Summary Basis of Decision for Lonsurf
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 Lonsurf is located below.
Recent Activity for Lonsurf
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 Lonsurf
Updated: 2023-08-14
The following table describes post-authorization activity for Lonsurf, a product which contains the medicinal ingredient trifluridine and tipiracil (supplied as tipiracil hydrochloride). 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 and Applications Guidance.
Drug Identification Number (DIN):
- DIN 02472104 - 15 mg trifluridine/6.14 mg tipiracil, tablet, oral administration
- DIN 02472112 - 20 mg trifluridine/8.19 mg tipiracil, tablet, oral administration
Post-Authorization Activity Table (PAAT)
| Activity/submission type, control number | Date submitted | Decision and date | Summary of activities |
|---|---|---|---|
| SNDS # 240186 | 2020-05-29 | Issued NOC 2020-12-22 | Submission filed as a Level I – Supplement to add an alternate supplier for a drug substance (trifluridine). The submission was reviewed and considered acceptable, and an NOC was issued. |
| SNDS # 235999 | 2020-02-12 | Issued NOC 2020-11-03 | Submission filed as a Level I – Supplement to make updates to the PM and to propose alternate dosing for patients with severe renal impairment. The submission was reviewed and considered acceptable. As a result of the SNDS, modifications were made to the Contraindications, Warnings and Precautions, Adverse Reactions, Drug Interactions, Dosage and Administration, and Overdosage sections of the PM, and corresponding changes were made to Part III: Patient Medication Information. An NOC was issued. |
| SNDS # 227070 | 2019-04-23 | Issued NOC 2019-11-19 | Submission filed as a Level I – Supplement for a new indication. The submission was reviewed under the Priority Review of Drug Submissions Policy. The indication authorized was: Lonsurf monotherapy is indicated for the treatment of adult patients with metastatic gastric cancer or adenocarcinoma of the gastroesophageal junction, who have been previously treated with at least two prior lines of chemotherapy including a fluoropyrimidine, a platinum, and either a taxane or irinotecan and if appropriate with HER2/neu-targeted therapy. The submission was reviewed and considered acceptable, and an NOC was issued. A Regulatory Decision Summary was published. |
| Drug product (DINs 02472104, 02472112) market notification | Not applicable | Date of first sale: 2018-03-22 |
The manufacturer notified Health Canada of the date of first sale pursuant to C.01.014.3 of the Food and Drug Regulations. |
| NDS # 205852 | 2017-05-30 | Issued NOC 2018-01-25 |
Notice of Compliance issued for New Drug Submission. |
Summary Basis of Decision (SBD) for Lonsurf
Date SBD issued: 2018-04-06
The following information relates to the New Drug Submission for Lonsurf.
Trifluridine and tipiracil (supplied as tipiracil hydrochloride), tablet, oral
Drug Identification Number (DIN):
- DIN 02472104 - 15 mg trifluridine/6.14 mg tipiracil (supplied as tipiracil hydrochloride), tablet, oral
- DIN 02472112 - 20 mg trifluridine/8.19 mg tipiracil (supplied as tipiracil hydrochloride), tablet, oral
Taiho Pharma Canada Inc.
New Drug Submission Control Number: 205852
On January 25, 2018, Health Canada issued a Notice of Compliance to Taiho Pharma Canada, Inc. for the drug product Lonsurf.
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 Lonsurf is favourable for the treatment of adult patients with metastatic colorectal cancer who have been previously treated with, or are not candidates for, available therapies including fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapies, anti-vascular endothelial growth factor (VEGF) biological agents, and, if RAS wild-type, anti-epidermal growth factor receptor (EGFR) agents.
1 What was approved?
Lonsurf, an antineoplastic agent, was authorized for the treatment of adult patients with metastatic colorectal cancer who have been previously treated with, or are not candidates for, available therapies including fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapies, anti-vascular endothelial growth factor (VEGF) biological agents, and, if RAS wild-type, anti-epidermal growth factor receptor (EGFR) agents.
The clinical effectiveness of Lonsurf is based on benefit observed in a pivotal study in patients who had been previously treated with all of the above available therapies.
Data regarding the use of Lonsurf in patients younger than 18 years of age have not been submitted to Health Canada. Consequently, Health Canada has not authorized an indication for pediatric use.
The effect of Lonsurf on overall survival in metastatic colorectal cancer was similar in patients under 65 years of age and those aged 65 years and over. Efficacy and safety data in patients aged 75 years and over are limited.
Lonsurf is contraindicated in patients who are hypersensitive to this drug or to any ingredient in the formulation, or component of the container closure.
Lonsurf was approved for use under the conditions stated in its Product Monograph taking into consideration the potential risks associated with the administration of this drug product.
Lonsurf, in both strengths, 15 mg trifluridine/6.14 mg tipiracil (as 7.065 mg tipiracil hydrochloride) and 20 mg trifluridine/8.19 mg tipiracil (as 9.420 mg tipiracil hydrochloride), is presented as a tablet. In addition to the medicinal ingredients, both tablets contain hypromellose, lactose monohydrate, magnesium stearate, polyethylene glycol, pharmaceutical ink, pregelatinized starch, stearic acid and titanium dioxide. The 20 mg trifluridine/8.19 mg tipiracil (as tipiracil hydrochloride) tablet also contains ferric oxide as a non-medicinal ingredient. Both tablets are imprinted with edible ink containing carnauba wax, FD&C Blue No. 2 Aluminum Lake, ferric oxide red, ferric oxide yellow, shellac, talc, and titanium dioxide.
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 Lonsurf Product Monograph, approved by Health Canada and available through the Drug Product Database.
2 Why was Lonsurf approved?
Health Canada considers that the benefit-risk profile of Lonsurf is favourable for the treatment of adult patients with metastatic colorectal cancer who have been previously treated with, or are not candidates for, available therapies including fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapies, anti-vascular endothelial growth factor (VEGF) biological agents, and, if RAS wild-type, anti-epidermal growth factor receptor (EGFR) agents.
Colorectal cancer is the second most common malignancy in Canada and the second leading cause of cancer death in Canada. Approximately 50% to 60% of patients diagnosed with colorectal cancer develop metastases, and 80% to 90% of these patients have unresectable metastatic liver disease.
In general, unresectable metastatic colorectal cancer remains an incurable disease. Main goals of its therapy are extension of survival and palliation of symptoms.
A number of different classes of drugs with antitumour activity in metastatic colorectal cancer are available in Canada: fluoropyrimidines (including 5-fluorouracil, which is usually given intravenously with leucovorin, and the oral agent capecitabine); irinotecan; oxaliplatin; cetuximab and panitumumab, two monoclonal antibodies directed against the EGFR; bevacizumab, a monoclonal antibody targeting the VEGF; and raltitrexed, a thymidylate synthase inhibitor. Regorafenib, an oral inhibitor of multiple protein kinases, is available for patients whose disease has progressed on standard therapies. Effective treatment options for metastatic colorectal cancer patients who have been previously treated with standard therapies are limited.
Lonsurf, a combination of an antineoplastic thymidine-based nucleoside analogue, trifluridine, and the thymidine phosphorylase inhibitor, tipiracil (as tipiracil hydrochloride), has been shown to be efficacious in patients with metastatic colorectal cancer. The market authorization of Lonsurf was based on efficacy and safety data derived from the pivotal Study TPU-TAS-102-301 (RECOURSE). RECOURSE was an international, randomized, double-blind, placebo-controlled Phase III trial, which included 800 patients with metastatic colorectal cancer, randomized in a 2:1 ratio to treatment with Lonsurf plus best supportive care or placebo plus best supportive care. Study patients had received prior therapy with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy as well as treatment with an anti-VEGF biological agent and, for patients with wild-type RAS tumours, an anti-EGFR agent. Key patient eligibility criteria included prior treatment with at least two lines of standard chemotherapy for metastatic colorectal cancer and being refractory to or intolerant of those therapies, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, absence of brain metastasis, and absence of ascites requiring drainage in the past four weeks. A total of 533 patients received Lonsurf as a single agent at a dose of 35 mg/m2 twice daily on Days 1 through 5 and Days 8 through 12 of each 28-day cycle. The mean duration of Lonsurf therapy was 12.7 weeks. The primary endpoint was overall survival.
The pivotal study demonstrated a statistically significant overall survival benefit of Lonsurf plus best supportive care as compared to placebo plus best supportive care.The median overall survival was 7.1 months in the Lonsurf arm as compared to 5.3 months in the placebo arm (hazard ratio [HR] = 0.68; 95% confidence interval [CI]: 0.58, 0.81; p<0.0001).
The overall safety dataset included a total of 761 patients who were exposed to Lonsurf at a dose of 35 mg/m2 twice daily, including 533 patients from the RECOURSE trial.
The identified safety concerns associated with the use of Lonsurf included primarily hematological and gastrointestinal toxicities. In the RECOURSE trial, the most frequently observed adverse reactions or laboratory abnormalities (all grades and with incidence of ≥10%) in Lonsurf-treated patients at a rate that exceeded the rate in patients receiving placebo were anemia, neutropenia, fatigue/asthenia, nausea, thrombocytopenia, decreased appetite, diarrhea, vomiting, pyrexia, and abdominal pain. The reported hematologic toxicities based on clinical laboratory assessments were often severe and life-threatening (grades 3 and 4) and included neutropenia (37.9%), leukopenia (21.4%), anemia (18.2%), thrombocytopenia (5.1%) and febrile neutropenia (3.8%). One patient (0.2%) died due to neutropenic infection considered related to Lonsurf treatment.
Myelosuppression and gastrointestinal toxicity associated with the use of Lonsurf are specifically addressed in a Serious Warnings and Precautions box of the Lonsurf Product Monograph. In addition, the Warnings and Precautions section of the Lonsurf Product Monograph highlights severe and life-threatening myelosuppression, neutropenia, leukopenia, anemia, and thrombocytopenia based on laboratory assessments from the RECOURSE trial.
Due to its safety profile, Lonsurf is not recommended for use in patients with moderate and severe hepatic impairment. In addition, Lonsurf is not recommended for use in patients with severe renal impairment (creatinine clearance below 30 mL/min), as it has not been studied in this patient population.
Based on findings in animal studies and its mechanism of action, Lonsurf may cause fetal harm and is not recommended in pregnant and nursing women.
A Risk Management Plan (RMP) for Lonsurf was submitted by Taiho Pharma 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 Lonsurf was accepted.
Overall, the benefit-risk profile of Lonsurf is considered favourable for the target patient population. The identified safety issues can be managed through labelling and adequate monitoring. Appropriate warnings and precautions are in place in the Lonsurf 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 Lonsurf?
The drug submission for Lonsurf was reviewed under the Priority Review Policy. The sponsor presented substantial evidence to demonstrate that Lonsurf will provide an effective treatment for patients with metastatic colorectal cancer, including for the subgroup of patients who have received prior treatment with regorafenib. Metastatic colorectal cancer is a life-threatening condition, and for patients who have received prior regorafenib, no drug is currently marketed in Canada.
Submission Milestones: Lonsurf
| Submission Milestone | Date |
|---|---|
| Pre-submission meeting: | 2016-11-08 |
| Request for priority status | |
| Filed: | 2017-02-28 |
| Approval issued by Director, Bureau of Medical Sciences: | 2017-04-06 |
| Submission filed: | 2017-05-30 |
| Screening | |
| Screening Deficiency Notice issued: | 2017-06-27 |
| Response filed: | 2017-07-11 |
| Screening Acceptance Letter issued: | 2017-07-31 |
| Review | |
| Biopharmaceutics Evaluation complete: | 2017-12-08 |
| Quality Evaluation complete: | 2018-01-18 |
| Clinical Evaluation complete: | 2018-01-19 |
| Review of Risk Management Plan complete: | 2017-12-20 |
| Labelling Review complete, including Look-alike Sound-alike brand name assessment: | 2018-01-17 |
| Notice of Compliance issued by Director General, Therapeutic Products Directorate: | 2018-01-25 |
The Canadian regulatory decision on the non-clinical and clinical review of Lonsurf was based on a critical assessment of the data package submitted to Health Canada. The foreign reviews completed by the European Medicines Agency (EMA) and the United States Food and Drug Administration (FDA) were used as added references.
For additional information about the drug submission process, refer to the Management of Drug Submissions Guidance.
4 What follow-up measures will the company take?
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
Lonsurf is a combination of an antineoplastic thymidine-based nucleoside analogue, trifluridine, and the thymidine phosphorylase (TPase) inhibitor, tipiracil (as tipiracil hydrochloride), at a molar ratio 1:0.5. Following uptake into cancer cells, trifluridine is phosphorylated by thymidine kinase, further metabolized in cells to a deoxyribonucleic acid (DNA) substrate, and incorporated directly into the DNA, thereby interfering with DNA function to prevent cell proliferation. However, trifluridine is rapidly degraded by thymidine phosphorylase and readily metabolized by a first-pass effect following oral administration, hence the inclusion of tipiracil. Tipiracil prevents degradation of trifluridine, thus increasing systemic exposure to trifluridine when trifluridine and tipiracil are administered together.
In non-clinical studies, trifluridine/tipiracil demonstrated antitumour activity against both 5-fluorouracil sensitive and resistant colorectal cancer cell lines. The cytotoxic activity of trifluridine/tipiracil against several human tumour xenografts correlated highly with the amount of trifluridine incorporated into DNA, suggesting this as the primary mechanism of action.
The clinical pharmacology data included reports on the human pharmacodynamic and pharmacokinetic studies. The data support the use of Lonsurf for the specified indication.
For further details, refer to the Lonsurf Product Monograph, approved by Health Canada and available through the Drug Product Database.
Clinical Efficacy
The clinical efficacy of Lonsurf was evaluated in Study TPU-TAS-102-301 (RECOURSE), a Phase III, multinational, double-blind, two-arm, parallel-group, randomized trial in patients with metastatic colorectal cancer. The patients enrolled had received at least two prior regimens of standard therapies (including fluoropyrimidines, oxaliplatin, irinotecan, bevacizumab, and cetuximab or panitumumab for patients with wild-type RAS tumours), and were refractory to or intolerant of those therapies. All of the aforementioned therapies constitute standard treatments for metastatic colorectal cancer in Canada. Patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or greater, patients with brain metastases, and patients with ascites requiring drainage in the past four weeks were excluded from the study. A total of 800 patients were randomized in a ratio of 2:1 to receive Lonsurf (number of patients [n] = 534) plus best supportive care or matching placebo (n = 266) plus best supportive care. Randomization was stratified by KRAS status (wild-type vs. mutant), time since diagnosis of first metastasis (<18 months vs. ≥18 months), and region (Japan vs. United States, Europe and Australia).
The primary efficacy endpoint was overall survival. Secondary efficacy endpoints included progression-free survival, overall response rate, and disease control rate.
A statistically significant overall survival benefit was observed with Lonsurf plus best supportive care as compared to placebo plus best supportive care (hazard ratio [HR] = 0.68; 95% confidence interval [CI]: 0.58, 0.81; p<0.0001). The median overall survival was 7.1 months in the Lonsurf arm as compared to 5.3 months in the placebo arm, a difference of 1.8 months. An improvement in progression-free survival with Lonsurf plus best supportive care as compared to placebo plus best supportive care was also observed (HR = 0.48; 95% CI: 0.41, 0.57; p<0.0001).
An updated overall survival analysis, carried out at 89% (n = 712) of events, confirmed the clinically meaningful and statistically significant survival benefit of Lonsurf plus best supportive care compared to placebo plus best supportive care (HR = 0.69; 95% CI: 0.59, 0.81; p<0.0001) and a median overall survival of 7.2 months vs 5.2 months; with 1-year survival rates of 27.1% and 16.6%, respectively. The overall survival benefit was observed consistently in all pre-specified subgroups.
Sixty one percent (61%, n = 485) of all randomized patients received a fluoropyrimidine as part of their last treatment regimen prior to randomization, of which 455 (94%) were refractory to the fluoropyrimidine at that time. Among these patients, the overall survival benefit with Lonsurf was maintained.
Eighteen percent (18%, n = 144) of all randomized patients received regorafenib prior to randomization. Among these patients, the overall survival benefit with Lonsurf was maintained. The effect was also maintained in regorafenib-naive patients.
Indication
The New Drug Submission for Lonsurf was filed by the sponsor with the following indication:
- Lonsurf is indicated for the treatment of adult patients with metastatic colorectal cancer who have been previously treated with, or are not considered candidates for, available therapies including fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapies, anti-VEGF agents, and anti-EGFR agents.
To ensure safe and effective use of the product, Health Canada revised the proposed indication to more accurately reflect the target patient population. Accordingly, Health Canada approved the following indication:
- Lonsurf (trifluridine and tipiracil [as tipiracil hydrochloride] tablets) is indicated for the treatment of adult patients with metastatic colorectal cancer who have been previously treated with, or are not candidates for, available therapies including fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapies, anti-VEGF biological agents, and, if RAS wild-type, anti-EGFR agents. Clinical effectiveness of Lonsurf is based on benefit observed in a pivotal study in patients who had been previously treated with all of the above available therapies.
For more information, refer to the Lonsurf Product Monograph, approved by Health Canada and available through the Drug Product Database.
Clinical Safety
The clinical safety of Lonsurf in patients with metastatic colorectal cancer who have been previously treated with standard therapies was evaluated in the pivotal Study TPU-TAS-102-301 (RECOURSE) (described in the Clinical Efficacy section).
The overall safety dataset included a total of 761 patients who were exposed to Lonsurf at a dose of 35mg/m2 twice daily, including 533 patients from the RECOURSE trial.
The most frequently reported toxicities associated with Lonsurf treatment were primarily hematologic and gastrointestinal events, and related to fatigue/asthenia and decreased appetite. In the RECOURSE trial, the most frequently observed adverse reactions or laboratory abnormalities (all grades and ≥10% in incidence) in Lonsurf-treated patients at a rate that exceeded the rate in patients receiving placebo were anemia, neutropenia, fatigue/asthenia, nausea, thrombocytopenia, decreased appetite, diarrhea, vomiting, pyrexia, and abdominal pain. The reported hematologic toxicities based on clinical laboratory assessments were often severe and life-threatening (grades 3 and 4) and included neutropenia (37.9%), leukopenia (21.4%), anemia (18.2%), thrombocytopenia (5.1%) and febrile neutropenia (3.8%). One patient died due to neutropenic infection considered related to Lonsurf treatment. Toxicities were managed with dose reductions and treatment discontinuations. Hospitalizations were not increased with Lonsurf treatment as compared to placebo. With dose modifications, patients were able to continue on treatment with Lonsurf longer than with placebo.
Myelosuppression and gastrointestinal toxicity associated with the use of Lonsurf are included in a Serious Warnings and Precautions box of the Lonsurf Product Monograph. In addition, the Warnings and Precautions section of the Lonsurf Product Monograph addresses severe and life-threatening myelosuppression, neutropenia, leukopenia, anemia, and thrombocytopenia based on laboratory assessments from the RECOURSE trial.
For more information, refer to the Lonsurf Product Monograph, approved by Health Canada and available through the Drug Product Database.
7.2 Non-Clinical Basis for Decision
Non-clinical data included toxicology assessment of trifluridine/tipiracil hydrochloride (the medicinal ingredients in Lonsurf) performed in rats, dogs and monkeys. The target organs identified were the lymphatic and hemopoietic systems, and the gastrointestinal tract.
Trifluridine was shown to be genotoxic in in vitro and in vivo genotoxicity tests. Therefore, Lonsurf should be treated as a potential carcinogen.
Placental transfer of trifluridine/tipiracil hydrochloride to the fetus was demonstrated in rats on Day 18 of pregnancy following a single oral administration of trifluridine/tipiracil hydrochloride with radiolabelled trifluridine or radiolabelled tipiracil hydrochloride. Trifluridine/tipiracil hydrochloride was shown to cause embryo-fetal lethality and embryo-fetal toxicity in pregnant rats when given at dose levels lower than the clinical exposure. Excretion of trifluridine/tipiracil hydrochloride and/or their metabolites into milk was also reported in animal studies.
In the cardiovascular studies in conscious monkeys, no treatment-related effects were seen on blood pressure, heart rate, PR interval, QRS time, QT interval and corrected QT interval up to 24 hours after oral administration of trifluridine/tipiracil hydrochloride (trifluridine at dose levels of up to 19-fold the maximum anticipated human dose and tipiracil hydrochloride at dose levels of up to 343-fold the maximum anticipated human dose).
In vitro assessment of trifluridine/tipiracil hydrochloride in the human ether-a-go-go related gene (hERG) assay demonstrated that trifluridine had no effect on hERG current at concentrations studied, which were much higher than the clinical maximum concentrations achieved for trifluridine and tipiracil hydrochloride at the recommended dose.
Based on the results from an in vitro study in human colon cancer cells, zidovudine attenuated the cell growth inhibitory effects of trifluridine, mainly at near clinical concentration of zidovudine. Thus, there is a possibility of attenuation of antitumour activity of Lonsurf with zidovudine if used concomitantly in clinical practice.
The results of the non-clinical studies as well as the potential risks to humans have been included in the Lonsurf Product Monograph. In view of the intended use of Lonsurf, there are no pharmacological or toxicological issues within this submission which preclude authorization of the product.
Appropriate warnings and precautionary measures are in place in the Lonsurf Product Monograph to address the identified safety concerns.
For more information, refer to the Lonsurf 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 Lonsurf 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 36 months is acceptable when the drug product is stored at room temperature (15ºC to 30ºC).
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.
Satisfactory information has been provided to establish that the excipients do not pose a risk of contamination with bovine spongiform encephalopathy/transmissible spongiform encephalopathy agents.
Related Drug Products
| Product name | DIN | Company name | Active ingredient(s) & strength |
|---|---|---|---|
| LONSURF | 02472104 | TAIHO PHARMA CANADA, INC. | TIPIRACIL (TIPIRACIL HYDROCHLORIDE) 6.14 MG TRIFLURIDINE 15 MG |
| LONSURF | 02472112 | TAIHO PHARMA CANADA, INC. | TIPIRACIL (TIPIRACIL HYDROCHLORIDE) 8.19 MG TRIFLURIDINE 20 MG |