Published: 21 October 2010

Consultations

Outcome of Consultation on the Revision of the New Zealand Good Clinical Research Practice Guideline

21 October 2010

To: Clinical trial sponsors, medicine sponsors, and regulatory affairs consultants

The purpose of this letter is to:

• Report the outcome of consultation on the proposed updates to the New Zealand Good Clinical Research Practice Guideline published by Medsafe in October 2009.
• Provide you with a copy of the guideline and associated forms following amendment to take account of submitters' comments.
• Advise you of the timeframe for implementation of the new guideline and forms.

Consultation process and outcomes

In October 2009, Medsafe published a draft revision of the New Zealand Good Clinical Research Practice Guideline for consultation. Submissions on the proposals reflected in the draft were sought by 30 November 2009.

Medsafe received 19 submissions - 3 from industry associations, 3 from professional bodies, 9 from pharmaceutical companies and regulatory consultants, and 4 from universities and hospitals.

Submitters supported the concept of bringing the New Zealand clinical trials guideline into line (as far as is possible in the New Zealand context) with the Note for Guidance on Good Clinical Practice (CPMP/ICH/135/95) which represents international consensus on standards for the design, conduct, record-keeping and reporting of clinical trials.

Detailed consideration of submitters' comments has resulted in extensive revision of the guideline. Key changes include:

• limiting the requirement for self-certification of clinical trial sites to those sites where trial participants are in residence at the site when trial medicines are administered
• no longer considering the supply of clinical trial medicines to trial participants to be subject to the limitations on prescribing or dispensing set out in the Medicines Regulations
• recognising that records relating to clinical trials may be maintained in hard-copy or electronic form, provided all relevant legislation is complied with and the records remain readily accessible throughout the required retention period
• maintaining the requirement for expedited reporting of Suspected Unexpected Serious Adverse Reactions (SUSARs), but no longer requiring adverse event reports to be sent to Medsafe with the six-monthly progress report.

The associated forms have also been revised. An application form is now required to be completed for all applications for approval of clinical trials, including those relating to gene or other biotechnology medicines.

Copies of the guideline document and forms (Microsoft Word document 3084kb) are attached for your information. While the appearance is likely to change somewhat when electronic forms are created, the content will remain the same.

A number of submissions contained questions about the regulation of clinical trials or requested clarification of particular points. Many of the issues raised have been dealt with by adding further explanation into the guideline. The attached table provides some additional information on a range of issues raised by submitters.

Implementation of the new guideline

Medsafe is in the process of updating its set of regulatory guidelines. The new Guideline on the Regulation of Therapeutic Products in New Zealand will be published and implemented in stages as each part is completed.

The new guideline on Good Clinical Practice (entitled Clinical trials - regulatory approval and good clinical practice requirements) is Part 11 of the Guideline on the Regulation of Therapeutic Products in New Zealand.

The new clinical trials guideline will come into effect on 1 January 2011. From this date, clinical trials conducted in New Zealand will be required to be conducted in compliance with the new guideline.

If you have any queries about the information provided in this letter, in the first instance please contact:

Becci Slyfield
Support Officer
Clinical Risk Management
becci.slyfield@health.govt.nz

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Medsafe Response to Questions Raised by Submitters

Question or issue	Medsafe response
The guideline does not specify that approval under section 30 would not be required for a trial using a medicine procured by a medical practitioner (under section 29).	Section 29 provides an exemption from the requirements for a medicine to be approved when the medicine is supplied to a medical practitioner for the treatment of a particular patient. It does not provide an exemption from compliance with section 30 when a new medicine is to be used in a clinical trial.
There are other definitions of the term 'clinical trial' that could or should be adopted for New Zealand.	There is no universally accepted definition for the term 'clinical trial'. However, since New Zealand is adopting the CPMP guideline which includes a definition of 'clinical trial', this is the definition that will apply. Modifications to the requirements in the CPMP guideline are being made only to the extent that is necessary to overcome any inconsistencies with current New Zealand legislation.
Who approves clinical trials - Medsafe, the Director-General of Health or a committee of the Health Research Council (SCOTT or GTAC)?	Section 30 of the Medicines Act 1981 specifies that: the approval of the Director-General of Health is required before a clinical trial using a new medicine commences in New Zealand; and the Director-General can only give approval on the advice of the Health Research Council. The Director-General's authority to approve clinical trials has been delegated to Medsafe. It is therefore Medsafe that seeks a recommendation from the Health Research Council and issues clinical trial approvals. Medsafe administers all aspects of the clinical trial approval process. This includes receiving and acknowledging applications, issuing invoices, liaising with applicants regarding the application, and handling all correspondence relating to the application. The Health Research Council (HRC), through its Standing Committee on Therapeutic Trials (SCOTT) or Gene Technology Advisory Committee (GTAC), considers clinical trial application referred to it by Medsafe and makes recommendations on whether the trial should be approved and whether the approval should be subject to any conditions. An application for approval of a clinical trial is made using the application form provided on the Medsafe website, and must be sent to Medsafe with any required supporting documentation. However, to avoid any delay that could result from applications being first received by Medsafe then forwarded on to the HRC, applicants are asked to send an additional copy of the application package directly to the appropriate HRC committee (SCOTT or GTAC). The HRC committee considers applications referred to it, and reports the outcome of its consideration to Medsafe. To help applicants ensure that they provide the information the committee will require in order to undertake its assessment of the application, the HRC publishes guidelines on requirements for clinical trial applications. These are available on the HRC website. On receipt of the SCOTT or GTAC recommendation, Medsafe liaises with the applicant regarding any requests for further information or conditions proposed to be placed on the approval. Once any issues have been satisfactorily resolved, Medsafe issues a letter of approval and the trial may proceed once any permissions required under other legislation (e.g. ethics approval, approval under the HSNO legislation) have been obtained.
Will consideration of a clinical trial application be delayed if payment of the invoice is not made within 7 days?	No. However, the applicant must ensure that arrangements are in place for prompt payment of the invoice because the trial will not be approved until payment has been received.
A pharmacist manufacturing a medicine (as provided for in section 26) is not required to hold a manufacturing licence. Does this mean that a medicine manufactured by a pharmacist for use in a clinical trial would not have to be made in accordance with GMP requirements?	Section 26 of the Medicines Act 1981 permits a pharmacist to manufacture a medicine for supply to a particular person, at that person's request. If the medicine is a prescription medicine, a prescription is required. This provision does not permit manufacture of medicines for use in clinical trials or provide any exemption from the requirements of Section 30.
Does a bioequivalence trial of a new generic medicine require approval under Section 30 of the Medicines Act? If so, are there any plans to develop an abbreviated approval process for such trials?	Approval under section 30 is required for any clinical trial using a new medicine, including bioequivalence trials. In such trials, the medicine being assessed for bioequivalence will be a new medicine. The comparator product may or may not be an approved medicine in New Zealand. The requirements, as set out in Section 30 of the Medicines Act, apply to all trials requiring approval under Section 30. Current legislation does not provide for different types of approvals.
How would a compassionate use extension protocol or an open extension phase of a trial be handled?	While the trial is still in progress, any amendment to the protocol would require approval. A request for approval of an amendment is made, in writing, to Medsafe. An extension to a trial would require a protocol amendment. Once a clinical trial is completed, further supply of the medicine on compassionate grounds will need to occur under the provisions of section 25 or section 29 of the Medicines Act until the medicine is approved. However, the medicine is no longer being used in a clinical trial and Section 30 does not apply.
Further consideration should be given to the question of when approval is required for a clinical trial. For example, approval should not be required when an approved medicine is used in a trial, but the dosage regimen varies from that approved for the medicine.	The approval of the Director-General of Health (given on the recommendation of the Health Research Council) is required for any clinical trial using a new medicine. A new strength of a product is a new medicine. Therefore a clinical trial using a new strength of a product requires approval under Section 30 of the Medicines Act. Conversely, a trial that uses an approved medicine to investigate a new dosage regimen would not require approval under Section 30 because it does not involve use of a new medicine.
Who would be the key personnel required to be listed in a trial site self-certification?	Key personnel would be the lead investigator and those people directly involved in patient management at the trial site (e.g. clinicians, nurses, pharmacists).
How long will it take for Medsafe to process a site certification? How will certifications be audited?	A site certification will normally be processed within 7 days. This will ensure there is no delay in approving a trial in situations where a new or updated site certification has been sent to Medsafe with the clinical trial application. The scheme relies on self-certification by the lead investigator at the site and does not involve audits conducted by the regulator.
Are there plans to develop a register of medical device clinical trials and require trials to be registered before ethics approval is granted?	Section 30 of the Medicines Act 1981 provides an exemption from the requirement for a medicine to be approved if the medicine is only to be used in a clinical trial and that trial has been approved by the Director-General. Under current legislation there is no requirement for approval of medical devices and no provision for placing regulatory controls on trials involving the use of medical devices. The requirement for ethics committee approval does apply to clinical trials using medical devices.
There needs to be acceptance of relevant overseas qualifications (e.g. the UK Diploma in Pharmaceutical Medicine) as providing evidence of expertise in clinical trials.	Investigators and other key personnel must hold qualifications that are appropriate to the role they are undertaking in the conduct of the trial. These qualifications must be recognised in New Zealand, either through registration with the relevant responsible authority under the Health Practitioners Competence Assurance Act (e.g. Medical Council, Pharmacy Council, Nursing Council) or through the New Zealand Qualifications Authority (NZQA).
What are the labelling requirements for medicines used in a clinical trial that does not require approval under Section 30 of the Medicines Act (because the trial does not involve the use of any new medicines).	Normal requirements for the labelling of dispensed medicines would apply in such situations. Note that regulation 23 of the Medicines Regulations 1984 permits use of a recognised code in place of the name of the medicine. Inclusion of the words "To be used by qualified investigators only" (or words of similar meaning) is not mandatory, but is encouraged.
Application of the draft guideline to independent researchers could have a significant impact on their ability to operate.	All those conducting clinical trials must comply with the requirements set out in the Medicines Act 1981. The new guidelines provide greater clarity on what clinical trial sponsors and investigators need to do to achieve compliance, but they do not introduce significant new requirements. Similarly, compliance with other relevant legislation is not a new requirement. Whilst Medsafe recognises that some investigators will be working under resource constraints, it would not be acceptable practice to 'exempt' some investigators from compliance with legislation designed to protect the health and safety of trial participants.