June 11-12, 2019: Joint Meeting of the Drug Safety and Risk Management Advisory Committee and the Anesthetic and Analgesic Drug Products Advisory Committee – 06/11/2019 – 06/12/2019

June 11-12, 2019: Joint Meeting of the Drug Safety and Risk Management Advisory Committee and the Anesthetic and Analgesic Drug Products Advisory Committee – 06/11/2019 – 06/12/2019

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Date:
June 11-12, 2019
Time:
June 11, 2019

UPDATED MEETING TIME AND OPEN PUBLIC HEARING TIME: June 11-12, 2019 Joint Meeting of the Drug Safety and Risk Management Advisory Committee and the Anesthetic and Analgesic Drug Products Advisory Committee

UPDATED INFORMATION (as of June 6, 2019):

The meeting time has been changed for the June 11-12, 2019 joint meeting of the Drug Safety and Risk Management Advisory Committee and the Anesthetic and Analgesic Drug Products Advisory Committee. On June 12, 2019, the meeting time has changed from 8:00 a.m. – 5:00 p.m. to 8:30 a.m. – 5:00 p.m. Additionally, the Open Public Hearing time has changed from 10:30 a.m. – 12:30 p.m. to 10:00 a.m. – 12:00 p.m. All other information remains the same.

ORIGINAL INFORMATION

Center Date Time Location
CDER June 11, 2019
June 12, 2019
8:00 a.m. to 5:00 p.m.
8:30 a.m. to 5:00 p.m.
FDA White Oak Campus
10903 New Hampshire Avenue
Building 31 Conference Center
The Great Room (Rm. 1503)
Silver Spring, MD 20993

Agenda

FDA is seeking public input on the clinical utility and safety concerns associated with the higher range of opioid analgesic dosing (both in terms of higher strength products and higher daily doses) in the outpatient setting. FDA is interested in better understanding current clinical use and situations that may warrant use of higher doses of opioid analgesics. We are also interested in discussing the magnitude and frequency of harms associated with higher doses of opioid analgesics relative to lower doses, as well as optimal strategies for managing these risks while ensuring access to appropriate pain management for patients.

FDA frequently hears from patients and healthcare providers that higher dose opioid analgesics continue to be a unique and necessary part of effective pain management for some patients. FDA is also cognizant of serious safety concerns associated with both higher strengths and higher daily doses of opioid analgesics, both in patients and in others who may access these drugs. Higher strength products may be more harmful in cases of accidental exposure and overdose and may also be more sought out for misuse and abuse. Along with a number of other factors, a higher daily opioid dose is associated with greater risk of overdose. Concerns have also been raised that higher dose opioid regimens may carry a higher risk of addiction, although robust evidence for a causal relationship is lacking. There is a strong association between higher opioid dose and duration/persistence of opioid analgesic therapy and assessing temporal relationships and independent effects of opioid dose and duration on the risks of both addiction and overdose is challenging. In addition, FDA acknowledges the complex and evolving landscape of the opioid epidemic, with myriad Federal, State, local, and payer efforts to encourage more judicious prescribing of opioid analgesics, and the growing threat of highly lethal illicit opioids.

To better understand both the clinical utility and harms of higher dose opioid analgesics in the current environment, and to discuss the advantages and disadvantages of various potential risk management strategies, FDA brings these issues to an advisory committee to seek input and advice from the clinical, patient, public health, and research communities.

In particular, FDA seeks to discuss: (1) The current clinical use and situations that may warrant pain management with opioid analgesics at higher product strengths and daily doses, factors influencing prescribing practices, and specific patient populations for whom there may be utility in prescribing these medications at higher doses; (2) the magnitude and frequency of harms associated with opioid analgesics at higher product strengths and daily doses, relative to lower strengths and daily doses, including the role of opioid dose in adverse health outcomes in both patients and in others who may access the drugs (e.g., risk for developing addiction, fatal overdose), the relevance of therapy duration and physical opioid dependence, and risks in different subpopulations (e.g., patients with chronic non-cancer pain, young children, adolescents); and (3) possible FDA interventions and their expected impact on patients and public health more broadly, including, for example, potential effects on prescribing and pain management practices, patient experience and behaviors, and adverse outcomes such as addiction and overdose.

Meeting Materials

FDA intends to make background material available to the public no later than two (2) business days before the meeting. If FDA is unable to post the background material on its web site prior to the meeting, the background material will be made publicly available at the location of the advisory committee meeting, and the background material will be posted on FDA’s web site after the meeting. Background material is available at: 2019 Meeting Materials, Drug Safety and Risk Management Advisory Committee

Public Participation Information

Interested persons may present data, information, or views, orally or in writing, on issues pending before the committee.

FDA is establishing a docket for public comment on this meeting. The docket number is FDA-2019-N-1646. The docket will close on June 30, 2019. Submit either electronic or written comments on this public meeting by June 30, 2019. Please note that late, untimely filed comments will not be considered. Electronic comments must be submitted on or before June 30, 2019. The https://www.regulations.gov electronic filing system will accept comments until 11:59 p.m. Eastern Time at the end of June 30, 2019. Comments received by mail/hand delivery/courier (for written/paper submissions) will be considered timely if they are postmarked or the delivery service acceptance receipt is on or before that date.

Comments received on or before May 28, 2019 will be provided to the committees. Comments received after that date but by June 30, 2019 will be taken into consideration by FDA. You may submit comments as follows:

Electronic Submissions

Submit electronic comments in the following way:

  • Federal eRulemaking Portal: www.regulations.gov. Follow the instructions for submitting comments. Comments submitted electronically, including attachments, to www.regulations.gov will be posted to the docket unchanged. Because your comment will be made public, you are solely responsible for ensuring that your comment does not include any confidential information that you or a third party may not wish to be posted, such as medical information, your or anyone else’s Social Security number, or confidential business information, such as a manufacturing process. Please note that if you include your name, contact information, or other information that identifies you in the body of your comments, that information will be posted on www.regulations.gov.
  • If you want to submit a comment with confidential information that you do not wish to be made available to the public, submit the comment as a written/paper submission and in the manner detailed (see “Written/Paper Submissions” and “Instructions”).

Written/Paper Submissions

Submit written/paper submissions as follows:

  • Mail/Hand delivery/Courier (for written/paper submissions): Dockets Management Staff (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
  • For written/paper comments submitted to the Dockets Management Staff, FDA will post your comment, as well as any attachments, except for information submitted, marked and identified, as confidential, if submitted as detailed in “Instructions.”

Instructions: All submissions received must include the Docket No. FDA-2019-N-1646 for “Joint Meeting of the Drug Safety and Risk Management Advisory Committee and the Anesthetic and Analgesic Drug Products Advisory Committee; Notice of Meeting; Establishment of a Public Docket; Request for Comments.” Received comments, those filed in a timely manner, will be placed in the docket and, except for those submitted as “Confidential Submissions,” publicly viewable at www.regulations.gov or at the Dockets Management Staff between 9 a.m. and 4 p.m., Monday through Friday.

  • Confidential Submissions–To submit a comment with confidential information that you do not wish to be made publicly available, submit your comments only as a written/paper submission. You should submit two copies total. One copy will include the information you claim to be confidential with a heading or cover note that states “THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.” FDA will review this copy, including the claimed confidential information, in its consideration of comments. The second copy, which will have the claimed confidential information redacted/blacked out, will be available for public viewing and posted on https://www.regulations.gov. Submit both copies to the Dockets Management Staff. If you do not wish your name and contact information be made publicly available, you can provide this information on the cover sheet and not in the body of your comments and you must identify the information as “confidential.” Any information marked as “confidential” will not be disclosed except in accordance with 21 CFR 10.20 and other applicable disclosure law. For more information about FDA’s posting of comments to public dockets, see 80 FR 56469, September 18, 2015, or access the information at: https://www.gpo.gov/fdsys/pkg/FR-2015-09-18/pdf/2015-23389.pdf.

Docket: For access to the docket to read background documents or the electronic and written/paper comments received, go to www.regulations.gov and insert the docket number, found in brackets in the heading of this document, into the “Search” box and follow the prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852.

Oral presentations from the public will be scheduled between approximately 10:00 a.m. to 12:00 p.m. on June 12, 2019. Those individuals interested in making formal oral presentations should notify the contact person and submit a brief statement of the general nature of the evidence or arguments they wish to present, the names and addresses of proposed participants, and an indication of the approximate time requested to make their presentation on or before May 17, 2019.

Time allotted for each presentation may be limited. If the number of registrants requesting to speak is greater than can be reasonably accommodated during the scheduled open public hearing session, FDA may conduct a lottery to determine the speakers for the scheduled open public hearing session. The contact person will notify interested persons regarding their request to speak by May 20, 2019.

Webcast Information

CDER plans to provide a free of charge, live webcast of the June 11-12, 2019 joint meeting of the Drug Safety and Risk Management Advisory Committee and the Anesthetic and Analgesic Drug Products Advisory Committee. While CDER is working to make webcasts available to the public for all advisory committee meetings held at the White Oak campus, there are instances where the webcast transmission is not successful; staff will work to re-establish the transmission as soon as possible. Further information regarding the webcast, including the web address for the webcast, will be made available at least 2 days in advance of the meeting at the following website: 2019 Meeting Materials, Drug Safety and Risk Management Advisory Committee 

CDER plans to post archived webcasts after the meeting, however, in cases where transmission was not successful, archived webcasts will not be available.

Contact Information

  • Moon Hee V. Choi, PharmD
    Center for Drug Evaluation and Research
    Food and Drug Administration
    10903 New Hampshire Avenue
    WO31-2417
    Silver Spring, MD  20993-0002
    Phone:  301-796-9001
    FAX:  301-847-8533
    Email:  DSaRM@fda.hhs.gov
  • FDA Advisory Committee Information Line
    1-800-741-8138
    (301-443-0572 in the Washington DC area)
    Please call the Information Line for up-to-date information on this meeting.

Event Materials


FDA Advisory Committee Information Line
1-800-741-8138
(301-443-0572 in the Washington DC area)

Please call the Information Line for up-to-date information on this meeting.

A notice in the Federal Register about last minute modifications that impact a previously announced advisory committee meeting cannot always be published quickly enough to provide timely notice. Therefore, you should always check the agency’s Web site and call the FDA Advisory Committee Information Line to learn about possible modifications before coming to the meeting.

Persons attending FDA’s advisory committee meetings are advised that the agency is not responsible for providing access to electrical outlets. FDA welcomes the attendance of the public at its advisory committee meetings and will make every effort to accommodate persons with disabilities. If you require accommodations due to a disability, please contact Lauren Tesh at (301) 796-9001 at least 7 days in advance of the meeting.

Answers to commonly asked questions including information regarding special accommodations due to a disability may be accessed at: Common Questions and Answers about FDA Advisory Committee Meetings.

FDA is committed to the orderly conduct of its advisory committee meetings. Please visit our Web site at Public Conduct During FDA Advisory Committee Meetings for procedures on public conduct during advisory committee meetings.

Notice of this meeting is given under the Federal Advisory Committee Act (5 U.S.C. app.2).

http://www.fda.gov/advisory-committees/advisory-committee-calendar/june-11-12-2019-joint-meeting-drug-safety-and-risk-management-advisory-committee-and-anesthetic-and

Controlled Substance Staff Organization Chart

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Dominic Chiapperino, PhD
Director

Chad J. Reissig, PhD
Supervisory Pharmacologist

Sandra L Saltz
Project Manager

Shalini Bansil, MD
Medical Officer

Silvia N Calderon, PhD
Senior Pharmacologist

Alicja Lerner, MD, PhD
Medical Officer

Vacant
Science Policy Analyst

Martin Rusinowitz, MD
Senior Medical Officer

Katherine (Kit) Bonson, PhD
Pharmacologist

Vacant
Medical Officer

Edward (Greg) Hawkins, PhD
Pharmacologist

James Hunter, RPh, MPH
Senior Program Manager

Jovita Randall-Thompson, PhD
Pharmacologist

Joshua Hunt, Pharm D
Senior Regulatory Reviewer

James Tolliver, PhD

Senior Pharmacologist

Valerie White
Program Specialist

Controlled Substance Staff (CSS)
White Oak Building 51, Suite 5100
10903 New Hampshire Avenue
Silver Spring, MD 20993
Main Phone: 301-796-5402, Fax: 301-847-8736

http://www.fda.gov/about-fda/center-drug-evaluation-and-research/controlled-substance-staff-organization-chart

June 20, 2019: Meeting of the Pediatric Oncology Subcommittee of the Oncologic Drugs Advisory Committee – 06/20/2019 – 06/20/2019

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Date:
June 20, 2019
Time:
June 20, 2019

UPDATED INFORMATION: (as of May 24, 2019)
The meeting time, agenda, and public participation portions have been changed for the June 20, 2019 Meeting of the Pediatric Oncology Subcommittee of the Oncologic Drugs Advisory Committee. There are no other changes.

The meeting time has changed to 9:00 a.m. to 3:30 p.m.

The Agenda portion has changed and reads as follows:
During the morning session, the particular matter for this meeting will be review and discussion of the FDA Reauthorization Act of 2017 (FDARA) mandated Relevant Pediatric Molecular Target List now posted on the FDA website: https://www.fda.gov/about-fda/oncology-center-excellence/pediatric-oncology. FDA is required by statute to review and update the previously approved and published lists. The focus of the discussion will be limited to two target “classes” included in the Relevant Pediatric Molecular Target List: (1) targets linked to cell lineage and (2) targets on normal immune cells and cells in the tumor microenvironment. Planned introductory presentations will be on: (1) cell-based therapy approaches to childhood cancer and (2) novel membrane antigen determinants in pediatric tumors.

During the afternoon session, information will be presented to gauge investigator interest in exploring potential pediatric development plans for two products in various stages of development for adult cancer indications. The subcommittee will consider and discuss issues concerning diseases to be studied, patient populations to be included, and possible study designs in the development of these products for pediatric use. The discussion will also provide information to the Agency pertinent to the formulation of written requests for pediatric studies, if appropriate. The product under consideration is ONC201, presentation by Oncoceutics Inc.

The Public Participation Information portion has changed and reads as follows:
Oral presentations from the public will be scheduled between approximately 10:50 a.m. and 11:20 a.m., and 1:50 p.m. and 2:20 p.m. Those individuals interested in making formal oral presentations should notify the contact person and submit a brief statement of the general nature of the evidence or arguments they wish to present, the names and addresses of proposed participants, and an indication of the approximate time requested to make their presentation on or before May 29, 2019.

Time allotted for each presentation may be limited. If the number of registrants requesting to speak is greater than can be reasonably accommodated during the scheduled open public hearing session, FDA may conduct a lottery to determine the speakers for the scheduled open public hearing session. The contact person will notify interested persons regarding their request to speak by May 30, 2019.


ORIGINAL INFORMATION:

Center Date Time Location
CDER June 20, 2019 8:00 p.m. to 4:30 p.m FDA White Oak Campus
10903 New Hampshire Avenue
Building 31 Conference Center
The Great Room (Rm. 1503)
Silver Spring, Maryland 20993

Agenda

During the morning session, the particular matter for this meeting will be review and discussion of the FDA Reauthorization Act of 2017 (FDARA) mandated Relevant Pediatric Molecular Target List now posted on the FDA website: https://www.fda.gov/about-fda/oncology-center-excellence/pediatric-oncology. FDA is required by statute to review and update the previously approved and published lists. The focus of the discussion will be limited to two target “classes” included in the Relevant Pediatric Molecular Target List: (1) targets linked to cell lineage and (2) targets on normal immune cells and cells in the tumor microenvironment. Planned introductory presentations will be on: (1) cell-based therapy approaches to childhood cancer and (2) novel membrane antigen determinants in pediatric tumors.

During the afternoon session, information will be presented to gauge investigator interest in exploring potential pediatric development plans for two products in various stages of development for adult cancer indications. The subcommittee will consider and discuss issues concerning diseases to be studied, patient populations to be included, and possible study designs in the development of these products for pediatric use. The discussion will also provide information to the Agency pertinent to the formulation of written requests for pediatric studies, if appropriate. The products under consideration are: (1) ONC201, presentation by Oncoceutics Inc., and (2) CD24Fc, presentation by OncoImmune, Inc.

Meeting Materials

FDA intends to make background material available to the public no later than two (2) business days before the meeting. If FDA is unable to post the background material on its web site prior to the meeting, the background material will be made publicly available at the location of the advisory committee meeting, and the background material will be posted on FDA’s web site after the meeting. Background material is available at: 2019 Meeting Materials, Oncologic Drugs Advisory Committee

Public Participation Information

Interested persons may present data, information, or views, orally or in writing, on issues pending before the committee.

FDA is establishing a docket for public comment on this meeting. The docket number is FDA-2019-N-1620. The docket will close on June 19, 2019. Submit either electronic or written comments on this public meeting by June 19, 2019. Please note that late, untimely filed comments will not be considered. Electronic comments must be submitted on or before June 19, 2019. The https://www.regulations.gov electronic filing system will accept comments until midnight Eastern Time at the end of June 19, 2019. Comments received by mail/hand delivery/courier (for written/paper submissions) will be considered timely if they are postmarked or the delivery service acceptance receipt is on or before that date.

Comments received on or before June 6, 2019, will be provided to the committee. Comments received after that date but by June 19, 2019 will be taken into consideration by the FDA. You may submit comments as follows:

Electronic Submissions

Submit electronic comments in the following way:

  • Federal eRulemaking Portal: https://www.regulations.gov. Follow the instructions for submitting comments. Comments submitted electronically, including attachments, to https://www.regulations.gov will be posted to the docket unchanged. Because your comment will be made public, you are solely responsible for ensuring that your comment does not include any confidential information that you or a third party may not wish to be posted, such as medical information, your or anyone else’s Social Security number, or confidential business information, such as a manufacturing process. Please note that if you include your name, contact information, or other information that identifies you in the body of your comments, that information will be posted on https://www.regulations.gov.
  • If you want to submit a comment with confidential information that you do not wish to be made available to the public, submit the comment as a written/paper submission and in the manner detailed (see “Written/Paper Submissions” and “Instructions”).

Written/Paper Submissions

Submit written/paper submissions as follows:

  • Mail/Hand delivery/Courier (for written/paper submissions): Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
  • For written/paper comments submitted to the Dockets Management Staff, FDA will post your comment, as well as any attachments, except for information submitted, marked and identified, as confidential, if submitted as detailed in “Instructions.”

Instructions: All submissions received must include the Docket No. FDA-2019-N-1620 for “Pediatric Oncology Subcommittee of the Oncologic Drugs Advisory Committee; Notice of Meeting; Establishment of a Public Docket; Request for Comments.” Received comments will be placed in the docket and, except for those submitted as “Confidential Submissions,” publicly viewable at https://www.regulations.gov or at the Division of Dockets Management between 9 a.m. and 4 p.m., Monday through Friday.

  • Confidential Submissions–To submit a comment with confidential information that you do not wish to be made publicly available, submit your comments only as a written/paper submission. You should submit two copies total. One copy will include the information you claim to be confidential with a heading or cover note that states “THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.” The Agency will review this copy, including the claimed confidential information, in its consideration of comments. The second copy, which will have the claimed confidential information redacted/blacked out, will be available for public viewing and posted on https://www.regulations.gov. Submit both copies to the Dockets Management Staff. If you do not wish your name and contact information to be made publicly available, you can provide this information on the cover sheet and not in the body of your comments and you must identify this information as “confidential.” Any information marked as “confidential” will not be disclosed except in accordance with 21 CFR 10.20 and other applicable disclosure law. For more information about FDA’s posting of comments to public dockets, see 80 FR 56469, September 18, 2015, or access the information at: https://www.gpo.gov/fdsys/pkg/FR-2015-09-18/pdf/2015-23389.pdf.

Docket: For access to the docket to read background documents or the electronic and written/paper comments received, go to https://www.regulations.gov and insert the docket number, found in brackets in the heading of this document, into the “Search” box and follow the prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852.

Oral presentations from the public will be scheduled between approximately 9:35 a.m. and 10:05 a.m., 1:10 p.m. and 1:25 p.m., and 3:10 p.m. and 3:25 p.m. Those individuals interested in making formal oral presentations should notify the contact person and submit a brief statement of the general nature of the evidence or arguments they wish to present, the names and addresses of proposed participants, and an indication of the approximate time requested to make their presentation on or before May 29, 2019.

Time allotted for each presentation may be limited. If the number of registrants requesting to speak is greater than can be reasonably accommodated during the scheduled open public hearing session, FDA may conduct a lottery to determine the speakers for the scheduled open public hearing session. The contact person will notify interested persons regarding their request to speak by May 30, 2019.

Webcast Information

CDER plans to provide a free of charge, live webcast of the June 20, 2019 Pediatric Oncology Subcommittee of the Oncologic Drugs Advisory Committee meeting. While CDER is making a webcast available to the public for this meeting, there are instances where the webcast transmission is not successful; staff will work to re-establish the transmission as soon as possible. Further information regarding the webcast, including the web address for the webcast, will be made available at least 2 days in advance of the meeting at the following website: 2019 Meeting Materials, Oncologic Drugs Advisory Committee

CDER plans to post archived webcasts after the meeting, however, in cases where transmission was not successful, archived webcasts will not be available.

Contact Information

  • FDA Advisory Committee Information Line
    1-800-741-8138
    (301-443-0572 in the Washington DC area)
    Please call the Information Line for up-to-date information on this meeting.

Event Materials


FDA Advisory Committee Information Line
1-800-741-8138
(301-443-0572 in the Washington DC area)

Please call the Information Line for up-to-date information on this meeting.

A notice in the Federal Register about last minute modifications that impact a previously announced advisory committee meeting cannot always be published quickly enough to provide timely notice. Therefore, you should always check the agency’s Web site and call the FDA Advisory Committee Information Line to learn about possible modifications before coming to the meeting.

Persons attending FDA’s advisory committee meetings are advised that the agency is not responsible for providing access to electrical outlets. FDA welcomes the attendance of the public at its advisory committee meetings and will make every effort to accommodate persons with disabilities. If you require accommodations due to a disability, please contact Lauren Tesh at (301) 796-9001 at least 7 days in advance of the meeting.

Answers to commonly asked questions including information regarding special accommodations due to a disability may be accessed at: Common Questions and Answers about FDA Advisory Committee Meetings.

FDA is committed to the orderly conduct of its advisory committee meetings. Please visit our Web site at Public Conduct During FDA Advisory Committee Meetings for procedures on public conduct during advisory committee meetings.

Notice of this meeting is given under the Federal Advisory Committee Act (5 U.S.C. app.2).

http://www.fda.gov/advisory-committees/advisory-committee-calendar/june-20-2019-meeting-pediatric-oncology-subcommittee-oncologic-drugs-advisory-committee-06202019

Fecal Microbiota for Transplantation: Safety Communication- Risk of Serious Adverse Reactions Due to Transmission of Multi-Drug Resistant Organisms

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[Posted 06/13/2019]

AUDIENCE: Patient, Healthcare Professional

ISSUE: The FDA is now aware of bacterial infections caused by multi-drug resistant organisms (MDROs) that have occurred due to transmission of a MDRO from use of investigational fecal microbiota for transplantation (FMT):

  • Two immunocompromised adults who received investigational FMT developed invasive infections caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (E.coli). One of the individuals died.
    • FMT used in these two individuals were prepared from stool obtained from the same donor.
    • The donor stool and resulting FMT used in these two individuals were not tested for ESBL-producing gram-negative organisms prior to use. After these adverse events occurred, stored preparations of FMT from this stool donor were tested and found to be positive for ESBL-producing E. coli identical to the organisms isolated from the two patients.

RECOMMENDATION: Patients considering FMT to treat C. difficile infection should speak to their health care provider to understand the potential risks associated with the product’s use.

Healthcare providers must obtain adequate consent for the use of FMT from the patient or his or her legally authorized representative. The consent should include, at a minimum, a statement that the use of FMT to treat C. difficile is investigational and a discussion of its potential risks. FDA is informing members of the medical and scientific communities and other interested persons of the potential risk of transmission of MDROs by FMT and the resultant serious adverse reactions that may occur. 

  • Donor screening with questions that specifically address risk factors for colonization with MDROs, and exclusion of individuals at higher risk of colonization with MDROs.
  • MDRO testing of donor stool and exclusion of stool that tests positive for MDRO. FDA scientists have determined the specific MDRO testing and frequency that should be implemented.

Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA’s MedWatch Safety Information and Adverse Event Reporting Program:

  • Complete and submit the report Online
  • Download form  or call 1-800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178

[06/14/2019 – Safety Communication – FDA]

http://www.fda.gov/safety/medwatch-safety-alerts-human-medical-products/fecal-microbiota-transplantation-safety-communication-risk-serious-adverse-reactions-due

Pharmacy Compounding Advisory Committee Roster

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Applying for Membership on FDA Advisory Committees

As part of the Food and Drug Administration’s (FDA’s) ongoing efforts to recruit qualified experts with minimal conflicts of interest who are interested in serving on FDA advisory committees, FDA is requesting nominations for members to serve on its advisory committees. More info (Posted 2/27/2007)

Current Number of Vacancies = 1

Note, one or more vacancies may be in the nomination process or a final appointment may have been made.

http://www.fda.gov/advisory-committees/pharmacy-compounding-advisory-committee/pharmacy-compounding-advisory-committee-roster

Dean Obeidallah Wins $4.1M In Defamation Suit Against Neo-Nazi Website

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NPR’s Michel Martin speaks with comedian Dean Obeidallah, who this week was awarded $4.1 million in damages for defamation from the neo-Nazi website, The Daily Stormer.

MICHEL MARTIN, HOST:

Continuing the conversation about new technologies, this week, lawmakers debated how to deal with information generated by artificial intelligence, which they fear could be used to smear candidates and interfere with elections. A comedian and commentator named Dean Obeidallah decided to tackle this conduct the old-fashioned way. He sued his defamers, and he won. This week, a judge ruled that the publisher of the neo-Nazi site The Daily Stormer must pay Obeidallah $4.1 million for falsely portraying him as a terrorist. Here to tell us more is Dean Obeidallah. He’s with us from our bureau in New York. Welcome. Thanks so much for joining us.

DEAN OBEIDALLAH: Thank you.

MARTIN: So let me just remind everybody again exactly what happened. What was your specific complaint against The Daily Stormer and its publisher, Andrew Anglin?

OBEIDALLAH: Well, what they did to me and what they wrote about me requires going backwards slightly a little bit. I wrote an article on May 31, 2017, for The Daily Beast, where I’ve been writing weekly for a few years. And in that article, I used the term white supremacist terrorism. And I said, why will Donald Trump not use the term white supremacist terrorism? Because this is three months before Charlottesville. There was already a spike in white supremacist violence going on.

And that so upset Andrew Anglin at The Daily Stormer, the publisher and founder. He wrote an article the next day smearing me. He fabricated tweets that made it look like I was tweeting that I was the mastermind of the bombing, I was cheering for it and I did it the name of Allah and my faith as a Muslim. And they looked exactly real, with retweets and likes and then directed his readership at The Daily Stormer to confront me was the exact term.

MARTIN: And what happened? Did people think this was you?

OBEIDALLAH: Well, yes.

MARTIN: And did people confront you?

OBEIDALLAH: The Daily Stormer readers clearly thought it was me from the comments that were directed at me that very clearly said that I hope – Dean better hope he dies of natural causes before we get him, things like we should hang him from an elm tree. And in their comments, they clearly saw – thought I was a terrorist. And just so it’s clear for people, The Daily Stormer is not your average white supremacist neo-Nazi publication, if there is such one. It is one where readers go to, they exchange information. They animate each other into action.

And readers of The Daily Stormer have committed acts of violence. James Jackson, who I wrote about that May 2017 article, came to New York in March from Maryland to start a race war and killed an elderly African American man and thankfully was arrested before he could kill others. And others have read this publication. So when they say confront you there, it’s not a normal publication saying, go challenge his opinions. It is direct action, encouraging people to literally confront me and to commit acts of violence.

MARTIN: OK. But I’m just curious about why, if you feel that these people are promoting and fomenting violence, why isn’t this a criminal matter as opposed to a civil matter? I mean, a civil matter is between two private parties, and the only consequence could be money, right? That’s the only way it can be a remedy. But if you feel that this group is actually encouraging violence, why isn’t this a criminal complaint?

OBEIDALLAH: It would be a harder case to prove from a criminal point of view because the direct – just as a lawyer, I can say, I mean, speech is protected and has more protections in the criminal setting. So to be charged criminally with inciting violence, you must directly say, go get this person at this place.

MARTIN: Go get him.

OBEIDALLAH: And we’re going to get him. And we’re going to kill him. Instead, it was slightly more ambiguous. But clearly, from a civil point of view, these tweets and this language was not protected by the First Amendment.

MARTIN: Before we let you go, how do you feel? I mean, I know this has not been a – this has not been a pleasant couple of years…

OBEIDALLAH: No.

MARTIN: …Dealing with this and being – first of all, just being falsely defamed for having associated with something, you know, so heinous and then being maligned in this way. I mean, was at least that moment in court when the judge ruled in your favor, like, how did that feel?

OBEIDALLAH: No, that felt great. Did it make up? I can’t go back to my life pre-June 1, 2017, where I’m getting smeared. And as a Muslim, being attacked with the worst anti-Muslim trope you can say is that I’m a Muslim and I’m a terrorist. So it was very painful. It was painful to have friends and family express concerns. It was painful to contact security at Daily Beast and my radio channel to say, hey, we might be visited by white supremacists coming to kill me. And they might kill innocent people I work with. That was all horrible.

But through this all, I’ve never once questioned doing this. This is the right thing to do. It’s the thing we have to do. And I’m happy we got the judgment. And we’re going to continue. And I hope it inspires others and gives them a roadmap to say, don’t be silent. There are lawyers who will represent you – I’m not kidding – free of charge for this kind of work to make it clear that we’re not going to cower from these people. We’re going to sue them. We’re going to win. We’re going to get their money.

MARTIN: That’s Dean Obeidallah. He’s the host of “The Dean Obeidallah Show” on Sirius XM. He’s a columnist for The Daily Beast. And he’s a comedian and a former lawyer. Dean, thanks so much for talking to us.

OBEIDALLAH: Thanks for having me on, Michel. I appreciate it.

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Evaluation of Bulk Drug Substances Nominated for Use in Compounding Under Section 503B of the Federal Food, Drug, and Cosmetic Act

admin No Comments

Docket Number:
FDA-2018-D-1067
Issued by:

Guidance Issuing Office

Center for Drug Evaluation and Research

The Food and Drug Administration (FDA or the Agency) is announcing the availability of a final guidance for industry entitled “Evaluation of Bulk Drug Substances Nominated for Use in Compounding Under Section 503B of the Federal Food, Drug, and Cosmetic Act.” This guidance describes policies that FDA intends to use in evaluating bulk drug substances nominated for use in compounding under section 503B of the Federal Food, Drug, and Cosmetic Act (FD&C Act) for inclusion on the list of bulk drug substances that can be used in compounding under section 503B.


Submit Comments

You can submit online or written comments on any guidance at any time (see 21 CFR 10.115(g)(5))

If unable to submit comments online, please mail written comments to:

Division of Dockets Management (HFA- 305)
Food and Drug Administration
5630 Fishers Lane, Rm. 1061
Rockville, MD 20852

All written comments should be identified with this document’s docket number: FDA-2018-D-1067.

http://www.fda.gov/regulatory-information/search-fda-guidance-documents/evaluation-bulk-drug-substances-nominated-use-compounding-under-section-503b-federal-food-drug-and

Product Development Under the Animal Rule

admin No Comments

Docket Number:
FDA-2009-D-0007
Issued by:

Guidance Issuing Office

Center for Drug Evaluation and Research

Center for Biologics Evaluation and Research

The Food and Drug Administration (FDA or Agency) is announcing the availability of a guidance for industry entitled “Product Development Under the Animal Rule.” When human efficacy studies are not ethical and field trials are not feasible, FDA may rely on adequate and well-controlled animal efficacy studies to support approval of a drug or licensure of a biological product under the Animal Rule. This guidance finalizes the 2014 revised draft guidance for industry “Product Development Under the Animal Rule.” It is intended to help potential stakeholders (industry, academia, and government) understand FDA’s expectations for product development under the Animal Rule.


Submit Comments

You can submit online or written comments on any guidance at any time (see 21 CFR 10.115(g)(5))

If unable to submit comments online, please mail written comments to:

Division of Dockets Management (HFA- 305)
Food and Drug Administration
5630 Fishers Lane, Rm. 1061
Rockville, MD 20852

All written comments should be identified with this document’s docket number: FDA-2009-D-0007.

http://www.fda.gov/regulatory-information/search-fda-guidance-documents/product-development-under-animal-rule

Drug Master Files (DMFs)

admin No Comments

Any of the following Type II DMFs:

  • used to support only NDAs or INDs
  • API intermediates
  • material used in the preparation of APIs 
  • drug product manufacturing intermediates
  • drug products.

See also Slide 48 in CDER’s Small Business Assistance Office Webinar entitled “Drug Master Files (DMFs) under Generic Drug User Fee Amendments (GDUFA)

See also the following Web sites:

The list of DMFs that have passed the Completeness Assessment and are available for reference by ANDAs under GDUFA is available at Type II Drug Master Files – Available for Reference List.

This is the only notification that the DMF has passed the Completeness Assessment.

Currently, the list is updated weekly.

DMFs for APIs submtted under GDUFA that have passed the Administrative review (have an active status) and have had the user fee paid are placed in the queue for a Completeness Assessment.  It is not necessary for there to be an LOA for the DMF to undergo a Completeness Assessment review.  The time frame for the Completeness Assessment depends on workload and may take a number of weeks.

Pre-assignment of DMF Numbers (Category 3)

DMF holders wishing to submit an electronic DMF must obtain a pre-assigned number.  See “Requesting a Pre-Assigned Application number.”  DMF holders can request a pre-assigned number for a paper DMF as well.

Companies wishing to obtain a pre-assigned DMF number for a Type V DMF should obtain clearance to file a Type V DMF (with the exception of a DMF for information regarding manufacturing site, facilities, operating procedures, and personnel for sterile manufacturing plants which do not require clearance.) See Type V DMFs below.  For Type V DFMFs that do not require clearance the request for a pre-assigned number should specify what the DMF covers e.g., Sterile Processing Facility.

Format and Content of the Chemistry, Manufacturing, and Controls Section of an Application (Category 1)

DMFs should be submitted following the Common Technical Document (CTD) format recommended in the “Guidance for Industry  M4Q: The CTD – Quality” (CTD-Q) and the “Draft Guidance for Industry Submitting Marketing Applications According to the ICH-CTD Format —General Considerations” (CTD Guidance).

A Manual of Policies and Procedures (MAPP 5015.10) covering reviewer responsibilities for review of applications submitted using the Question-based Review (QbR) format has been issued.  All Type II DMFs for Drug Substances and Drug Products may be submitted using the QbR format, although this is not required.

  • Conversion to CTD

Companies may convert an existing paper DMF in non-CTD format to paper CTD format.  In such cases DMF holders are advised to submit an amendment containing all sections specified in the CTD format that are applicable to the material covered by the DMF.  Each section should be complete and contain up-to-date information.  For drug substances and excipients all sections of 3.2.S in Module 3 and of 2.3.S in Module 2 should be submitted.   For drug products all sections of 3.2.P in Module 3 and of 2.3.P in Module 2 should be submitted.  If there are any changes in the technical content of the DMF as a result of the reformatting, e.g. addition of new information, the cover letter for the new submission should specify what areas of technical information have been changed.

DMFs in CTD format should follow the recommendations in the Appendix “Granularity” the ICH Harmonised Tripartite Guideline:  Organisation Of The Common Technical Document For The Registration Of Pharmaceuticals For Human Use:  M4.  This supersedes the recommendation in the DMF Guidance.

For conversion of a paper DMF to electronic CTD format, see Electronic DMF.

It is not necessary to submit all Modules i.e. it is not necessary to submit Module 4 and 5.  However, Module 1 and all Sections within Modules  2 and 3 S or P (as appropriate) should be submitted for ALL types of DMFs. 

DMF holders submitting DMFs for Sterile Manufacturing can consult the following Guidances

Products manufactured at separate facilities do not need to be filed as separate DMFs unless the manufacturing processes are different.  Note that the Initial CA Guidance contains recommendations regarding the submission of DMFs for multiple processes.

Module 1 should contain the following information

  • Section 1.2  

According to the DMF Guidance (Section IV.B.1.c), the Statement of Commitment is:

“A signed statement by the holder certifying that the DMF is current and that the DMF holder will comply with the statements made in it.“

  • Section 1.3:    Administrative Information
    • 1.3.1 Contact/sponsor/Applicant information
      • 1.3.1.1 Change of address or corporate name
        Can be used to supply addresses of DMF holder.
      • 1.3.1.2 Change in contact/agent
        Can be used to supply the name and address of contact persons and/or agents, including Agent Appointment Letter.
      • 1.3. Debarment Certification.
  • Section 1.4:    Reference Section
    • 1.4.1 – Letter of Authorization (LOA)
      Submission by the owner of information, giving authorization for the information to be used by Authorized Party.  An Agent Appointment Letter is NOT an LOA and should not be called “Letter of Authorization” and should not be submitted in Section 1.4.1.

    • 1.4.2 – Statement of Right of Reference
      This section should be completed in an application (IND, NDA, ANDA, or DMF) submitted by the Authorized Party that references a DMF. It should contain a copy of the Letter of Authorization from the holder giving the Authorized Party permission to reference the DMF.  If a DMF holder references other DMFs a list of those DMFs can be provided in this section, similar to Section 30 on Form 356h used for NDAs and ANDAs. This is not the same as the list of authorized parties to be provided in 1.4.3.

    • 1.4.3 – List of authorized persons to incorporate by reference
      This is a list of companies for whom LOAs have been submitted to the DMF. This list should be submitted in DMF annual reports.

This does NOT mean a list of individuals within the DMF holder’s company who are authorized to submit information to the DMF.

As stated in 21 CFR 314.420(d):

“The drug master file is required to contain a complete list of each person currently authorized to incorporate by reference any information in the file, identifying by name, reference number, volume, and page number the information that each person is authorized to incorporate.”

The term “reference number” means any code or number used by the holder to identify a particular item in a DMF, where applicable.

English Translations of DMF in a Foreign Language (Category2)

FDA regulations (21 CFR.1(a)(1)) state:

“If any part of the application is in a foreign language, an accurate and complete English translation shall be appended to such part.”

The same is true for DMFs.

Debarment Certification for DMF Holders (Category 3)

According to the Draft Guidance for Industry: Submitting Debarment Certification Statements, DMF Holders are included in the category of “Persons whose services were used in any capacity in connection with the application” required under Section 306(k)(1) of the Food Drug and Cosmetic Act.  DMF holders may include a Debarment Certification statement in their DMF.

TYPES OF DMFs

Type I DMFs (Category 1)

Type I DMFs are no longer accepted per a Final Rule published January 12, 2000 (65 FR 1776). See Type V DMFs below.

Holders of Type II, III, and IV DMFs do not need to place information regarding facilities, personnel or general operating procedures in these DMFs.  Only the addresses of the DMF holder and manufacturing site and contact personnel should be submitted. See Administrative Information in a DMF.

Type II DMFs (Category 1)

Note that GDUFA includes requirements for Type II DMFs for Active Pharmaceutical Ingredients (APIs).

Drug Product and Drug Product Intermediate 

Type II DMFs for drug products should be submitted in the format for “Drug product” in the Guidance for Industry  M4Q: The CTD – Quality. (Category 3) 

It is not necessary to include a Methods Validation Package (3.2.R.3).  Methods Validation information should be submitted in Section 3.2.P.5.3.

Separate DMFs should be submitted for drug substances and drug products.

Active Pharmaceutical Ingredient (API) (Category 4)

The term ‘active pharmaceutical ingredient’ means (SEC.744A(2) in GDUFA):

(A) a substance, or a mixture when the substance is unstable or cannot be transported on its own, intended—

(i) to be used as a component of a drug; and
(ii) to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease, or to affect the structure or any function of the human body; or

(B) a substance intended for final crystallization, purification, or salt formation, or any combination of those activities, to become a substance or mixture described in subparagraph (A)”

Type III DMFs (Category 1)

The applicable Guidance for Type III DMFs is the Guidance for Industry: Container Closure Systems for Packaging Human Drugs and Biologics:  Chemistry, Manufacturing, and Controls Documentation  and Questions and Answers.  (Category 3)

A Manual of Policies and Procedures covering reviewer responsibilities for review of Type III DMFs has been implemented.  MAPP 5015.5  CMC Reviews of Type III DMFs for Packaging Materials.  This MAPP instructs reviewers to look for information regarding many packaging materials in the application (IND, NDA, or ANDA) for the drug product that utilizes the packaging material before reviewing the DMF.  Much of the information needed for review can be provided directly to the applicant for inclusion in the application, thereby avoiding the need to review the DMF.

CTD format:  Single components and materials of construction may be submitted as if they were drug substances i.e., the preparation of the item should be in S.2.  An assembled container closure systems may be treated as if it were a drug product e.g. the Materials of construction would be in P.1, the finished packaging material release specification would be in P.5. 

Type IV DMFs (Category 3)

See relevant section in the DMF Guidance.  CTD format: Single entities may be submitted as if they were drug substances e.g., the preparation of the item should be in S.2.  Mixtures e.g., as flavor mixtures, may be treated as if it were a drug product, i.e.. the Components and Composition would be in P.1, the finished material release specification would be in P.5.

If toxicology studies are submitted in the same DMF (in paper) as the CMC information, they should be in a separate volume or volumes, although it is preferable for holders to submit such information as a separate Type V DMF.  Toxicology studies in an electronic DMF for an excipient should be submitted in the appropriate module.  See also the Guidance for Industry: Nonclinical Studies for the Safety Evaluation of Pharmaceutical Excipients.

Note that, in keeping with the recommendation in the DMF Guidance, components of flavor mixtures should include a CFR citation, where applicable, in addition to any other reference, e.g. GRAS or FEMA references.

Type V DMFs (Category 3)

As specified in 21 CFR 314.420(a)(5), DMF holders wishing to submit a Type V DMF must obtain clearance from the FDA (See below for an exception to this requirement for sterile processing facilities). Prospective Type V DMF holders should send their request to dmfquestion@cder.fda.gov, including the following:

    1. An explanation of the necessity for filing the information in a Type V DMF
    2. The proposed Subject (Title) of the DMF
    3. The rationale for not submitting the information in an IND, NDA, or ANDA.
    4. The clinical division that will be reviewing the information, if applicable.

Information regarding manufacturing site, facilities, operating procedures, and personnel for sterile manufacturing plants can be filed as a Type V DMF without clearance.  The Subject field should specify what the DMF covers e.g., “Sterile Processing Facility.”

See Guidance for Industry for the Submission Documentation for Sterilization Process Validation in Applications for Human and Veterinary Drug Products

Administrative Information in a DMF (Category 3)

The elements of the administrative information that should be in a DMF are:

  • The name and address of the holder
  • The name and address of manufacturing facility
  • For the contact person:
    • Name
    • Mailing Address
    • Telephone number
    • Fax number
    • E-mail address
  • The name and address of the agent (if applicable)
  • For the contact person at the agent (if applicable):
    • Name
    • Mailing Address
    • Telephone number
    • Fax number
    • E-mail address
  • Statement of Commitment

The appointment of an Agent is optional.  See discussion below under Agents.

Submission of Amendments, Annual Reports, and Letters of Authorization (Category 3)

To facilitate processing of documents that are submitted to an existing DMF, list the Submission Type and the Category/Subcategory of the Amendment (Supporting Document) in bold type in the header on the Cover Letter (transmittal letter).  See list below.  More than one Submission Type/Category/Subcategory can be used but all should be listed. 

Example:  If updated stability data is submitted at the same time as a Letter of Authorization, the heading of the Cover Letter should state:

Letter of Authorization
Original: Quality/Stability

Important New Information: Annual Reports for DMFs in eCTD can be submitted on the same date as any other submission but they must have a different Sequence Number.

FDA’s database is structured as follows:

Application:

Submission

Amendment (called “Supporting Document”) in the database

Amendments (Supporting Documents) are named by a Category and Subcategory

For the Application Type “Drug Master File” the Submission Types are:

  • Original:  Amendments containing changes to technical information are filed in the “Original” submission and the Category/Subcategory should be specified in the header of the Cover Letter.  A new DMF does not need a “Category/Subcategory” designation by the holder.  See Categories and Subcategories below.
  • Annual Report: There is only one Category with two Subcategories:
    • Annual Report
    • Amendment
  • Letter of Authorization: There is only one Category with two Subcategories:
    • Letter of Authorization
    • Withdrawal of Authorization
  • General Information (Reactivation, Closure Request, Administrative Information)
    • Categories of Amendments (Supporting Documents) in General Information 

Categories of Amendments (Supporting Documents) in Original Submission:  

Category: Quality

Subcategories under Quality Category (with corresponding CTD Sections, where applicable).   Applicable Section in modules 2 and 3   Changes to a Subsection not specifically listed below should be reported as the next level up e.g. changes in Control of Materials (S.2.3) should be reported as Manufacture Information S.2. Subcategory
New item:  Additional item e.g. flavor added to a multi-item DMF  
Controls Information (specifications)  S.4 and P.5
Dissolution Data (Usually applies to drug product only) P.5
Facility Information (changes in manufacturing and or testing sites) S.2.1 and P.3.1
Formulation Information  (Usually applies to drug product only) P.1 and related sections
Lot Release (batch analysis) S.4.4 and P.5.4
Manufacture Information S.2 and P.3
Microbiology Information  
New Strength (Usually applies to drug product only) P.1 and related sections
Quality (Not covered by other subcategories)  
Packaging Information (Applies to packaging of the material that is the subject of the DMF e.g. plastic bags for packaging a bulk drug substance in a Type II DMF) S.6 and P.7
Stability Information S.7 and P.8
Response to Information Request  
Response to Deficiency Letter   
Response to Complete Response Letter  

Category: Non-clinical

  • Non-clinical
  • Carcinogenicity Information

Submissions that cover multiple DMFs should have a copy submitted for each DMF.

When a change is made to one part of a DMF the entire DMF does not need to be resubmitted.  For DMFs in CTD format, the entire changed “Document” (Section) should  be submitted e.g. a change in the material used in the synthesis should be included in a resubmission of Section S.2.3.

All submissions should be paginated within the submission.  Pages that replace an already-numbered page from a previous submission should also contain the page number in the current submission (e.g. a page replacing Page 10 in the original submission may be page 14 in the new submission).  For DMFs in CTD format, only the pages within the changed “Document” (Section) are subject to re-numbering.

No pages are ever physically replaced in a paper DMF.

Response to Overdue Notice Letter

A response to an Overdue Notice Letter (ONL) to retain activity of a DMF should be identified as an Annual Report and contain the information listed below for an Annual Report.  Additional administrative and technical information may be included as amendments.  As noted above, Annual Reports submitted at the same time as amendments in eCTD must have separate Sequence Numbers.  A submission that states that an update will be submitted in the future is not sufficient to retain the Active status of a DMF.

 

REPORTING CHANGES TO A DMF (Category 2)

Any addition, change, or deletion of information in a DMF is required to be submitted to the DMF.  In addition the DMF holder must notify each person authorized to reference the DMF (authorized party) (See 21 CFR 314.420(c))  There are no reporting categories for DMFs.  All changes must be reported as amendments.  The DMF holder should notify each authorized party of the nature of the changes, providing as much detail as is consistent with the confidentiality agreement between the DMF holder and the authorized party, so that the authorized party can determine how to report the changes in their approved NDA or ANDA.  See 21 CFR 314.70 and related Guidances.

Also Guidance for Industry:  Changes to an Approved NDA or ANDA and the Q&A
CMC Postapproval Manufacturing Changes Reportable in Annual Reports (Draft Guidance)

ELECTRONIC DMFs (Category 3)

The FDA has published a Final Guidance, Providing Regulatory Submissions in Electronic Format — Certain Human Pharmaceutical Product Applications and Related Submissions Using the eCTD Specifications (5/15/2015) regarding electronic submissions.  See the Guidance for further information regarding requirements for electronic DMF submissions (eCTD Guidance).  The Guidance applies to ALL DMFs, whether or not they are being referenced by an application.  The compliance date for submitting a DMF in electronic format is May 5, 2018.

All electronic submissions must have an application number.  For a new DMF, the holder must request a pre-assigned number in order to populate the US Regional.xml.   The ECTD format provides the backbone for the submission and a guide as to where to place information.  It is not necessary to submit modules that are not applicable to the subject of the DMF e.g. it is not necessary to submit Module 4 and 5 for a Type II DMF for a drug substance.  For new electronic DMFs, all Sections within Modules 1, 2 and 3 should be submitted.  DMF holders are encouraged to submit all subsequent submissions electronically after the initial electronic submission.  See also Electronic Common Technical Document (eCTD).  Electronic signatures are accepted for electronic DMFs.

Electronic DMFs may be submitted either through the Gateway or by sending a disc (one copy) to the Central Document Room at the address provided above.  DMF holders are reminded of the following requirement in the ECTD Guidance:

  • “For all submissions that are 10 gigabytes (GB) or smaller, you must use the FDA ESG .For submissions that are greater than 10 GB, refer to the FDA technical specification “Specification for Transmitting Electronic Submissions using eCTD Specifications.”

See Specification for Transmitting Electronic Submissions using eCTD.

It is not necessary for a DMF holder to submit a form with the DMF for automated processing.  The DMF will be automatically processed in the absence of a form.  If a DMF in eCTD format is flagged with a validation error due to the form heading element not being included in the index.xml when there is no physical form in the eCTD directory, the DMF holder should ignore the error message and continue to submit. 

CONVERSION OF PAPER DMFS TO ELECTRONIC DMFS (Category 3)

An existing DMF number may be used when converting a paper DMF to electronic format.  If the existing number is 4-digits, e.g. 1234, the DMF holder should pad left with zeroes to convert to a 6-digit format, e.g. 001234.  There is no requirement to submit or resubmit DMFs in electronic format.  However, if a paper DMF is converted to eCTD format, and there are any changes in the technical content of the DMF as a result of reformatting, e.g. addition of new information, the cover letter for the new submission should specify what areas of technical information have been changed.  The numbering of the submissions should start with 0001.

LETTERS OF AUTHORIZATION (Category 2)

All Letters of Authorization (LOAs) should be submitted in two copies to the DMF, if the DMF is in paper format.  If the DMF is in CTD format, whether in paper or eCTD, the LOA should be submitted in Section 1.4.1.  A copy of the LOA must then be sent by the DMF holder to the Authorized Party (company or individual authorized to incorporate the DMF by reference).  Failure to submit the original LOA to the DMF may result in a delay in review of the DMF. LOAs should specify the name of the specific item being referenced and the date of the submission of information about that item. The LOA should not be called a “Letter of Access.”

An LOA should be submitted even if the DMF holder is the same company as the authorized party.

LOAs should NOT be submitted with original paper DMFs (unless the DMF has received a pre-assigned number) because the LOA should contain the DMF number. Therefore, if there is no pre-assigned number, DMF holders should wait before submitting an LOA until they have received an acknowledgment letter containing the DMF number.

It is not necessary to reissue LOAs if there have been no changes in the holder, authorized party, subject of the DMF or item referenced.

If the holder changes its name, whether this represents a change in ownership or not, new LOAs should be submitted to the DMF and copies sent to the authorized party(ies). 

If an authorized party changes its name, the new authorized party should request a new LOA from the DMF holder.  Failure to do so may result in a delay in review of the DMF.

If there has been a name change, it is not necessary to submit a Withdrawal of Authorization Letter for the holder or authorized party’s previous name.

If a company has a Master File submitted to another Center in the FDA, e.g. a Biologics Master File (MF) submitted to the Center for Biologics Evaluation and Research, the Letter of Authorization should be submitted to the Master File in that other Center rather than CDER.

  • LOA Template

Note: The “Subject” field in the Letter Templates refers to the Subject of the DMF, not the Item within the DMF being referenced. The Item name should be included in the body of the letter.

AGENTS (Category 2)

There is no regulatory requirement for an agent for any DMF, foreign or domestic. An agent for DMF purposes is not the same as an agent for the purposes of the Drug Listing and Registration System. (DRLS).  Holders should not include the name of the agent for Registration purposes in the DMF unless the same person or company is the agent for both the DMF and DRLS.  Also note that in the US, the process of “Registration” applies ONLY to “registering” an establishment with the FDA.

All “Agent Appointment Letters” for DMFs should be signed by the holder. FDA recommends that such letters include the phrase “appoint AGENT NAME as the agent for DMF” rather than “authorize AGENT NAME to act as the agent for DMF,” since the latter can be confused with a “Letter of Authorization.”

Agents for DMF purposes are not required to be located in the United States, although this is recommended.

An “Agent Appointment Letter” may be included in an original DMF.

If possible, the word “Agent” should be used for the legal entity (whether a company or an individual) who is authorized to act on behalf of the DMF holder.  The word “Representative” or “Contact Person” should be used for an individual who is employed by the Agent or Holder as the contact point for FDA.

If a company acting as an Agent changes its name, the DMF holder should issue a new Agent Appointment Letter.

A different agent can be appointed for different DMFs submitted by the same holder.

HOLDER NAMES (Category 2)

When the company that owns a DMF (DMF holder) changes its name, whether through sale of the company or simply a change in the company’s name, the DMF holder must notify FDA.  See Section VII.E. in the DMF Guidance for further recommendations on the procedure for transferring ownership.  A change in the name of a company for registration purposes under DRLS will not change the DMF holder name.

When a DMF is transferred from one company to another, the original holder should submit an administrative amendment stating that they are TRANSFERRING the DMF to the new holder.  The new holder should then submit an administrative amendment stating that they are ACCEPTING the DMF from the former holder.

If the holder changes names, whether this represents a change in ownership or not, new LOAs should be submitted to the DMF and copies sent to the authorized party. 

If the authorized party changes its name the new authorized party should request a new LOA from the DMF holder.  Failure to do so may result in a delay in review of the DMF.

It is not necessary to submit a Withdrawal of Authorization Letter for the holder or authorized party’s previous name.

A DMF holder is expected to retain a complete reference copy that is identical to, and maintained in the same chronological order as, their submissions to FDA (See Section IV.D.1 in the DMF Guidance).  Therefore the old owner of the DMF is expected to transfer that copy to the new owner of the DMF.

In general FDA expects the manufacturer to be the holder. If a manufacturer (Company A) of a MATERIAL wishes to have the DMF submitted by another company (Company B) and Company B wishes to act as the holder, the DMF should include statements from both companies that Company B takes full responsibility for all the information in the DMF and for all the processes and testing performed by the manufacturer.

If Company B changes its name, whether through an internal name change or a through sale of the company, the new holder should notify the FDA of the name change.  This submission should contain a statement that the new holder of the DMF takes full responsibility for all the information in the DMF and for all the processes and testing performed by the manufacturer.

ANNUAL REPORTS (Category 2)

According to the DMF Guidance, Annual Reports are NOT to be used to report changes in the DMF.  As noted above, Annual Reports submitted at the same time as amendments in eCTD must have separate Sequence Numbers.

The Annual Report should contain (for Cover Letter see Templates below):

1. An administrative page containing the Administrative Information specified above (Administrative Information in a DMF)

AND   2. One of the following

  • Date(s) of the amendment(s) reporting changes since the last Annual Report or the original DMF filing date, whichever is most recent.

Or

  • A statement that no amendments have been submitted since the last Annual Report or the original DMF filing date, whichever is most recent.

AND   3. One of the following:

  • A complete list of all parties authorized to make reference to the DMF, identifying by name, reference number, volume, date, and page number the information that each person is authorized to incorporate by reference and the date of the LOA. 

Or

  • A statement that there are no Authorized Parties.

AND   4. List of all parties whose authorization has been withdrawn

Note that the DMF Guidance uses the terms “Annual Update” and “Annual Report” interchangeably.  All submissions of Annual Reports should be labeled “Annual Report.”  The term “Annual Update” should not be used.

Note that the Annual Report should contain a COMPLETE list of Authorized Parties, even if the list of Authorized Parties is unchanged.

BIOLOGICS MASTER FILES (Category 3)

Master Files submitted in support of products regulated by the Center for Biologics Evaluation and Research (CBER) should be submitted as MFs.  See the CBER web site for the products regulated by CBER.

BINDERS (Category 2)

See FDA IND, NDA, ANDA, or Drug Master File Binders

The “binders” are actually covers.  These may be ordered from the U.S. Government Printing Office (GPO) Web site: http://bookstore.gpo.gov/ or by calling 202-512-1800 to speak with a GPO customer service representative.  The binders may be obtained from another supplier, provided they meet the requirements specified on the GPO Web site.

The direct links for online ordering are

One copy of the DMF should use the blue cover and one should use the red cover.

Fasteners must be obtained separately. Use 2 Piece Prong Fasteners, 8 1/2″ Center to Center, 3 1/2″ Capacity.  Binders should be used for all subsequent submissions to FDA that are more than 10 pages.

If a DMF is submitted using any other kind of binder, it should be a loose-leaf type of binder so that the pages can be removed and placed in FDA-approved binders.  DMFs should not be submitted as “bound” books.

FEES (Category 4)

GDUFA requires DMF fees for Type II DMFs for drug substances (Active Pharmaceutical Ingredients (APIs)) used to support Abbreviated New Drug Applications (ANDAs).  See definition of API above.

Since GDUFA does not apply to any other type of DMF or to Type II DMFs used to exclusively support NDAs or INDs, there are no fees for these types of DMFs.

FORMS  (Category 2)

Certain forms are required for submission of NDAs and INDs.  However there are no forms required or available for DMFs, except for the forms discussed above under Binders and the Generic Drug User Fee Cover Sheet.  The latter applies only to Type II DMF submitted to support ANDAs under GDUFA.

CONFIDENTIALITY OF DMFs (Category 2)

The public availability of the contents of DMFs is covered in 21 CFR 314.430(g).  There are no “open” or “closed” parts of DMFs filed with the FDA.  The decision as to how much information DMF holders share with their authorized parties is a business decision between the parties involved and is not covered by FDA regulations or Guidances.  All requests for information about DMFs beyond that provided in the Drug Master File lists above must be made through the CDER Freedom of Information Web site.

FILING DMFs AND PATENT EXPIRATION AND EXCLUSIVITY ISSUES (Category 2)

DMFs may be filed at any time.  The Patent Expiration date and the Exclusivity Expiration dates listed in the Orange Book have no impact on DMF filing.  The submission of Abbreviated New Drug Applications (ANDAs) that reference DMFs is subject to the regulations regarding filing of ANDAs.

ENVIRONMENTAL ASSESSMENTS (Category 2)

Since DMFs are neither approved nor disapproved, there is no need to file an Environmental Assessment. However the DMF should contain a commitment by the firm that its facilities will be operated in compliance with applicable environmental laws.

REORGANIZATION OF A DMF (Category 1)

The advice in the Guidance does not apply.  It is not necessary to consult with FDA before reorganizing a DMF.

REQUEST FOR CLOSURE OF A DMF BY THE HOLDER (Category 2).

It is not necessary to include a statement that “the holder’s obligations as detailed in Section VII have been fulfilled,” as recommended in the DMF Guidance.  It is sufficient to include a statement that all of the parties authorized to reference the DMF have been notified that the DMF is being closed.

LETTER TEMPLATES AND COVER LETTERS (Category 2)

Note that a “Transmittal Letter” and a “Cover Letter” are the same thing.

See Drug Master File Letter Templates below.

All submissions should have a Cover Letter. 

Drug Master File Lists

Drug Master File Letter Templates

http://www.fda.gov/drugs/forms-submission-requirements/drug-master-files-dmfs

Endocrinologic and Metabolic Drugs Advisory Committee Roster

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Applying for Membership on FDA Advisory Committees

As part of the Food and Drug Administration’s (FDA’s) ongoing efforts to recruit qualified experts with minimal conflicts of interest who are interested in serving on FDA advisory committees, FDA is requesting nominations for members to serve on its advisory committees.

Current Number of Vacancies = 0

Note, one or more vacancies may be in the nomination process or a final appointment may have been made.

http://www.fda.gov/advisory-committees/endocrinologic-and-metabolic-drugs-advisory-committee/endocrinologic-and-metabolic-drugs-advisory-committee-roster

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