Review of National Gene Technology Scheme - Online Submissions

With the advancement in technology, first generation viral vectors which were commonly used as tools to manufacture GMO products have been refined over time to rise to second, third or more generational vectors. Generational vector refinement has in many cases resulted in a vector tools with little to no potential risk compared to its first generation cousin.

Using the above as an example, we feel the Scheme should accommodate this continual refinement of GT tools to lower the regulatory burden of GMOs manufactured using what can be shown to be very stable and safe GT production systems (from a process perspective).

The ability to make small edits in DNA without the introduction of foreign DNA using techniques such as site-directed mutagenesis and now, more commonly, artificial gene synthesis is not a new innovation and has been used by researchers to generate candidates for medical use since the 1990s. Moreover, small changes in DNA occur spontaneously without the use of molecular techniques, with and without the assistance of selective breeding.

We see one of the main challenges being how to define if a particular product could spontaneously occur in nature to one that could only be created using DNA-editing techniques. If a definition around this can be created, it would allow for a clear definition of the appropriate regulatory process.

With regard to medicinal products such as vaccines which use this technique (which could arguably be resultant of a spontaneous mutation to give the same product as one manufactured using gene editing), we feel the current Scheme sufficiently regulates these types of products on the basis of potential risk. As with other technologies currently regulated under the Scheme, we feel there should be a greater emphasis on the benefit of any GMO weighted against any potential risk, especially where the risks are extremely low.

Emerging technologies such as synthetic biology, human germline gene therapy and gene drives have exciting possibilities in medicine, crop yields and pest control. We feel that as more novel technologies are invented and widely used the current Scheme will fall short of capturing the totality of the risks and benefits of the technologies. The solution may come, in part, in the form of customized guidances for industry and researchers to cover individual technologies, in much the same fashion as regulatory authorities such as the European Medicines Agency have released a number of scientific guidelines for the clinical development medicinal products for specific indications e.g. CPMP/EWP/1080/00 Rev. 1 Guideline on clinical investigation of medicinal products in the treatment or prevention of diabetes mellitus (note this guideline is adopted in Australia).

However, making changes to the current scheme to address some issues and 'future proof' the scheme for evolving technologies will no doubt introduce new challenges to the scheme that are not currently issues.

Although the potential for using such technologies as gene drives to eradicate pest species in Australia could be a very powerful and effective tool, we feel there is a need for caution and contingency planning (such as a gene drive reversal mechanism available), in at least some situations. In the example given in the consultation document of European carp, with global transport of vertebrates either intentionally or unintentionally, such a modification could potentially decimate native carp species in other global jurisdictions.

No comment

As discussed in the Phase II consultation document, Canada’s approach to gene technology is based on a product trigger, where the emphasis in regulation is on the GMO rather than the methods used to produce the modified traits. It is our opinion that although there are potentially beneficial safety advantages of Australia’s regulation basis using the process trigger, these are outweighed (in our experience), by the regulatory burden this approach to GT regulation incurs. In addition, although the process trigger is the underpinning mechanism of GT regulation in Australia, there is already a “hybrid” (process/product) assessment of the production technology and resulting GMO.

We feel a hybrid approach focused more heavily on a product trigger, would be appropriate for regulation of GMOs in the future. This would reduce the weight of consideration of production detail that in some cases (especially medicine production), poses a very low risk if the product is not a GMO.

Where a hybrid approach is practical but also creates challenges is where GMO products are part of the process.

As mentioned above, we feel the approach to regulation of GMOs whether process or product, should be based on the risk/benefit of the individual or type of process product.

In our experience working with products for clinical trial, review of GT therapies for human use is adequately covered by the current scheme from the perspective of protecting people and the environment. The Therapeutic Goods Administration, although does not review the environmental impact of investigational GMOs for human use, does review the safety of these products under the clinical trial exemption scheme, before first in human use, as GMOs are Class 4 biologicals as defined under the Australian Biological Framework. In addition, any unexpected adverse events experienced by the patient receiving a GMO during a clinical trial are reported to the TGA. Therefore, we feel this there is some overlap in the assessment of safety of human participants both before and during release. Noting that the current scheme does not assess the effect of the GMO directly on patient safety, however, in practice, the OGTR request this information.

To address this, we feel the OGTR reporting during release should focus only on events that affect people other than the patients (or healthy volunteers) receiving the therapy e.g. secondary transmission events. In addition to those events that could have adverse effects on the environment e.g. loss of containment.

Provide a clear definition of safety reporting to the OGTR for clinical trials more clearly taking into considerations the other mandatory procedures in place for safety reporting to the TGA/ethics committees.

This should require input from a number of areas in the community and could include a working group diverse specialists (e.g. industry, university, general public) to generate appropriate messaging.

This is an interesting dilemma. With the luxury of hindsight, it could argued that this issue should have been given more extensive consideration many years ago before the general public and some organisations have become very and possibly avoidably polarized regarding the risk/benefit profile of GMOs and other science-based technology.

Our experience in the area of therapeutic products, especially for potentially life-saving indications, the acceptance of the use of science-based technologies to drive the development of new medicines to address unmet need is widely accepted by the medical community and the patients that receive treatment. In addition, there appears to be little resistance from the general public to the development of these technologies as, although they may not understand the science, the risk/benefit profile falls more heavily toward the benefit. One exception is germ-line gene therapy that although has clearly conceivable benefits, does potentially pose ethical issues and is not a GT technique currently approved for use in Australia.

Unfortunately, there does not appear to be a simple solution to educate the general public on the benefits of science-based technology, especially in the area of plant research, without generating an underlining feeling of suspicion or ulterior (mainly commercial) motive.

Our only suggestion is to find media outlets to introduce simple informative and reassuring messages regarding the stringency around the regulation of GT and science-based technology in Australia. In addition, describe the benefits to people and the necessity of this technology with real life stories e.g. drought-resistant crops and higher yielding crops.

Regarding regulation, we feel there needs to be a clear separation of the government’s role in regulation to the interests of the applicant – especially where there is a clear commercial gain for the applicant and perhaps little conceived benefit to the public.

As mentioned above, we feel there is confidence in the area of GT used in medicinal research. This is partially aided by the respect of the community for scientists and health care professionals who, in our opinion, are seen largely as altruistic professions.

Over a period of time a mantra seems to have evolved in the community that for passionate drivers such as “find a cure for cancer” we need to invest in medical research and medical research equates to science-based technologies such as GT. To what level the community understand that there is any regulation around this type of use of GT is questionable and perhaps not overly consequential in gaining their support.

As opposed to medical research, there appears to be less confidence in the community relating to genetic modification of plants. As discussed in point 1 of this section, the community and some organizations have become quite polarized with respect to the necessity, benefits and motivation behind the use of plants that are genetically modified. This could be extended to live stock that are in anyway chemically assisted to exhibit traits that make them more profitable to farm e.g. faster growth, weight gain or medication to stop disease spread required at least partially as a consequence of living in close proximity to one another.

We don’t think the basis of this opposition is the lack of confidence in gene technology regulation in Australia, although making the community aware of regulation (as discussed in point 1), could be part of the solution. The causes for resistance and lack of confidence are more likely due to a lack of education as to why GT is required if we are going to be able to generate sufficient food to feed a growing human population; the “if it isn’t broken don’t fix it” opinion. We feel another reason is the lingering and perhaps embedded distrust of the commercial use of GT caused by the media portrayal of GT crops produced by commercial industry. In addition, with little or no knowledge of the risks of GT used to produce food, when there is a non-GT alternative, it is not surprising that a proportion of the general community see no benefit using GT to generate anything in their food supply. We note that GT crops have been used to manufacture general foodstuffs for many years without the requirement to disclose this information on packaging.

Primarily, the public need to know how GT will benefit them and the larger community and why it is necessary. Providing simple messaging informing the community about what GT involves and the stringent requirements, including risk assessments performed by different government Agencies, would aid in this messaging.

We feel the best outlet for this information would be in a format that didn’t in any way appear to be generated by a party that had financial gain from the messaging.

Perhaps a starting point would be to discuss the regulation of GT in the context of life-saving medicines, where some may consider these to be over-regulated resulting in slower than necessary entry to the market. From there, the messaging for GT regulation could progress into arguably move controversial areas.