Summary Basis of Decision for Kisqali
Review decision
The Summary Basis of Decision explains why the product was approved for sale in Canada. The document includes regulatory, safety, effectiveness and quality (in terms of chemistry and manufacturing) considerations.
Product type:
Summary Basis of Decision (SBD) documents provide information related to the original authorization of a product. The SBD for Kisqali is located below.
Recent Activity for Kisqali
SBDs written for eligible drugs approved after September 1, 2012 will be updated to include post-authorization information. This information will be compiled in a Post-Authorization Activity Table (PAAT). The PAAT will include brief summaries of activities such as submissions for new uses of the product, and whether Health Canada's decisions were negative or positive. PAATs will be updated regularly with post-authorization activity throughout the product's life cycle.
Post-Authorization Activity Table (PAAT) for Kisqali
Updated:
The following table describes post-authorization activity for Kisqali, a product which contains the medicinal ingredient ribociclib. For more information on the type of information found in PAATs, please refer to the Frequently Asked Questions: Summary Basis of Decision (SBD) Project: Phase II and to the list of abbreviations that are found in PAATs.
For additional information about the drug submission process, refer to the Management of Drug Submissions Guidance.
Drug Identification Number (DIN)
- DIN 02473569 - 200 mg, ribociclib, tablet, oral
Post-Authorization Activity Table (PAAT)
| Activity/submission type, control number | Date submitted | Decision and date | Summary of activities |
|---|---|---|---|
| SNDS # 220948 | 2018-10-12 | Issued NOC2019-09-09 | Submission filed as a Level I - Supplement to provide an efficacy update to the PM based on longer term follow up of patients in the pivotal trial CLEE011A2301. As a result of the SNDS, modifications were made to the Clinical Trials section of the PM. Based on the data presented to date, the benefit-risk ratio of the product is considered to remain favourable. The submission was reviewed and considered acceptable, and an NOC was issued. |
| NC # 220114 | 2018-09-13 | Issued NOL2018-11-26 | Submission filed as a Level II (90 day) Notifiable Change to update the PM with safety-related changes. As a result of the NC, modifications were made to the Warnings and Precautions, Dosage and Administration, and Action and Clinical Pharmacology sections of the PM. The submission was reviewed and considered acceptable, and an NOL was issued. |
| Drug product (DIN 02473569) market notification | Not applicable | Date of first sale:2018-04-24 | The manufacturer notified Health Canada of the date of first sale pursuant to C.01.014.3 of the Food and Drug Regulations. |
| NDS # 203884 | 2017-03-17 | Issued NOC2018-03-02 | Notice of Compliance issued for New Drug Submission. |
Summary Basis of Decision (SBD) for Kisqali
Date SBD issued: 2018-06-18
The following information relates to the new drug submission for Kisqali.
Ribociclib
200 mg, tablet, oral
Drug Identification Number (DIN):
- 02473569
Novartis Pharmaceuticals Canada Inc.
New Drug Submission Control Number: 203884
On March 2, 2018, Health Canada issued a Notice of Compliance to Novartis Pharmaceuticals Canada Inc. for the drug product Kisqali.
The market authorization was based on quality (chemistry and manufacturing), non-clinical (pharmacology and toxicology), and clinical (pharmacology, safety, and effectiveness) information submitted. Based on Health Canada's review, the benefit-risk profile of Kisqali in combination with letrozole is favourable for treatment of postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer as an initial endocrine-based therapy.1 What was approved?
Kisqali, an anti-neoplastic agent, was authorized for use in combination with letrozole for the treatment of postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer as an initial endocrine-based therapy.
Kisqali (ribociclib tablets) should be administered by health professionals experienced with anti-cancer agents.
In the Phase III MONALEESA-2 study, of the 334 patients who received Kisqali in combination with letrozole, 45% of patients were ≥65 years of age. No overall differences in safety or efficacy of Kisqali were observed between patients <65 and ≥65 years of age.
The safety and efficacy of Kisqali in pediatric patients (≤18 years of age) have not been established.
Kisqali is contraindicated for patients with hypersensitivity to this drug or to any ingredient in the formulation. Kisqali is also contraindicated for patients with untreated congenital long QT syndrome, a QTcF (using Fridericia's correction formula) interval of ≥450 msec at baseline, and those who are at significant risk of developing QTc prolongation.
Kisqali was approved for use under the conditions stated in Kisqali's Product Monograph taking into consideration the potential risks associated with the administration of this drug product.
Kisqali (200 mg ribociclib, as ribociclib succinate) is presented as a tablet. In addition to the medicinal ingredient ribociclib, the tablet also contains the following non-medicinal ingredients: colloidal silicon dioxide; crospovidone (Type A); iron oxide black (E172); iron oxide red (E172); lecithin (soy) (E322); low-substituted hydroxypropylcellulose; magnesium stearate; microcrystalline cellulose; polyvinyl alcohol (partially hydrolysed); talc; titanium dioxide (E171); xanthan gum.
For more information, refer to the Clinical, Non-clinical, and Quality (Chemistry and Manufacturing) Basis for Decision sections.
Additional information may be found in the Siliq Product Monograph, approved by Health Canada and available through the Drug Product Database.
2 Why was Kisqali approved?
Health Canada considers that the benefit-risk profile of Kisqali in combination with letrozole is favourable for the treatment of postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer as an initial endocrine-based therapy.
Hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer is a life-threatening disease and incurable. Estrogen deprivation using endocrine therapy is the standard first-line treatment for patients with HR-positive, HER2-negative advanced or metastatic breast cancer, except for individuals with immediate life-threatening disease. First-line endocrine therapy agents include selective non-steroidal aromatase inhibitors, letrozole and anastrozole, steroidal aromatase inhibitor exemestane and selective estrogen receptor modulators (for example tamoxifen). However, resistance to these agents and hence recurrence of disease ultimately develop in all patients. Overall, a medical need still remains to develop new therapies to prolong survival and/or maintain or improve quality of life.
Kisqali (Ribociclib [as ribociclib succinate]) is a new small molecule CDK 4/6 inhibitor. Kisqali has been shown to be efficacious in advanced or metastatic HR-positive, HER2-negative breast cancer patients. The market authorization was based on an international, multicentre, randomized, double-blind, placebo-controlled Phase III clinical study MONALEESA-2 which compared Kisqali in combination with letrozole (Kisqali + letrozole) to placebo in combination with letrozole (placebo + letrozole). The primary endpoint of the MONALEESA-2 study was progression-free survival. Results from the MONALEESA-2 study showed a statistically significant and clinically meaningful improvement in progression-free survival in patients treated with Kisqali + letrozole compared to patients treated with placebo + letrozole.
Kisqali treatment was associated with increased adverse events when compared to placebo. The most common (≥20%) Grade 3 and 4 adverse events in Kisqali-treated patients were neutropenia, leukopenia, abnormal liver function test, lymphopenia, hypophosphatemia, vomiting, nausea, fatigue and back pain. The adverse events were generally manageable by dose Kisqali interruption, dose reduction and/or symptomatic treatment, as indicated.
The following adverse drug reactions associated with Kisqali were considered serious: QT interval prolongation, hepatotoxicity, neutropenia and thromboembolic events. These issues have been addressed through appropriate labelling (a Serious Warnings and Precautions box and Warnings and Precautions) in the Kisqali Product Monograph.
A Risk Management Plan (RMP) for Kisqali was submitted by Novartis Pharmaceuticals Canada Inc. to Health Canada. Upon review, the RMP was considered to be acceptable. The RMP is designed to describe known and potential safety issues, to present the monitoring scheme and when needed, to describe measures that will be put in place to minimize risks associated with the product.
A Look-alike Sound-alike brand name assessment was performed and the proposed name Kisqali was accepted.
Overall, the therapeutic benefits of Kisqali therapy seen in the MONALEESA-2 are positive and Kisqali has been shown to have a favourable benefit-harm-uncertainty profile based on non-clinical and clinical studies. Appropriate warnings and precautions are in place in the Kisqali Product Monograph to address the identified safety concerns.
This New Drug Submission complies with the requirements of sections C.08.002 and C.08.005.1 and therefore Health Canada has granted the Notice of Compliance pursuant to section C.08.004 of the Food and Drug Regulations. For more information, refer to the Clinical, Non-clinical, and Quality (Chemistry and Manufacturing) Basis for Decision sections.
3 What steps led to the approval of Kisqali?
Submission Milestones: Kisqali
| Submission Milestone | Date |
|---|---|
| Pre-submission meeting: | 2016-09-14 |
| Submission filed: | 2017-03-17 |
| Screening | |
| Screening Acceptance Letter issued: | 2017-05-08 |
| Review | |
| Biopharmaceutics Evaluation complete: | 2017-12-21 |
| Review of Risk Management Plan complete: | 2018-02-20 |
| Labelling Review complete, including Look-alike Sound-alike brand name assessment: | 2018-02-27 |
| Quality Evaluation complete: | 2018-03-01 |
| Clinical Evaluation complete: | 2018-03-01 |
| Notice of Compliance issued by Director General, Therapeutic Products Directorate/Biologics and Genetic Therapies Directorate: | 2018-03-02 |
4 What follow-up measures will the company take?
Requirements for post-market commitments are outlined in the Food and Drugs Act and Regulations.
6 What other information is available about drugs?
Up to date information on drug products can be found at the following links:
- See MedEffect Canada for the latest advisories, warnings and recalls for marketed products.
- See the Notice of Compliance (NOC) Database for a listing of the authorization dates for all drugs that have been issued an NOC since 1994.
- See the Drug Product Database (DPD) for the most recent Product Monograph. The DPD contains product-specific information on drugs that have been approved for use in Canada.
- See the Notice of Compliance with Conditions (NOC/c)-related documents for the latest fact sheets and notices for products which were issued an NOC under the Notice of Compliance with Conditions (NOC/c) Guidance Document, if applicable. Clicking on a product name links to (as applicable) the Fact Sheet, Qualifying Notice, and Dear Health Care Professional Letter.
- See the Patent Register for patents associated with medicinal ingredients, if applicable.
- See the Register of Innovative Drugs for a list of drugs that are eligible for data protection under C.08.004.1 of the Food and Drug Regulations, if applicable.
7 What was the scientific rationale for Health Canada's decision?
7.1 Clinical basis for decision
Clinical Pharmacology
Hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer is a life-threatening disease and incurable.
Ribociclib (the medicinal ingredient in Kisqali) is an inhibitor of cyclin-dependent kinase (CDK) 4 and 6. These kinases are activated upon binding to D-cyclins and play a crucial role in signaling pathways which lead to cell cycle progression and cellular proliferation. The cyclin D-CDK4/6 complex regulates cell cycle progression through phosphorylation of the retinoblastoma protein.
The clinical pharmacology submission components included reports on the human pharmacodynamic and pharmacokinetic studies.
Population pharmacokinetic analysis conducted in cancer patients indicated that mild hepatic impairment and mild to moderate renal impairment had no effect on the exposure to ribociclib. A pharmacokinetic trial evaluated the pharmacokinetics of ribociclib after a single oral dose of 400 mg ribociclib in healthy subjects with normal hepatic function and non-cancer subjects with impaired hepatic function. However, Kisqali has not been studied in breast cancer patients with moderate to severe hepatic impairment or severe renal impairment.
Ribociclib is a substrate and inhibitor of cytochrome P450 (CYP) 3A. Based on drug-drug interaction studies, co-administration of a strong CYP3A4 inducer rifampin decreased the plasma exposure of ribociclib in healthy subjects by 89%; co-administration of a strong CYP3A4 inhibitor ritonavir increased ribociclib exposure by 3.21-fold. Therefore, co-administration of Kisqali with a strong CYP3A inducer or inhibitor should be avoided, if possible.
For further details, please refer to the Kisqali Product Monograph, approved by Health Canada and available through the Drug Product Database.
Clinical Efficacy
The efficacy of Kisqali (ribociclib) for the treatment of postmenopausal women with HR-positive, HER2-negative, advanced breast cancer who received no prior therapy for advanced disease was demonstrated in the MONALEESA-2 study. This study was a randomized, double-blind, placebo controlled Phase III clinical study which evaluated the use of Kisqali + letrozole in comparison to a placebo + letrozole. Letrozole was the standard treatment option for the disease at the time of study initiation.
In the MONALEESA-2 study, a total of 668 patients were randomized in a 1:1 ratio to receive either Kisqali (600 mg once daily, Days 1 to 21 in a 28-day cycle) + letrozole (2.5 mg once daily) or placebo (once daily, Days 1 to 21 in a 28-day cycle) + letrozole (2.5 mg once daily). Randomization was stratified by the presence of liver and/or lung metastases (yes and no). Patients received study treatment until disease progression, unacceptable toxicity, death, or discontinuation from the study treatment for any other reason. Patients were followed for survival regardless of the reason for treatment discontinuation, except if consent was withdrawn or patient was lost to follow-up.
Patients enrolled in this study had a median age of 62 years (range 23 to 91) with 44.2% older than 65 years of age. The patients included were Caucasian (82.2%), Asians (7.6%), and Black (2.5%). All patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. A total of 43.6% of patients had received chemotherapy in the neoadjuvant or adjuvant setting and 51.8% had received anti-hormonal therapy in the neoadjuvant or adjuvant setting prior to study entry. 34.1% of patients had de novo metastatic disease. 20.7% of patients had bone only disease and 59.0% of patients had visceral disease. Patients with central nervous system metastases documented at baseline were not permitted in this study.
The primary endpoint for the study was progression-free survival using Response Evaluation Criteria in Solid Tumors (RECIST v1.1), based on the investigator assessment in the full population (all randomized patients). The median duration of study follow-up was 15.3 months.
The efficacy results demonstrated a statistically significant improvement in progression-free survival in patients receiving Kisqali + letrozole compared to patients receiving placebo + letrozole in the full analysis set (hazard ratio [HR] = 0.56 with 95% confidence interval [CI]: 0.43, 0.72; one sided stratified log-rank test p-value 0.000003). The median progression-free survival was 14.7 months (95% CI, 13.0, and 16.5) in the placebo + letrozole treatment group and not reached (NR) in the Kisqali + letrozole treatment group (95% CI: 19.3, NR) at the time of primary analysis.
Overall response rate was higher in patients treated with Kisqali + letrozole (40.7%; 95% CI: 35.4%, 46.0%) compared to patients treated with placebo + letrozole (27.5%; 95% CI: 22.8%, 32.3%). Overall survival was a key secondary endpoint in the MONALEESA-2 study; however, the results were immature at the time of primary efficacy analysis. Health-related quality of life was also measured in the study and no trend of detrimental impact on quality of life was observed with the addition of Kisqali to letrozole compared to placebo + letrozole.
Study results were generally consistent across the subgroups of age, race, prior adjuvant or neo-adjuvant chemotherapy or hormonal therapies, liver and/or lung involvement, and bone only metastasis disease.
Indication
The New Drug Submission for Kisqali was filed by the sponsor with the following indication: Kisqali (a cyclin-dependent kinase inhibitor, CDKi) in combination with letrozole is indicated for the treatment of postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer, as initial endocrine-based therapy.
Health Canada approved the following indication: Kisqali (ribociclib as ribociclib succinate) is indicated in combination with letrozole for the treatment of postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer as an initial endocrine-based therapy.
For more information, refer to the Kisqali Product Monograph, approved by Health Canada and available through the Drug Product Database
Clinical Safety
The clinical safety of Kisqali was primarily based on the pivotal Phase III MONALEESA-2 study previously described in the Clinical Efficacy section. A total of 668 postmenopausal women were enrolled in the study with 664 receiving treatment with either Kisqali + letrozole or placebo + letrozole. The median duration of exposure to Kisqali + letrozole was 13 months with 58.1% patients exposed for >12 months.
Based on the MONALEESA-2 study, the administration of Kisqali + letrozole was associated with increased adverse events when compared to placebo + letrozole. Grade 3 and Grade 4 adverse events were experienced by 66.2% and 15.0% of patients, respectively in the Kisqali + letrozole arm, compared to 31.8% and 0.9%, respectively, in the placebo + letrozole arm. The most common (>2%) Grade 3 or 4 adverse events in the Kisqali + letrozole arm were neutropenia (59.3%), leukopenia (21.0%), abnormal liver function test (9.6%), lymphopenia (6.9%), hypophosphatemia (3.6%), vomiting (3.6%), nausea (2.4%), fatigue (2.4%) and back pain (2.1%). These adverse events were generally manageable by Kisqali dose interruption, reduction and/or symptomatic treatment as indicated. Dose reductions due to adverse events occurred in 44.6% of patients receiving Kisqali + letrozole compared to 3% of patients receiving placebo + letrozole.
A total of 7.5% of patients in the Kisqali + letrozole arm discontinued study treatment (both Kisqali/placebo and letrozole) due to adverse events compared to 3.1% in the placebo + letrozole arm. The most common adverse events leading to treatment discontinuation in the Kisqali + letrozole arm were alanine aminotransferase (ALT) increase (2.7%), aspartate aminotransferase (AST) increase (2.4%) and vomiting (1.5%). Three (0.9%) patients in the Kisqali + letrozole arm within 30 days of the last dose; these deaths were due to breast cancer disease progression, death of unknown cause, and sudden death in the setting of Grade 3 hypokalemia and Grade 2 QT prolongation. One (0.3%) patient in the placebo + letrozole arm died due to breast cancer disease progression.
In the MONALEESA-2 study, the following adverse drug reactions related to Kisqali were considered serious: QT interval prolongation, hepatotoxicity, neutropenia, and thromboembolic events.
QT interval prolongation
Administration of Kisqali + letrozole showed a concentration-dependent prolongation of the QTc interval, with the mean increase from baseline of approximately 20 msec (90% CI: 18.0, 21.2) during the steady-state treatment at 2 hours post-dosing on Day 15. One patient had a QTcF (using Fridercia's correction formula) interval >500 msec, and 9 patients (2.7%) had a >60 msec QTcF interval increase from baseline. One event of sudden death (0.3%) occurred during treatment with Kisqali + letrozole in a patient with Grade 2 QT prolongation and Grade 3 hypokalemia. Syncope occurred in 9 patients (2.7%) in the Kisqali + letrozole treatment group compared to 3 patients (0.9%) who received placebo in combination with letrozole (placebo + letrozole).
In the MONALEESA-2 study, routine electrocardiogram monitoring at steady-state was only performed during the first cycle on Day 15. Given the effect of ribociclib (medicinal ingredient in Kisqali) on QT interval is expected to be maximal at steady-state treatment, this monitoring schedule may not be sufficient to detect asymptomatic QTc interval prolongations in successive cycles in the study. In order for health professionals and patients to better understand and manage the risk of QTc prolongation, the Kisqali product monograph contains the following: warnings in the Serious Warnings and Precautions section, contraindications in patients with a higher risk to develop severe QTc prolongation, information about potential drug interactions that can affect the QTc interval, dose adjustment schedule in the event of QTc interval prolongation and a recommendation for periodic monitoring of electrolytes and electrocardiograms at steady-state treatment while receiving Kisqali.
Hepatotoxicity
Increase in transaminases was observed. Grade 3 or 4 increases in alanine aminotransferase (ALT, 10.2% versus 1.2%) and aspartate aminotransferase (AST, 6.9% versus 1.5%) were reported in the Kisqali + letrozole and placebo + letrozole arms respectively. Concurrent elevations of ALT or AST greater than three times the upper limit of normal (ULN) and of total bilirubin greater than two times the ULN, with normal ALP levels, and in the absence of cholestasis (Hy's Law) occurred in 4 (1.2%) patients; one with hepatic failure. All 4 patients recovered with normal liver function tests after discontinuation of Kisqali. Increases in transaminases improved upon dose adjustment, including dose interruption, reduction and/or discontinuation.
Neutropenia
Neutropenia was the most frequently reported adverse drug reaction (74.3%) and a Grade 3 or 4 decrease in neutrophil counts (based on laboratory findings) was reported in 59.6% of patients receiving Kisqali + letrozole. Among the patients who had Grade 2, 3 or 4 neutropenia, the median time to Grade 2, 3 or 4 neutropenia was 16 days. The median time to resolution of Grade ≥3 (to normalization or Grade <3) was 15 days in the Kisqali + letrozole treatment arm. Severity of neutropenia is concentration dependent. Febrile neutropenia was reported in 5 patients (1.5%) in the Kisqali + letrozole treatment arm. The risk of neutropenia is prominently labelled in the Kisqali Product Monograph in the Serious Warnings and Precautions section. A dose adjustment schedule is also provided in the Kisqali Product Monograph for the management of neutropenia.
Thromboembolic Events
Thromboembolic events occurred in 9 patients (2.7%) in the Kisqali + letrozole arm, compared with 3 (0.9%) in the placebo + letrozole arm. Pulmonary embolism was reported in 4 patients (1.2%) receiving Kisqali + letrozole and 1 patient (0.3) receiving placebo + letrozole. The risk of increased thromboembolic events is added in the Warnings and Precautions section of the Kisqali Product Monograph.
For more information, refer to the Kisqali Product Monograph, approved by Health Canada and available through the Drug Product Database.
7.2 Non-Clinical Basis for Decision
The non-clinical review of Kisqali (ribociclib) included the evaluation of non-clinical and safety pharmacology, pharmacokinetic, toxicology, and reproductive and developmental toxicology studies.
In vitro, ribociclib decreased retinoblastoma protein (pRb) phosphorylation leading to arrest in the G1 phase of the cell cycle and reduced cell proliferation in breast cancer cell lines. In vivo, treatment with single agent ribociclib led to tumor regressions which correlated with inhibition of pRb phosphorylation at well tolerated doses.
In vivo studies using patient-derived estrogen receptor positive breast cancer xenograft models, the combination of ribociclib and antiestrogens (i.e., letrozole) resulted in superior inhibition of tumor growth compared to each drug alone.
In rats with intact blood brain barriers, there was low brain penetration by ribociclib following oral and intracarotid injection.
In vitro metabolism studies showed that cytochrome P450 (CYP) 3A4 was the major enzyme involved in the oxidative metabolism of ribociclib. Ribociclib exposure may be altered when a strong CYP3A4 inhibitor or inducer is co-administered. Ribociclib also inhibited CYP3A4 in a time-dependent manner and the exposure to a CYP3A4 substrate may be altered when ribociclib is co-administered. Ribociclib was a reversible inhibitor of CYP1A2.
In vitro transporter studies indicated that ribociclib may inhibit Breast Cancer Resistance Protein (BCRP), Organic Cation Transporter 2 (OCT2), Multidrug and Toxic Compound Extrusion Protein-1 (MATE1), and human Bile Salt Export Pump (BSEP) at clinically relevant concentrations and drug-drug interactions may occur when ribociclib is co-administered with substrates of these transporters.
In repeated-dose toxicology studies in dogs and rats, adverse findings in the male reproductive tract, lung, and liver are observed, although these effects showed signs of reversibility upon cessation of dosing. Decreases in red blood cells (RBCs) and white blood cells (WBC), lymphocyte depletion from lymphoid tissues and bone marrow hypocellularity with little or no safety margin were all considered related to ribociclib pharmacology, generally mild and reversible upon treatment discontinuation.
Ribociclib was terotogenic in rabbits with a maternal exposure comparable to that of the recommended human dose. In lactating rats that received a single dose of 50 mg/kg, exposure to ribociclib was 3.56-fold higher in milk than in maternal plasma. These observations indicate that Kisqali can cause fetal harm when administered to a pregnant woman, and infants may be exposed to ribociclib if a lactating woman is taking Kisqali at the recommended dose.
No carcinogenic studies have been conducted with ribociclib. This is acceptable considering the proposed indication for advanced cancer. Ribociclib was not genotoxic in bacterial and mammalian cell assays with and without metabolic activation and in an in vivo study in rats.
Ribociclib was shown to absorb light in the ultraviolet B and ultraviolet A range. An in vitro phototoxicity test did not identify a relevant phototoxicity potential for ribociclib. The risk is considered low for Kisqali to cause photosensitization in patients.
For more information, refer to the Kisqali Product Monograph, approved by Health Canada and available through the Drug Product Database.
7.3 Quality Basis for Decision
The Chemistry and Manufacturing information submitted for Kisqali has demonstrated that the drug substance and drug product can be consistently manufactured to meet the approved specifications. Proper development and validation studies were conducted, and adequate controls are in place for the commercial processes. Changes to the manufacturing process and formulation made throughout the pharmaceutical development are considered acceptable upon review. Based on the stability data submitted, the proposed shelf life of 24 months is acceptable when the drug product is stored at or below 30oC) and kept in the original packaging and protected from moisture.
Proposed limits of drug-related impurities are considered adequately qualified (i.e., within International Council for Harmonisation limits and/or qualified from toxicological studies).
All sites involved in production are compliant with Good Manufacturing Practices.
All non-medicinal ingredients (described earlier) found in the drug product are acceptable for use in drugs according to the Food and Drug Regulations.
None of the excipients used in the formulation of Kisqali is of human or animal origin. Magnesium stearate used during the formulation is of vegetable origin.
Related Drug Products
| Product name | DIN | Company name | Active ingredient(s) & strength |
|---|---|---|---|
| KISQALI | 02473569 | NOVARTIS PHARMACEUTICALS CANADA INC | RIBOCICLIB (RIBOCICLIB SUCCINATE) 200 MG |