, or if 
187  there are no administrative issues, FDA will send an acknowledgement letter to the DMF holder 
188  listing the DMF number, the subject (title) of the DMF, the DMF holder name, and a statement 
                                                 
12 Revision 7 of Providing Regulatory Submissions is available as a draft guidance. When final, this guidance will 
represent the FDAs current thinking on this topic. 
13 See Providing Regulatory Submissions for information about other DMF types. 
14 See the eCTD Technical Conformance Guide at https://www.fda.gov/media/93818/download. 
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189  that the submission is a Type V DMF. The submission will then be made available for technical 
190  review.  
191   
192  D.  Technical Review Process  
193   
194  Before FDA can initiate the technical review of the Type V DMF information in support of an 
195  application, the DMF holder should submit a letter of authorization (LOA) to the DMF. The 
196  LOA, which can be included in the original or in a subsequent submission, permits FDA to 
197  review the Type V DMF and permits authorized parties to incorporate the DMF information into 
198  the application. See section V.B.4 for LOA content recommendations. 
199   
200  During the technical review process, the Type V DMF information will be reviewed in 
201  conjunction with the authorized application for the combination product. If issues are identified 
202  during this review, they will be conveyed to the DMF holder per current procedures for DMF 
203  submissions. At the same time, FDA will notify any applicants who have referenced the Type V 
204  DMF that additional information is needed.15 The general subject of the issues will be identified, 
205  but the details of the issues will only be disclosed to the DMF holder. 
206   
207  When a DMF holder amends a DMF, he or she must notify each person (i.e., applicant) 
208  authorized to reference the DMF (21 CFR 314.420). It is the responsibility of each applicant to 
209  then determine whether a submission to an approved or pending application is necessary. An 
210  amendment to the Type V DMF used to support an approved NDA, BLA, and ANDA will be 
211  reviewed according to current FDA procedures. Generally, this review is triggered by an 
212  applicants submission of an amendment, supplement, or annual report. 
213   
214  If an amendment to a Type V DMF is submitted and no supplement or annual report to an 
215  approved application is received, FDA intends to evaluate the changes reported in the DMF 
216  amendment to determine whether a supplement to one or more approved applications is needed. 
217  If an applicant has determined that a supplement is not necessary and FDA does not agree with 
218  that decision (refer to 21 CFR 314.70 and 314.97), FDA will notify the affected applicant. 
219   
220   
221  V.  CONTENT RECOMMENDATIONS FOR TYPE V DMF SUBMISSIONS 
222   
223  Type V DMF submissions should contain a cover letter, administrative information, and 
224  technical information regarding the device constituent part of the combination product.  
                                                 
15 For information regarding communications with DMF holders and applicants who reference them, refer to the 
DMF guidance. 
 
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225   
226  A.  Cover Letter 
227     
228  The cover letter should clearly state that the submission is an original, FDA-accepted, Type V 
229  DMF for a device constituent part of a combination product.16 In addition to the cover letter 
230  content identified in the DMF guidance and in the cover letter template on the DMF web page 
231  (e.g., DMF information, statement of commitment,17 DMF holder information), cover letters for 
232  Type V DMFs should also include the following information: 
233   
234    Identification of applications, if known, that the DMF is intended to support, including 
235  the name and address of each sponsor, applicant, or holder and all relevant document 
236  numbers. 
237   
238    Identification of the device constituent part and the name of the combination product(s) 
239  that uses the device constituent part, if known. 
240   
241    Statement that a letter of intent was submitted to FDA, the date of that letter, and the date 
242  of FDAs response. 
243   
244  B.  Administrative Information 
245   
246  The administrative information should include information about the DMF holder and relevant 
247  contact information, a reviewers guide, a copy of the communication from FDA granting 
248  permission to submit the Type V DMF, a copy of the LOA provided to the applicant referencing 
249  the Type V DMF, and LOAs for any other applications referenced in the Type V DMF 
250  submission (if applicable).  
251   
252  1.   DMF Holders Information 
253   
254  DMF holders should include their name and address and the names and addresses of their 
255  corporate headquarters, manufacturing/processing facilities, contacts for FDA correspondence, 
256  agents (if any), and the title and responsibilities of each person listed in the administrative 
257  information.  
258   
259  2.  Reviewers Guide  
260   
261  A reviewers guide identifies the type and location of information provided in the Type V DMF. 
262  This information should be separate from, and referenced after, the cover letter. The reviewers 
263  guide should provide a high-level overview of the submissions content with hyperlinks to the 
264  information and should identify the location of the information in the DMF by page number or 
                                                 
16 FDA is developing a form to replace the cover letter used for most DMF submissions (original and subsequent). 
The form should be available by the time this guidance is finalized. 
17 Statements of commitment are signed statements from DMF holders certifying that their DMFs are current and 
that they will comply with the statements made in them. They can be included in the cover letter or separately in the 
eCTD. See the DMF guidance for more information. 
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265  section of the eCTD. It should include the general subject areas identified in the Technical 
266  Information section of this guidance (see section V.C), when applicable, and should clearly 
267  identify information that addresses the device constituent part and information that addresses the 
268  combination product attributes related to the device constituent part. 
269   
270  3.  Communication Granting Permission for Type V DMF Submission 
271   
272  The administrative information should include a copy of the communication from FDA granting 
273  permission to submit the Type V DMF. 
274   
275  4.  Letter of Authorization 
276   
277  The LOA permits FDA to review the DMF and should include specific information about the 
278  DMF and the authorized party as indicated in the LOA template on the DMF web page. 
279   
280  The DMF holder should send a copy of the LOA to the relevant applicants, sponsors, or other 
281  holders who are authorized to incorporate by reference the specific information contained in the 
282  DMF. The LOA should indicate if the complete DMF or only limited information (identified by 
283  submission date, section numbers, and page numbers) may be incorporated by reference. The 
284  applicants, sponsors, or other holders referencing the DMF should include a copy of this LOA in 
285  their applications for combination products.  
286   
287  5.  Reference to Other Applications 
288   
289  If the DMF references information included in another DMF or an application, such as a 510(k), 
290  PMA, De Novo request, IND, NDA, ANDA, or BLA, the DMF holder should provide an LOA 
291  from that applicant permitting the incorporation of the identified application information into the 
292  DMF. The LOA should include the following:  
293   
294    Date. 
295   
296    Name of the applicant for the referenced 510(k), PMA, De Novo request, IND, NDA, 
297  ANDA, or BLA. 
298   
299    Application number and supplement or amendment number (if applicable). 
300   
301    Subject of the application. 
302   
303    Name of the specific products, items, or information referenced by the LOA. Include the 
304  submission date, section numbers, and page numbers.  
305   
306    Name of people authorized to incorporate information in the application by reference. 
307   
308    Statement granting authorization to the DMF holder to reference the identified 
309  information. 
310   
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311    Name, title, and signature of official authorizing reference to the application.  
312   
313  C.  Technical Information 
314   
315  Because the technical information provided in the Type V DMF may need to be reviewed by 
316  other centers, offices, or divisions, DMF holders should clearly identify the technical information 
317  applicable to the device constituent part only (if applicable) and the combination product 
318  attributes related to the device constituent part (if known). The following list identifies some of 
319  the general subject areas that may apply: 
320   
321    Indication for use. 
322    Device description.  
323    Software information and documentation. 
324    Human factors information and testing for the device. 
325    Sterility assurance. 
326    Shelf life/Expiration date and testing. 
327    Biocompatibility information and testing. 
328    Electrical safety and electromagnetic compatibility testing. 
329    Bench testing. 
330    Manufacturing information.18 
331   
332  If the technical information references any other premarket submissions, including those 
333  reviewed in other centers such as a 510(k), PMA, or De Novo request, the DMF holder should 
334  clearly identify the device name, manufacturer, and applicable submission number for the 
335  referenced information; the specific information that is being referenced; and the location of this 
336  information in the referenced submission. In addition, the technical information should include a 
337  scientifically valid explanation regarding how the referenced information is applicable to the 
338  Type V DMF submission, the device constituent part, and/or the combination product attributes 
339  related to the device constituent part. (See also section V.B.5.) 
340   
341  If the device constituent part is a modification of a previously approved/cleared device or if 
342  modifications are made to the device constituent part to allow use with different drug products, 
343  the device description information should also include a summary of and the rationale for the 
344  modifications. 
345   
346   
347  VI.  CONTENT RECOMMENDATIONS FOR TYPE V DMF AMENDMENTS 
348   
349  A Type V DMF amendment may be submitted for changes to the device constituent part (e.g., 
350  design or software changes), testing of the device constituent part, or testing of the combination 
351  product for attributes related to the device constituent part. When a DMF holder amends a DMF, 
352  he or she must also notify the applicants authorized to reference the DMF (21 CFR 314.420). 
                                                 
18 For additional information regarding manufacturing requirements applicable to combination products, see the 
guidance for industry and FDA staff Current Good Manufacturing Practice Requirements for Combination Products 
(January 2017).  
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353  Applicants are responsible for determining whether submissions to approved or pending 
354  applications are necessary. 
355   
356  The Type V DMF amendment should include administrative and technical information as 
357  described above, with the provided information focusing on the proposed changes for which the 
358  amendment is being submitted.  
359   
360  A.  Cover Letter and Administrative Information 
361   
362  The cover letter and administrative section should include the same type of information as 
363  described above for the original Type V DMF submission, with the following exceptions: 
364   
365  1.   Cover Letter  
366   
367  To help determine the impact of any changes or new information provided in the Type V DMF 
368  amendment, the cover letter should briefly describe the change, summarize the analysis and 
369  evaluation of the change, and identify the device constituent parts and combination products 
370  affected by the change, especially if the Type V DMF is referenced by multiple products. These 
371  recommendations are in addition to those identified in the DMF guidance and in the cover letter 
372  template for subsequent submissions on the DMF web page. The cover letter should also include 
373  a confirmation statement that the DMF holder has notified affected applicants of the change to 
374  the DMF and the dates of the notifications. 
375   
376  2.  Letter of Authorization 
377   
378  If the DMF amendment is referenced in an application, an LOA should be provided in the Type 
379  V DMF amendment.  
380    
381  B.  Technical Information 
382   
383  The technical information should include the same type of information as described above for the 
384  original Type V DMF submission, but should focus on the proposed changes for which the 
385  amendment is being submitted. For changes submitted in the amendment, the technical 
386  information should include a detailed description of the change, the rationale for the change, and 
387  the testing information or supporting documentation for the change.  
388   
389  For new information submitted in the amendment, the technical information should include a 
390  detailed description of the new information and the rationale for the submission of this 
391  information. In addition, if the new information is replacing information for a Type V DMF 
392  submitted previously in a paper copy, the technical information should clearly identify the 
393  information that is being replaced, including its location (section and page numbers) and the date 
394  of the initial submission. For a Type V DMF submitted in electronic format, the new information 
395  should replace the applicable section. 
396     
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397   
398  VII.  CONTENT RECOMMENDATIONS FOR TYPE V DMF ANNUAL REPORTS 
399   
400  As indicated in the DMF guidance, an annual report should be submitted every year to the DMF. 
401  This submission should be clearly labeled as an annual report and should include a cover letter, a 
402  statement of commitment, DMF administrative information, and the following information: 
403   
404    A list of any amendments reporting changes and the dates of the amendments submitted 
405  since the last annual report, or the original DMF filing date, whichever is most recent, or 
406  a statement that no amendments have been submitted since the last annual report or the 
407  original filing date, whichever is most recent. 
408   
409    A complete list of all parties authorized to reference the DMF, the date of the LOA, and 
410  the name, reference number, volume, date, and page numbers of the information that each 
411  person is authorized to incorporate by reference. The annual report should contain a 
412  complete list, even if it is unchanged from the last annual report. If there are no parties 
413  authorized to reference the DMF, that should be indicated in the annual report. 
414   
415    A complete list of all parties for whom authorization to reference the DMF has been 
416  withdrawn. 
417   
418  See the subsequent submissions cover letter template and the annual report template, which 
419  includes statement of commitment language, on the DMF web page at 
420  https://www.fda.gov/drugs/forms-submission-requirements/drug-master-files-dmfs. Annual 
421  reports should not be used to report changes in the DMF; however, DMF holders may submit an 
422  annual report at the same time as an amendment containing changes.  
423   
424   
425  VIII.  GLOSSARY  
426    
427  The following definitions are for purposes of this guidance only: 
428     
429  Agent: A legal entity, whether a company or an individual, that is not employed by but is 
430  authorized to act on behalf of a DMF holder.  
431   
432  Applicant: Any person who submits an application to obtain FDA approval or license to market 
433  a drug or biologic.  
434   
435  Authorized party: Any person who is authorized to reference a DMF. 
436   
437  Combination product: A product composed of any combination of a drug and device, a 
438  biological product and a device, a drug and a biological product, or a drug, device, and a 
439  biological product, as defined in 21 CFR 3.2(e).  
440   
441  Constituent part: A drug, device, or biological product that is part of a combination product (21 
442  CFR 4.2). 
  11  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
443   
444  Contact person: An employee of the DMF holder or agent to whom communication from FDA 
445  should be sent. The contact person may or may not be the same individual as the responsible 
446  official. 
447   
448  DMF holder: A person who owns a DMF. 
449   
450  Letter of authorization: A letter from a DMF holder that authorizes an applicant or another 
451  DMF holder to incorporate by reference all or part of the DMFs contents to support an 
452  application, supplement, or another DMF or an amendment to any of these documents. The LOA 
453  also authorizes FDA to review applicable portions of the DMF. 
454   
455  Person: An individual, partnership, corporation, or association (section 201(e) of the FD&C 
456  Act). 
457   
458  Responsible official: The employee of the DMF holder or agent who is responsible for 
459  submitting information to the DMF. 
460   
461  Right of reference: The authority to rely upon, and otherwise use, an investigation for the 
462  purpose of obtaining approval for an application, including the ability to make available the 
463  underlying raw data from the investigation for FDA audit, if necessary (21 CFR 314.3(b)).  
464   
465  Sponsor: A person or agency who assumes responsibility for an investigation of a CDER-led 
466  combination product, including responsibility for compliance with applicable provisions of the 
467  act and regulations. The sponsor may be an individual, pharmaceutical or device company, 
468  governmental agency, academic institution, private organization, or other organization. 
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