I, Tony Ryall, Minister of Health, pursuant to section 96C(1) of the Medicines Act 1981, hereby authorise Living Cell Technologies Ltd (LCT) to conduct a clinical trial involving xenotransplantation as described in its application dated the 28th day of September 2007, subject to the conditions already imposed by the Northern X Regional Health and Disability Ethics Committee, and the following additional conditions:
General conditions
1. In the event that LCT ceases trading in New Zealand, it will transfer its tissue stores and patient data relating to the trial to the Ministry of Health.
2. LCT is, on request, to provide to the Ministry of Health (or such other person or organisation as the Minister may nominate for the purpose) any patient information and tissue samples required for the purposes of establishing and maintaining a government-administered national patient register and tissue archive.
3. All LCT laboratory facilities are subject to inspections from Medsafe, International Accreditation New Zealand, or any person nominated by the Minister at any time during the trial, within normal working hours.
4. LCT will, when directed by Medsafe, provide a report on their compliance with any new or amended international guidelines on xenotransplantation (including those being developed by the World Health Organization), including details of how they will amend their study, if required, to bring it into compliance.
Protocol amendment requirements
5. LCT will provide Medsafe with evidence that the Northern X Health and Disability Ethics committee has considered and approved a study protocol that has been updated and amended to include:
5.1 A requirement that patient information and tissue samples relating to the clinical trial be held in a patient register and tissue archive to be housed at Middlemore Hospital, to which the Ministry of Health (or such other person or organisation as the Minister may nominate for the purpose) will have unrestricted access.
5.2 An improved description of the systems of information collection and specimen labelling
that can cross link samples from individual xenotransplantation product recipients to specific xenotransplantation products as well as to the herds and pigs that served as sources for that product.
5.3 More detailed information on the biological specimens that will be collected from participants and contacts, how those specimens will be processed, handled, and stored, including specific indication of temperature, and provisions in place to prevent power failure or provide back-up management in the event of equipment or power failure. This should specifically include testing that will be performed and specimens that will be collected and stored at autopsy in the event of a fatal event.
5.4 A requirement that all trial participants must provide written consent to their patient information and tissue samples being supplied, held by and
used for the purposes of a government-administered national patient register and tissue archive.
5.5 Amendment to the membership and terms of reference of the independent Data Safety Management Board (as agreed with Medsafe).
5.6 Revised patient inclusion criteria limiting participation in the study to subjects with:
? established brittle Type 1 diabetes with a well-documented chronic history of severe metabolic instability who cannot achieve acceptable metabolic control without experiencing multiple episodes of severe hypoglycemia, often with unawareness; or
? degrees of hypoglycemia, who cannot be adequately managed with intensive insulin therapy alone despite intensive diabetes management delivered by a qualified diabetes team for at least six months prior to enrolment.
5.7 A revised definition of serious adverse event which includes adverse events that result in death, hospitalisation or time off work, and other events identified in the study protocol, including negative changes in health status, unexplained fever, or evidence of possible infection in study participants, and reports of all positive testing for infections and negative changes in health status of the pigs being used in the study.
5.8 A requirement that all serious adverse events
to be reported by LCT to the relevant regulatory authorities (including Medsafe, the Northern X Regional Health and Disability Ethics Committee) immediately, and within 24 hours of LCT becoming aware of the adverse event at the latest. The outcome of any investigation carried out in response to an adverse event must also be reported as soon as possible to the relevant regulatory authorities.
5.9 A requirement to provide three-monthly progress reports to Medsafe, or such other person or body as the Minister may nominate.
5.10 A requirement to provide a final report to Medsafe within eight weeks of the conclusion of the trial.
5.11 Updating of the patient information leaflet to state clearly that the primary purpose of the trial is to test the safety of the procedure; and to include more information supporting the need for long term/life long monitoring and the importance of the patient cooperating with the required follow up.
This authorisation revokes and replaces the previous conditional authorisation issued by the former Minister of Health dated the 21st day of October 2008* and will remain in effect for the period that the clinical trial has been approved by the Northern X Regional Health and Disability Ethics Committee, unless sooner varied or revoked, pursuant to section 96C(4) of the Medicines Act 1981.
Dated this 22nd day of June 2009.
HON TONY RYALL, Minister of Health.
*New Zealand Gazette, 23 October 2008, No. 162, page 4250