Summary Basis of Decision for Enspryng
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 Enspryng is located below.
Recent Activity for Enspryng
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.
Summary Basis of Decision (SBD) for Enspryng
Date SBD issued: 2020-09-08
The following information relates to the new drug submission for Enspryng.
Satralizumab
Drug Identification Number (DIN):
- DIN 02499681 - 120 mg/mL solution, subcutaneous administration
Hoffmann‑La Roche Ltd.
New Drug Submission Control Number: 233642
On June 1, 2020, Health Canada issued a Notice of Compliance to Hoffmann‑La Roche Limited for the drug product Enspryng.
The market authorization was based on quality (chemistry and manufacturing), non‑clinical (pharmacology and toxicology), and clinical (pharmacology, safety, and efficacy) information submitted. Based on Health Canada's review, the benefit‑risk profile of Enspryng is favourable as monotherapy or in combination with immunosuppressive therapy for the treatment of neuromyelitis optica spectrum disorders (NMOSD) in adult and adolescent patients who are anti‑aquaporin 4 (anti‑AQP4) seropositive.
Enspryng is not intended for acute treatment of an NMOSD relapse.
1 What was approved?
Enspryng, an interleukin receptor inhibitor, was authorized as monotherapy or in combination with immunosuppressive therapy for the treatment of neuromyelitis optica spectrum disorders (NMOSD) in adult and adolescent patients who are anti‑aquaporin 4 (anti‑AQP4) seropositive.
Enspryng is not intended for acute treatment of an NMOSD relapse.
The safety and efficacy of Enspryng in children younger than 12 years of age have not been established. Enspryng was authorized for use in adolescent patients aged 12 years or older based on clinical pharmacology data and extrapolation of efficacy and safety from adult NMOSD patients.
The safety and efficacy of Enspryng have been studied in a limited number of geriatric patients up to 74 years of age (4 patients, 65‑73 years of age).
Enspryng is contraindicated in patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non‑medicinal ingredient, or component of the container.
Enspryng 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.
Enspryng (120 mg/mL satralizumab) is presented as a solution. In addition to the medicinal ingredient, the solution contains L‑arginine, L‑aspartic acid, L‑histidine, poloxamer 188, and water for injection.
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 Enspryng Product Monograph, approved by Health Canada and available through the Drug Product Database.
2 Why was Enspryng approved?
Health Canada considers that the benefit‑risk profile of Enspryng is favourable as monotherapy or in combination with immunosuppressive therapy for the treatment of neuromyelitis optica spectrum disorders (NMOSD) in adult and adolescent patients who are anti‑aquaporin 4 (anti‑AQP4) seropositive.
Enspryng is not intended for acute treatment of an NMOSD relapse.
Neuromyelitis optica spectrum disorders (NMOSD) are rare, severe, and disabling autoimmune inflammatory disorders of the central nervous system. They primarily affect the optic nerve and spinal cord, and less commonly, the brain. Neuromyelitis optica spectrum disorders are typically characterized by recurrent relapses of optic neuritis or transverse myelitis. These result in a stepwise accumulation of potentially irreversible relapse‑related neurologic disability, including blindness, paralysis, and/or death.
An estimated 80% of patients with NMOSD have specific antibodies against AQP4 (anti‑AQP4), a protein expressed in cells of the central nervous system. The prevalence of the disease is approximately 0.5 to 10 cases per 100,000 people, with significant variation by region and ethnicity. The estimated 5‑year mortality rate in relapsing patients is 32%, though prognosis has been improving over time with increased awareness, diagnosis, and off‑label use of immunosuppressive therapies.
Early initiation of immunosuppressive therapy is used to prevent relapses and thus accumulated disability. Prednisolone, azathioprine, mycophenolate mofetil, rituximab, mitoxantrone, and methotrexate have been used off‑label for this purpose. Eculizumab, a complement system inhibitor, is authorized in Canada for the treatment of NMOSD in adults who are anti‑AQP4 seropositive.
Satralizumab, the medicinal ingredient in Enspryng, is an antibody directed against the interleukin‑6 receptor (anti‑IL‑6R). Interleukin‑6 is a pro‑inflammatory cytokine potentially implicated in the pathophysiology of NMOSD through the stimulation of production of anti‑AQP4 antibodies. Plasmablasts, a type of B‑lymphocyte whose survival is promoted by IL‑6, also increase the production of anti‑AQP4 antibodies.
The clinical efficacy of Enspryng was demonstrated primarily through two Phase III pivotal studies in patients with NMOSD. Study BN40898 evaluated the efficacy of Enspryng in adults and adolescents (aged 12 years and older) in combination with stable immunosuppressive therapies. Study BN40900 evaluated the efficacy of Enspryng in adults as monotherapy. The two studies had double‑blind, randomized, and placebo‑controlled designs, and similar inclusion and exclusion criteria. In line with the recommended regimen, doses were administered subcutaneously every two weeks for the first four weeks of the study (at Weeks 0, 2, and 4), and once every four weeks thereafter.
The primary efficacy endpoint, which was met in both studies, was the time to first relapse (TFR). The TFR was defined as a clinical relapse confirmed as a protocol‑defined relapse (PDR) by a clinical endpoint committee. Treatment with Enspryng resulted in a statistically significant reduction in the risk of experiencing a PDR when compared to placebo (hazard ratio, HR [95% confidence interval, CI]: 0.38 [0.16-0.88]) when administered in combination with stable IST. When used as monotherapy Enspryng resulted in a statistically significant reduction in the risk of experiencing a PDR when compared to placebo (HR [95% CI]: 0.45 [0.23‑0.89]). In a subgroup analysis of the primary endpoint by anti‑AQP4 status at screening, a clinically relevant risk reduction was observed in the seropositive subgroups, but not in the seronegative subgroups.
The safety profile of Enspryng was based primarily on data from the two pivotal studies. The most commonly reported adverse events included headache, upper respiratory tract infection, and urinary tract infection in both studies, as well as nasopharyngitis in Study BN40898 (combination therapy), and nausea and arthralgia in Study BN40900 (monotherapy).
The most common treatment‑related adverse events in patients treated with Enspryng were injection site reactions and clinical laboratory abnormalities such as neutropenia (grade 3 in severity). In both pivotal studies, serious infections were reported in patients treated with Enspryng or placebo, including cases of enterocolitis and endocarditis in Enspryng‑treated patients that were determined to be treatment‑related. Fractures were also reported, for which the underlying causes were determined to be visual and gait disturbances associated with NMOSD. Serious cardiovascular events were reported in patients with pre‑existing risk factors and/or concurrent conditions.
Overall, the safety profiles of Enspryng in the two studies were similar. This indicates that there was no marked increase in risk when Enspryng was used in combination with immunosuppressive therapies relative to the risk when used as monotherapy.
A Risk Management Plan (RMP) for Enspryng was submitted by Hoffmann‑La Roche Limited 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.
The submitted inner and outer labels, package insert and Patient Medication Information section of the Enspryng Product Monograph meet the necessary regulatory labelling, plain language and design element requirements.
A Look‑alike Sound‑alike brand name assessment was performed and the proposed name Enspryng was accepted.
Enspryng has an acceptable safety profile based on the non‑clinical data and clinical studies. The identified safety issues can be managed through labelling and adequate monitoring. Appropriate warnings and precautions are in place in the Enspryng 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 Enspryng?
The drug submission for Enspryng was reviewed under the Priority Review Policy. Substantial evidence was submitted demonstrating that Enspryng provided an effective treatment for neuromyelitis optica spectrum disorder (NMOSD), a serious and severely debilitating disease. At the time of approval of Priority Review status, no drug was marketed in Canada for the treatment of NMOSD.
Submission Milestones: Enspryng
| Submission Milestone | Date |
|---|---|
| Pre-submission meeting: | 2019-08-27 |
| Request for priority status | |
| Filed: | 2019-09-06 |
| Approval issued by Director, Centre for Evaluation of Radiopharmaceuticals and Biotherapeutics: | 2019-09-17 |
| Submission filed: | 2019-11-15 |
| Screening | |
| Screening Acceptance Letter issued: | 2019-12-04 |
| Review | |
| Review of Risk Management Plan complete: | 2020-03-30 |
| Labelling Review complete, including Look-alike Sound-alike brand name assessment: | 2020-05-29 |
| Quality Evaluation complete: | 2020-05-29 |
| Clinical/Medical Evaluation complete: | 2020-06-01 |
| Notice of Compliance issued by Director General, Biologic and Radiopharmaceutical Drugs Directorate: | 2020-06-01 |
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?
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
Satralizumab, the medicinal ingredient in Enspryng, is a humanized immunoglobulin G2 (IgG2) monoclonal antibody. It binds to soluble and membrane‑bound human interleukin‑6 receptor (IL‑6R), and thereby prevents IL‑6 downstream signalling through these receptors.
Interleukin‑6 has been shown to be involved in disease‑relevant pro‑inflammatory mechanisms. The precise mechanism by which satralizumab exerts its therapeutic effect in neuromyelitis optica (NMO) and neuromyelitis optica spectrum disorders (NMOSD) is unknown, but is presumed to involve reduced production of antibodies against aquaporin 4 (anti‑AQP4 autoantibodies) through inhibition of IL‑6 signalling.
The pharmacokinetic profile of satralizumab was characterized in healthy subjects and in patients with NMO or NMOSD. Administered subcutaneously, satralizumab exhibited non‑linear pharmacokinetics across a dose range of 30‑240 mg. In adult patients following the proposed dosage regimen, steady state was achieved at 8 weeks. The mean half‑life of satralizumab was 30 days (range: 22‑37 days).
Pharmacokinetic data in adolescents was limited to seven patients aged 13‑17 years. At steady state, similar geometric mean (coefficient of variation [CV]) trough concentrations (Ctrough) were observed in adolescents and adults (17.9 [12.5%] mcg/mL and 19.0 [13.9%] mcg/mL, respectively).
Exposure to satralizumab was approximately twofold lower in patients who were positive for post‑treatment anti‑drug antibodies (ADAs) or with body weight ≥75.0 kg, compared with patients who were negative for post‑treatment ADAs and lighter body weight (57.3‑75 kg). The clinical response to satralizumab was similar across subgroups based on an exposure‑response analysis, and therefore dose adjustments are not considered necessary. The pharmacokinetics of satralizumab has not been studied in patients with renal or hepatic impairment.
For further details, please refer to the Enspryng Product Monograph, approved by Health Canada and available through the Drug Product Database.
Clinical Efficacy
Evidence of the clinical efficacy of Enspryng was provided primarily through two Phase III pivotal studies in patients with NMOSD. Study BN40898 evaluated the efficacy of Enspryng in adults and adolescents (aged 12 years and older) in combination with stable immunosuppressive therapies (IST). Study BN40900 evaluated the efficacy of Enspryng in adults as monotherapy. The two studies had similar designs and inclusion and exclusion criteria. The enrollment of anti‑AQP4 seronegative patients in each study was limited to no more than 30%.
Study BN40898 evaluated the effect of Enspryng as combination therapy with stable IST in adult and adolescent patients with NMOSD. This double‑blind, placebo‑controlled study enrolled 76 adult and 7 adolescent patients (number of patients [n] = 83), 55 (66.3%) of whom were anti‑AQP4 seropositive. Patients were randomized in a 1:1 ratio to receive either Enspryng (n = 41) or placebo (n = 42) in combination with stable IST. Doses were administered subcutaneously every two weeks for the first four weeks of the study (at Weeks 0, 2, and 4), and once every four weeks thereafter. Along with Enspryng or placebo, adult patients also received oral corticosteroids (OC), azathioprine (AZA), or mycophenolate mofetil (MMF), while adolescent patients received a combination of OC and AZA or OC and MMF.
Study BN40900 evaluated the effect of Enspryng as monotherapy in adult patients with NMOSD. This double‑blind, placebo‑controlled study enrolled 95 patients, 64 (67.4%) of whom were anti‑AQP4 seropositive. Patients were randomized in a 2:1 ratio to receive either Enspryng (n = 63) or placebo (n = 32). Doses were administered subcutaneously every two weeks for the first four weeks of the study (at Weeks 0, 2, and 4), and once every four weeks thereafter.
In both studies, the primary efficacy endpoint was the time to first relapse (TFR), which was a clinical relapse confirmed as a protocol‑defined relapse (PDR) by a clinical endpoint committee. Key secondary endpoints included change in the visual analog scale (VAS) pain score from baseline to Week 24, and change in the Functional Assessment of Chronic Illness Therapy (FACIT)‑fatigue score from baseline to Week 24.
The primary endpoint was met in both clinical studies. Treatment with Enspryng resulted in a statistically significant reduction in the risk of experiencing a PDR when compared to placebo (hazard ratio, HR [95% confidence interval, CI]: 0.38 [0.16‑0.88]) when administered in combination with stable IST. When used as monotherapy Enspryng resulted in a statistically significant reduction in the risk of experiencing a PDR when compared to placebo (HR [95% CI]: 0.45 [0.23‑0.89]). In a subgroup analysis of the primary endpoint by anti‑AQP4 status at screening, a clinically relevant risk reduction was observed in the seropositive subgroups, but not in the seronegative subgroups. Key secondary endpoints for pain and fatigue were not met.
Indication
| Sponsor's proposed indication | Health Canada-approved indication |
| Enspryng (satralizumab) is indicated as monotherapy or in combination with immunosuppressive therapy (IST) for the treatment of adult and adolescent patients with neuromyelitis optica spectrum disorders (NMOSD). | Enspryng (satralizumab) is indicated as monotherapy or in combination with immunosuppressive therapy (IST) for the treatment of neuromyelitis optica spectrum disorders (NMOSD) in adult and adolescent patients who are anti‑aquaporin 4 (AQP4) seropositive. Enspryng is not intended for acute treatment of an NMOSD relapse. |
The proposed indication was revised to reflect the findings of the pivotal studies regarding the statistically significant clinical benefit for anti‑AQP4 seropositive patients (but not for seronegative patients). A statement was included in the Product Monograph to specify that the safety and efficacy of Enspryng have not been established in children younger than 12 years of age. Its authorization for use in adolescent patients is based on clinical pharmacology data and extrapolated efficacy and safety data from adult patients with NMOSD.
For more information, refer to the Enspryng Product Monograph, approved by Health Canada and available through the Drug Product Database.
Clinical Safety
The clinical safety evaluation of Enspryng was based primarily on data from the two pivotal studies, BN40898 and BN40900, which are described in detail in the Clinical Efficacy section. In both studies, the rates at which different adverse events were observed were adjusted for differences in the length of exposure between the two treatment groups (Enspryng vs. placebo).
In Study BN40898, the combination therapy study, similar rates of treatment‑emergent adverse events (TEAEs), serious adverse events, and severe adverse events were reported in each group (approximately 93%, 19%, and 12%, respectively). Exposure‑adjusted rates of other safety variables were higher or similar in the placebo group. During the double‑blind period, a higher proportion of patients in the placebo group had serious infections. In patients treated with Enspryng, the most commonly reported adverse events were nasopharyngitis, upper respiratory tract infection, headache, and urinary tract infection.
In Study BN40900, the monotherapy study, exposure‑adjusted rates of TEAEs were similar between the two treatment groups. Higher incidences of severe adverse events were reported in patients treated with Enspryng (32.1 severe events per 100 patient‑years) than in patients who received the placebo (9.85 severe events per 100 patient‑years). Other safety endpoints were similar between the two treatment groups, or more favourable in patients treated with Enspryng. The most commonly reported adverse events in patients treated with Enspryng were urinary tract infection, nausea, arthralgia, upper respiratory tract infection, and headache.
In both pivotal studies, serious infections were reported in patients treated with Enspryng or placebo, including cases of enterocolitis and endocarditis in Enspryng‑treated patients that were determined to be treatment‑related. Fractures were also reported in both studies, for which the underlying causes were determined to be visual and gait disturbances associated with NMOSD. Serious cardiovascular events were reported in patients with pre‑existing risk factors and/or concurrent conditions. One patient treated with Enspryng in Study BN40900 experienced two severe, systemic injection‑related reactions of vertigo. In Study BN40898, a higher incidence of pre‑existing suicidal ideation or behaviour history was observed at baseline in patients randomized to the Enspryng treatment group. One patient treated with Enspryng in this study attempted suicide.
The most common treatment‑related adverse events in patients treated with Enspryng were injection site reactions and clinical laboratory abnormalities such as neutropenia (grade 3 in severity). Elevated levels of blood lipids and liver enzymes were also observed in patients treated with Enspryng. Decreased fibrinogen was more common in patients treated with Enspryng, as it is a known effect of its medicinal ingredient, satralizumab. It was observed to be of moderate severity, and no bleeding events were reported in these studies.
Overall, the safety profiles of Enspryng in the two studies were similar. This indicates that there was no marked increase in risk when Enspryng was used in combination with ISTs relative to the risk when used as monotherapy.
Health Canada has determined that appropriate risk management measures are in place to address the safety concerns identified for Enspryng, and to promote its safe and effective use. For more information, refer to the Enspryng Product Monograph, approved by Health Canada and available through the Drug Product Database.
7.2 Non-Clinical Basis for Decision
Repeat‑dose toxicity studies were conducted in mature cynomolgus monkeys, for durations of 4 weeks and 26 weeks. Doses of 2, 10, or 50 mg/kg satralizumab were administered subcutaneously once per week. Anti‑drug antibodies (ADAs) against satralizumab were detected in most of the treated animals, but did not affect the pharmacological response and were not associated with any adverse effects. No effects were observed on reproductive organs in female monkeys. However, testicular and prostate atrophy and changes to sperm morphology were observed in male monkeys. A no‑observed‑adverse‑effect level (NOAEL) could not be established in this study, as testicular atrophy was observed in male monkeys that received the lowest dose of satralizumab.
In an enhanced pre‑ and postnatal development study, doses of 2 or 50 mg/kg satralizumab were administered subcutaneously to pregnant animals once per week, from gestational day 20 until parturition. Satralizumab was found to cross the placental barrier. The frequency of prenatal losses did not differ considerably between maternal monkeys given satralizumab and those given the vehicle control. One neonate in the high‑dose group died due to infection. Infants exposed to satralizumab in utero also showed reduced and/or delayed immunoglobulin (Ig) G and IgM responses to keyhole limpet hemocyanin antigen challenge. No adverse effects on maternal animals, fetal development, pregnancy outcome, or infant development were associated with satralizumab. The NOAEL for the developmental toxicity of satralizumab was determined to be 2 mg/kg/week, which corresponds to three times the human exposure at the maximum recommended dose. Very low concentrations of satralizumab were detected in breast milk, corresponding to <0.9% of maternal plasma levels.
Satralizumab inhibited soluble and membrane‑bound interleukin‑6‑receptor (IL‑6R) pathways in vitro and in vivo.
No dedicated carcinogenicity or genotoxicity studies have been conducted for satralizumab.
The results of the non‑clinical studies as well as the potential risks to humans have been included in the Enspryng Product Monograph. Considering the intended use of Enspryng, there are no pharmacological or toxicological issues within this submission which preclude authorization of the product.
For more information, refer to the Enspryng Product Monograph, approved by Health Canada and available through the Drug Product Database.
7.3 Quality Basis for Decision
Characterization of the Drug Substance
Satralizumab, the medicinal ingredient in Enspryng, is a humanized monoclonal antibody based on the structure of immunoglobulin G2 (IgG2). It binds to both the soluble and membrane‑bound forms of the interleukin‑6 receptor (IL‑6R), thereby preventing downstream signalling by IL‑6 through these receptors. Interleukin‑6 is involved in various inflammatory processes including B‑cell activation, differentiation of B cells to plasmablasts and production of autoantibodies, Th17‑cell activation and differentiation, regulatory T‑cell inhibition, and changes in blood‑brain barrier permeability.
Comprehensive characterization studies were performed to provide evidence that satralizumab consistently exhibits the expected structure and biological properties essential to its function. Primary and higher order structures, post‑translational modifications, and various physicochemical and biological properties were examined and found to be satisfactory.
Manufacturing Process and Process Controls of the Drug Substance and Drug Product
The drug substance, satralizumab, is manufactured from Chinese hamster ovary (CHO) cells using recombinant deoxyribonucleic acid (DNA) technology. The cell culture is initiated from a single working cell bank vial or unused cell mass from a seed train, and allowed to expand to commercial scale. Recombinant satralizumab is harvested from the growth medium, and purified through a series of chromatography, viral inactivation, and filtration steps. This process results in a fully formulated drug substance, which is stored frozen at ≤-50°C.
The drug product, Enspryng, is produced by thawing, pooling, and mixing the drug substance, followed by filtration and aseptic filling into syringes. The syringes are stoppered, and then shipped under controlled conditions to another facility where they are labelled, assembled, and packaged.
The drug substance and drug product batches examined in process validation studies met the relevant pre‑defined acceptance criteria. Overall, the process validation results show that the commercial process is capable of consistently producing a drug substance and drug product of acceptable quality.
All non‑medicinal ingredients (excipients) found in the drug product are acceptable for use in drugs according to the Food and Drug Regulations. The compatibility of satralizumab with the excipients is supported by the stability data provided.
Control of the Drug Substance and Drug Product
Enspryng is a Schedule D (biologic) drug and is, therefore, subject to Health Canada's Lot Release Program as per the Guidance for Sponsors: Lot Release Program for Schedule D (Biologic) Drugs. For post‑approval monitoring, Enspryng is considered a low‑risk product.
The data obtained through validation studies reflect consistency in the manufacturing process. The drug substance manufacturing process was scaled up, and the drug substance and drug product manufacturing processes were optimized during drug development. The batch analysis and stability data provided showed that the products from these processes are comparable. Process validation lots were examined and met all pre‑defined acceptance criteria and release specifications.
In‑house testing was not feasible due to the impact of the coronavirus disease 2019 (COVID‑19) pandemic. A paper‑based assessment was conducted in its place, which involved examination of the standard operating procedures and raw data from multiple lots of the drug product. The methods used in the control strategy were found to be fit for use, and additional risk mitigation measures are not required.
Stability of the Drug Substance and Drug Product
Based on the stability data submitted, the proposed shelf life and storage conditions for the drug substance and drug product were adequately supported and are considered to be satisfactory. The proposed 24‑month shelf life at 2‑8°C is considered acceptable for Enspryng.
The drug product must not be frozen or shaken, and the prefilled syringe should be stored in its carton to protect it from light. Additional special handling instructions are listed in the Enspryng Product Monograph.
Facilities and Equipment
On‑site evaluations (OSEs) were not conducted in connection with the submission for Enspryng. A risk assessment conducted by Health Canada indicated that OSEs were not warranted for the drug substance or drug product manufacturing and release testing sites.
Adventitious Agents Safety Evaluation
The cell banks used in the manufacture of Enspryng were qualified according to relevant International Council for Harmonisation (ICH) guidelines, and were found to be well controlled for endogenous and adventitious viral agents.
The purification process demonstrates a high level of viral clearance for a variety of virus types. Appropriate small‑scale studies demonstrated that the satralizumab purification process has an acceptable safety margin, and is capable of consistently reducing contamination to levels below the acceptable limits.
The biologic raw materials used during manufacturing originate from sources with no or minimal risk of transmissible spongiform encephalopathy or other human pathogens.
Related Drug Products
| Product name | DIN | Company name | Active ingredient(s) & strength |
|---|---|---|---|
| ENSPRYNG | 02499681 | HOFFMANN-LA ROCHE LIMITED | SATRALIZUMAB 120 MG / ML |