Pursuant to section 23(1) of the Medicines Act 1981, the Minister of Health hereby provisionally consents to the sale, supply or use in New Zealand of the new medicines which were referred to the Minister of Health under the provisions of section 24(5) of the Act and set out in the Schedule hereto:

Schedule

Provisional consent is granted until 3 November 2023.

This consent is given subject to the following conditions.

The New Zealand Sponsor must fulfil the following obligations within the timelines specified, which may be altered by mutual agreement with Medsafe:

1. The New Zealand site of batch release will only release batches for distribution in New Zealand once the sponsor has verified that the shipping temperature profile meets specifications.
2. Provide Certificates of Analysis to Medsafe for the first three batches of vaccine of each presentation intended to be distributed in New Zealand, prior to distribution.
3. Provide independent batch certification, such as UK National Institute for Biological Standards and Control (NIBSC) certification, EU Official Control Authority Batch Release (OCABR) certification, Australian TGA batch release assessment, or any other certification agreed with Medsafe, on request for all batches distributed in New Zealand.
4. Reassess and revise the finished product specifications acceptance limits for RNA and lipid content as further data becomes available. Due date: 31 December 2022.
5. Provide any reports on the duration of efficacy and the requirement for booster doses within five working days of these being produced.
6. Provide any reports on efficacy including asymptomatic infection in the vaccinated group, vaccine failure, immunogenicity, efficacy in population subgroups and results from post-marketing studies, within five working days of these being produced.
7. Provide the final Clinical Study Reports for Study C4591007 within five working days of these being produced.
8. Provide Periodic Safety Update Reports according to the same schedule as required by the EMA.
9. Provide monthly safety reports, as well as all safety reviews they conduct or become aware of.
10. Perform the required pharmacovigilance activities and interventions detailed in the agreed RMP and any agreed updates to the RMP. An RMP should be submitted at the request of Medsafe or whenever the risk management system is modified, especially as the result of new information being received that may lead to a significant change to the benefit/risk profile or as the result of an important milestone being reached.

Provisional consent is granted until 3 November 2023.

This consent is given subject to the following conditions.

The New Zealand Sponsor must fulfil the following obligations within the timelines specified, which may be altered by mutual agreement with Medsafe:

1. The New Zealand site of batch release will only release batches for distribution in New Zealand once the sponsor has verified that the shipping temperature profile meets specifications.
2. Provide Certificates of Analysis to Medsafe for the first three batches of vaccine of each presentation intended to be distributed in New Zealand, prior to distribution.
3. Provide independent batch certification, such as UK National Institute for Biological Standards and Control (NIBSC) certification, EU Official Control Authority Batch Release (OCABR) certification, Australian TGA batch release assessment, or any other certification agreed with Medsafe, on request for all batches distributed in New Zealand.
4. Reassess and revise the finished product specifications acceptance limits for RNA and lipid content as further data becomes available. Due date: 31 December 2022.
5. Provide any reports on the duration of efficacy and the requirement for booster doses within five working days of these being produced.
6. Provide any reports on efficacy including asymptomatic infection in the vaccinated group, vaccine failure, immunogenicity, efficacy in population subgroups and results from post-marketing studies, within five working days of these being produced.
7. Provide the final Clinical Study Reports for Study C4591001 and Study BNT162-01 within five working days of these being produced.
8. Provide Periodic Safety Update Reports according to the same schedule as required by the EMA.
9. Provide monthly safety reports, as well as all safety reviews they conduct or become aware of.
10. Perform the required pharmacovigilance activities and interventions detailed in the agreed RMP and any agreed updates to the RMP. An RMP should be submitted at the request of Medsafe or whenever the risk management system is modified, especially as the result of new information being received that may lead to a significant change to the benefit/risk profile or as the result of an important milestone being reached.

Provisional consent is granted until 3 November 2023.

This consent is given subject to the following conditions.

The New Zealand Sponsor must fulfil the following obligations within the timelines specified, which may be altered by mutual agreement with Medsafe:

1. The New Zealand site of batch release will only release batches for distribution in New Zealand once the sponsor has verified that the shipping temperature profile meets specifications.
2. Provide Certificates of Analysis to Medsafe for the first three batches of vaccine intended for the New Zealand market, prior to distribution.
3. To provide independent batch certification, such as UK National Institute for Biological Standards and Control (NIBSC) certification, EU Official Control Authority Batch Release (OCABR) certification, Australian TGA batch release assessment, or any other certification agreed with Medsafe, on request for all batches distributed in New Zealand.
4. Provide the final clinical study reports from Study C4591007 within five working days of these being produced.
5. Provide any reports on efficacy and safety including duration and the requirement for booster doses within five working days of these being produced.
6. Provide Periodic Safety Update Reports according to the same schedule as required by the EMA.
7. Provide any safety reports and safety reviews conducted or they become aware of.
8. Perform the required pharmacovigilance activities and interventions detailed in the agreed RMP and any agreed updates to the RMP. An RMP should be submitted at the request of Medsafe or whenever the risk management system is modified, especially as the result of new information being received that may lead to a significant change to the benefit/risk profile or as the result of an important milestone being reached.

Provisional consent is granted until 3 November 2023.

This consent is given subject to the following conditions:

The New Zealand Sponsor must fulfil the following obligations within the timelines specified, which may be altered by mutual agreement with Medsafe:

1. The New Zealand site of batch release will only release batches for distribution in New Zealand once the sponsor has verified that the shipping temperature profile meets specifications.
2. Provide independent batch certification, such as UK National Institute for Biological Standards and Control (NIBSC) certification, EU Official Control Authority Batch Release (OCABR) certification, Australian TGA batch release assessment, or any other certification agreed with Medsafe, on request for all batches distributed in New Zealand.
3. Provide any reports on the duration of efficacy and the requirement for booster doses within five working days of these being produced.
4. Provide any reports on efficacy including asymptomatic infection in the vaccinated group, vaccine failure, immunogenicity, efficacy in population subgroups and results from post-marketing studies, within five working days of these being produced.
5. Provide the final Clinical Study Reports for Study C4591001 and Study BNT162-01 within five working days of these being produced.
6. Provide Periodic Safety Update Reports according to the same schedule as required by the EMA.
7. Provide monthly safety reports, as well as all safety reviews they conduct or become aware of.
8. Perform the required pharmacovigilance activities and interventions detailed in the agreed RMP and any agreed updates to the RMP. An RMP should be submitted at the request of Medsafe or whenever the risk management system is modified, especially as the result of new information being received that may lead to a significant change to the benefit/risk profile or as the result of an important milestone being reached.

Provisional consent is granted until 3 November 2023.

This consent is given subject to the following conditions.

The New Zealand Sponsor must fulfil the following obligations within the timelines specified, which may be altered by mutual agreement with Medsafe:

1. Prepare a "Dear Healthcare Professional" letter or comparable instructive material and provide this to Medsafe for review and approval prior to distribution of this product.
2. The New Zealand site of batch release will only release batches for distribution in New Zealand once the sponsor has verified that the shipping temperature profile meets specifications.
3. Provide Certificates of Analysis to Medsafe for the first three batches of vaccine intended for the New Zealand market, prior to distribution.
4. To provide independent batch certification, such as UK National Institute for Biological Standards and Control (NIBSC) certification, EU Official Control Authority Batch Release (OCABR) certification, Australian TGA batch release assessment, or any other certification agreed with Medsafe, on request for all batches distributed in New Zealand.
5. To reassess the acceptance criteria for RNA ratio in the finished product specifications. Due date: 30 June 2023.
6. Provide the final clinical study report that includes for immunogenicity and safety data after the second booster (fourth) dose in subjects 55 years of age and older from Study C4591031 Phase III Substudy E within five working days of the report being produced.
7. Provide the final clinical study report that includes for immunogenicity and safety data after the second booster (fourth) dose in subjects 18 to 54 years of age from Study C4591031 Phase III Substudy D within five working days of the report being produced.
8. Provide interim and final clinical study reports that include immunogenicity and safety data after the first booster (third) dose of in subjects 12 to 17 years of age from Study C4591031 Phase III Substudy C within five working days of the reports being produced.
9. Provide the final clinical study report that includes safety data after the first booster (third) dose in subjects 12 to 17 years of age from Study C4591031 Phase III Substudy B within five working days of the report being produced.
10. Provide Periodic Safety Update Reports according to the same schedule as required by the EMA.
11. Provide any safety reports and safety reviews conducted or they become aware of.
12. Perform the required pharmacovigilance activities and interventions detailed in the agreed RMP and any agreed updates to the RMP. An RMP should be submitted at the request of Medsafe or whenever the risk management system is modified, especially as the result of new information being received that may lead to a significant change to the benefit/risk profile or as the result of an important milestone being reached.

Provisional consent is granted until 3 November 2023.

This consent is given subject to the following conditions.

The New Zealand Sponsor must fulfil the following obligations within the timelines specified, which may be altered by mutual agreement with Medsafe:

1. The New Zealand site of batch release will only release batches for distribution in New Zealand once the sponsor has verified that the shipping temperature profile meets specifications.
2. Provide Certificates of Analysis to Medsafe for the first three batches of vaccine intended for the New Zealand market, prior to distribution.
3. Provide independent batch certification, such as UK National Institute for Biological Standards and Control (NIBSC) certification, EU Official Control Authority Batch Release (OCABR) certification, Australian TGA batch release assessment, or any other certification agreed with Medsafe, on request for all batches distributed in New Zealand.
4. Reassess the acceptance criteria for RNA ratio in the finished product specifications. Due date: 30 June 2023.
5. Provide the final clinical study report that includes for immunogenicity and safety data after the second booster (fourth) dose in subjects 55 years of age and older from Study C4591031 Phase III Substudy E within five working days of the report being produced.
6. Provide the final clinical study report that includes for immunogenicity and safety data after the second booster (fourth) dose in subjects 18 to 54 years of age from Study C4591031 Phase III Substudy D within five working days of the report being produced.
7. Provide interim and final clinical study reports that include immunogenicity and safety data after the first booster (third) dose of in subjects 12 to 17 years of age from Study C4591031 Phase III Substudy C within five working days of the reports being produced.
8. Provide the final clinical study report that includes safety data after the first booster (third) dose in subjects 12 to 17 years of age from Study C4591031 Phase III Substudy B within five working days of the report being produced.
9. Provide the final clinical study report that includes safety and immunogenicity data for Cohorts 2 and 3 through 6 months after a booster dose in subjects 12 years of age and older from Study C4591044 Phase II within five working days of the report being produced.
10. Provide Periodic Safety Update Reports according to the same schedule as required by the EMA.
11. Provide any safety reports and safety reviews conducted or they become aware of.
12. Perform the required pharmacovigilance activities and interventions detailed in the agreed RMP and any agreed updates to the RMP. An RMP should be submitted at the request of Medsafe or whenever the risk management system is modified, especially as the result of new information being received that may lead to a significant change to the benefit/risk profile or as the result of an important milestone being reached.

Provisional consent is granted until 2 March 2024.

This consent is given subject to the following conditions.

The New Zealand Sponsor must fulfil the following obligations within the timelines specified, which may be altered by mutual agreement with Medsafe:

1. Confirm the synthetic route used to manufacture starting materials used in commercial manufacture and provide relevant discussion of possible impurities, carry-over reagents and solvents from the process. Due date: 30 September 2022.
2. Provide revised starting material specifications with appropriate limits for each impurity, and any other tests such as for residual solvents. Due date: 30 September 2022.
3. Provide an updated set of intermediate specifications, which include an identification parameter and any further tests (impurities, reagents or solvents) as required. Due date: 30 September 2022.
4. Provide details of further in-process controls to be used in the drug substance manufacturing process. Due date: 30 September 2022.
5. Provide a risk assessment and batch testing data for carry-over benzene in the drug substance. Due date: 30 September 2022.
6. Provide full method validation in line with ICH Q2 for the assay/identification/achiral impurity test, which should include specific discussion of validation for each impurity. Due date: 30 September 2022.
7. Provide 12-month stability data for primary drug substance batches manufactured by Route F and G. Due date: 31 March 2023 and 30 June 2023.
8. Provide the results of further studies for the nirmatrelvir substance particles size. Due date: 30 September 2022.
9. Provide an update from the continued assessment of the necessity to include microbiological tests in the drug product specifications. Due date: 30 September 2022.
10. Provide process validation data along with the manufacturing process validation protocol for the maximum scale commercial batches of the nirmatrelvir 150 mg film-coated tablets. Due date: 30 September 2022.
11. Provide the results of additional studies for the formulation and manufacturing process development, critical steps and intermediates. Due date: 30 September 2022.
12. Provide the results of studies for the hold times to be implemented to the manufacturing process. Due date: 30 September 2022.
13. Implement a suitability justified control limit for assay at release and expiry. Due date: 30 September 2022.
14. Continually review the dissolution acceptance criteria as additional batch experience is gained and provide in vitro and in vivo data to justify the final control limit. Due date: 30 September 2022.
15. Provide 6-month and 12-month stability data from the three primary drug product batches. Due dates: 31 March 2022 and 30 September 2022.
16. Provide confirmatory clinical trial data as identified in the sponsor's plan to submit comprehensive safety and efficacy data within six years from consent being granted within five working days of any reports being produced.
17. Provide updates regarding the clinical activity, efficacy, and effectiveness against the current and future Variants of Concern and Variants of Interest identified by the World Health Organization (WHO) within five working days of any reports being produced.
18. Provide further data relating to efficacy in immunocompromised subjects, pregnant women, lactating mothers, paediatric subjects, patients with hepatic impairment as well as additional pharmacology and long-term safety data and information relating to post-market safety and efficacy studies with five working days of any reports being produced.
19. Provide long-term data from study C4671005 (i.e. at Week 34) to ensure that no further events onset potentially impacting the main outcomes. Due date: 30 September 2022.
20. Provide interim reports for study 1002 and 1006. Due date: 30 June 2022.
21. Provide the final study reports for ongoing studies proposed in the clinical development plan: study 1010, 1012, and 1013 within five working days of the reports being produced.

Dated this 25th day of October 2023.

CHRIS JAMES, Group Manager, Medsafe, Ministry of Health (pursuant to delegation given by the Minister of Health on 11 September 2013).