BREAKING NEWS!!!

Pfizer´s Argentinian phoney Study finally exposed!!

CONCLUSIONS REGARDING THE PFIZER TRIAL AT HOSPITAL MILITAR CENTRAL (ARGENTINA)

1st CEI SUPERVISION REPORT Buenos Aires, March 5, 2021

CEI: CIREC INSTITUTION: Central Military Hospital Chief Surgeon Dr. Cosme Argerich

PRESIDENT: Lic. Silvia MargalejoRaffin SUPERVISORS: Claudia Vukotich (DNI: 18,557,971), Cecilia Mariela Serrano (DNI: 21,588,865) and María Laura Garau (DNI 14,566,860)

Supervised period: from December 2019 to date

It is displayed in book No. 1

1.7 Research studies

1.7.1 Types of studies evaluated They have studies in vulnerable populations, children, neonates. Observational studies are reviewed by the teaching committee. Only the protocols of sponsored clinical and observational trials are evaluated.

All other research goes through CODEI

1.9.3 Communication with Management The CEI is dependent on the General Management, two members of the committee are assistants to the general director (institutional figure)

3. REGULATORY CONTROLS

No interviews were conducted with patients or family members .

Vaccine monitoring was carried out with access to the HC, medication safekeeping, and informed consent was done in person, without conclusive evidence that they have supporting documentation. There were many queries regarding the vaccine study (complaints, reports and consultations), without being certain that all of them were recorded in the minutes .

Specifically regarding the breaking of the blind, they have received Amendment 10, which deals with this issue.

Its content indicates that the sponsor is committed to vaccinating all those who received placebo as long as they are available; this prevents – a posteriori – evaluating the side effects of the compound to be tested, since both cohorts will have received the same thing.

It was presented on December 15, 2020 and approved on December 23, 2020

SUPPORTING DOCUMENTATION

4.1 ESSENTIAL DOCUMENTS

Book No. 4 is unsigned.

The file of confidentiality agreements and conflict of interest declarations is not complete.

4.3 CONFORMATION ACCORDING TO ACCREDITATION

Observations

The CV of the secretary Andrea Vale is found

The confidentiality agreement is recorded.

The archive contains the CEI report, Annex 7 and 8 of Resolution 1376.

Lucila Barbara, a member of the previous community, resumed her activity in the CEI, collaborating as secretary for 5 months.

The date of the document is July 22, 2020, but next to the signature it is dated July 22, 2019.

The confidentiality agreement: - The agreements are of different PON according to the accreditation .

Fausto Barbara has no document or signature date.

Juan Sebastián Río incomplete document header Page 21 of 48.

Myriam Scherer incomplete header, date missing.

4.4 MINUTES BOOK Number of minutes books: 4

5. DOCUMENTATION OF THE SELECTED STUDY

NAME: “PHASE 1/2/3, PLACEBO-CONTROLLED, RANDOMIZED, OBSERVER-BLACKED, DOSE-FINDING STUDY TO EVALUATE THE SAFETY, TOLERABILITY, IMMUNOGENICITY, AND EFFICACY OF POSSIBLE SARS-COV-2 RNA VACCINES AGAINST COVID-19 IN HEALTHY ADULTS”

Study Code: C4591001 Sponsor: ICON ClinicalResearch PI: Fernando Polack Team Members: GolzaloPerez Marc, Studycoordinator Virginia Braem. Hospital/Research Center: Hospital General Central Cosme Argerich Subrogated: no PRIISA.BA Registration Code: 2133 Electronic Record: not applicable CEI Risk Categorization: higher risk CCE Risk Categorization: higher risk

Approval 08/14/2020 in PRIISA.BA 622 dated July 14, 2020 of the president's story.

Approval figure in minutes 625 of July 24, 2020 65

4 4.Closing From the story it emerges that recruitment is closed.

There is no record.

5. SUPERVISION OF A CENTER/SUBROGATE/REJECTED STUDY

CEI members were not approved to participate as sub-investigators in the same way as the researchers presented in PRIISA.BA

The CEI did not have on file the list of the research team with the details of the tasks delegated to each one.

The overlapping of functions (investigator and member of the committee that evaluates the actions of the investigators) is a flagrant alteration of the procedures, which renders the whole of them null and void.

5.2 STUDY DOCUMENTATION

Approval of the study:

Inconsistencies are observed in relation to the following points:

The president's account indicates that the study was approved on July 14, 2020; however, there is no record of the approval in the minutes 622 dated July 14, 2020.

The details of the documents received without a decision are observed.

The approval of the protocol and the same documents that appear in minutes 622 are recorded again in minutes 625 of July 24, 2020.

Informed consents: It arises from what was supervised, that the CIREC received and approved the INFORMED CONSENT TEMPLATE FOR PHASE 1/2/3 CLINICAL STUDY 07-01-2019. Version of the sponsor's consent (study) Stage 3, June 30, 2020 - Argentina July 3, 2020 in minutes 622 of July 14, 2020 and that it received and then approved the INFORMED CONSENT TEMPLATE FOR PHASE 1/2/3 CLINICAL STUDY 07-01-2019. Version of the sponsor's consent (study) Stage 3, June 30, 2020 - Argentina July 16, 2020 in minutes 625 of July 24, 2020

However, at PRIISA.BA, they made observations on 08/12/2020 to the INFORMED CONSENT FORM FOR PHASE 1 CLINICAL STUDY

1/2/3 01-Jul-2019 . Sponsor consent (study) version Stage 3,

June 30, 2020 – Argentina

July 3, 2020 , which had already been approved as recorded in the minutes on July 14 and that another subsequent consent had been approved.

The IP responds to the CEI's observation by uploading the same document observed, without modifications.

The IEC approves this document without any revision.

Other documentation in paper format: There is a note of documentation update with the insurance policy dated 07/15/2020 Meridional Seguro N° 406483

Document sealed and signed by the president of CIREC is displayed.

It is approved in minutes 625 dated July 24, 2020

The first patient was admitted on August 6, 2020

Informed consent was used DCI Stage 3 July 16, 2020

Page 31 of 48 Minutes 627 Record of receipt of Conflict Declaration Notes from Drs. Casado and Gelman for study 2133.

They report that they will participate as co-investigators.

5.3 DISCUSSION AND APPROVAL

There was a submission of consent for minors that was not approved.

There was a major deviation related to the administration of the correct dose by non-blinded nurses. This was reported to ANMAT.

The report shows that participants abandoned the study without prior notice.

From follow-up telephone calls, they verified that the participants had antibodies developed to determine whether they had received the vaccine or placebo.

The researchers followed up with patients who dropped out of the study.

The IP submitted a Strategic Recruitment Plan that could not be fulfilled.

Observations by PRIISA.BA X Date: 12/08/2020

Comments were uploaded by CIREC on document: CT05-GSOPRF04 7.0 Phase 1/2/3 Clinical Study Informed Consent Template (July 1, 2019) TMF Document ID: 173.13 (study); 173.07 (country/central); 173.23 (center) Sponsor Consent (study) Version Stage 3, June 30, 2020 – Argentina July 03, 2020 Protocol No.: C4591001 PFIZER CONFIDENTIAL Comments were made after informed consent was approved on 07/14/2020

Responses to requests for changes by PRIISA.BA X Date: 12/08/2020 The researcher uploaded the same document without the modifications requested by CIREC

Approval at meeting X Date: July 24, 2020 Minutes No. 625, Book No. 4, folio 67 of 200 Approval opinion by PRIISA.BA X Date: July 14, 2020 Signed according to POE, but said document does not coincide with the meeting date.

Approval/acceptance by the highest authority Date: July 6, 2020 Signature: Colonel Sergio Maldonado General Director H Grl 601 – HMC ( see at the end ).

Observations:

Inconsistencies are observed between:

record in minutes, approvals and registration and opinion in PRIISA.BA –

Two members of CIREC, Drs. Casado and Gelman, submitted notes declaring a conflict of interest for belonging to the research team. It is recorded in Minutes 627, dated August 5, 2020. –

From the report it emerges that the CIREC did not review the list of the complete investigation team –

That having received the notice of the inclusion of the first patient on August 6, 2020 with the informed consent DCI Stage 3 July 16, 2020, observations were made in PRIISA.BA on August 12, 2020 on: CT05-GSOP-RF04 7.0 Informed consent form for the phase 1/2/3 clinical study (July 1, 2019) Version of the sponsor's consent (study) Stage 3, June 30, 2020 – Argentina July 3, 2020 which was already approved in the minutes. –

That the same document observed was approved in PRIISA.BA without any change because the IP responded to the CIREC observation, uploading the same document observed without changes

5.4 ETHICAL MONITORING AND FOLLOW-UP

Deviation reports: Date: monthly Some receptions are observed in the minutes: Minutes No. 648, Book No. 4, folio 86 of 200

Discussion follow-up: Date: Minutes No., Book No., folio of No record available

Selection of monitor/s: Date: Minutes No., Book No., folio of No record available

Evaluation of the monitoring report: Date: Minutes No., Book No., Decision folio: No record available

Corrective actions: Date: Minutes No., Book No., folio of No record available

Follow-up of corrective actions: Date: Minutes No., Book No., Decision folio:

No record is available Closing of monitoring: Date: Minutes No., Book No., folio of There is no record of receipt of the IP monitoring report at the time of supervision

MINUTES: - Progress reports were not recorded in minutes until October 2020. - The receipt of the EAS is recorded without any other comment.

PROGRESS REPORTS: - Received monthly - It is observed that the report dated August 23, illegible signature date: reports the incorporation of 4,501 patients.

Details a major deviation in the administered dose of the vaccine that occurred on August 23, 2020, affecting multiple participants due to human error (data that arises from a field investigation organized by the sponsor regarding the major deviation).

The temporary pause in patient recruitment and staff training is described

Since this last procedure was essential BEFORE starting the test.

The participants who were affected were 52 due to the administration error (the error occurred in the dilution that resulted in an estimated dose of approximately 58 mcg of BNT162b2 (SARS-CoV2 mRNA Vaccine), instead of the dose selected for the study of 30 mcg . Pfizer and BioNTech recommended to the PI in their note to inform the participants what happened. They emphasize that the safety of the participants is the priority, emphasizing the importance of follow-up, beyond the acceptance of the second dose of the vaccine.

The sponsor generates a document to inform the participant and offer to receive the second dose: ADDENDUM TO INFORMED CONSENT FOR A PHASE 1/2/3, PLACEBO-CONTROLLED, RANDOMIZED, OBSERVER-MASKED, DOSE-FINDING STUDY TO EVALUATE THE SAFETY, TOLERABILITY, IMMUNOGENICITY AND EFFICACY OF POSSIBLE SARS-COV-2 RNA VACCINES AGAINST COVID-19 IN OLDER ADULTS. ASSOCIATED CONSENT JULY 30, 2020. ICD 10 SEP 2020 - From EFCA JANUARY 3 TO FEBRUARY 2, 2020 EFCAS 5.2 V2 PAGE 2 12315324 One death is reported .

It is noteworthy that there was no follow-up or request for information from the CEI.

From the report it emerges that the study has closed recruitment.

The information that was not in the file at the time of the visit is pending receipt.

The report shows that CIREC did not follow up on the cases or request additional information.

MONITORING - The visit is recorded. Date: September 9, 2020. Minutes No. 632, Book No. 4, folio of 72 OF 200

- There is no record of the selection of the study or the designation of the monitors

- There is no record of the discussion of the results or findings of the monitoring in the minutes.

- It was not confirmed that those who took the IC were delegated for that purpose.

It is recorded in minutes as an audit, although the results or decisions are not recorded.

5.5 OTHER AUDITS/COMPLAINTS

Audit EMEA, FDA, etc: NO It is recorded in IF.2020-77056986-APNDERM#ANMAT said that there was an audit, that reports were issued that required responses. Reference: Form EFCA5.1 Period between: 10/03/2020 and 11/02/2020 Dated November 10, 2020

Other audits: Date: Act No., Book No., Complaints folio X Date: Act No., Book No., Observations folio: The report shows that there were requests to open the blind, but they are not recorded in the minutes.

6. FINDINGS

The following findings were recorded during monitoring:

1. OPENING MEETING It emerges that the CIREC should be expanded, especially in relation to administrative issues.

Depending on the workload, at least two administrators with knowledge of computer tools are required and preferably they are trained in research ethics/good clinical practices and are trained in the use of the PRIISA.BA platform.

2. REGISTRATION IN PRIISA.BA Difficulties were observed in the use of PRIISA.BA.

However, improvements in registration and use have been noted in the adaptation to use stage.

3. REGULATORY CONTROLS Poor regulatory control of the supervised protocol and other protocols approved by CIREC was observed.

The information has been monitored from the record in the minutes book No. 4.

4. SUPPORTING DOCUMENTATION Minutes: discrepancies arise in the records.

The information recorded in the minutes is insufficient. Some of the documentation was not accessible and/or organized.

5. SUPERVISION OF A STUDY OF THE APPROVAL CENTER: Serious discrepancies were observed between the records of minutes, opinions and registration in PRIISA.BA.

- Observations were made in PRIISA.BA to a consent on August 12, 2020. - That document had been approved in minutes on July 14, 2020.

- The researcher uploaded the same document observed as a response without any changes. - The IEC approved without checking the changes.

ETHICAL MONITORING/AUDIT: From the supervised documents it appears that they have not carried out monitoring in accordance with the SOPs.

The forms approved by CIREC that were in the monitoring file but were not completed were not used to obtain the data.

The record of the data obtained was observed.

The report was sent to the Principal Investigator, dated October 30, 2020, Signed by TC (R) EnfProf Silvia Margalejo. It states that the monitoring process was carried out by TC (R) Silvia Margalejo, Dr. Emilio Batagelj and lawyer Mercedes Ramírez.

The codes for the 26 revised consents and 11 with signed reconsents are detailed.

There are no versions or revised dates.

Nor the current versions approved at the time of the signatures.

It was not reviewed whether professionals were delegated to take informed consent.

Verification of medical records: they were given access to the computerized medical records system.

There were no comments

Drug circuit verification: from the information provided on the error in drug administration and unblinding of participants, it is indicated that more non-blind personnel were incorporated for the randomization check and drug preparation. Signed by TC (R) EnfProf Silvia Margalejo FILE: Some of the documentation was not organized and/or accessible. The CEI requested the IP for documentation that had to be controlled in order to monitor the study as indicated by the supervision. RESEARCH TEAM: At the time of the visits, the file did not have the forms for delegating duties or certifications for the members of the research team. A researcher, Dr. Gonzalo Pérez Marc, and a Study Coordinator, Virginia Braem, were approved by PRIISA.BA as a team. They did not verify the correct delegation for taking informed consent.

From the information received, it appears that other participants in the research team carried out tasks without being delegated and/or trained.

INFORMED CONSENTS/ADDENDA/INFORMATION FOR PREGNANT COUPLES

Informed consent for phase 1/2/3 clinical study. ICD version date: stage 3, 07/03/2020 ICD version. Stage 3, 07/03/2020 07/14/2020 PRIISA BA 622 07/14/2020 Signed by Mercedes Ramírez.

The document is detailed in the record of minutes 622 dated July 14, 2020, but there is no record of approval.

Informed consent form for phase 1/2/3 clinical study. ICD version date: stage 3, 07/16/2020 ICD version. Stage 3, 07/16/2020 07/23/2020 625 07/24/2020 Signed by Silvia Margalejo.

Amendment to Protocol V4_30 June 2020 approved The opinion is dated prior to the meeting at which the consent is approved.

Informed consent form for phase 1/2/3 clinical study. July 24, 2020. Date of the ICD version: Phase 2/3, 07/30/2020 ICD version. Stage 3, 07/30/2020 Signed by Silvia Margalejo. Request a copy of the opinion and the minutes in which the record is recorded.

Informed consent form for phase 1/2/3 clinical study Study level, phase 2/3, September 9, 2020, Argentina phase 2/3, September 9, 2020, customized for center 1231 Version 09/09/2020 20/9/2020 636 20/9/2020 In the opinion dated September 20, 2020, it is stated that in the minutes dated September 20, 2020 (Minutes 636) it is approved.

There is no record of approval of the consent document. Only Amendment 6 is approved.

Dose error. Clinical trial informed consent addendum. ICD addendum version date: 09/22/2020 ICD addendum version: 09/22/2020 9/25/2020 638 9/25/2020 Signed by Silvia Margalejo. No comments C4591001_Informed consent form for phase 1/2/3 clinical study Study level, phase 2/3, October 7, 2020, Argentina phase 2/3, October 8, 2020 (Administrative Change A), customized for center 1231 - 4444 Version 10/08/2020 11/19/2020 646 11/18/2020 Not verified Request C4591001_

Informed Consent Form for Phase 1/2/3 Clinical Study Study Level, Phase 2/3, October 7, 2020, Argentina Phase 2/3, October 8, 2020 (Administrative Change A), customized for your site Pregnant Partner Information Disclosure Form – Argentina as per Version 3.0 Effective Date July 15, 2016. C4591001 / Argentina November 11, 2020 Version 3.0 07/15/2020. Effective 11/11/2020 11/19/2020 646 11/18/2020 Signed by Silvia Margalejo.

Opinion dated 11/19/2020. The date of the meeting 11/18/2020 appears in the opinion, recorded in Minutes 646 Informed consent form for a phase 1/2/3 clinical study. Date of the ICD version: Phase 2/3, 12/09/2020 ICD version: 12/09/2020 Signed by Fausto Barbara Request a copy of the record in the minutes and opinion

Informed consent appendix for the study. Date of the ICD appendix version: 09/12/2020 Version of the ICD appendix: 09/12/2020 Signed by Fausto Barbara

Request a copy of the record in the minutes and the approval opinion Amendment 10 to the Protocol Dated 01/12/2020 651 23/12/2020 No comments Request a copy of the approval opinion

Addendum to informed consent dated January 5, 2021, personalized for center 1231-4444 (final copy) Dated 1/5/2021 1/20/2021 655 1/20/2020 Signed by Silvia Margalejo.

Comments: An opinion dated prior to the meeting date was supervised. Amendment 10 specifically addresses unblinding and vaccination of participants.

MONITORING OF REPORTS: The president's account shows that they receive the monthly progress reports (EFCA), but they were not evaluated, nor were decisions made based on the information.

Regarding the follow-up of participants who were affected by the medication error, CIREC received the information, but there was no subsequent follow-up.

The error occurred in the dilution, resulting in an estimated dose of 58 mcg of BNT162b2 (SARS-CoV2 mRNA Vaccine) being administered instead of the selected study dose of 30 mcg.

From the lists received and evaluated by this supervision, it emerges that: Participant 12313414 is registered in the EFCA 5.2 V2 23/08/2020 list but not in the List and status of patients with medication errors

Participant 12311057 who has signed an informed consent (received), is not listed in the EFCA 5.2 V2 08/23/2020 or in the List and status of patients with medication errors –

The supervision has not received the consents of 12313446, 12313503, 12313533, nor of 12313414 for which further information is requested.

SECURITY REPORTS.

The registration in the minutes is done as follows: "The following documentation is received and evaluated: - title of the study and SAE Reports. For other studies: Safety reports related to the protocols (...)" and 3 study codes are detailed.

There is no record of any evaluation or analysis (Minutes 632, folio 72-73/200).

Regarding the follow-up of participants who were affected by the medication error, CIREC received the information, but there was no subsequent follow-up.

The error occurred in the dilution, resulting in an estimated dose of 58 mcg of BNT162b2 (SARS-CoV2 mRNA Vaccine) being administered instead of the selected study dose of 30 mcg.

From the lists received and evaluated by this supervision, it emerges that: − Participant 12313414 is registered in the EFCA 5.2 V2 23/08/2020 list but not in the List and status of patients with medication errors

Participant 12311057 who has signed an informed consent (received) is not listed in the EFCA 5.2 V2 08/23/2020 or in the List and status of patients with medication errors − Supervision has not received consents from 12313446, 12313503, 12313533, or 12313414 for whom further information is requested

LIST AND STATUS OF PATIENTS WITH MEDICATION ERRORS

ID SIGNATURE ADDENDUM: 2nd dose received status in study ci received 03/15/2021 listed in efca 5.2 v2 08/23/2020 observations 12313414 additional information, 12313446 i continues in study not received if requested, 12313503 yes yes continues in study not received requested, 12313533 i continues in study not received if requested. 12313503 continues in study not received requested, 12313533 continues in study not received if requested,

. Analysis of the addenda signed by the participants in the dose administration error and delegation of functions list (CCE MSGC)

12313429 10/09/2020 Mirta Becerra Pons 15/09/2020 19/08/2020 15/09/2020, 12313456 10/09/2020 Lionel Schuster (illegible) 15/09/2020 17/08/2020 15/09/2020.

Observations: Sub-Investigators Mirta Becerra Pons and Lionel Schuster were not delegated to take consents at the time of signing.

Cases of pregnancy, pregnant couple and spontaneous abortions reported as SAE,

It is noted that only the reports were received, but that there was no follow-up or request for additional information from the CEI. This supervision has requested additional documentation on the case.

A report dated March 25, 2020 was received describing what was evaluated by the CIREC medical members who did not participate in the study as sub-investigators. Among the data evaluated in the HC of pregnant participants and/or pregnant couples, they report that: “All cases were followed up, with records of the studies corresponding to any pregnancy, including laboratory reports, ultrasounds or any other complementary study.”

However, it is not reported in which branch each one was assigned (vaccine/placebo). In relation to the EFCA signed on February 12, 2021 by Dr. Polack for the period: JANUARY 3 TO FEBRUARY 2, 2020 Participant 12315324, one death is reported as discontinuation.

This supervision requested additional documentation.

A note signed by the president of CIREC, dated March 23, 2021, and a summary of the Clinical History Summary - Volunteer ID: 12315324 (Dr. Ignacio Esteban, Medical Coordinator of the Surveillance Team, unsigned) was received.

The event was not opened blind at the start because the treating physicians at the institution where the patient was treated did not consider that this information would modify the treatment/conduct to be followed.

The blind was opened at the request of the patient's sister, with the consent of the principal investigator. It was confirmed that she was in the PLACEBO group (cohort that also received the compound under study). There was no follow-up of the case by CIREC.

BLIND OPENING

A note signed by the president of CIREC, dated March 23, 2021, is received. Signed by TC (R) EnfProf Silvia Margalejo. It is stated in point 1. Opening of the blind. a. Total number of patients who requested opening of the blind: 5503 b. Amount of placebo: 2697 c. Number of vaccinated: 2694 d. Number of patients who refused to be vaccinated: 3

7. RISK

CIREC has not performed any analysis of safety reports with deviations and RAMSI.

At the time of closing the supervision, the information on the unblinding and compliance with the participants' access to vaccination had not been fully analyzed. They had partial information that was transmitted verbally.

7.1 SUMMARY OF FINDINGS

Not included:

1. OPENING MEETING

6. SUPERVISION OF A CENTER/SUBROGATE/REJECTED STUDY

7.2 FINDINGS-SEVERITY OF NON-COMPLIANCES

According to Provision 404-DGDIYDP-2019. “General guidelines for assessing the seriousness of non-compliance by Research Ethics Committees in the City of Buenos Aires”

FINDING CATEGORIZATION POINTS:

Findings Minutes Book without signature and/or pagination and/or with insufficient data registration. MINOR Absence of essential IEC documents MINOR Deficiencies in the filing of documentation for the studies evaluated (in the event that the documents are not available and/or arranged chronologically in the same file). MINOR Inconsistencies between the dates of the opinions and the approval dates listed in the Minutes. MINOR Lack of timely control and/or poor follow-up of serious adverse events that occurred to participants in the protocols approved by the IEC SERIOUS Failure to comply with the monitoring duty in studies with greater than minimum risk. SERIOUS Lack of follow-up of research with greater than minimum risk (progress/final report) SERIOUS Inaction by the IEC in the face of irregularities that may put the vulnerable population or people in vulnerable situations under investigation at risk. SERIOUS Absence of relevant documentation of research with greater than minimal risk (IEC opinions, reports of serious adverse events, authorizations from regulatory entities). SERIOUS

8. INDICATIONS OF CORRECTIVE ACTIONS

Based on the findings arising from the supervision, the following indications are made:

INDICATIONS

Mandatory compliance actions with follow-up, Prepare an additional report to answer the supervision questions., Adaptation Plan focused on the findings CEI retraining Attach supporting documentation

The IEC must:

8.1 Prepare an additional report to respond to the supervision questions and report requirements, detailing each point answered.

8.1.2 Did CIREC verify the reliable communication to the 58 patients who participated in the dose administration error? Attach a copy of the visit in which the information was provided in HC.

8.1.3 Send supporting information:

8.1.4 DOCUMENTS PENDING SUBMITTAL: Study recruitment closing report.

8.1.5 FURTHER INFORMATION. a) Send a copy of the minutes stating the entry of the FORM EFCA5.2 v2 8/23/2020 b) Clarify the differences observed that arise from the analysis between: c) List and status of patients with medication errors, list of FORM EFCA5.2 v2 8/23/2020 and informed consents (addendum) signed by the participants who received information and who agreed to receive the 2nd. dose d) Participant 12313414 is registered on the EFCA 5.2 V2 23/08/2020 list but not on the List and status of patients with medication errors. e) Participant 12311057 who has signed an informed consent, received it, is not registered on the EFCA 5.2 V2 23/08/2020 or on the List and status of patients with medication errors. f) Send a copy of the consents of 12313446, 12313503, 12313533, 12313414.

8.1.6 Expand information with a copy of reports sent and requested by ANMAT on patient 12311057

8.1.7FURTHER INFORMATION.

In the LETTER from Pfizer to IP Dr. Polack, dated January 5, 2021. Follow-up to the on-site control visit carried out from December 14, 2020 to December 18, 2020, it is reported that 439 reports are pending to the CEI. a) Question: Did the CIREC carry out the controls on the pending ones? b) Send supporting documentation indicating the resolution of this point

8.1.8 FURTHER INFORMATION. The List and Status of Patients with Medication Errors states that patient 12313492 withdrew consent on 01-05-2021. However, in the EFCA dated 12 Feb 2021 for the period from 01-03-2021 to 02-02-2021, this patient's withdrawal of consent does not appear. a) Question: Is the patient continuing in the study or did he/she withdraw consent? b) Send a copy of information clarifying whether the patient withdrew consent or continues in the study (attach a copy of the CI).

8.1.9 FURTHER INFORMATION Follow-up of pregnant participants and pregnant couples. a) Did the IEC become aware if any pregnant participant and/or participant with spontaneous abortion requested unblinding? And what were the results? Attach supporting documentation.

8.1.10 DOCUMENTS APPROVED BY CIREC A copy is requested: a) Copy of the approval opinion and minutes of: Informed consent form for phase 1/2/3 clinical study. July 24, 2020. INN version date: Phase 2/3, 07/30/2020 b) Copy of approval report: Informed consent form for phase 1/2/3 clinical study Study level, phase 2/3, September 9, 2020, Argentina phase 2/3, September 9, 2020, customized for center 1231 c) Copy of C4591001 Informed consent form for phase 1/2/3 clinical study Study level, phase 2/3, October 7, 2020, Argentina phase 2/3, October 8, 2020 (Administrative Change A), customized for center d) Copy of approval opinion and report of: Informed consent form for phase 1/2/3 clinical study. Date of DCI version: Phase 2/3, 09/12/2020 e) Copy of approval opinion: Amendment 10

8.1.11 ETHICAL MONITORING a) Was it verified that the signed versions were valid at the time of signature? b) Was it verified that the professionals who took the consents were delegated for this purpose? c) Was it verified that the dates of the signing of the consent coincided with the record of participation in the HC? d) Was it verified that the professional who developed the HC was the same one who took the IC?

8.1.12 Send a copy of the Memo with recommendations from the safety monitoring committee and DCM, dated 09/30/2020 8.1.13 Send a copy of the Memo with recommendations from the safety monitoring committee and DCM, dated 11/25/2020 8.1.14 EXPANSION OF INFORMATION ON OPENING OF THE BLIND. Envelope signed by the president of CIREC, dated March 23, 2021, Signed by TC (R) EnfProf Silvia Margalejo When it is mentioned that they were vaccinated: a) Does it mean that those who were assigned to the placebo arm were vaccinated? b) What is the total number of patients vaccinated with the study product? 8.1.15 Complete the IEC file with conflict of interest declarations and confidentiality agreements 8.3 Present an Adaptation Plan focused on the findings, observing all points 8.4 IEC Retraining (according to the findings) 8.5 Receive Supervision Follow-up with all the indications fulfilled

9. CONCLUSIONS

9.1 Acknowledge receipt of this report within 7 (calendar) days of being notified. 9.1.2 Send a response to the indicated points within 10 (calendar) days of being notified. 9.2 The information must be sent to: ccesupervisiones@gmail.com

COMMUNICATION OF CIREC SUPERVISION RESULTS

CIREC Institutional Review Committee for Clinical Trials Fri 05/28/2021 8:02

To: cceticainvestigacion@buenosaires.gob.ar CC: dir_med@hmc.mil.ar ; Cecilia Serrano Maria Laura Garau Claudia Vukotich

On Fri, May 28, 2021 at 6:03 PM, cceticainvestigacion@buenosaires.gob.ar wrote:

Attached is the Official Communication, the final report of the supervision and the Provision of provisional revocation of the accreditation of the Institutional Committee of Clinical Trials (CIREC)

CEI SUPERVISION MONITORING REPORT Buenos Aires, August 20, 2021

FINDINGS

1. REGULATORY CONTROLS

2. SUPPORTING DOCUMENTATION

3. SUPERVISION OF A STUDY BY THE CENTER Regarding the supervised protocol “PHASE 1/2/3, PLACEBO-CONTROLLED, RANDOMIZED, OBSERVER-MASKED, DOSE-FINDING STUDY TO EVALUATE THE SAFETY, TOLERABILITY, IMMUNOGENICITY AND EFFICACY OF POSSIBLE SARS-COV-2 RNA VACCINES AGAINST COVID-19 IN HEALTHY ADULTS”, CIREC requested information on the closing of recruitment.

The sponsor informed him that regardless of what the IP had communicated, the protocol was still open and he would be notified in due course.

The amendments have been evaluated, observed and approved and at the time of the visit they had one under evaluation.

4. SUPERVISION OF A STUDY CENTER/SUBROGATE/REJECTED Not applicable

5. RISK

During this last visit, Brigadier General Sergio Maldonado was present and expressed his support for the committee. It should be noted that the support of the Director of the Institution is not a reliable guarantee for its continuation.

Findings : -

The lack of an informed consent record was detected in the minutes, which record the approval of the study .

In the protocol supervised in which ethical monitoring was carried out, as established in the adequacy plan, the discussion of the findings was not recorded in the minutes. Recommendations - CIREC should avoid reiterating the findings on recording in minutes in future studies.

- Regarding PRIISA.BA, when CIREC receives a REVIEW, it must respond as soon as possible. Please verify this pending matter in your approved studies.

- Those studies approved by subrogation must enter the CIREC, to be followed and monitored by its accredited committee.

- It should be noted that those studies that are being evaluated in other CEIs and that, at the time of accreditation registration, have not been approved or are close to being approved by subrogation must enter the CIREC for evaluation and eventual approval.

- Regarding the protocols that CIREC receives for evaluation, remember that the committees are accredited and have the responsibility of evaluating, approving or rejecting all research carried out in the institution, except for those that do not require approval from a CEI. Conclusions

- The adaptation plan sent in response has been duly completed. - CIREC members have begun the training process in research ethics and good clinical practices.

- And with regard to the monitoring and follow-up of studies, a positive change is observed. –

This Supervision considers that the CEI CIREC “…has satisfactorily resolved the findings…”

Buenos Aires, Wednesday, May 26, 2021

Reference: EX-2021-06522187- GCABA-DGDIYDP SEEN: Law No. 3301, Decree No. 58/2011, Resolution No. 716 / MSGC / 2011, and Electronic File No. EX-2021-06522187- GCABA-DGDIYDP, and

THE DIRECTOR GENERAL OF THE GENERAL DIRECTORATE OF TEACHING, RESEARCH AND PROFESSIONAL DEVELOPMENT ORDERS:

Article 1.- The accreditation of the Institutional Committee for the Review of Clinical Trials (CIREC) is provisionally revoked for a period of 90 (ninety) calendar days, during which it may not issue opinions for new projects, and must maintain the monitoring of those projects that have already been approved as of the date of signature of this document. Article 2.- It is noted that this measure may be extended in the event that the CIREC does not prove, prior to the expiration of the same, that it has complied with the indications indicated in the report that appears as an Annex under No. IF IF-2021-15839423-DGDIYDP. Article 3.- Publish in the Official Gazette of the Autonomous City of Buenos Aires. Notify the Institutional Committee for the Review of Clinical Trials (CIREC). Once complied, file.

Ref: Evaluation of response to the CIREC final supervision report

Buenos Aires, July 21, 2021

President TC (R) EnfProf SILVIA MARGALEJO RAFFIN

We are writing to you to send you the evaluation and conclusions regarding your response to the final monitoring report.

4. On the adaptation plan

Training – Retraining: They must complete the training over the next few months and send the corresponding certificates upon completion.

CIREC response: CEI members have begun to provide training in research ethics. Details are provided below.

Status: PARTIALLY RESOLVED 1 Partially resolved until supporting documentation is verified

5. Audits:

b) Prepare a remote ethical audit/monitoring procedure, in case the health situation does not allow for the monitoring found in the current PON.

In any case, CIREC must take into account what information it will request in order to comply with the protection of subjects participating in approved research, particularly in special cases where the current audit procedure is not sufficient.

The CEI must respect what is established in its PON for carrying out the

audits/ethical monitoring, and make use of the annexes approved therein. If necessary, information will be added in observations within the same models.

CIREC response: The CEI responds that remote monitoring will be carried out on protocols that have electronic HC or use of remote access platforms. This will be implemented according to the health situation and may vary in the monitoring calendar.

scheduled. This point is expanded in the adaptation plan. The CIREC PON does NOT have an ethical monitoring form, so the preparation of ANNEX to the PON Item 14 and 15 of the PON Version 9.0 Dated January 29, 2020 begins.

Status: PARTLY RESOLVED 3

5. MANDATORY COMPLIANCE INDICATIONS WITH FOLLOW-UP

CIREC must:

2. Send the pending documentation.

Status: PARTIALLY RESOLVED 4 . Partially resolved until supporting documentation is verified

5. Especially for high-risk studies, early phases, participation of healthy volunteers, forecast of high recruitment and/or incorporation of population

vulnerable, the CIREC must analyze its operational capacity from both the point of view

administrative as well as to carry out the correct follow-up and monitoring that guarantees the

protection of research participants prior to their approval. The IEC

must request the incorporation of the necessary resources for this purpose before whom

corresponds.

Status: PARTIALLY RESOLVED 5 Partially resolved until supporting documentation is verified

CONCLUSIONS

Once the changes in the conformation have been communicated, the CIREC must initiate the “accreditation due to change of conformation” process. The process must be completed at the same time as the end date of the suspension. In order to begin activities with the new conformation approved by accreditation.

Changes in the CIREC PON will be evaluated in a timely manner during the “accreditation due to expiration of term” process.

What has been reported as completed by CIREC, what has been partially resolved and what has been declared in the new adaptation plan will be reviewed during the monitoring visit(s).

2/6/2021 Email: cceticainvestigacion@buenosaires.gob.ar - Outlook https://outlook.office.com/mail/deeplink?popoutv2=1&version=20210524004.11 1/2 Re: Communication of the result of the CIREC supervision CIREC Institutional Review Committee for Clinical Trials Sat 05/29/2021 6:33 AM To: cceticainvestigacion@buenosaires.gob.ar CC: dir_med@hmc.mil.ar ; GABRIEL ALEJO GONZALEZ VILLA MONTE

TC (R) Enf Prof Silvia Margalejo Raffín President CIREC Institutional Committee for the Review of Clinical Trials H Grl 601 Central Military Hospital "Cir My Dr Cosme Argerich

On Fri, May 28, 2021 at 6:03 PM, cceticainvestigacion@buenosaires.gob.ar () wrote:

Dear All:

According to what was reported in the meeting held today through the Zoom platform, the Official Communication, the final report of the supervision and the Provision of provisional revocation of the accreditation of the Institutional Committee of Clinical Trials CIREC are attached.

Dr. Maria Laura Garau Member of the Board

Central Committee on Research Ethics

DGDYDP-Ministry of Health

Monastery 480 CABA

CIREC Institutional Review Committee for Clinical Trials March 27, 2021 , 6:50 AM To: Claudia Vukotich, Central Ethics Committee Supervisions MSGC

As requested, we report the evaluation of the pregnancy cases that arose in the protocol: "Phase 1/2/3, placebo-controlled, randomized, observer-blinded, dose-finding study to evaluate the safety, tolerability, immunogenicity and efficacy of potential SARS-COV-2 RNA vaccines against COVID-19 in healthy people." The medical members who did not participate in the study reviewed the 16 Medical Records (HC) of the participants involved as detailed:

UBJECT ID Start Date Resolution Type 1 12313879 12/9/2020 Ongoing Pregnancy 2 12314372 1/12/2020 Ongoing Pregnancy 3 12314531 9/30/2020 Ongoing Pregnancy 4 12311387 11/7/2020 Ongoing Pregnancy 5 12311448 11/9/2020 Ongoing Pregnancy 6 12314134 12/7/2020IVE knowledge 3/8/21 7 12312529 11/30/2020 Ongoing Pregnancy 8 12315677 12/12/20 LMP IVE 9 12312378 12/24/2020 Ongoing Pregnancy 10 44441435 12/30/20 LMP Negative Beta Sub Unit 11 12313998 12/25/20 LMP Miscarriage 12 12314308 12/10/2020 Ongoing Pregnancy 13 12311812 01/05/21 LMP Miscarriage 14 44441979 9/25/2020 CI Withdrawal 15 12314059 8/25/2020IVE 16 12312205 9/29/2020 Miscarriage.

1. In all cases, in the visits prior to pregnancy, there are records that the importance of using safe contraceptive methods was explained to the mother and that the use of these methods was recommended. In particular, those who habitually only used barrier methods.

2. There is no record in all HC of what contraceptive method was used at the time of pregnancy.

3. All cases were followed up, with records of studies corresponding to any pregnancy, including laboratory reports, ultrasounds or any other complementary studies.

4. Inconsistencies were found in the HC regarding pregnancy monitoring.

ADDENDUM I

ANMAT REPORT ADDRESSED TO NATIONAL DEPUTY RUBÉN H. MANZI

Argentine Republic - National Executive Branch

2021 - Year of Tribute to the Nobel Prize in Medicine Dr. César Milstein

Note

Number:

Reference: Request for public information - National Deputy RUBÉN HORACIO MANZI - EX-202101607578-APN-ANMAT#MS

To: RUBEN HORAZIO MANZI (.),

With Copy To: Natalia Soledad Jakubowski (DRI#ANMAT), Martín Gonzalo DE BIASE (DRI#ANMAT), Estefania Mariel Gerez (ANMAT#MS), Carla Plauti (ANMAT#MS),

To my greatest consideration:

I am pleased to address you in my capacity as ANMAT's public information access officer regarding the request made by National Deputy RUBÉN HORACIO MANZI under the terms of Law No. 27,275 that regulates the Right of Access to Public Information, which was processed by EX-2021-

01607578-APN-ANMAT#MS

In this regard, I bring to your attention that in order to provide a satisfactory response, the National Institute of Medicines of this National Administration was consulted through note NO-2021-01854004-APN- ANMAT#MS, who prepared the following technical report, by note NO-2021-07628565-APN-INAME#ANMAT, and it is attached embedded herein, transcribed below:

“1- Linked to the information from the pivotal study that generated the authorization of the vaccine investigated and produced by the Pfizer laboratory, to prevent SARS CoV2 infection, I request that you report whether among the adverse events, mild, moderate or severe, any case of intolerance was recorded that could be related to Alpha-1 Antitrypsin deficiency (DAAT).

To date, the deadline for submitting preliminary results reports is in effect, and this is the situation; there are no reports with this information.

2- In the same sense, I request to be informed if the technical-scientific body of ANMAT has any information referring to the fact that vaccines that act on messenger RNA could generate adverse effects in the population that genetically presents Alpha-1 Antitrypsin deficiency, in any of its allelic variants and, if so, if the research protocols presented to you foresee any special measures to detect these cases or to treat possible complications.

In the analysis of the protocol, all available information has been taken into account. It should be noted that this is part of the evaluation procedures, and these parameters consulted are part of the selection processes for the population to be included.

It should be added at this point and again that the deadlines for submitting preliminary reports and analyses are in force.

3- I also request that information be provided on whether any deaths were reported during the Phase III study conducted by Pfizer, whether or not they were linked to vaccination (as a concomitant event).

Reiterating that the schedule for presenting results is in force; notwithstanding this, there are no reported deaths.”

Without further ado, best regards.

ADDENDA II

DECLASSIFIED REPORT FROM PFIZER FILES CORRESPONDING TO THE MULTICENTER STUDY (ARGENTINA, BRAZIL, USA), AT THE REQUEST OF JUDGE MARK T. PITTMAN

ADDENDUM III

FINAL CONSIDERATIONS

Errors by Pfizer:

1) International standards for categorizing the volunteers involved were not followed.

2) There was no timely information about pregnant volunteers at the time of the trial.

In this regard, it is clear from the above reports that 4 of the 12 pregnant women had abortions during the trial.

3) The observations made by the Supervisory Committee were not taken into account.

4) The results of each particular case were not accurately transcribed.

5) The few transcribed cases were not initialed and were therefore null and void.

6) The same compound was administered – at different stages – to both cohorts, causing the incidence of side effects to be statistically diluted.

7) The trial was based on apocryphal and/or one-sided opinions, lacking scientific basis and/or without supporting documentation.

Errors by the Central Military Hospital:

1) Quality controls were not carried out on the trial in question.

2) The Oversight Committee was moved, distorting its actions.

The absence of a Committee invalidates everything carried out afterwards, and “the endorsement of the Hospital Director” is not a valid argument for the continuation of the trial.

Errors by ANMAT:

1) A trial involving human beings was authorized without the proper ethical and methodological standards.

Since no centre was designated for the referral of patients during interruptions in the trial, its continuation should not have been approved (provision 6766/2010).

Conducting a multicenter trial (Brazil, Argentina, USA) implies observing the same procedural standards in all the centers involved.

In the United States, participating volunteers received financial compensation for their participation; in Argentina, such compensation did not exist.

2) Mishandling alarms were hidden during the course of the trial.

3) The deaths during the clinical trial were not disclosed, and even lied about.

4) The same thing happened with the abortions that occurred during it.

Errors by the Ministry of Health of CABA:

1) The test was declared satisfactorily completed, without any detailed evaluation of it being recorded.

2) This report was cited without the joint and majority signature of the members of the Evaluation Committee.

ROBERTO R. HIRSCH HECTOR E. CARVALLO