Questions & answers about the Regulation of Human Cellular and Tissue Therapies (HCTs) under ANZTPA.
May 2007
Australian and New Zealand Ministers have agreed to include Human Cellular and Tissue Therapies (HCTs) into the range of therapeutic products overseen by the Australia New Zealand Therapeutic Products Authority (ANZTPA). HCTs require regulatory systems which recognise the differences to medicines and medical devices, areas of therapeutic goods subject to previous consultations. In order to ensure the best outcomes for the two countries, input from interested stakeholders is necessary.
Australia and New Zealand currently regulate HCTs differently and both countries recognise that their current frameworks should be amended such that future regulation of cell and tissue therapies is appropriate, consistent, and, where appropriate, are harmonised with international requirements.
Yes. In the vast majority of cases HCTs are regulated under the existing frameworks in both Australia and New Zealand, many as either 'medicines' or 'therapeutic devices'. Since HCTs differ in a number of ways from medicines, even when they have a medicinal action, a new regulatory framework for Biologicals has been developed by the Australian Therapeutic Goods Administration (TGA) and the New Zealand Medicines and Medical Devices Safety Authority (Medsafe).
How will HCTs be regulated in the future?
For the most part, the principles applied will not differ significantly from current arrangements. Depending on the level of risk, HCTs will be subject to the need for manufacture under defined conditions and review of product safety, quality and efficacy through submission of data to the ANZTPA.
Briefly summarised, the following four classes are proposed:
Class 1 - Defined as:
- unbanked and unprocessed
- produced in hospital units for direct transfer to patients other than through a single surgical procedure
It should be noted that the types of HCTs that will be included in Class 1 are subject to further consideration and agreement by the Australian and New Zealand governments.
Class 2 - Defined as a tissue or cell that is stored, maintained or preserved for future use and:
- is not a Class 3 or 4 HCT
- is not for direct transfer from donor to recipient
Class 3 – Defined as a cell or tissue processed in a manner that may alter the structure and properties of the cell or tissue but does not purposefully alter the biological activity.
Class 4 - Defined as a cell or tissue processed:
- so that biological properties are deliberately manipulated
- for a purpose for which the cell or tissue is intended to be used is not its usual biological function
The Draft Rule will reference appropriate definitions of terms (eg 'Bank', 'processing' and 'cryopreserved').
Are there different types of regulation that will be applied to each classification?
Yes. The proposed levels of regulation are based on a risk benefit analysis of the type of HCT.
The proposed regulatory requirements are:
Class 1: Proposed declaration of compliance with relevant Standards which will be developed by the relevant sector
Class 2: Demonstrated compliance with Standards and Manufacturing Principles
Class 3: Demonstrated compliance with Standards and Manufacturing Principles and demonstration of safety, quality and efficacy of the product. The Dossier will need to include all manufacturing, pre-clinical and clinical information to support the product.
Class 4: As for Class 3 with additional requirement for more detailed and relevant clinical data and analysis (including clinical trials information). Detailed data requirements will be agreed with sponsors, depending on the nature of the product.
Will there be any exemptions for HCTs?
Yes. In the case of single medical procedures the following medical procedures would be exempt from regulation under the joint regulatory scheme:
- Single surgical procedures performed on one patient (autologous transplant) such as bone grafts and vein transplants.
- Single surgical procedures involving two patients (non-autologous or allotransplant) such as organ donation from a live donor within the same facility as the transplant recipient.
The ANZTPA recognises that medical factors may influence the precise environment under which a surgical procedure is carried out so that HCTs in this situation may be stored temporarily.
Under the joint regulatory scheme, it is intended that units receiving or sending haemopoetic stem cells from or to overseas transplant units would be exempt from any licensing requirements additional to those applying to the agency performing the actual activity.
What are the adverse events reporting requirements for HCTs?
Each licence holder must have an appropriate system of product vigilance in place. The intention is that serious events be reported, with relevant information communicated to the Authority to allow system failures to be identified and to minimise the risk of such failures being repeated.
Specific guidelines will be developed to provide assistance to stakeholders regarding reporting procedures and responsibilities in respect of each class of HCT.
Further information is provided in the Consultation Document entitled "Product Vigilance in the ANZTPA (pdf,94kb)" <http://www.anztpa.org/consult/dr-vigilance.pdf>
What are the clinical trial regulatory arrangements in relation to HCTs?
The same clinical trial regulatory arrangements (including risk-management principles) that are proposed for medicines and medical devices will be applied for HCTs.
The proposed Clinical Trial Assessment (CTA) and Clinical Trial Certification (CTC) schemes will continue to require that all clinical trials adhere to relevant ethical standards, as well as meet international standards of Good Clinical Practice.
It is intended that trials with Class 4 human cells or tissues will normally follow the CTA route.
Further information is provided in the Consultation Document entitled "Proposed clinical trial regulatory arrangements under ANZTPA (pdf,609kb)" <http://www.anztpa.org/consult/clintrials.pdf>
When is a product licence for HCTs required?
A product licence will be required to import HCTs into Australia and New Zealand, export to a third country from Australia and New Zealand, or supply in Australia and New Zealand.
In addition to a normal product licence, an HCT product could also be issued with:
- A provisional product licence to be used in the prevention or treatment of life-threatening illnesses and where, based on data provided, the Managing Director is satisfied that the HCT is likely to provide meaningful therapeutic benefits to patients over existing treatments
- An export only product licence for exporting only
- A licence applying to only one country in exceptional circumstances where the Authority deems such a restriction necessary
Are product licences essential for HCTs?
Yes. Product licences are mandatory and generally the licence issued will be for supply in both Australia and New Zealand. During the assessment of the application for a product licence the Authority may need to approve product information documents, labelling and possibly any certifications made by the applicant prior to approval.
Generally*, a separate product licence will be required for each HCT. The circumstances in which an HCT is a new product (ie separate and distinct from other therapeutic products) and therefore requiring a new licence, will depend on the classification of the HCT and the nature of the difference or change.
*In some circumstances it will be possible to ‘group’ more than one product on a product licence. These circumstances will vary depending on the type of product and will be set out in Orders.
How do you apply for a product licence for HCTs?
Applications to obtain a licence for any Biological (including HCTs) must be made to ANZTPA in the form specified in the Rules and be accompanied by the prescribed fee. Generally the process for obtaining a product licence for each class of Biological other than Class 1 will be same but the data requirements will differ depending on the classification of product.
How long will it take to consider an application for a product licence?
Statutory timeframes for the consideration of applications for product licences are yet to be confirmed. However, existing statutory timeframes for high risk medicines and therapeutic devices provide a useful guide of the maximum times.
Applications for Class 3 and 4 HCTs product licences are expected to be accepted or rejected for evaluation within 40 working days of receipt. If the application is accepted for evaluation then it is expected to be no longer than 255 working days before a decision is made.
In addition to Statutory timeframes, the ANZTPA will develop target timeframes for consideration of applications which, for most classes, may be significantly shorter.
Further information can be found under Part I: Applications for a Product Licence - Section F: Timeframes for Assessment (pdf,219kb) <http://www.anztpa.org/consult/hct.pdf>
How will experts participate in the regulatory system?
An Expert Advisory Committee on Biologicals will be established to consider, and provide advice on the regulatory framework for Biologicals. The Committee will perform a range of functions which will include:
- advising on the development of a risk management framework for Biologicals in Australia and New Zealand which includes impact assessment and consideration of the cost of the risk management framework; and
- advising on standards for collection, processing and manufacture of Biologicals.
Members of the Committee will have practical experience in the manufacture, testing and regulation of biological therapeutic products or other experience relevant to the functions of the Committee.
For what period will a product licence be valid?
A product licence will not expire (ie validity period will be perpetual) provided that the licence holder complies with all conditions attached to the product licence (including payment of all associated fees and charges).
What fees and charges will be charged for application assessment and maintenance of a product licence?
The schedule of fees and charges for the assessment of applications and granting/maintenance of product licences is yet to be confirmed. The fees and charges will be designed to recover the full costs of the joint regulatory scheme in an efficient and equitable manner and will comply with such other principles or requirements as may be prescribed in the Rules.
Further details regarding fees and charges for Biologicals will be incorporated into a Draft Rule.
Further information is provided in the Consultation Document entitled "Fees and charges under the Australia New Zealand Therapeutic Products Regulatory Scheme (pdf,353kb)" <http://www.anztpa.org/consult/dr-fees.pdf>
What guarantee does the manufacturer have to data protection?
Provisions will be included to protect data from 'unfair commercial use' or disclosure.
When evaluating a biological for a product licence, the Authority must not use information regarding another Biological if that information is protected.
What product licence conditions will be imposed on HCTs?
As is the case with medicines and therapeutic devices, there will be some mandatory conditions that apply to all licensed Biologicals (including HCTs). In addition to any statutory conditions, the Authority may also impose some specific conditions as part of a decision to issue a product licence.
Further information can be found under Part J: Conditions and other particulars on a Product Licence (pdf,219kb) <http://www.anztpa.org/consult/hct.pdf> of the HCT Consultation Paper.
Will manufacturers of HCTs also require a manufacturing licence?
Australian and New Zealand manufacturers of Class 2, Class 3 and Class 4 HCTs will need to hold a manufacturing licence issued by the Authority. The process to obtain a manufacturing licence for HCTs will be the same as any other therapeutic product under the joint scheme.
It is anticipated that, whilst individual product licences would be required for separate and distinct products, a manufacturing licence would be issued on the basis of compliance with standards and manufacturing principles and therefore could relate to the manufacture of a number of Biologicals.
Further information can be found under Part L: Manufacture of HCTs (pdf,219kb) <http://www.anztpa.org/consult/hct.pdf> of the HCT Consultation Paper.
How will applications be assessed if they are submitted prior to the commencement of the joint regulatory scheme?
Until the commencement of the joint regulatory scheme (the Scheme), applications will be received and assessments will be undertaken in accordance with existing arrangements (ie by the TGA under the Therapeutic Goods Act and by Medsafe under the Medicines Act).
Provisions for applications under consideration at the commencement of the joint regulatory scheme allow for the applicant to elect to have their application considered either by the ANZTPA under the joint regulatory scheme, or by TGA/Medsafe in accordance with the legislation under which it was submitted.
Transition arrangements are comprehensively addressed in Part Q: Transition Provisions of the HCT (pdf,219kb) <http://www.anztpa.org/consult/hct.pdf> Consultation Paper.
What is meant by "processing"?
Processing is currently defined as "Manufacturing using a process other than minimal primary separation". Primary separation is familiar to those involved in HCTs, and involves centrifugation, freezing, storage, trimming, flushing, washing and similar simple measures which do not involve industrial type processes in the manufacture.
Will Rules, Orders and Guidelines be public before the commencement of the joint regulatory scheme?
Yes.
Will the ANZTPA require manufacturing licences for laboratories providing contract testing for HCT facilities?
Facilities in Class 1 of the framework will continue to use accredited hospital laboratories for the purpose of conforming to the product standard. Facilities manufacturing in Classes 2, 3 and 4 will be expected to use testing laboratories which conform to the HCT facility's quality system.
URL: http://www.anztpa.org/bt/qahct.htm