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Ciptunec/Ardalicip
Sponsor
ARTGs
Device/Product name
Ciptunec/Ardalicip
Active Ingredient
Adalimumab
Date of decision
Published
Submission type
New biosimilar medicine
ATC codes
L04AB04
Decision
Approved
What was the decision based on
The decision was based on quality (chemistry and manufacturing), nonclinical (pharmacology and toxicology), clinical (pharmacology, safety and efficacy) and risk management plan information submitted by the sponsor. The benefit-risk profile of Ciptunec/Ardalicip was considered favourable for the therapeutic use approved.
What steps were involved in the decision process
Registration timeline
The following table summarises the key steps and dates for this application.
|
Description |
Date |
|
Submission dossier accepted and first round evaluation commenced |
31 August 2021 |
|
First round evaluation completed |
15 March 2022 |
|
Sponsor provides responses on questions raised in first round evaluation |
30 March 2022 |
|
Second round evaluation completed |
19 August 2022 |
|
Delegate’s Overall benefit-risk assessment |
29 July 2022 |
|
Sponsor’s pre-Advisory Committee response |
Not applicable |
|
Advisory Committee meeting |
Not applicable |
|
Registration decision (Outcome) |
23 August 2022 |
|
Completion of administrative activities and registration on ARTG |
6 September 2022 |
|
Number of working days from submission dossier acceptance to registration decision* |
147 |
*Statutory timeframe for standard applications is 255 working days
Date of entry onto ARTG
Black triangle scheme
No
Dose forms
Solution for injection
Strength
100 mg/mL (40 mg/0.4 mL and 80 mg/0.8 mL)
Other ingredients
Sodium chloride, sucrose, polysorbate 80, and water for injections
Containers
Pre-filled syringe and pre-filled pen
Pack sizes
One (for 80 mg/0.8 mL pre-filled syringes only) 2 and 6
Routes of administration
Subcutaneous
Dosage
Dosage is based on multiple factors, including the condition being treated, the age and weight of the patient.
Ardalicip is intended for use under the guidance and supervision of a physician.
This product is for one dose in one patient only.
Healthcare providers should be advised that there is no dosage form of Ardalicip available which allows dosing of less than 40 mg. As a result, there are no suitable Ardalicip dosage forms available for a subset of the following paediatric indications:
- Juvenile idiopathic arthritis: children weighing less than 30 kg.
- Paediatric Crohn’s disease (6 to 17 years): maintenance therapy in children weighing less than 40 kg.
- Paediatric plaque psoriasis (4 to 17 years): children weighing less than 40 kg.
For further information refer to the Product Information.
Pregnancy category
C
Drugs which, owing to their pharmacological effects, have caused or may be suspected of causing, harmful effects on the human fetus or neonate without causing malformations. These effects may be reversible. Accompanying texts should be consulted for further details.
The use of any medicine during pregnancy requires careful consideration of both risks and benefits by the treating health professional. This must not be used as the sole basis of decision making in the use of medicines during pregnancy. The TGA does not provide advice on the use of medicines in pregnancy for specific cases. More information is available from obstetric drug information services in your State or Territory.
Drugs which, owing to their pharmacological effects, have caused or may be suspected of causing, harmful effects on the human fetus or neonate without causing malformations. These effects may be reversible. Accompanying texts should be consulted for further details.
The use of any medicine during pregnancy requires careful consideration of both risks and benefits by the treating health professional. This must not be used as the sole basis of decision making in the use of medicines during pregnancy. The TGA does not provide advice on the use of medicines in pregnancy for specific cases. More information is available from obstetric drug information services in your State or Territory.
What was approved
Ciptunec/Ardalicip (adalimumab) was approved for the following therapeutic use:
Rheumatoid arthritis
Ciptunec and Ardalicip are indicated for reducing signs and symptoms, as well as inhibiting the progression of structural damage in adult patients with moderate to severely active rheumatoid arthritis. This includes the treatment of patients with recently diagnosed moderate to severely active disease who have not received methotrexate.
Ciptunec and Ardalicip can be used alone or in combination with methotrexate.
Juvenile idiopathic arthritis
Polyarticular juvenile idiopathic arthritis
Ciptunec and Ardalicip in combination with methotrexate is indicated for reducing the signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis in patients 2 years of age and older weighing ≥ 30 kg who have had an inadequate response to one or more disease modifying anti-rheumatic drugs (DMARDs). Ciptunec and Ardalicip can be given as monotherapy in case of intolerance to methotrexate or when continued treatment with methotrexate is inappropriate.
Enthesitis-related arthritis
Ciptunec and Ardalicip are indicated for the treatment of enthesitis-related arthritis in children, who have had an inadequate response to, or who are intolerant to, conventional therapy.
Psoriatic arthritis
Ciptunec and Ardalicip are indicated for the treatment of signs and symptoms, as well as inhibiting the progression of structural damage, of moderate to severely active psoriatic arthritis in adult patients where response to previous DMARDs has been inadequate.
Ankylosing spondylitis
Ciptunec and Ardalicip are indicated for reducing signs and symptoms in patients with active ankylosing spondylitis.
Crohn’s disease in adults and children (≥ 6 years; weighing ≥ 40 kg)
Ciptunec and Ardalicip are indicated for the treatment of moderate to severe Crohn’s disease, to reduce the signs and symptoms of the disease and to induce and maintain clinical remission in patients;
- who have had an inadequate response to conventional therapies or,
- who have lost response to or are intolerant to infliximab.
Ulcerative colitis
Ciptunec and Ardalicip are indicated for the treatment of moderate to severe ulcerative colitis in adult patients who have had an inadequate response to conventional therapy or who are intolerant to or have medical contraindications for such therapies. Patients should show a clinical response within 8 weeks of treatment to continue treatment beyond that time (see section 5.1 Pharmacodynamic properties -clinical trials).
Psoriasis in adults and children
Ciptunec and Ardalicip are indicated for the treatment of moderate to severe chronic plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy.
Ciptunec and Ardalicip are indicated for the treatment of severe chronic plaque psoriasis in children and adolescent patients from 4 years of age weighing ≥ 40 kg who have had an inadequate response to or are inappropriate candidates for topical therapy and phototherapy.
Hidradenitis suppurativa in adults and adolescents (from 12 years of age)
Ciptunec and Ardalicip are indicated for the treatment of active moderate to severe hidradenitis suppurativa (acne inversa) in patients with an inadequate response to conventional systemic hidradenitis suppurativa therapy.
Uveitis
Ciptunec and Ardalicip are indicated for the treatment of non-infectious intermediate, posterior and pan-uveitis in adult patients who have had an inadequate response to corticosteroids, in patients in need of corticosteroid sparing, or in whom corticosteroid treatment is inappropriate.
What is this medicine and how does it work
Ardalicip (adalimumab) is a biosimilar medicine to Humira.
Adalimumab binds to tumour necrosis factor (TNF) and neutralises the biological function of TNF by blocking its interaction with the p55 and p75 cell surface TNF receptors. TNF is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. Elevated levels of TNF are found in the synovial fluid of rheumatoid arthritis, including juvenile idiopathic arthritis, psoriatic arthritis and ankylosing spondylitis patients and play an important role in both the pathologic inflammation and the joint destruction that are hallmarks of these diseases. Increased levels of TNF are also found in psoriasis plaques, which contribute to the inflammatory response, to the proliferation and decreased maturation of keratinocytes and to the associated vascular damages that are characteristic of the disease.
Adalimumab also modulates biological responses that are induced or regulated by TNF, including changes in the levels of adhesion molecules responsible for leukocyte migration (endothelial leukocyte adhesion molecule-1(ELAM-1), vascular cell adhesion molecule-1 (VCAM 1), and intercellular adhesion molecule 1 (ICAM-1) with a half maximal inhibitory concentration (IC50) of 1 to 2 x 10-10 M).
Adalimumab binds to tumour necrosis factor (TNF) and neutralises the biological function of TNF by blocking its interaction with the p55 and p75 cell surface TNF receptors. TNF is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. Elevated levels of TNF are found in the synovial fluid of rheumatoid arthritis, including juvenile idiopathic arthritis, psoriatic arthritis and ankylosing spondylitis patients and play an important role in both the pathologic inflammation and the joint destruction that are hallmarks of these diseases. Increased levels of TNF are also found in psoriasis plaques, which contribute to the inflammatory response, to the proliferation and decreased maturation of keratinocytes and to the associated vascular damages that are characteristic of the disease.
Adalimumab also modulates biological responses that are induced or regulated by TNF, including changes in the levels of adhesion molecules responsible for leukocyte migration (endothelial leukocyte adhesion molecule-1(ELAM-1), vascular cell adhesion molecule-1 (VCAM 1), and intercellular adhesion molecule 1 (ICAM-1) with a half maximal inhibitory concentration (IC50) of 1 to 2 x 10-10 M).
What post-market commitments will the sponsor undertake
- The adalimumab European Union (EU)-risk management plan (RMP) (version 0.3, dated 30 July 2021, data lock point 12 March 2020), with Australia specific annex (version 1.1, dated 5 July 2022), included with Submission PM-2021-02447-1-3, 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 (revision 1), Part VII.B structures and processes. Note that submission of a PSUR does not constitute an application to vary the registration.
- Laboratory testing and compliance with Certified Product Details (CPD)
- All batches of Ciptunec and Ardalicip (adalimumab) supplied in Australia must comply with the product details and specifications approved during evaluation and detailed in the Certified Product Details (CPD).
- When requested by the TGA, the sponsor should be prepared to provide product samples, specified reference materials and documentary evidence to enable the TGA to conduct laboratory testing on the product. Outcomes of laboratory testing are published biannually in the TGA Database of Laboratory Testing Results https://www.tga.gov.au/resources/lab-test-reports and periodically in testing reports on the TGA website.
Certified Product Details
The Certified Product Details (CPD), as described in Guidance 7: Certified Product Details of the Australian Regulatory Guidelines for Prescription Medicines (ARGPM) [https://www.tga.gov.au/industry/pm-argpm-guidance-7.htm in PDF [Portable Document 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.
- For all injectable products the Product Information must be included with the product as a package insert.