Document text
First Committee 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
Applicant: BioNTech Manufacturing GmbH
Meeting date & time: June 3, 2021; 4:00PM - 5:30PM EDT
Committee Chair: Ramachandra Naik, Ph.D.
Meeting Recorder s: CAPT Michael Smith, Ph.D. and
Laura Gottschalk, Ph.D.
Table 1: Review Committee (attendees are listed in bold font)
Review responsibility Committee Member Team Leader / Supervisor (s) Division Director
Chairperson Ramachandra Naik, PhD TL: Kirk Prutzman, PhD
BC: Elizabeth Sutkowski , PhD DD: Loris McVittie , PhD
SA: Kirk Prutzman, PhD (acting)
Regulatory Project
Managers CAPT Mike Smith, PhD
Laura Gottschalk, PhD TL: Kirk Prutzman, PhD
BC: Elizabeth Sutkowski, PhD DD: Loris McVittie, PhD
SA: Kirk Prutzman, PhD (acting)
Clinical Susan Wollersheim, MD
CAPT Ann Schwartz, MD TL: Lucia Lee, MD
BC: Maria Allende, MD DD: Doran Fink, MD, PhD
Product (CMC)
DVP Regulatory coordinator ,
DVP Product Specialist Haruhiko Murata, MD, PhD
Xiao Wang, PhD
Anissa Cheung, MSc BC: Keith Peden, PhD
BC: Keith Peden, PhD DD: Jerry Weir, PhD
DDD: Robin Levis, PhD
DS and DP release assays
DS and DP release assays
DS and DP release assays
DS and DP release assays
DS and DP release assays
LRP and Testing Plan Dev. Hsiaoling Wang, PhD
Emnet Yitbarek, PhD
Karla Garcia, MS
Anil Choudhary, PhD , MBA
Esmeralda Alvarado, PhD
Marie Anderson, PhD TL: Tao Pan, PhD
TL: Tao Pan, PhD
BC: CDR James Kenney, DSc
BC: Muhammad Shahabuddin, PhD
BC: Muhammad Shahabuddin, PhD
Maryna Eichelberger, PhD DD: Maryna Eichelberger, PhD
DDD: N/A
Toxicology Nabil Al -Humadi, PhD BC: Martin Green, PhD DD: Doran Fink, MD, PhD
Statistics, both Clinical data
& assays Lei Huang, PhD BC: Tsai-Lien Lin , PhD DD: John Scott , PhD
DDD: Shiowjen Lee, PhD
Epidemiology/
Pharmacovigilance Deborah Thompson, MD,
MSPH TL: LCDR Jane Baumblatt, MD
BC: Manette Niu, MD DD: Narayan Nair, MD
DDD: Meghna Alimchandani, MD
DMPQ Reviewer /Inspector
DMPQ Reviewer /Inspector
DMPQ Reviewer
DMPQ Inspector
DMPQ Inspector
DMPQ Inspector
Lot Release
DMPQ RPM Kathleen Jones , PhD
Laura Fontan, PhD
Gregory Price, PhD
Zhongren Wu , PhD
CDR Donald Ertel , MS
Ekaterina Allen , PhD
Cheryl Hulme
Iryna Zubkova , PhD TL: Nicole Li
BC: Lori Peters, MS
TL: CDR Donald Ertel , MS
BC: Lori Peters , MS
BC: Anthony Lorenzo
BC: Joseph Quander
BC: James Crim DD: John Eltermann, RPh, MS
DDD: Carolyn Renshaw
BIMO Haecin Chun ,
MT(ASCP)SBB, MS BC: Dennis Cato DD: Carrie Mampilly, MPH
APLB Labeling
reviewer CDR Oluchi Elekwachi,
PharmD, MPH
Dana Jones BC: Lisa Stockbridge, PhD DD: Robert Sausville
Container Labeling Daphne Stewart BC: Timothy Nelle, PhD DD: Loris McVittie , PhD
Electronic integrity CDR David Schwab, MSIS Loris McVittie , PhD DD: Loris McVittie, PhD
CDISC consult Brenda Baldwin, PhD
Kirk Prutzman, PhD BC: Elizabeth Sutkowski, PhD DD: Loris McVittie, PhD
FDA-CBER-2021-5683-0652168
STN 125742/0 First Committee Meeting dated June 3, 2021
First Committee Meeting Agend a 2 Other attendees that were not listed in the review committee table: Maureen Hess, Leslie
Taylor, Laura Montague, Konstan tin Vernik, Cassandra Overking, David Cho, Varsha
Garnepudi , Hector Izurieta, Jeff Roberts, Joseph Kulinski , Nicki DeVore, Douglas Pratt , Sara
Gagneten, D avid Rouse, Sudhakar Agnihothram , Tatiana ClarodaSilva, S wati Verma and
Nadine Kaelber
Review Timetable ( PDUFA Milestones are in blue )
Review Milestone Target Due Date
Submitted
Roll 1 Submission : 06-MAY -2021
Roll 2 Submission (final): 18- MAY -2021
Received: 18- MAY -2021
Committee Assignment: 09- JUN- 2021
First Committee Meeting: 03-JUN- 2021
Proper name designation: 08-JUN- 2021
Filing checklist /reviews complete: 23- JUN- 2021
Filing Meeting: 29-JUN- 2021
Filing Action: 1 6-JUL-2021
Deficiencies Identified: 31-JUL -2021
Initial proprietary name review: 1 6-AUG -2021
Primary Draft Reviews & Reviewer Reports Due
(4 days prior to Mid- Cycle meeting): 25-AUG -2021
Mid-Cycle Meeting (Internal): 31-AUG -2021
Mid-Cycle Communication : 13-SEP- 2021
Final draft primary reviews with supervisory
Concurrence (upload not required) : 01-SEP- 2021
PLI Inspections completed: 30-JUL-2021
BiMO Inspections completed: 30-JUL-2021
PeRC briefing materials due to PeRC: 27- JUL-2021
PeRC Meeting: 10-AUG -2021
Final reviews & addenda signed & uploaded: 15-SEP- 2021
Lot release protocol & testing plan finalized: 30-AUG -2021
Notify OCOD of pending approval: 30
-AUG -2021
Draft SBRA 30-AUG -2021
Labeling Comments to Applicant: 30-AUG -2021
Notify Applicant of PMC/PMR: 30-AUG -2021
Targeted Action Due Date (ADD) 30-SEP- 2021
PDUFA ADD: 16-JAN- 2022
Table 2: Scheduled Meetings
PDUFA Meetings:
• First Committee Meeting: June 3, 2021, 4:00PM – 5:30PM
• Filing Meeting: June 29, 2021, 2:00PM – 3:30PM
FDA-CBER-2021-5683-0652169
STN 125742/0 First Committee Meeting dated June 3, 2021
First Committee Meeting Agend a 3 • Internal Mid -Cycle: August 31, 2021, 2:00PM – 3:30PM
• Mid-Cycle Communication: September 13 , 2021, 3:00PM – 4:00PM
Monthly Committee Meetings:
• July 15, 2021, 3:30PM – 5:00PM
• August 9, 2021, 1:30PM – 3:00PM
• September 10, 2021, 12:30PM – 2:00PM
Labeling Meetings:
• August 4, 2021, 3:00PM – 5:00PM
• August 6, 2021, 3:00PM – 5:00PM
• August 11, 2021, 3:00PM – 5:00PM
• August 16, 2021, 11:00AM – 12:30PM (Carton & Container)
• August 18, 2021, 3:30PM – 5:00PM (Carton & Container)
• September 2, 2021, 4:00PM – 5:30PM
• September 7, 2021, 2:00PM – 4:00PM
• September 21, 2021, 3:00PM – 5:00PM
Background and Purpose:
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
(COMIRNATY, pronounced “koh- MER nah -tee”), for active immunization to prevent COVID -19
caused by SARS- CoV-2 in individuals ≥16 years of age. This is a Rolling BLA submission , so it
will be handled in RMS -BLA, not eMRP . The first roll containing eCTD sections 2, 4, and 5 w as
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.
The purpose of this First Committee Meeting was to discuss the milestones, roles and
responsibilities of each member of the review team.
Discussion S ummary:
The Chair provided a brief overview of the submission and highlighted several important
points for the review of the BLA.
• A table of the full review committee and their corresponding team leaders,
managers and directors , was included in the agenda for the meeting. The review
committee was asked to review it and let the regulatory review team know if
anything needs to be corrected.
• The submission is a n 8-month Priority Review BLA with a PDUFA Action Due
Date ( ADD) of January 16, 2022 . However, the targeted ADD is September 30,
2021.
• The Chair summarized the review milestones (as shown on page 2).
FDA-CBER-2021-5683-0652170
STN 125742/0 First Committee Meeting dated June 3, 2021
First Committee Meeting Agend a 4 • A Late Cycle Meeting (LCM) will likely not take place since the PDUFA deadline
for the LCM is November 1, 2021, and this is after the Target Action Due Date of
September 30, 2021.
• In an effort to reduce the burden for reviewers, the Chair questioned whether
Filing Checklists should be completed for this submission. Management said that
they will check with CBER IOD about the requirement for Filing Checklists and let
the review team know.
• It was confirmed that a n Advisory Committee Meeting will not be needed for the
BLA since five Advisory Committee Meetings would have occurred from October
22, 2020 to June 10, 2021 to di scuss the development, Emergency Use
Authorization and licensure of COVID -19 vaccines.
• The Chair asked about the best method for the review team to provide regular
status updates to Management. Management will discuss this internally and will
provide an answer to the review team soon .
• The Chair announced that an internal meeting is scheduled for Friday, June 4,
2021, with the DVP and DBSQC teams to discuss tests that will be part of the lot release protocol and in -support testing.
Updates from Discipline Reviewers:
1. Chair (Ramachandra Naik) :
• See discussion summary above.
2. Clinical ( Susan Wollersheim and Ann Schwartz ):
• The clinical reviewers have found the review to be more burdensome than
expected since much of the clinical information is referenced from the prior
IND and EUA , plus the clinical information was not well organized and a
summary document would be helpful . They will discuss internally to see if
there is something that can be requested from the Applicant that can aid
them in their review, including potentially having a teleconference with the Applicant . The clinical team thought they will likely have a safety data
information request, but they were going to discuss with the statistical team first.
3. CMC ( Haruhiko Murata and Xiao Wang ):
• No issues have been identified.
FDA-CBER-2021-5683-0652171
STN 125742/0 First Committee Meeting dated June 3, 2021
First Committee Meeting Agend a 5 4. DBSQC ( Hsiaoling Wang, Emnet Yit barek, Karla Garcia, Anil Choudhary,
Esmeralda Alvarado and Marie Anderson):
• No issues have been identified. However, the Lot Release Protocol
appears to be missing and an i nformation request will be sent to the
Applicant to request this document .
5. Toxicology (N abil Al- Humadi) :
• Dr. Green informed the regulatory team prior to the meeting that the
toxicology team will not be able to attend the meeting, but no issues have
been identified and there should be no problem making the deadlines.
6. Statistics (Lei Huang) :
• No issues have been identified.
7. Epidemiology/Pharmacovigilance (Deborah Thompson) :
• The reviewer noted that a pregnancy registry was mentioned in the
submission, and it will need to be determined if it will be considered a PMC.
8. DMPQ (Kathleen Jones, Laura Fontan, Gregory Price, Zhongren Wu, Donald Ertel, Ekaterina Allen , Cheryl Hulme and Iryna Zubkova):
• No issues have been identified and inspections for Wyeth BioPharma
Division of Wyeth Pharmaceuticals LLC (FEI: 1222181, referred to as Pfizer, Andover ) and Pfizer Manufacturing Belgium NV (FEI: 100654629,
referred to as Pfizer, Puurs) sites are tentatively being planned for July 19th
– 23
rd and June 24th - July 2nd, respectively. They are waiting on the EIR
from the Pharmacia & Upjohn Company (FEI: 1810189, referred t o as
Pfizer, Kalamazoo) site that was issued by TeamBio to see if the inspection
can be waived since the site was recently inspected (May 11 -20, 2021) .
9. BiMO (Haecin Chun) :
• Bi MO is not planning on issuing any more inspections since inspections of
10 study sites were already conducted under the IND and EUA, under 2
protocols . The BiMO team stated that the inspections that occurred under
the IND and EUA did not inspect data integrity because there wasn’t anything to inspect at the time. However, if th e clinical and stat istical
reviewers encounter issues relevant to data integrity, BIMO should be made aware as soon as possible so that arrange ments for inspections can
be made. Lastly, the BiMO team noted that the agenda for this meeting
included a BiMO inspections completed milestone of July 30, 2021, and
FDA-CBER-2021-5683-0652172
STN 125742/0 First Committee Meeting dated June 3, 2021
First Committee Meeting Agend a 6 they mentioned that this is not feasible and too early in the review cycle if
inspections were to be assigned.
10. APLB (Oluchi Elekwachi) :
• No issues have been identified and the propriety name review will be
similar to what was submitted under the IND.
11. Container Labeling (Daphne Stewart) :
• The reviewer noted that she will have a few minor comments on the carton and container label s early next week.
12. CDISC (Brenda Baldwin and Kirk Prutzman):
• D ataset validation will not be done for this BLA . The included datasets are
the same as those in the EUA amendment for adolescents 12 through 15
years of age, which were validated during the review of the EUA amendment.
Action Items:
• Management
o Find out if Filing Checklists will be required.
o Determine the best method for the review team to keep management apprised of
the review progress .
• Clinical
o Determine , as soon as possible, if there are issues that will prevent the review
from being completed on time and keep management informed on what is
decided.
Post -meeting update s:
• CBER IOD informed the regulatory team that discipline reviewer checklists do not need to be completed for this BLA. The reviewers were informed of this decision on June 7,
2021 and encouraged to refer to the checklists for guidance during the review of the
BLA. The RPM filing checklist will be completed and uploaded to RMS -BLA/EDR.
Explanation of Milestones
First Committee Meeting: Committee must meet by this date to discuss the review of the BLA.
Filing Meeting: Meeting at which the review committee determines whether
the BLA can be filed. Reviewers must determine whether the information included in the BLA is sufficient to allow the
reviewer to conduct an adequate review. The purpose is not
FDA-CBER-2021-5683-0652173
STN 125742/0 First Committee Meeting dated June 3, 2021
First Committee Meeting Agend a 7 to determine the acceptability of the data but rather to
determine whether the appropriate information was submitted to allow the reviewer to conduct a meaningful review.
Filing Action: Date by which a filing letter (either accepting or refusing to
file the BLA) must be issued.
Deficiencies Identified: Date by which a letter must be issued in which review issues identified to date are conveyed to the applicant.
Mid-cycle Meeting: Meeting at which each reviewer is expected to document
their review progress and discuss the relevant content of the submission and present an overview. A draft review memorandum identifying key issues should be completed by the time of the meeting. First line supervisors for each review discipline as well as the Director and Deputy Director for DVRPA and OVRR, or their representative, should attend
the meeting.
Action Due Date: Date by which final action regarding the BLA must be conveyed to the applicant (issue Approval or Complete Response letter, depending on review decision). All review memos, regardless of the Action being taken, must be signed and uploaded to the EDR prior to the date of Action.
Explanation of Roles and Responsibilities (See CBER SOPP 8401 for more detail)
• Chair – Manages the administrative processing of reviews and ensures the
regulatory and scientific content of submissions and their reviews are appropriate.
• Director and/or Deputy Director – the Signatory Authority who signs action
letters and is responsible for content of reviews.
• Regulatory Project Manager (RPM) – Manages the review of submissions,
including reviewing assigned portions, performing quality control checks, capturing review committee communications, and ensures that the review and
review file is administratively complete. The RPM(s) works in tandem with the Chair to ensure that amendments are disseminated to the appropriate reviewers and that a meaningful short summary is entered into eMRP. Throughout the review c ycle, the RPM ensures that all FDA documents are
uploaded into the EDR as they are generated, and the documentation review
memo is maintained in real -time.
• Review Committee – Perform review of all assigned areas of submissions,
participate in review meetings, and perform and document a review of the submission that is scientifically sound and follows Good Review Management Principles. Documentation of a discipline review may be in the form of a
FDA-CBER-2021-5683-0652174
STN 125742/0 First Committee Meeting dated June 3, 2021
First Committee Meeting Agend a 8 primary review, discipline review letter, and a review addendum. It is imperative
that the review committee endeavor to follow the review timetable and finish reviews in a timely manner to allow for adequate supervisory review. It is critical that the review committee keeps management, including senior
management, abreast of any significant review issues.
• Supervisors – Ensure the overall content of reviews are appropriate, all
administrative processing steps are being completed, including database data entry, and all deadlines are met. Reviews and approves employees’ review memorandums and other submission documents per CBER policies and procedures. Supervisory review is considered the Secondary Review.
Documentation of Review
Each discipline reviewer is expected to prepare a written review documenting th eir
review of the file. Timely submissions are imperative to allow time for adequate management review. The following is recommended:
• Identify all materials assigned for review and include an executive summary in
each final or complete review memo.
• List and summarize all material reviewed. The summary should identify each
amendment reviewed and include a list of the submission dates, sections and
page numbers etc. , as applicable.
• A list of questions communicated to the applicant, in letter -ready format, along
with the responses received and reviewed should be clearly identified.
• A recommendation for action, approval or CR, based upon the review summary should be clearly stated.
• Draft reviews should be prepared and discussed with the reviewer’s supervisor and a copy should be given to the Chair by the draft due date(s). Draft reviews should not be uploaded to the EDR.
• Reviewer’s and supervisor’s electronic signatures should be placed on the final
PDF version of the review. A Word version should be attached, and the PDF should be certified and locked to prevent modification. The review should be
entered into eMRP using the date of the Reviewer’s approval stamp as the date
of the memo and the certified PDF should be uploaded into the EDR.
• If a Complete Response (CR) Letter is issued, a complete written review is expected and should reflect all amendments that have been reviewed through the date of the CR decision. The final signed and certified PDF version of the
review should be uploaded by the date of the CR action.
Communication Plan
We can communicate with the applicant via several methods such as telecon, secure e-mail, and letter. The following is recommended:
• All communicatio n regarding requests for information or advice for the applicant
will be coordinated by the RPM s and communicated either via telecon or secure
email. Please contact Ramachandra Naik (Chair), Mike Smith and Laura
Gottschalk (RPMs) if you need to communicate with the applicant.
FDA-CBER-2021-5683-0652175
STN 125742/0 First Committee Meeting dated June 3, 2021
First Committee Meeting Agend a 9 • Although every effort should be made to include the RPMs and/or Chair when
communicating with the applicant, in rare instances it may be appropriate, with permission from Ramachandra Naik and/or Laura Gottschalk and Mike Smith ,
to co mmunicate some requests for information (e.g., something that is relatively
simple) to the applicant via a telecon. Please ensure that all such communication is formally documented (i.e., write up a telecon memo and send it to the RPMs to include in the f ile).
• Formal telecons with the applicant can be scheduled to address issues for which a direct discussion is helpful. The RPMs will coordinate this if/when it is needed.
• Letters can also be used to communicate review issues to the applicant. Although both secure e- mail and letters provide the necessary documentation
for the file, letters are a more formal process than secure e- mail (letters must go
through more levels of supervisory review and concurrence) so typically letters are reserved for communication of policy or serious review issues.
• Please “cc” the Chair on significant e- mail communication and meetings
(internal and external). It is helpful for the Chair to have a general overview of the review status and review issues in the various disciplines (allows for more effective communication with internal upper level management and the applicant when necessary).
• Supervisory concurrence will be sought, when appropriate, prior to sending communications to the applicant (e.g., memos with request for information, providing advice, etc.).
FDA-CBER-2021-5683-0652176