2. General Questions

2.1 Name of Regulatory Authority

Health Research Council (HRC) - http://www.hrc.govt.nz/

Section 30 of the Medicines Act authorizes the Director-General of Health to approve a clinical trial involving the use of new and unregistered medicines on the recommendation of the Health Research Council of New Zealand (HRC). The HRC maintains two standing committees to consider clinical trial applications and make recommendations to the Director-General. The Standing Committee on Therapeutic Trials (SCOTT) considers applications for new pharmaceutical-type medicines, and the Gene Technology Advisory Committee (GTAC) considers applications for trials involving new and unregistered gene and other biotechnology therapies. The Terms of Reference for these committees are published on the HRC website. 

The HRC website provides guidance on the committee processes and the data requirements for applications to be considered by each committee.

Medsafe - https://www.medsafe.govt.nz/index.asp

Medsafe is the Medicines and Medical Devices Regulatory Authority for New Zealand. Medsafe administers the regulatory application for clinical trials under Section 30 of the Medicines Act 1981, involving the use of new medicines, unregistered medicines, scientific assessment of gene technology and medical devices. Approvals are issued by Medsafe under a delegation from the Director-General of Health. 

Medsafe receives and processes applications, liaises with the relevant Health Research Council committee (Standing Committee On Therapeutic Trials (SCOTT) or Gene Technology Advisory Committee (GTAC) and the applicant, and issues approval letters. All communication regarding an application for approval of a clinical trial must be addressed to the Clinical Trial Co-ordinator at Medsafe.

The application and approval process for clinical trials is administered by Medsafe. The application and approval procedure are summarized here:

1. An application is received at Medsafe, which forwards the application to the Health Research Council of New Zealand (HRC). 
2. A committee of the HRC considers the application. 
3. The HRC makes a recommendation to the Director-General on the clinical trial application. 
4. The applicant is issued approval, provisional approval, or a decline letter by Medsafe based on the HRC recommendation, under authority delegated from the Director-general of Health. (https://www.health.govt.nz/)

Medsafe does not regulate or approve clinical trials for medical devices in New Zealand but does request that it be informed of such trials. Ethics approval only is required for medical device trials. 

Note: Approval from a Health and Disability Ethics Committee (HDEC) is required for all clinical trials conducted in New Zealand. This is a separate application and approval and is not administered by Medsafe.

2.2 Name of Ethics Committee

New Zealand Health and Disability Ethics Committee (HDEC) - https://ethics.health.govt.nz/home

The New Zealand Health and Disability Ethics Committee administers the ethics approval system, which applies to interventional clinical trials regardless of whether they are trials that require approval under Section 30 of the Medicines Act. Clinical trials that require sample collection and storage, or the use of disclosure of health information are in most cases also subject to ethics approval. 

Ethics committee approval is a separate process from regulatory approval under Section 30 of the Medicines Act and is not administered by Medsafe. In New Zealand, only one ethics committee review is required per trial New Zealand, and this covers all sites. It takes around 4-6 weeks from submission to full approval. Requirements relating to the New Zealand Health and Disability Ethics Committee's approval of clinical trials are provided on the New Zealand Health and Disability Ethics Committee website. 

New Zealand has two types of approved Ethics Committees (EC) that conduct ethical reviews of clinical trials:

1. HDECs which are used for most clinical trial approvals.
2. Institutional Ethics Committees (IEC) which are used for late-phase research involving humans, originating from that specific institution.

https://credevo.com/articles/2019/01/17/clinical-trial-regulatory-new-zealand/ 

https://ethics.health.govt.nz/

Ethics Committee Sub-Committees

The Health Research Council Ethics Committee (HRCEC) (Ethics Committee) is responsible for approving all the Health and Disability Ethics Committees (HDECs) and Institutional Ethics Committees (IECs) in New Zealand.

HRCEC produces guidelines around research with Māori and Pacific peoples, so the rights of participants are respected.

• The Data Monitoring Core Committee (DMCC) provides objective, independent monitoring of HRC-funded clinical trials in New Zealand when needed.
• The Standing Committee on Therapeutic Trials (SCOTT) checks clinical trials for safety and efficacy.
• The Gene Technology Advisory Committee (GTAC) assesses the scientific merit of studies to transfer genes from one species to another.

2.3 Clinical Trial Application Language

English

2.4 Is regulatory approval required from both regulatory authorities and/or EC?

Yes, but not for medical devices.

2.5 Can regulatory authority and EC submission be done in parallel?

Yes.

For all trials, the application for Ethics Committees' approval may be made at any time before, during, or after consideration of the application for clinical trial approval under section 30.

2.6 Requirement of any import permit/license before investigational product/study product is shipped from point of origin

the Ministry of Health (Medsafe) approval is required for the trial before drugs can be imported into New Zealand.

The Medsafe Standing Committee on Therapeutic Trials (SCOTT) Approval Letter can be used as evidence of import approval if required.

• An import license is not required. (Approval for the clinical trial must be approved before the product for the clinical trial can be imported. However, once the approval is received, an import license is not required.)
• Export approval is not required for investigational products shipped from the U.S. to New Zealand.

Materials used in Clinical trials

• All imports into New Zealand are subject to the Ministry of Agriculture & Forestry (MAF) and New Zealand Customs Import regulations.
• A commercial invoice is required to accompany all goods.

2.7 Biological Specimen Export Requirements

The requirements in relation to the handling and shipping of biological samples from decentralized clinical trials are described in a Standard Operating Procedures issued by the New Zealand Association of Clinical Research. 

Decentralized Clinical Trials NZ Handling and Shipping of Biological Samples

2.8 Are studies of GMOs permitted (e.g., GMOs used in vaccines/vaccine manufacture and other modified products)?

Yes, by approval of the Gene Technology Advisory Committee (GTAC).

GTAC undertakes scientific assessments of clinical trials that involve the introduction of nucleic acids, genetically manipulated microorganisms, viruses, or cells into human subjects. It also makes recommendations to the Director-General of Health on whether or not trials should be approved.

Applicants also need to seek approval from the Environmental Protection Authority (EPA) for the importation of the proposed material. 

The process and guidelines for application for approval of trials involving gene and other biotechnology therapies are described here.

2.9 Is in-country sponsor presence/representation required?

The sponsor must be a person residing in New Zealand and be a citizen of NZ.

https://www.medsafe.govt.nz/regulatory/Guideline/GRTPNZ/Part11.pdf

2.10 Is there any mandatory requirement to identify a local PI or can a PI be based in a foreign country?

The principal investigator must be a resident of New Zealand. All investigators must have New Zealand-recognized qualifications.

According to MedSafe, the "principal investigator is the person with overall responsibility for the conduct of the clinical trial in New Zealand. There is only one principal investigator for a trial, regardless of the number of trial sites involved".

https://www.medsafe.govt.nz/regulatory/Guideline/GRTPNZ/Part11.pdf 

2.11 Is there any mandatory requirement to identify a local chief or coordinating investigator?

Yes. A lead PI (or coordinating investigator) should be identified to oversee all sites where the study is conducted across multiple locations. 

HDEC has adopted the GCP definitions of Coordinating Investigator (CI) as defined in the guidelines below and in accordance with the definition within the ICH GCP guidelines. 

https://www.medsafe.govt.nz/regulatory/Guideline/GRTPNZ/Part11.pdf 

Coordinating Investigator: A principal investigator assigned the responsibility for the coordination of investigators at different centers participating in a multicentre study [Guidance for Industry E6 Good Clinical Practice: Consolidated Guidance (GCP E6) 1.19].

2.12 If the applicant is CRO or a third party, does regulatory authority need any authorization or transfer of obligations from the sponsor? Does the authorization letter need to be notarized and/or apostilled?

Once the trial is approved, the applicant becomes the sponsor, assuming responsibility (including legal liability) for the trial in New Zealand. The sponsor, who must be a person in New Zealand, is responsible for:

• The preservation of records 
• Reporting adverse events 
• Notifying and seeking approval for any changes in the clinical trial protocol to the Director-General of Health (through Medsafe, and for ethics approval through HDEC) 
• Informing the Director-General of Health of the identifying name or mark by which the trial medicine may be recognized before the trial medicine is distributed (section 30(7)(a) of the Medicines Act 1981)

While the supporting documentation required to be submitted with an application may be prepared by the overseas sponsor of the trial, it is the person responsible for the trial in New Zealand (the applicant) who must make the application to the Director-General for approval of the trial.  

This role may be performed by a CRO on behalf of the applicant. A transfer of responsibility form is required. There is no set format for this information, and it does not need to be apostilled or notarized. 

2.13 Is there a requirement to register clinical trials on a local registry or database?

Trials conducted in New Zealand must be registered on The Australian New Zealand Clinical Trials Registry (ANZCTR).

ANZCTR is an online register of clinical trials being undertaken in Australia, New Zealand, and elsewhere. The ANZCTR includes trials from the full spectrum of therapeutic areas of pharmaceuticals, surgical procedures, preventive measures, lifestyle, devices, treatment and rehabilitation strategies, and complementary therapies. 

ANZCTR is an online public registry of clinical trials, held at the NHMRC Clinical Trials Centre, University of Sydney. It is a Primary Registry in the World Health Organization (WHO) Registry Network, which means that it fulfills certain criteria for content, quality, validity, accessibility, unique identification, technical capacity, and administration.

The ANZCTR accepts both interventional and observational studies for registration from all countries and from the full spectrum of therapeutic areas including trials of pharmaceuticals, surgical procedures, preventive measures, lifestyle, devices, treatment and rehabilitation strategies, and complementary therapies.

2.14 What is the local requirement for clinical study documents archival; minimum of years for the archival, specific format followed (electronic/paper and/or both)?

In August 2023, the New Zealand Association of Clinical Research issued a Standard Operating Procedure describing the procedures for Decentralized Clinical Trials NZ Essential Document Management. 

This SOP describes the key documents that must be created and retained in support of a decentralized trial.  

2.15 Requirements around periodic safety reporting and timelines on SAEs/AEs/ADRs/SUSARs/DSURs.

1) AEs

Adverse reactions to unapproved medicines being used in clinical trials are to be reported to Medsafe. 

The reporting requirements for adverse events of unapproved medicines used in clinical trials are detailed in points 6.3 and 6.4 of the CHMP GCP guideline. 

The reporting requirements in New Zealand differ from those set out in the CHMP GCP guideline in that only expedited reports of serious adverse events occurring in New Zealand trial participants must be sent to Medsafe. 

In line with the CHMP GCP guideline, the investigator should report adverse events (as detailed in the protocol) to the sponsor.

The sponsor is required to hold reports of all (worldwide) SUSARs (suspected unexpected serious adverse reactions, as defined in ICH guideline E2A). These reports should not be routinely sent to Medsafe but must be held in an accessible form and made available to Medsafe on request. 

The adverse event reporting requirements of the Health and Disability Ethics Committees are outlined in their standard operating procedures. 

All serious adverse reactions to approved medicines used in clinical trials should be reported to the Centre for Adverse Reactions Monitoring (CARM). Sponsors should follow the process for reporting adverse reactions in the Guideline on the Regulation of Therapeutic Products in New Zealand, Part 8: Pharmacovigilance.

2) SUSARs

The sponsor is required to report all fatal or life-threatening suspected unexpected serious adverse reactions (SUSARs) occurring in New Zealand trial participants where the treatment is known. 

Adverse reactions occurring in a clinical trial’s participants are considered to be unexpected if they are not outlined in the protocol and investigator’s brochure and are not defined study endpoints.

Within 7 days of the sponsor receiving an investigator’s report of a fatal or life-threatening SUSAR, the sponsor must send the report to Medsafe. Follow-up reports are required only if there is significant new information. 

Medsafe does not require all other SUSARs that are not fatal or life-threatening to be reported within 15 days. These reports should not be routinely sent to Medsafe but must be held in an accessible form and made available to Medsafe on request.

2.16 Requirement on any periodic clinical study update, specific template, and its frequency (e.g., interim or annual progress report and final report, etc.)? 

Study Progress Reports

Section 30(7)(d)(ii) of the Act requires the sponsor to submit routine progress reports to Medsafe. Reports should be submitted online. 

The first report should be sent to Medsafe not more than 6 months after the date of approval of the trial, whether or not recruitment of New Zealand trial participants has commenced. 

Subsequent reports should be submitted at 6-month intervals throughout the duration of the trial in New Zealand. 

Medsafe should be informed when the New Zealand trial, or the New Zealand arm of a multinational trial, is completed. There is no need to continue submitting 6-month progress reports once the New Zealand arm has been completed, even if the trial continues elsewhere.

Final Report

Section 30(7)(d)(iii) of the Medicines Act 1981 requires a final report to be sent to Medsafe upon termination of the clinical trial.

Prior to the End-of-Trial report being available, Medsafe should be sent a 'Notification of Conclusion of the Study' using a Post Approval Form (PAF) under Online Forms. This allows Medsafe to be informed that the study has ended in New Zealand, yet may be ongoing globally. 

At the global end of trial, a synopsis of the final report should be sent to Medsafe when available, using a Post Approval Form (PAF) under Online Forms. 

The full report should not be routinely sent to Medsafe but must be held in an accessible form and made available to Medsafe on request. 

2.17 Does the local regulation require notification of “serious breaches” of GCP or the trial protocol?

Yes, sponsors are required to notify Medsafe of serious breaches of GCP.

2.18 Does RA/CA require insurance and indemnity to cover the sponsor and investigator’s potential liability?

Clinical trials sponsored by a manufacturer of a pharmaceutical or medical device and conducted in NZ public health organizations must be covered by a standard Indemnity and Compensation Agreement (sICA) between the site and the trial sponsor.

The intention is that this sICA can be used by all NZ DHBs without modification to speed the process of approval of clinical trials and remove the need for lengthy and difficult negotiation.

This sICA does not cover clinical trials that are:

• sponsored by collaborative clinical trial groups;
• are investigator-initiated;

as compensation for injuries caused to participants because of their participation in these clinical trials is covered by NZ’s statutory no-fault compensation scheme (Injury Prevention, Rehabilitation, and Compensation Act 2001).