Priority review designation eligibility criteria

Including supporting documentation

7 July 2017

This guidance helps sponsors understand the eligibility criteria and supporting documentation required for a medicine to be eligible for Priority Review designation.

To assist with the process of applying for Priority Review designation, please refer to the guidance on the Priority Review designation: A step-by-step guide for prescription medicines.

Eligibility for Priority Review designation

Consider the eligibility criteria and supporting documentation before notifying the TGA of your intent to lodge a Priority Review designation application proposed one month prior to designation application.

Priority designation may be granted only for the following medicines:

  1. a new prescription medicine which contains:
    1. a chemical, biological or radiopharmaceutical active ingredient that has not previously been included in the Register; or
    2. a fixed combination of chemical, biological or radiopharmaceutical active ingredients at least one of which has not previously been included in the Register
  2. an already registered prescription medicine with a new indication (a new indications medicine) that contains:
    1. the same chemical, biological or radiopharmaceutical active ingredient (or fixed combination of such ingredients) as another prescription medicine included in the Register; and
    2. does not have the same indications as that other medicine

The designation will apply to the corresponding registration application for a new prescription medicine or new indications medicine:

Priority review eligibility criteria

A medicine may be eligible for Priority Review designation if all three eligibility criteria in the table below are satisfied.

Eligibility criteria for the Priority Review designation
  1. Serious condition
an indication of the medicine (the priority indication) is the treatment, prevention or diagnosis of a life-threatening or seriously debilitating condition; AND
  1. Comparison against existing therapeutic good

either:

  1. no therapeutic goods that are intended to treat, prevent or diagnose the condition are included in the Register; OR
  2. if one or more therapeutic goods that are intended to treat, prevent or diagnose the condition are included in the Register-there is substantial evidence demonstrating that the medicine provides a significant improvement in the efficacy or safety of the treatment, prevention or diagnosis of the condition compared to those goods; AND
  1. Major therapeutic advance
there is substantial evidence demonstrating that the medicine provides a major therapeutic advance

Priority Review designation

The Priority Review designation for a medicine is specific to the:

  • the person who is the priority applicant ; and
  • each active ingredient of the medicine; and
  • the priority indication

The priority designation therefore applies to a specific medicine for a specific indication.

The proposed Priority Review therapeutic indication may be different to that approved at the time of registration as a result of the assessment of the quality, safety and efficacy data submitted with the submission for registration.

You can apply for only one indication in a designation application. If you are seeking designation for multiple indications, you must submit one application for each indication. Multiple designations may apply to one registration application. A registration application that is a combination of Priority Review and non-priority review indications will not be eligible for review under the Priority Review pathway.

If the application for which you are seeking a priority review is supported by clinical trials where an in vitro diagnostic device was used to select patients who should or should not be treated, or monitor patients with the aim of improving safety or efficacy of the medicine, it is important that you:

  • specify the name of the manufacturer/sponsor for that in vitro device
  • ensure that the requisite application as a Class 3 in vitro device has been made already or is planned for lodgement at the same time as your registration application

Supporting documentation requirements

The main body of your application should be no more than 10 pages. Additional attachment of supporting documentation can be included as attachments. The main body should address:

  • justifications for addressing relevant eligibility criteria

Attachments can include:

  • summaries of pivotal studies (e.g. 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 available other 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)
  • other forms of literature references or unpublished reports and expert statements may also be used in addition to the pivotal study summaries but would be considered low-level evidence
  • an abbreviations list

Content of the designation application

We will determine the validity of the justifications on a case-by-case basis. Upon receipt of a priority application designation it should be noted that revocation by TGA may take place at any time prior to a section 23 application being accepted and deemed effective. However, we will not routinely review designation decisions during their validity, and would do so in exceptional circumstances.

Criterion 1: Provide a justification of the life-threatening or seriously debilitating nature of the condition

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

Your designation 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

Furthermore, the serious debilitation or fatal outcome should be a prominent feature of both the target disease or condition and therapeutic indication, i.e. affect an important portion of the target population.

Criterion 2: Comparison against existing therapeutic goods for diagnosis, prevention or treatment in Australia

You must establish that there are no existing therapeutic goods for diagnosis, prevention or treatment of the condition in question included on the ARTG, or if such therapeutic goods exists that the medicine will provide a significant improvement in efficacy or safety.

Any reference to a registered therapeutic good must be limited to the conditions of the relevant register entry. Therefore, a product that is administered or applied outside the approved summary of product characteristics ('off-label' use) cannot be considered an existing therapeutic good for the purposes of the Therapeutic Goods Regulations 1990.

Existing therapeutic goods

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

  • details of any existing therapeutic goods for diagnosis, prevention or treatment (Overview table of Tradename(s), holder of the ARTG entry, and the registered indication) AND
  • either a declaration that there are no existing therapeutic goods in Australia in accordance with ARTG entries at the date of designation lodgement OR
  • a justification demonstrating a significant improvement in safety or efficacy against existing therapeutic goods

Justification of significant improvement in safety or efficacy

You must demonstrate that there is substantial evidence that the medicine provides an advantage over existing therapeutic goods for the indication that is the subject of the designation application (for either treatment, prevention or diagnosis of the condition) by addressing either of the following:

  • improved efficacy for the entire population relevant to the therapeutic indication; OR
  • a better safety profile for the entire population relevant to the therapeutic indication

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/justification for the significant improvement in safety or efficacy of the medicine 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 (eligibility criterion 2,ii), we will evaluate whether there is a high probability that patients will experience a clinically relevant benefit. Therefore, this claim has to be supported by robust evidence from summaries of full study reports that form the basis of the intended registration application, and justifications presented by the sponsor. The evidence/data must be considered in light of the particular characteristics of the condition (life expectancy, symptoms) and the existing medicines for the treatment, prevention or diagnosis of the proposed therapeutic indication. The TGA will not assess significant benefit against comparators that are a subject of concurrent designation applications.

For diagnostic agents you should consider diagnostic performance (sensitivity and specificity), predictive values and likelihood ratios, among other endpoints. Further information is available in the Guideline on Clinical Evaluation of Diagnostic Agents. You should justify safety in the same way as for all medicines.

Criterion 3: Justification of major therapeutic advance

Your designation application must provide a justification that there is substantial evidence that the medicine 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 taking into account both safety and efficacy
  • the magnitude of the advance in relation to other therapeutic goods registered for the indicated population. Where no product is on the ARTG, the comparison should occur against the standard of care
  • the strength of evidence (general TGA adopted guidelines about appropriate trial design apply)

You must include an assessment of the magnitude of the demonstrated improvement in safety or efficacy based on established safety and efficacy endpoints. The demonstration of a medicine's clinically significant benefit based on improved safety and/or efficacy is not sufficient. Rather, there should be demonstration of a major benefit, i.e. beyond the level that could be described as clinically significant (e.g. a major improvement in mortality endpoints). Even if the benefit appears in one aspect only, you must assess the overall impact on patient outcomes taking into account both safety and efficacy. Patient-reported outcomes may be provided, but are not a universal requirement (depending on the setting).

The medicine should provide a therapeutic advance, in comparison with other therapeutic goods, by addressing a major or urgent unmet need for Australian patients in a substantial way. You must describe how and to what extent the medicine is expected to fulfil a major or urgent unmet medical need with reference to the therapeutic goods registered for the indicated population, the importance of the effects of the proposed medicine, and the added value of the proposed medicine.

The description of the strength of evidence should include a brief outline of the main available evidence (e.g. number and type of clinical trials with clear delineation of pivotal versus supporting studies, sample size, design and key results) on which the claim is based. In this context, weak data evidence would be weighted less than comprehensive data evidence. Refer to the section above for further information on cross study comparisons.

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

Definitions

The following definitions are applicable in the context of this guideline:

  1. condition: any deviation(s) from the normal structure or function of the body, as manifested by a characteristic set of signs and symptoms (typically a recognised distinct disease or a syndrome)
  2. therapeutic indication: the proposed indication for the ARTG registration, based on the proposed indication at the time of the designation application
  3. medicine:
    1. therapeutic goods (other than biologicals) that are represented to achieve, or are likely to achieve, their principal intended action by pharmacological, chemical, immunological or metabolic means in or on the body of a human; and
    2. any other therapeutic goods declared by the Secretary, for the purpose of the definition of therapeutic device, not to be therapeutic devices
  4. new indications medicine means a prescription medicine that:
    1. has the same chemical, biological or radiopharmaceutical active ingredient (or fixed combination of such ingredients) as another prescription medicine included in the Register; and
    2. ii. does not have the same indications as that other medicine
  5. new prescription medicine means a prescription medicine that contains:
    1. a chemical, biological or radiopharmaceutical active ingredient that has not previously been included in an entry in the Register; or
    2. a fixed combination of chemical, biological or radiopharmaceutical active ingredients at least one of which has not previously been included in an entry in the Register
  6. life-threatening: a prominent feature of the condition (i.e. affecting an important portion of the target population) is serious illness from which death is reasonably likely to occur within a matter of months, or from which premature death is reasonably likely to occur in the absence of treatment based on mortality and life expectancy data
  7. seriously debilitating condition: a prominent feature of the condition (i.e. affecting an important portion of the target population) is morbidity with a well-established, major impact on the functioning of the person based on objective and quantifiable medical or epidemiologic information. Short lived and /or self-limiting morbidity is not considered seriously debilitating
  8. existing therapeutic goods: therapeutic goods (medicines or medical devices or biologicals) included in the ARTG that are indicated for the treatment, prevention or diagnosis of the condition
  9. major therapeutic advance: An improvement in the safety and/or efficacy of the medicine, that is of a magnitude well beyond the minimum threshold of clinical significance. The impact on patient outcomes for the indicated population will take into account effects on both efficacy and safety. The magnitude of the demonstrated improvement in safety and/or efficacy will be assessed in relation to other therapeutic goods registered for the indicated population

Related designation applications for Priority Review and Orphan Drug designation may be submitted either together or sequentially. The proposed therapeutic indication for Priority Review must be identical to, or a subset of, the orphan indication. You may wish to submit joint justifications for overlapping criteria. The table below sets out circumstances in which joint justifications are permitted.

Conditions under which joint justifications are permitted
Designation criteria Description Applies to Priority Review (PR) / Orphan Drug designation (OD) Joint justification permitted
Serious condition the medicine is indicated for the treatment, prevention or diagnosis of a life threatening or seriously debilitating condition PR,OD Yes
Comparison against existing therapeutic goods there are no existing therapeutic goods registered in Australia that are indicated for the treatment, prevention or diagnosis of the condition PR,OD Yes
Improved safety or efficacy there is substantial evidence demonstrating that the medicine provides a significant improvement in efficacy or safety (or both) over existing therapeutic goods registered in Australia that are indicated for the treatment, prevention or diagnosis of the condition

PR

(may apply to OD)

May be permitted
Major therapeutic advance there is substantial evidence demonstrating that the medicine provides a major therapeutic advance PR No
Significant benefit if there are existing therapeutic goods registered in Australia that are indicated for the treatment, prevention or diagnosis of the condition, the medicine represents a significant benefit over these therapeutic goods OD May be permitted when addressing safety and efficacy, but not where a major contribution to patient care is addressed
Orphan prevalence threshold or lack of financial viability

the medicine is intended for the treatment, prevention or diagnosis of a condition affecting not more than five in 10 thousand persons in Australia when the application is made

OR

it is unlikely that it would be financially viable for the sponsor of the Orphan Drug to market the medicine presentation in Australia without a waiver of the application and evaluation fees that would otherwise apply for the registration of the medicine (and, where relevant, the priority designation fee)

OD No
Medical plausibility
  1. the rationale for use of the medicinal product in the proposed orphan indication is established
  2. where the orphan indication refers to a subset of a particular condition, a justification of the medical plausibility for restricting the medicine in the subset is required
OD No

Version history

Version Description of change Author Effective date
V1.0 Original publication Policy and Reform Facilitation, Prescription Medicines Authorisation Branch June 2017
V1.1 Minor text corrections Policy and Reform Facilitation, Prescription Medicines Authorisation Branch July 2017