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1FILING MEETING SUMMARY
Application number: BLA STN 125742/0
Product name: COVID-19 mRNA Vaccine (COMIRNATY)
Proposed Indication: Active immunization to prevent COVID-19 caused by
SARS-CoV-2 in individuals 16 years of age and older
Applicant: BioNTech Manufacturing GmbH
Meeting date & time: June 29, 2021; 2:00 - 3:30 PM EDT
Committee Chair: Ramachandra Naik, Ph.D.
Meeting Recorders: CAPT Michael Smith, Ph.D. and Laura Gottschalk, Ph.D.
Background:This meeting was to discuss the new original BLA (STN 125742/0) from BioNTech Manufacturing GmbH (in partnership with Pfizer, Inc.) for COVID-19 mRNA Vaccine, for active immunization to prevent COVID-19 caused by SARS-CoV-2 in individuals 16 years of age and older. This is a Rolling BLA submission. The first roll containing eCTD sections 2, 4, and 5 was submitted and received on May 6, 2021. The second and final roll containing eCTD Section 3 (and the rest of Section 1 items) was submitted and received on May 18, 2021. As agreed during the Pre-BLA interaction, the COVID-19 case strain sequencing report was submitted on June 7, 2021.
The purpose of this meeting was to discuss 1) the completeness of the BLA submission
and 2) whether it is acceptable to be filed.
Table 1: Review Committee and Discipline Filing Decision Summary
Discipline/Organization Name
Attended
meeting
Fileable
RTF
Deficiencies
Identified
Regulatory Project Managers
(RPM )CAPT Michael Smith, PhD
Laura Gottschalk, PhD9
99
Chair Ramachandra Naik, PhD 99
Division Director - Clinical Doran Fink, MD, PhD 99
Division Director/Deputy
(Actin g)–R e gulator yLoris McVittie, PhD/
Kirk Prutzman, PhD99
Office Director/Deputy Marion Gruber, PhD/
Philip Krause, MD, PhD9
99
Clinical Reviewers Susan Wollersheim, MD
CAPT Ann Schwartz, MD999
Toxicolo gy Reviewer Nabil Al-Humadi, PhD 99
CMC Reviewers Xiao Wang, PhD
Anissa Cheun g, MSc99Ramachandra
Naik -SDigitally signed by Ramachandra Naik -S DN: c=US, o=U.S. Government, ou=HHS, ou=FDA, ou=People, 0.9.2342.19200300.100.1.1=2001232361, cn=Ramachandra Naik -S Date: 2021.07.26 10 58:23 -04'00'
FDA-CBER-2021-5683-0652178
STN 125742/0 Filing Meeting dated: June 29, 2021
Filing Meeting Summary 2Discipline/Organization Name
Attended
meeting
Fileable
RTF
Deficiencies
Identified
OCBQ/DMPQ Reviewers Kathleen Jones, PhD
Laura Fontan, PhD
Gregory Price, PhDZhongren Wu, PhDCDR Donald Ertel, MSEkaterina Allen, PhDCheryl HulmeIr
yna Zubkova, PhD9
9
99
OCBQ/APLB Reviewers CDR Oluchi Elekwachi, PharmD,
MPH
Dana Jones (Back up )9
9
OCBQ/BIMO Reviewer Haecin Chun, MT (ASCP) SSB, MS99
OCBQ/DBSQC Reviewers Hsiaoling Wang, PhD
Emnet Yitbarek, PhD Karla Garcia, MSAnil Choudhary, PhD, MBAEsmeralda Alvarado, PhDMarie Anderson, PhD9
9
9
99
Statistical Reviewer of clinical
and nonclinical dataLei Huang, PhD 99
Postmarketing Safety Epidemiological/Pharmacovi
gilance ReviewerDeborah Thompson, MD, MSPH 9
9
Labelin g Reviewer Daphne Stewart 99
CDISC Consult Brenda Baldwin, PhD
Kirk Prutzman, PhD9
Other Attendees:Maria Allende, Nicolette Devore, Maryna Eichelberger, John Eltermann, Karen Farizo, Theresa Finn, Sara Gagneten, Varsha Garnepudi, Dave Green, Marion Gruber, Hector Izurieta, Philip Krause, Lucia Lee, Robin Levis, Nicole Li, Carrie Mampilly, Narayan Nair, Manette Niu, Tim Nelle, Cassandra Overking, Tao Pan, Keith Peden, Lori Peters, Douglas Pratt, Joseph Quander, Carolyn Renshaw, Jeff Roberts, David Rouse, Muhammad Shahabuddin, Lisa Stockbridge, Elizabeth Sutkowski, Swati Vermaand Jerry Weir
FDA-CBER-2021-5683-0652179
STN 125742/0 Filing Meeting dated: June 29, 2021
Filing Meeting Summary 3Review Timetable (PDUFA Milestones are in blue)
Review Milestone Target Due Date
Submitted
Roll 1 Submission: 06-MAY-2021Roll 2 Submission (final): 18-MAY-2021
Received: 18-MAY-2021Committee Assignment: 09-JUN-2021First Committee Meeting: 03-JUN-2021Filing checklist/reviews complete: 23-JUN-2021Filing Meeting: 29-JUN-2021 Filing Action: 16-JUL-2021Deficiencies Identified: 31-JUL-2021Initial proprietary name review: 16-AUG-2021Draft Primary Reviews & Reviewer Reports Due(4 days prior to Mid-Cycle meeting): 25-AUG-2021Mid-Cycle Meeting (Internal): 31-AUG-2021Mid-Cycle Communication: 13-SEP-2021
Final Draft Primary Reviews with Supervisory Concurrence (upload not required): 01-SEP-2021PLI Inspections completed: 30-JUL-2021BiMO Inspections completed: 30-JUL-2021PeRC briefing materials due to PeRC: 27-JUL-2021PeRC Meeting: 10-AUG-2021Final reviews & addenda signed & uploaded: 15-SEP-2021Lot release protocol & testing plan finalized: 30-AUG-2021Notify OCOD of pending approval: 30-AUG-2021Draft SBRA: 30-AUG-2021Labeling Comments to Applicant: 30-AUG-2021Notify Applicant of PMC/PMR: 30-AUG-2021Targeted Action Due Date (ADD): 30-SEP-2021PDUFA ADD: 16-JAN-2022
Table 2: Scheduled Meetings
PDUFA Meetings:
xFirst Committee Meeting: June 3, 2021, 4:00PM – 5:30PM
xFiling Meeting: June 29, 2021, 2:00PM – 3:30PM
xInternal Mid-Cycle Meeting: August 31, 2021, 2:00PM – 3:30PM
xMid-Cycle Communication: September 13, 2021, 3:00PM – 4:00PM
Monthly Committee Meetings:
xJuly 15, 2021, 3:30PM – 5:00PM
xAugust 9, 2021, 1:30PM – 3:00PM
xSeptember 10, 2021, 12:30PM – 2:00PM
Labeling Meetings:
FDA-CBER-2021-5683-0652180
STN 125742/0 Filing Meeting dated: June 29, 2021
Filing Meeting Summary 4xAugust 4, 2021, 3:00PM – 5:00PM
xAugust 6, 2021, 3:00PM – 5:00PM
xAugust 11, 2021, 3:00PM – 5:00PM
xAugust 16, 2021, 11:00AM – 12:30PM (Carton & Container)
xAugust 18, 2021, 3:30PM – 5:00PM (Carton & Container)
xSeptember 2, 2021, 4:00PM – 5:30PM
xSeptember 7, 2021, 2:00PM – 4:00PM
xSeptember 21, 2021, 3:00PM – 5:00PM
DISCUSSION SUMMARY
The Chair highlighted updates that had taken place since the First Committee Meeting:
1. No Filing Checklists are required
xADRM agreed that the discipline reviewers don’t need to complete the filing
checklists for this BLA. However, the discipline reviewers were reminded to refer to the filing checklists to initiate the process and look for special items that should be included in the submission.
xThis exception to policy, not requiring filing checklists, is intended to help
facilitate the expedient review of the application, but in no way alleviates
reviewers from performing their due diligence to ensure that the application is complete for the purposes of filing.
xNormally, major issues or IRs being dra fted will be listed in Filing Checklists.
However, as this is the Priority Review BLA with the short review timeline, the
reviewers have already started sending IRs and inspecting the vaccine manufacturing facilities (see below for additional details).
2. BLA License Number generated in advance of approval
xThe Applicant requested a US License Number for BioNTech Manufacturing GmbH with agreement that they will not use it until after the BLA is approved.
xDr. Joneckis wrote a memo to the file authorizing release of the BLA license number in advance of the typical notification in the approval letter.
xRIMS generated the license number which will be provided to the Applicant,after filing, in an email message.
3. PeRC meeting is scheduled for August 10, 2021
UPDATES FROM REVIEW DISCIPLINES:
1. Chair (Ram Naik):
xSee discussion summary above.
2. Regulatory Project Managers (Mike Smith and Laura Gottschalk):
xThe RPMs summarized the IRs and Amendments to the BLA to date (please see details at end of document).
FDA-CBER-2021-5683-0652181
STN 125742/0 Filing Meeting dated: June 29, 2021
Filing Meeting Summary 5xThe BLA is fileable.
xTo ensure the regulatory items were covered in the submission, the
RPM Checklist was completed and will be uploaded to the file.
3. Clinical (Susan Wollersheim and Ann Schwartz):
xThe BLA is fileable and the clinical reviewers agree with the Priority Review designation.
4. CMC (Xiao Wang):
xThe BLA is fileable and no major issues have been identified that warrant discussion.
xThe CMC reviewer noted that she used the Filing Checklist during her review and no major deficiencies were identified.
xA list of clarification Information Requests is being generated for the Applicant.
5. DBSQC (Hsiaoling Wang, Emnet Yitbarek, Karla Garcia, Anil Choudhary,
Esmeralda Alvarado and Marie Anderson):
xThe BLA is fileable.
6. Toxicology (Nabil Al-Humadi):
xThe BLA is fileable.
7. Statistics (Lei Huang):
xThe BLA is fileable.
8. Epidemiology/Pharmacovigilance (Deborah Thompson):
xThe BLA is fileable.
9. DMPQ (Kathleen Jones, Laura Fontan, Gregory Price, Zhongren Wu,
Donald Ertel, Ekaterina Allen, Cheryl Hulme and Iryna Zubkova):
xThe BLA is fileable.
xLaura Fontan is currently in Belgium carrying out inspections of the Pfizer, Puurs facilities.
xThere will most likely be a waiver for inspections of the Pfizer, Kalamazoo site.
xKathleen Jones will be leading the in spections of the Pfizer, Andover
site scheduled for July 19-23, 2021.
10.BiMO (Haecin Chun):
xThe BLA is fileable.
xAt this time, they are not planning on issuing inspections in support of this BLA (inspections of 9 clinical sites were conducted for Protocol C4590001 under the IND/EUA).
11.APLB (Oluchi Elekwachi):
xThe BLA is fileable.
FDA-CBER-2021-5683-0652182
STN 125742/0 Filing Meeting dated: June 29, 2021
Filing Meeting Summary 612.Container Labeling (Daphne Stewart):
xThe BLA is fileable.
xThe labeling reviewer is finalizing an IR.
13.CDISC (Brenda Baldwin and Kirk Prutzman):
xThe BLA is fileable.
xAs previously noted, the datasets submitted with this BLA will not be
validated since they were already validated under an amendment to
EUA 27034.
UPDATES FROM MANAGEMENT:
1. Advisory Committee Meeting
xThe Office Director confirmed that, unless a significant new safety concern or other important issue is discovered during the review of the submissionthat would necessitate convening the VRBPAC, an Advisory Committee Meeting will not be needed for this BLA.
2. Regular Updates to Mana gement on Review Progress
xThe Office Director noted that at this time, review progress updates provided during the Monthly Review Committee Meetings would suffice.This plan can be revisited during August and September to determine ifmore frequent updates to Managers should be provided.
REGULATORY CONCLUSIONS / DEFICIENCIES:
1. Does the application, on its face, appear to be suitable for filing or is the
application unsuitable for fili ng and require an RTF letter?
The application appears to be suitable for filing.
2. If fileable, list any substantive deficiencies or issues that have significant
impact on the ability to complete the review or approve the application :
No substantive deficiencies or issues have been identified that would have a significant impact on the ability to complete the review or approve the application.
3. If RTF, list any substantive deficiencies or issues that would make this
application unsuitable for filing:NA
FILING MEETING DISCUSSION, IF FILED:
4. Indicate any comments on the status of the proprietary name review (PNR).
The IND PNR memo for COMIRNATY was completed on November 9, 2020 and the decision was communicated to the Sponsor on November 20, 2020. The BLAPNR review memo is being finalized.
FDA-CBER-2021-5683-0652183
STN 125742/0 Filing Meeting dated: June 29, 2021
Filing Meeting Summary 75. Indicate whether the product sh/woul d be subject to lot release,
surveillance, or exempt from lot release. Verify sample availability.
The product is subject to lot release. DBSQC’s request for Lot Release Protocol, samples and reagents, was sent to the Applicant on June 25, 2021.
6. Confirm review schedule for the appli cation. If priority review, include
justification from clinical reviewer filing review checklist. [Standard Review, Priority Review, or Expedited Review]The review schedule for this BLA submission is an 8-month Priority Review with a PDUFA Action Due Date (ADD) of January 16, 2022. However, the targeted expedited ADD is September 30, 2021. The review timeline may be revised to address public health needs and as feasible. (See Review Timetable above for dates)
7. Indicate the decision regarding the need for an Advisory Committee.
At this time, an Advisory Committee Meeting will not be needed for the BLA. Five Advisory Committee Meetings have occurred from October 22, 2020 to June 10, 2021 to discuss the development, Emergency Use Authorization and licensure of COVID-19 vaccines.
8. Indicate whether the submission triggers PREA. If yes, a PeRC meeting is
needed. Verify whether the applicant has an initial pediatric study plan
(iPSP) in place.The submission triggers PREA because it contains a new active ingredient, and a meeting with PeRC has been scheduled for August 10, 2021. The Applicant has an iPSP in place.
9. Indicate whether the submission contains a proposed REMS. If yes, or if a
REMS may be needed as a condition of approval, schedule an internal REMS meeting between the Pr oduct Office and OBE/DE.
The submission does not contain a proposed REMS.
10. Is a comprehensive and readily located li st of all clinical sites included or
referenced in the application?A comprehensive and readily located list of all clinical sites is included in the application.
11. Is a comprehensive and readily located list of all manufacturing facilities
included or referenced in the application?A comprehensive and readily located list of all manufacturing facilities is included
in the application.
12. Indicate any updates since the First Committee Meeting on pre-license
inspection, pre-approval inspection, or BIMO sites requiring inspections (Is
the establishment(s) ready for inspection?)See updates from the DMPQ reviewers above.
FDA-CBER-2021-5683-0652184
STN 125742/0 Filing Meeting dated: June 29, 2021
Filing Meeting Summary 8BIMO is not issuing any inspections under this BLA; see updates from the BIMO
reviewer above.
13. If the application is affected by the Application Integrity Policy (AIP), has
the division made a recommendation regarding whether an exception to
the AIP should be granted to permit review based on medical necessity or public health significance?The application is not affected by the AIP.
14. Is the product an Original Biological Product or a New Molecular Entity
(NME) for an NDA? The product is an Original Biological Product.
FOR APPLICATIONS IN THE PDUFA PROGRAM (NME NDAs/Original BLAs), IF FILED:
15. Confirm that any late submission components were submitted within 30
days. List any late submission com ponents that arrived after 30 days.
As agreed, a strain sequence analysis report for all COVID-19 cases wassubmitted in amendment 5 (sequence 0006) dated June 7, 2021. There were no late submission components that arrived after 30 days.
16. Was the application otherwise complete upon submission, including those
applications where there were no agreements regarding late submission components?The application was complete upon submission.
ADMINISTRATIVE DETAILS, IF FILED:
17. Review the Milestone Schedule and indicate if there are any issues with the
schedule. Note: This is a confirmation to capture any changes made since
the First Committee Meeting. No changes have occurred in the Milestone Schedule since the First Committee Meeting. Please see Review Timetable above.
INFORMATION REQUESTS (IRs):
1.05/18/2021: Three questions regarding datasets (Response in 125742/0.3)
2.05/20/2021: Four facilities questions and a request for a telecon on 5/25/21 or
5/26/21 to discuss production schedule and the shutdown activities planned for the Puurs, Belgium site (Response in 125742/0.4)
3.06/08/2021: Three clinical questions regarding datasets and the PI (Response in125742/0.6)
FDA-CBER-2021-5683-0652185
STN 125742/0 Filing Meeting dated: June 29, 2021
Filing Meeting Summary 94.06/09/2021: Clinical IR requesting dates for PREA deferred studies (Response in
125742/0.7)
5.06/25/2021: DBSQC IR regarding the lot release protocol (LRP) template andsamples and reagents (Awaiting response)
6.06/25/2021: Clinical IR regarding the do cument titled “bnt1 62-01-intrim3-report-
body” (Awaiting response)
AMENDMENTS:
1.05/18/2021: Second roll and final piece of the BLA, which started the review clock.
This amendment was not submitted in response to an IR.
2.05/19/2021: Request for Proprietary Name Review. This amendment was not submitted in response to an IR.
3.05/19/2021: Response to May 18, 2021, IR RE three dataset questions.
4.05/24/2021: Response to DMPQ’s May 20, 2021, IR RE four facilities questions and
a request for a t-con on 5/25/21 or 5/26/21 to discuss production schedules and the shutdown activities planned for the Puurs, Belgium site.
5.05/24/2021: COVID-19 case strain sequencing data. This amendment was not submitted in response to an IR.
6.06/16/2021: Response to June 8, 2021, clinical IR on three clinical questions regarding datasets and the PI.
7.06/17/2021: Response to June 9, 2021, clinical IR requesting dates for PREA deferred studies.
FDA-CBER-2021-5683-0652186