Biologicals (priority applicant) determination - Eligibility criteria and supporting documentation requirements

Guidance for sponsors

This guidance is to help sponsors understand the eligibility criteria and supporting documentation requirements for a biological to be eligible for priority determination.

For guidance on the process of applying for priority determination, refer to Biologicals (priority applicant) Determination: A step-by-step guide.

Priority determination applications

If you intend to lodge a priority determination application and either of the following applies, email bloodandtissues@health.gov.au at least 1 month before lodgement:

• you have not had a pre-submission meeting with us to discuss your prospective application for priority determination
• your pre-submission meeting with us was more than six months ago

Before notifying us of your intent to lodge a priority determination application, consider all the following eligibility criteria and supporting documentation requirements.

Priority determination eligibility criteria

A biological product may be eligible for priority determination if all eligibility criteria in the following table are satisfied (regulation 16W of the Therapeutic Goods Regulations 1990).

Eligibility criteria for priority determination applications

Eligibility criteria	Requirements for satisfying the eligibility criteria
1. Biological	The biological is a separate and distinct Class 2 ,3 or 4 biological, generally it will be either:  a new biological, not currently in the Australian Register of Therapeutic Goods (ARTG) an existing biological in the ARTG but has a new intended use for a Class 2 biological or a new therapeutic indication for a Class 3 or 4 biological.
2. Serious condition	The biological is indicated for either: the treatment, prevention or diagnosis of a life-threatening a seriously debilitating condition.
3. Comparison against registered therapeutic goods	Either: no therapeutic goods that are intended to treat, prevent, or diagnose the condition are included in the ARTG if one or more therapeutic goods that are intended to treat, prevent or diagnose the condition are included in the ARTG (except in the part of the ARTG for goods known as provisionally registered goods) - there is substantial evidence demonstrating that the biological provides a significant improvement in the efficacy or safety of the treatment, prevention or diagnosis of the condition compared to those goods
4. Major therapeutic advance	There is substantial evidence demonstrating that the biological provides a major therapeutic advance.

Priority determination

Under subregulation 16W(3) of the Therapeutic Goods Regulations 1990, a priority determination is specific to the:

• priority applicant
• active ingredient of the biological to which the determination relates
• priority indication

A priority determination only applies to a specific biological for a specific indication. 

The proposed priority indication at the time of determination may be different to that subsequently approved at the time of inclusion of a biological in the Australian Register of Therapeutic Goods (ARTG).

The approved indication will be based on our assessment of the quality, safety and efficacy data submitted with the inclusion application.

Priority determination for one indication and one biological 

You can apply for only one biological and one priority indication in a determination application.

If you are seeking determination for multiple priority indications, you must submit one application for each indication.

An application that includes a combination of priority and non-priority indications will not be eligible for assessment under the priority review pathway.

However, multiple priority determinations may apply to one priority review application.

Supporting documentation requirements

The main body of your application should be no more than 10 pages. Include any additional supporting documentation as attachments.

The main body should address:

• justifications for addressing relevant eligibility criteria
• overseas regulatory status 

Attachments can include:

• summaries of pivotal studies.
  For example, the study synopsis included as part of the body of the clinical study report, or where study synopses are not available, a summary of the study with sufficient detail to inform assessment. A full module 2 summary is not required. Do not submit full study reports.
• summaries of any other available important safety data obtained in the preclinical and clinical setting
• where published papers are highly relevant, the full text of such literature (including supplementary appendices) and its relevance to the submission
• other forms of literature references or unpublished reports and expert statements may also be used in addition to the pivotal study summaries. However, these would be considered low-level evidence.
• abbreviations list.

Addressing the criteria

We will determine the validity of the justifications against the eligibility criteria on a case-by-case basis.

As part of the routine determination process, the extent to which criteria are met will be assessed at the time a decision is made on the application.

Criterion 1: Separate and distinct biological

The biological must be a Class 2, 3 or 4 biological which is separate and distinct.

A separate and distinct biological is generally either:

• a biological that has not previously been included in the ARTG
• an existing biological with a new therapeutic indication or intended use.

Criterion 2: Provide a justification of the life-threatening or seriously debilitating nature of the condition

You need to justify the severity of the disease (that is, its seriously debilitating or life- threatening nature) in Australia based on objective and quantifiable medical information.

Your determination application must justify the:

• life-threatening nature of the disease or condition based on figures of mortality and life expectancy in Australia
• seriously debilitating nature of the condition based on morbidity over the course of the disease and its consequences on patients’ day-to-day functioning

The serious debilitation or fatal outcome should be a prominent feature of both the target disease or condition and therapeutic indication (that is, affect an important portion of the target population).

The priority indication associated with your determination application should be the same as that proposed for inclusion in the Australian Register of Therapeutic Goods (ARTG).

Criterion 3: Comparison against other therapeutic goods in the ARTG for diagnosis, prevention, or treatment

You must establish either that:

• there are no therapeutic goods in the ARTG for diagnosis, prevention, or treatment of the condition in question
• your biological will provide a significant improvement in efficacy or safety over existing therapeutic goods in the ARTG

Any reference to a therapeutic good in the ARTG must be limited to the conditions of the relevant ARTG entry. A therapeutic good that is used outside the approved product information (that is, ‘off-label’ use) cannot be considered an existing therapeutic good for the purposes of the Therapeutic Goods Regulations 1990.

Provisionally registered goods in the ARTG are excluded from this comparison.

Therapeutic goods in the ARTG

You must review goods in the Australian Register of Therapeutic Goods (ARTG) for diagnosis, prevention, or treatment for the proposed priority indication in Australia and provide:

• details of any therapeutic goods in the ARTG for diagnosis, prevention, or treatment (Overview table of Trade name(s), holder of the ARTG entry and the registered indication)
• either:
  • a declaration that there are no therapeutic goods in Australia in accordance with ARTG entries at the date of determination application lodgement
  • a justification demonstrating a significant improvement in safety or efficacy against therapeutic goods in the ARTG
• a justification that the new indication should be considered if the biological is already included for a similar condition

Justification of significant improvement in safety or efficacy

You must demonstrate that there is substantial evidence that the biological provides an advantage over therapeutic goods in the ARTG for the priority indication (for treatment, prevention, or diagnosis of the condition) that is the subject of the determination application.

You can do this by addressing either of the following:

• improved efficacy for the entire population relevant to the priority indication
• a better safety profile for the entire population relevant to the priority indication

If new therapeutic goods for the diagnosis, prevention or treatment of your proposed priority indication are included in the ARTG after you lodge your application, you will have the opportunity to submit a further justification of significant improvement in safety or efficacy in relation to those goods before a decision is made on your application.

Supporting evidence

Supporting evidence should be based on clinical trial data. Increased safety or efficacy should be demonstrated through established safety and efficacy endpoints that demonstrate direct clinical benefit.

Comparator studies are expected to be generated (pivotal study reports). Scientific argument and/or justification for the significant improvement in safety or efficacy of the biological relative to products not studied in available clinical trials (this may involve cross study comparisons) may be considered.

For a claim of improved efficacy or safety, we will evaluate whether there is a high probability that patients will experience a clinically relevant benefit. It is critical this claim be supported by robust evidence from summaries of full study reports that form the basis of the intended inclusion application and justifications presented by the sponsor.

The evidence and/or data must take into account the particular characteristics of the condition (life expectancy, symptoms) and existing therapeutic goods in the ARTG for the treatment, prevention or diagnosis of the proposed therapeutic indication.

We will not assess significant benefit against comparator products that are the subject of:

• concurrent determination or ARTG inclusion applications
• provisional registration applications under review by us
• medicines that are currently provisionally registered

Diagnostic agents

Safety of diagnostic agents should be justified in the same way as for all other therapeutic goods. However, you should also consider diagnostic performance (sensitivity and specificity), predictive values and likelihood ratios in addition to other endpoints.

For further information refer to Guideline on Clinical Evaluation of Diagnostic Agents. 

Criterion 4: Justification of major therapeutic advance

Your determination application must provide justification that there is substantial evidence that the biological is a major therapeutic advance based on the following aspects:

• the magnitude of the demonstrated improvement in safety and/or efficacy
• endpoints that directly demonstrate clinical benefit
• the impact on patient outcomes considering both safety and efficacy
• the magnitude of the advance in relation to other therapeutic goods registered for the indicated population
• Where no products are in the ARTG, the comparison should occur against the standard of care
• the strength of evidence (general TGA adopted guidelines about appropriate trial design apply)

Magnitude of demonstrated improvements in safety or efficacy

You must include an assessment of the magnitude of the demonstrated improvement in safety or efficacy based on established safety and efficacy endpoints. 

Demonstration of a biological’s clinically significant benefit based on improved safety and/or efficacy is not sufficient. You must demonstrate that there is a major benefit beyond the level that could be described as clinically significant. For example, a major improvement in mortality endpoints.

Even if the benefit appears in one aspect only, you must assess the overall impact on patient outcomes considering both safety and efficacy. 

Patient-reported outcomes may be provided but are not a universal requirement (dependent on the setting).

Therapeutic advance compared to existing therapeutic goods

The biological should provide a substantial therapeutic advance in comparison with other therapeutic goods in the Australian Register of Therapeutic Goods (ARTG).

You must demonstrate that your biological substantially addresses a major or urgent unmet need for Australian patients. You must describe:

• how and to what extent the biological is expected to fulfil a major or urgent unmet medical need with reference to the therapeutic goods in the ARTG for the indicated population
• the importance of the effects of the proposed biological
• the added value of the proposed biological

Strength of evidence

The description of the strength of evidence should include a brief outline of the main available evidence on which the claim is based. For example, the number and type of clinical trials with clear delineation of pivotal versus supporting studies, sample size, design and key results. For further information on cross study comparisons, refer to the section on supporting evidence under Criterion 3.

A biological that demonstrates significant improvement in safety or efficacy may constitute a major therapeutic advance if for example, the biological demonstrates beneficial therapeutic effects that are considerably higher than those observed in previous treatment options. It may also replace standard treatment which has poor tolerability and potential for serious side effects.