The following table summarises the key steps and dates for this application, evaluated through Priority Review.
|Positive Designation (Orphan)||25 June 2019|
|Submission dossier accepted and first round evaluation commenced||28 August 2019|
|Evaluation completed||3 January 2020|
|Second round evaluation completed||6 January 2020|
|Delegate's overall benefit-risk assessment and request for Advisory Committee advice||2 January 2020|
|Sponsor's pre-Advisory Committee response||Not applicable|
|Advisory Committee meeting||7 February 2020|
|Registration decision (Outcome)||17 March 2020|
|Completion of administrative activities and registration on ARTG||2 April 2020|
|Number of working days from submission dossier acceptance to registration decision*||137|
*Target timeframe for priority applications is 150 working days from acceptance for evaluation to the decision.
Histidine, Sucrose, Polysorbate 20, Water for injections, Hydrochloric acid (for pH adjustment)
Qarziba must be administered under the direction of a physician experienced in the use of oncological therapies. The infusion must be initiated by a healthcare professional prepared to manage severe allergic reactions including anaphylaxis in an environment where full resuscitation services are immediately available.
Treatment with Qarziba consists of 5 consecutive courses, each course comprising 35 days.
- For patients weighing > 12 kg, the individual dose is determined based on the body surface area and should be a total of 100 mg/m2 per course.
- For patients weighing > 5 kg and ≤ 12 kg, the individual dose is determined based on body weight and should be a total of 3.3 mg/kg per course.
Two modes of administration are possible:
- a continuous infusion over the first 10 days of each course (a total of 240 hours) at the daily dose of 10 mg/m2 (for patients weighing > 12 kg) or 0.33 mg/kg (for patients weighing > 5 kg and ≤ 12 kg).
- or five daily infusions of 20 mg/m2 (for patients weighing > 12 kg) or 0.66 mg/kg (for patients weighing > 5 kg and ≤ 12 kg) administered over 8 hours, on the first 5 days of each course.
Prior to starting each treatment course, the following clinical parameters should be evaluated and treatment should be delayed until these values are reached:
- pulse oximetry > 94% on room air.
- adequate bone marrow function: absolute neutrophil count ≥ 500/µL, platelet count ≥ 20,000/µL, haemoglobin > 8.0 g/dL.
- adequate liver function: alanine aminotransferase (ALT)/ aspartate aminotransferase (AST) < 5 times upper limit of normal (ULN).
- adequate renal function: creatinine clearance or glomerular filtration rate (GRF) > 60 mL/min/1.73 m2.
For further information refer to the Product Information.
Qarziba (dinutuximab beta) was approved for the following therapeutic use:
Qarziba is indicated for the treatment of high-risk neuroblastoma in patients who have previously received induction chemotherapy and achieved at least a partial response.
- It is a condition of registration that all batches of Qarziba (dinutuximab beta) imported into/manufactured in Australia must comply with the product details and specifications approved during evaluation and detailed in the Certified Product Details (CPD).
- It is a condition of registration that up to 5 initial batches of Qarziba (dinutuximab beta) imported into/manufactured in Australia is not released for sale until samples and/or the manufacturer's release data have been assessed and endorsed for release by the TGA Laboratories Branch. Outcomes of laboratory testing are published biannually in the TGA Database of Laboratory Testing Results.
- The sponsor should be prepared to provide product samples, reference materials and documentary evidence as defined by the TGA Laboratories branch. The sponsor must contact Biochemistry.Testing@health.gov.au for specific material requirements related to the batch release testing/assessment of the product. More information on TGA testing of biological medicines is available at Testing of biological medicines. This batch release condition will be reviewed and may be modified on the basis of actual batch quality and consistency. This condition remains in place until the sponsor is notified in writing of any variation.
- The Certified Product Details (CPD), as described in Guidance 7: Certified Product Details of the Australian Regulatory Guidelines for Prescription Medicines (ARGPM), in PDF format, for the above products should be provided upon registration of these therapeutic goods. In addition, an updated CPD should be provided when changes to finished product specifications and test methods are approved in a Category 3 application or notified through a self-assessable change.
- Qarziba (Dinutuximab beta) is to be included in the Black Triangle Scheme. The Product Information (PI) and Consumer Medicines Information (CMI) for Qarziba must include the black triangle symbol and mandatory accompanying text for five years, which starts from the date that the sponsor notifies the TGA of supply of the product.
- The Qarziba European Union-Risk Management Plan (EU-RMP) (version 8.0, date 29 March 2017; data lock point (DLP) 11 November 2015), with Australian specific Annex (version 1.0, dated 10 July 2019), included with submission PM-2019-03174-1-4, and any subsequent revisions, as agreed with the TGA will be implemented in Australia.
An obligatory component of risk management plans is routine pharmacovigilance. Routine pharmacovigilance includes the submission of periodic safety update reports (PSURs).
Reports are to be provided in line with the current published list of EU reference dates and frequency of submission of PSURs until the period covered by such reports is not less than three years from the date of the approval letter.
The reports are to at least meet the requirements for PSURs as described in the European Medicines Agency's Guideline on Good Pharmacovigilance Practices (GVP) Module VII-periodic safety update report (Rev 1), Part VII.B Structures and processes. Note that submission of a PSUR does not constitute an application to vary the registration.
- For all injectable products the Product Information must be included with the product as a package insert.