Product Overview

Ceritinib (LDK378, Zykadia, CAS 1032900-25-6, C₂₈H₃₆ClN₅O₃S, MW 558.14 g/mol) is a second-generation ALK (Anaplastic Lymphoma Kinase) tyrosine kinase inhibitor and the second FDA-approved ALK TKI for ALK-positive metastatic non-small cell lung cancer (NSCLC). ALK rearrangements — predominantly EML4-ALK fusion oncogenes — drive approximately 3–7% of NSCLC cases, typically in younger never-smokers or light smokers with adenocarcinoma histology, representing ~40,000+ new patients globally each year. Ceritinib is an ATP-competitive inhibitor that binds the ALK kinase domain in its DFG-in (active) conformation, occupying the ATP-binding pocket and blocking ALK autophosphorylation at Y1278/Y1282/Y1283 with an IC50 of ~0.15 nM — approximately 20× more potent than crizotinib (IC50 ~3 nM), the first-generation ALK inhibitor. Ceritinib’s enhanced potency derives from its optimized 2,4-pyrimidinediamine scaffold: the 5-chloro substitution on the pyrimidine core, the 2-isopropoxy-5-methyl-4-(4-piperidinyl)phenyl moiety at the N2 position, and the 2-(isopropylsulfonyl)phenyl group at the N4 position collectively enable deep binding within the ALK ATP pocket with extended residence time. At the cellular level, ceritinib potently inhibits ALK downstream signaling through STAT3 (Tyr705), AKT (Ser473), ERK1/2 (Thr202/Tyr204), and mTOR pathways, inducing G1/S cell-cycle arrest (via p27 upregulation, cyclin D1 downregulation) and caspase-3/7-mediated apoptosis selectively in ALK-driven tumor cells. Ceritinib is metabolized primarily by CYP3A4 and is a substrate of CYP3A4 and CYP2C9; it is also an inhibitor of CYP3A4 (time-dependent), CYP2C9, and CYP2B6 — important considerations for drug-drug interaction assessment in generic development.

Ceritinib was discovered by Novartis through structure-based drug design targeting crizotinib-resistant ALK variants and received FDA accelerated approval in April 2014 (converted to full approval in 2017) under the brand name Zykadia. The recommended dose is 750 mg orally once daily on an empty stomach (at least 2 hours before or after a meal) — though a lower 450 mg/day dose with food was subsequently approved based on comparable exposure with reduced GI toxicity. Ceritinib was the first ALK inhibitor to demonstrate CNS (central nervous system) activity — a critical clinical advantage because 30–60% of ALK+ NSCLC patients develop brain metastases, and crizotinib’s poor CNS penetration (CSF-to-plasma ratio ~0.0026 due to P-glycoprotein efflux) makes the brain a common sanctuary site for disease progression. Ceritinib achieves therapeutic CNS concentrations, enabling intracranial response rates of 35–73% in patients with measurable brain metastases. The global ALK inhibitor market exceeds $2 billion annually, encompassing crizotinib (Xalkori, Pfizer), ceritinib (Zykadia, Novartis), alectinib (Alecensa, Roche/Chugai), brigatinib (Alunbrig, Takeda), and lorlatinib (Lorbrena, Pfizer) — representing a major commercial opportunity for generic API development as patents expire. UPOR Biotech supplies ceritinib as a pharmaceutical intermediate for R&D, reference standard for analytical method development, and GMP-grade API for generic drug product development and ANDA filings.

Ceritinib vs Crizotinib vs Alectinib — Generational Comparison of ALK Inhibitors: Why Ceritinib Remains a Critical Generic API Target

Comparing the three FDA-approved ALK inhibitors reveals ceritinib’s strategic position in the ALK+ NSCLC treatment landscape and generic API market. Crizotinib (Xalkori, Pfizer, 2011) is the first-generation ALK/MET/ROS1 inhibitor with IC50 ~3 nM against ALK. It demonstrated median PFS of 10.9 months (PROFILE 1014) but is limited by poor CNS penetration (CSF-to-plasma ratio ~0.0026, P-gp substrate), CNS as common first progression site (~35–50% of patients), and emergence of ALK resistance mutations (L1196M gatekeeper, G1269A, C1156Y, G1202R solvent-front). Crizotinib’s CNS failure rate and growing resistance drove the development of second-generation inhibitors. Ceritinib (Zykadia, Novartis, 2014) is 20× more potent (IC50 ~0.15 nM), retains activity against L1196M, G1269A, and S1206Y resistance mutations, and achieves meaningful CNS penetration with intracranial responses of 35–73%. In the ASCEND-4 trial, treatment-naive patients achieved median PFS of 16.6 months — a significant improvement over crizotinib. Ceritinib’s patent portfolio has begun expiring in major markets, creating substantial generic API demand. Alectinib (Alecensa, Roche/Chugai, 2015) offers superior potency (IC50 ~1.9 nM), broader resistance mutation coverage including partial G1202R activity, best-in-class CNS penetration, and median PFS of 25.7 months in treatment-naive patients (ALEX trial) with a more favorable GI tolerability profile. However, alectinib’s later patent expiry extends branded exclusivity. Strategic conclusion for generic developers: Ceritinib is the most commercially accessible second-generation ALK inhibitor for generic API development — its earlier approval (2014) means earlier patent expiry and first-to-file ANDA opportunities, established clinical efficacy in both treatment-naive and crizotinib-resistant settings, and well-characterized CMC and bioequivalence pathways. The comprehensive dataset from ASCEND-1 through ASCEND-8 provides robust clinical references for bioequivalence study design. UPOR Biotech’s ceritinib API with Type II DMF, GMP manufacturing, and full CMC documentation is positioned to support generic ANDA filings, 505(b)(2) NDA development, and global regulatory submissions.

Technical Specifications

PropertySpecification
Product NameCeritinib — Pharma API/Research Grade (≥99% HPLC) / Reference Standard (≥99.5%) / GMP Grade
INN / USANCeritinib
Common Name / SynonymsCeritinib; LDK378; Zykadia; 5-Chloro-N²-[2-isopropoxy-5-methyl-4-(4-piperidinyl)phenyl]-N⁴-[2-(isopropylsulfonyl)phenyl]-2,4-pyrimidinediamine
CAS Number1032900-25-6
Molecular FormulaC₂₈H₃₆ClN₅O₃S
Molecular Weight558.14 g/mol
Drug ClassSecond-generation ALK (Anaplastic Lymphoma Kinase) tyrosine kinase inhibitor — ATP-competitive, DFG-in conformation binder
Key Advantage20× more potent than crizotinib (IC50 ~0.15 nM vs ~3 nM). Active against crizotinib-resistant ALK mutations (L1196M, G1269A, S1206Y). CNS-penetrant with demonstrated intracranial activity against brain metastases. FDA-approved for ALK+ metastatic NSCLC.
Description / AppearanceWhite to off-white crystalline powder
Assay (Pharma API / Research Grade)≥99.0% (HPLC, anhydrous and solvent-free basis)
Assay (Reference Standard)≥99.5% (HPLC, mass balance method — HPLC purity, water content, residual solvents, residue on ignition)
IdentificationIR spectrum conforms to ceritinib reference standard; HPLC retention time matches ceritinib RS; ¹H-NMR (DMSO-d₆) and ¹³C-NMR consistent with assigned structure; HRMS [M+H]⁺ consistent with molecular formula C₂₈H₃₆ClN₅O₃S
Related Substances / Impurity ProfilePer ICH Q3A: Specified impurities (known/identified) ≤0.10% each; Unspecified impurities ≤0.10% each; Total impurities ≤1.0%. Impurity profiling includes process impurities, degradation products (acid/base/oxidative/thermal/photolytic stress), and isomeric impurities by HPLC-UV and LC-MS.
Loss on Drying≤0.5% (105°C, 2 hours, or Karl Fischer titration for water determination)
Residue on Ignition≤0.1% (sulfated ash)
SolubilitySoluble in DMSO (>10 mg/mL), sparingly soluble in methanol and ethanol; practically insoluble in water (BCS Class IV — low solubility, low permeability). For in vitro studies: dissolve in DMSO to prepare stock solution, dilute in aqueous buffer with ≤0.1% DMSO final concentration.
Polymorphic FormMultiple polymorphic forms identified; commercial form matches Reference Listed Drug (RLD/Zykadia) polymorph per XRPD and DSC. Polymorphic identity confirmed by XRPD diffractogram overlay vs. RLD reference; DSC melting endotherm consistent with RLD polymorph.
Particle Size Distribution (PSD)D10 / D50 / D90 by laser diffraction (Malvern Mastersizer or equivalent). PSD specification matched to innovator product for solid oral dosage form development; micronized grade available for dissolution/bioequivalence optimization.
Heavy Metals (Total)≤10 ppm (as Pb)
Elemental ImpuritiesICH Q3D compliant: Class 1 (As ≤1.5 ppm, Cd ≤0.5 ppm, Hg ≤0.3 ppm, Pb ≤0.5 ppm); Class 2A (Co ≤0.5 ppm, Ni ≤6.0 ppm, V ≤1.2 ppm); Class 2B and Class 3 elements within permitted daily exposure (PDE) limits per ICH Q3D Table A.2.1 — oral route, Option 1 assessment. Validated by ICP-MS per USP <232>/<233>.
Microbial LimitsTAMC ≤100 CFU/g; TYMC ≤10 CFU/g (USP <61> / EP <2.6.12>); Pathogens (E. coli, Salmonella, S. aureus, P. aeruginosa, Bile-tolerant gram-negative bacteria) — Absent in 10 g (USP <62> / EP <2.6.13>)
Residual SolventsUSP <467> / EP <5.4> / ICH Q3C Class 2 (solvents to be limited) and Class 3 (solvents with low toxic potential) compliant. Validated by GC-HS. Class 1 solvents (benzene, carbon tetrachloride, 1,2-dichloroethane, 1,1-dichloroethene, 1,1,1-trichloroethane) — Not used in manufacturing process per ICH Q3C.
Chiral Purity / Enantiomeric ExcessCeritinib is achiral (no stereogenic centers). Enantiomeric purity: N/A.
Mutagenic ImpuritiesPer ICH M7(R1): Nitrosamine risk assessment conducted (per FDA guidance “Control of Nitrosamine Impurities in Human Drugs,” 2021/2024 revision). Potential genotoxic impurities (PGIs) controlled at TTC (Threshold of Toxicological Concern) ≤1.5 μg/day for >10-year lifetime exposure. Confirmation of absence of NDMA, NDEA, and other N-nitrosamines by LC-MS/MS (LOQ ≤0.03 ppm).
Grade / StandardsPharma API/Research Grade (≥99% HPLC) / Reference Standard (≥99.5%, mass balance qualified) / GMP Grade (ICH Q7, 21 CFR 210/211, EU GMP Part II compliant)
DMFType II Drug Master File (DMF) submitted to US FDA — Letter of Authorization (LOA) available upon executed Confidentiality Disclosure Agreement (CDA) and Quality Agreement (QAA)
StabilityICH Q1A-compliant: Long-term 25°C/60%RH (36 months), Intermediate 30°C/65%RH (12 months), Accelerated 40°C/75%RH (6 months). Forced degradation studies: acid (0.1N HCl, 24h), base (0.1N NaOH, 24h), oxidative (3% H₂O₂, 24h), thermal (60°C, 14 days), photolytic (ICH Q1B Option 2, visible + UV). Photostability confirmed per ICH Q1B.
PackagingResearch grade: 10 mg / 50 mg / 100 mg amber glass vials with PTFE-lined caps under argon. Pharma API grade: 100 g / 500 g / 1 kg double LDPE bags in sealed aluminum foil bags. GMP grade: 1 kg / 5 kg double LDPE bags in fiber drums with tamper-evident seals.
Storage2–8°C (refrigerated), tightly sealed in original container, protect from light and moisture. Long-term storage at -20°C recommended for Reference Standard grade. Avoid repeated freeze-thaw cycles. Ship at ambient temperature with temperature logger (excursion ≤25°C for ≤72 hours validated).
Shelf Life3 years from date of manufacture under recommended storage conditions. Retest period: 24 months (real-time stability data). Reference Standard: re-qualify every 12 months per internal SOP.
CertificationsISO 9001:2015, ISO 22000, HACCP, FDA Facility Registration, HALAL, KOSHER, Non-GMO, BSE/TSE-Free

Key Benefits — Ceritinib (LDK378, Zykadia)

20× More Potent Than Crizotinib Against ALK — IC50 ~0.15 nM

Ceritinib achieves 20-fold greater ALK inhibitory potency than crizotinib (IC50 ~0.15 nM vs ~3 nM). This potency advantage is driven by an optimized 2,4-pyrimidinediamine scaffold with extended ATP-pocket residence time — enabling robust ALK autophosphorylation blockade at clinically achievable concentrations and translating to superior cellular anti-proliferative activity in ALK-driven NSCLC models.

20× ALK Potency

CNS-Penetrant — Intracranial Activity Against Brain Metastases

Unlike crizotinib (CSF-to-plasma ratio ~0.0026, P-gp efflux substrate), ceritinib crosses the blood-brain barrier and achieves therapeutic CNS concentrations. Clinical trials (ASCEND-1/2/4) demonstrated intracranial overall response rates of 35–73% in patients with measurable brain metastases — addressing a major unmet need in ALK+ NSCLC where brain is a common first site of progression.

CNS Active

Active Against Crizotinib-Resistant ALK Mutations — L1196M, G1269A, S1206Y

Ceritinib retains inhibitory activity against key crizotinib-resistant ALK secondary mutations: L1196M gatekeeper mutation (steric hindrance to crizotinib binding, ceritinib accommodates with flexible diaminopyrimidine scaffold), G1269A (ATP-binding pocket mutation, reduced crizotinib affinity), and S1206Y (solvent-proximal mutation). This resistance coverage enables ceritinib efficacy in crizotinib-refractory patients.

Resistance Coverage

GMP API with Type II DMF — Supporting Generic ANDA & 505(b)(2) Development

UPOR Biotech supplies ceritinib in three grades with full CMC documentation: Pharma API/Research Grade (≥99% HPLC) for R&D, Reference Standard (≥99.5%, mass balance qualified) for analytical development, and GMP Grade (ICH Q7, 21 CFR 210/211) with Type II DMF and LOA for generic ANDA filings and 505(b)(2) NDA development. Comprehensive documentation package supports global regulatory submissions.

GMP + DMF Available

Applications

ALK-Positive Metastatic NSCLC — First-Line & Post-Crizotinib Therapy

Ceritinib as active pharmaceutical ingredient for generic solid oral dosage forms (150 mg hard gelatin capsules — RLD: Zykadia, Novartis). First-line treatment of ALK-positive metastatic NSCLC (ASCEND-4: median PFS 16.6 months) and post-crizotinib setting (ASCEND-1/2: ORR 38–58%). GMP-grade API with Type II DMF supports ANDA first-to-file opportunities as Zykadia patents expire.

Crizotinib-Resistant & ALK Secondary Mutation NSCLC

Ceritinib for crizotinib-refractory NSCLC patients with confirmed ALK secondary resistance mutations (L1196M, G1269A, S1206Y). In vitro sensitivity profiling and clinical response data support ceritinib as the logical second-line ALK TKI after crizotinib failure — a key clinical niche for generic development targeting the post-crizotinib patient population.

Brain Metastases — CNS-Penetrant ALK Inhibitor

Ceritinib for ALK+ NSCLC patients with brain metastases — the first clinically validated CNS-active ALK inhibitor. Intracranial response rates of 35–73% in patients with measurable baseline brain metastases. For generic development, CNS penetration equivalence (in vitro P-gp substrate assay, in vivo rodent brain-to-plasma Kp ratio) is a critical bioequivalence parameter.

Reference Standard — Analytical Method Development & QC Release Testing

Ceritinib Reference Standard (≥99.5%, mass balance qualified) for HPLC assay/impurity method development, dissolution method validation, ANDA batch release testing, and stability-indicating method qualification. Structure elucidation package (NMR, HRMS, FT-IR, elemental analysis) and comprehensive CoA provided. Re-qualification every 12 months.

Pharmaceutical R&D — In Vitro & In Vivo Pharmacology Studies

Ceritinib (Pharma API/Research Grade, ≥99% HPLC) for preclinical pharmacology: ALK wild-type and mutant kinase inhibition assays (IC50 determination), Ba/F3 EML4-ALK cellular proliferation assays, in vivo ALK+ NSCLC xenograft/syngeneic models, CNS penetration PK/PD studies, and CYP450 drug-drug interaction (DDI) liability screening.

Bioequivalence & Formulation Development — Generic 505(b)(2) Programs

Ceritinib GMP-grade API with Type II DMF for generic formulation development: immediate-release hard gelatin capsules (150 mg base), solid dispersion and amorphous solid dispersion (ASD) technologies for BCS Class IV solubility enhancement, dissolution method development (USP apparatus with biorelevant media — FaSSGF/FaSSIF/FeSSIF), and pilot bioequivalence study support.

Frequently Asked Questions

Ceritinib (LDK378, Zykadia, CAS 1032900-25-6) is a second-generation ALK (Anaplastic Lymphoma Kinase) tyrosine kinase inhibitor developed by Novartis and FDA-approved in 2014 for ALK-positive metastatic non-small cell lung cancer (NSCLC). ALK gene rearrangements — predominantly EML4-ALK fusion oncogenes — occur in 3–7% of NSCLC patients (~40,000+ new cases globally per year), typically in younger never-smokers or light smokers with adenocarcinoma histology. Ceritinib is an ATP-competitive inhibitor that binds the ALK kinase domain in its DFG-in (active) conformation with an IC50 of ~0.15 nM — approximately 20× more potent than crizotinib (IC50 ~3 nM). The 2,4-pyrimidinediamine scaffold of ceritinib — with 5-chloro substitution on the pyrimidine core, 2-isopropoxy-5-methyl-4-(4-piperidinyl)phenyl at N2, and 2-(isopropylsulfonyl)phenyl at N4 — enables deep binding within the ALK ATP-binding pocket with extended residence time. Ceritinib potently inhibits ALK autophosphorylation (Y1278/Y1282/Y1283) and downstream oncogenic signaling through STAT3, AKT, ERK1/2, and mTOR pathways, inducing G1/S cell-cycle arrest (p27 upregulation, cyclin D1 downregulation) and caspase-3/7-mediated apoptosis in ALK-driven tumor cells. Critically, ceritinib retains activity against crizotinib-resistant ALK secondary mutations including the L1196M gatekeeper mutation, G1269A, and S1206Y — though it is not active against the G1202R solvent-front mutation. CNS penetration is a major differentiating feature: ceritinib crosses the blood-brain barrier (not a P-gp substrate like crizotinib), achieving therapeutic CNS concentrations and demonstrating intracranial response rates of 35–73% in patients with brain metastases — addressing the most common site of ALK+ NSCLC progression. Ceritinib is metabolized primarily by CYP3A4 and undergoes hepatic elimination. UPOR Biotech supplies ceritinib in three grades: Pharma API/Research Grade (≥99% HPLC) for R&D, Reference Standard (≥99.5%, mass balance qualified) for analytical method development, and GMP Grade with Type II DMF for generic ANDA filings.

Crizotinib (1st-gen, Xalkori, Pfizer, 2011): ALK/MET/ROS1 inhibitor, IC50 ~3 nM against ALK. Median PFS 10.9 months (PROFILE 1014, 1st-line). Major limitations: poor CNS penetration (CSF-to-plasma ratio ~0.0026, P-gp substrate) — CNS is first progression site in ~35–50% of patients; resistance emerges ~10–12 months through ALK secondary mutations (L1196M gatekeeper, G1269A, C1156Y, G1202R solvent-front) and bypass pathway activation (EGFR, KIT, SRC). Crizotinib was a major advance in genetically-guided NSCLC therapy but CNS failure and acquired resistance created the need for next-generation ALK inhibitors. Ceritinib (2nd-gen, Zykadia, Novartis, 2014): ALK inhibitor, IC50 ~0.15 nM — 20× more potent than crizotinib. Active against L1196M, G1269A, S1206Y resistance mutations (not G1202R). CNS-penetrant with intracranial responses of 35–73%. Median PFS 16.6 months (ASCEND-4, 1st-line) and 5.4–6.9 months (post-crizotinib). Dose: 750 mg/day fasted (later 450 mg/day with food approved). Common AEs: GI (diarrhea 86%, nausea 80%, vomiting 60% — mechanism-based, partially manageable with dose modification and food intake), transaminase elevation (ALT >5× ULN in 27%), fatigue. Alectinib (2nd-gen, Alecensa, Roche/Chugai, 2015): Highly selective ALK inhibitor, IC50 ~1.9 nM. Active against most crizotinib-resistant mutations including partial G1202R activity — the most significant resistance coverage difference vs. ceritinib. Best-in-class CNS penetration and superior PFS: 25.7 months 1st-line (ALEX trial) vs. crizotinib’s 10.4 months (HR 0.47). Better GI tolerability than ceritinib (constipation 36% vs. diarrhea 86%). 600 mg BID with food. Strategic conclusion for generic development: Ceritinib is the most commercially accessible 2nd-gen ALK inhibitor — earlier approval (2014) means earlier U.S. patent expiry, established clinical efficacy in both 1st-line and post-crizotinib settings, and well-characterized CMC/bioequivalence pathway. The ASCEND clinical program (8 trials, 2,200+ patients) provides robust clinical references for BE study design. UPOR Biotech’s ceritinib API with Type II DMF, GMP manufacturing, polymorph control, PSD specification, and full ICH-compliant CMC documentation is optimized for ANDA development.

CNS (central nervous system) penetration is one of ceritinib’s most clinically significant advantages over first-generation crizotinib. Brain metastases occur in 30–60% of ALK+ NSCLC patients during the course of their disease, and the brain is frequently the first and only site of progression on crizotinib due to inadequate CNS drug exposure. Crizotinib is a substrate of the P-glycoprotein (P-gp, ABCB1) efflux transporter at the blood-brain barrier, actively pumped out of the CNS, resulting in a CSF-to-plasma concentration ratio of only ~0.0026 — far below the therapeutic threshold. This pharmacokinetic sanctuary makes the brain a common site of treatment failure in crizotinib-treated patients, with CNS progression rates of ~35–50%. Ceritinib is not a potent P-gp substrate, enabling passive diffusion across the BBB and achievement of therapeutic CNS concentrations. In clinical practice, ceritinib demonstrated intracranial overall response rates of 35–73% in ALK+ NSCLC patients with measurable brain metastases at baseline across the ASCEND-1/2/4 trials, including in crizotinib-pretreated patients. The clinical significance extends beyond tumor shrinkage: effective intracranial disease control prevents or delays neurological deterioration (seizures, cognitive decline, motor deficits), preserves quality of life, reduces the need for whole-brain radiotherapy (WBRT) or stereotactic radiosurgery (SRS), and contributes to overall survival benefit. For generic API development, CNS penetration equivalence is a critical pharmaceutical parameter. Demonstration of equivalent CNS penetration may require: (1) in vitro bidirectional permeability assay (Caco-2 or MDCK-MDR1 monolayers) with P-gp substrate assessment — confirming ceritinib API is not a P-gp substrate, matching the innovator; (2) rodent brain-to-plasma concentration ratio (Kp,brain) at steady-state; and (3) confirmation that polymorphic form, PSD, and solid-state properties do not alter dissolution rate and oral bioavailability in a manner that would affect CNS exposure. UPOR Biotech’s ceritinib API is fully characterized for these CNS-relevant quality attributes and supported by comprehensive analytical documentation.

UPOR Biotech provides a comprehensive GMP manufacturing and regulatory documentation package to support generic ceritinib API development, ANDA (Abbreviated New Drug Application) filings with the US FDA, and global regulatory submissions (EMA MAA, PMDA J-NDA, NMPA ANDA). Manufacturing: GMP-grade ceritinib is manufactured in compliance with ICH Q7 (GMP for Active Pharmaceutical Ingredients), 21 CFR Parts 210/211, and EU GMP Part II. The synthetic route is fully validated with defined critical process parameters (CPPs), in-process controls (IPCs), and quality target product profile (QTPP) aligned with the Reference Listed Drug (RLD — Zykadia, Novartis). Type II Drug Master File (DMF): Submitted to US FDA with complete CMC Module 3 content including: S.1 General Information (nomenclature, structure, general properties), S.2 Manufacture (manufacturer, facility, synthetic route flow diagram with reagents/solvents/catalysts, CPPs and IPCs, process validation protocol), S.3 Characterization (structure elucidation by ¹H-NMR, ¹³C-NMR, HRMS, FT-IR, UV-Vis, elemental analysis, XRPD, DSC, TGA; impurity profile with origin, fate, and control strategy per ICH Q3A), S.4 Control of API (specification with justification, analytical procedures and validation per ICH Q2(R1), reference standard program, batch analysis data — minimum 3 consecutive GMP lots), S.5 Reference Standards (primary and working reference standard qualification, purity assignment by mass balance, re-qualification protocol), S.6 Container Closure System (specification, compatibility), S.7 Stability (ICH Q1A-compliant protocol: long-term 25°C/60%RH 36 months, intermediate 30°C/65%RH 12 months, accelerated 40°C/75%RH 6 months; forced degradation per ICH Q1B photostability, acid/base/oxidative/thermal stress; stability-indicating HPLC method; shelf-life/retest period designation; post-approval stability commitment). Letter of Authorization (LOA): Available upon executed Confidentiality Disclosure Agreement (CDA) and Quality Agreement (QAA). Additional regulatory support: Pre-ANDA meeting briefing package preparation, deficiency letter (IR/CRL) response support, PAIs (Pre-Approval Inspections) readiness, and post-approval change management (PACMP, SUPAC). UPOR Biotech’s DMF and GMP ceritinib API are designed to meet the requirements of ANDA first-to-file and first-to-market generic development programs.

Every ceritinib shipment from UPOR Biotech includes a comprehensive documentation package: COA (HPLC purity ≥99.0% Pharma API or ≥99.5% Reference Standard, full impurity profile per ICH Q3A — specified impurities ≤0.10% each, unspecified ≤0.10%, total ≤1.0%, elemental impurities per USP <232>/<233> / ICH Q3D — Class 1/2A/2B/3 elements within PDE limits, residual solvents per USP <467> / ICH Q3C by GC-HS, microbial panel per USP <61>/<62>, polymorph confirmation by XRPD, PSD by laser diffraction D10/D50/D90), MSDS/SDS (GHS-compliant, 16-section format), HPLC Chromatogram (signed and dated by QC analyst and QA reviewer, with integration parameters and system suitability results), Structure Elucidation Data Package (¹H-NMR, ¹³C-NMR, HRMS, FT-IR, UV-Vis, elemental analysis — all spectra annotated with peak assignments), Type II DMF Letter of Authorization (GMP grade, upon executed CDA and QAA), GMP Certificate (GMP grade, issued by qualified person per EU GMP Part II / ICH Q7), Stability Summary Report (ICH Q1A-compliant: long-term 25°C/60%RH 36 months, intermediate 30°C/65%RH 12 months, accelerated 40°C/75%RH 6 months with stability-indicating HPLC method and statistical trend analysis per ICH Q1E), Forced Degradation Study Report (acid 0.1N HCl, base 0.1N NaOH, oxidative 3% H₂O₂, thermal 60°C, photolytic ICH Q1B — mass balance ≥95%, peak purity confirmed by PDA/LC-MS), Nitrosamine Risk Assessment Report (per FDA guidance “Control of Nitrosamine Impurities in Human Drugs,” 2021/2024 revision — confirmation of absence of NDMA, NDEA, and other N-nitrosamines by LC-MS/MS, LOQ ≤0.03 ppm), Mutagenic Impurity Risk Assessment (ICH M7(R1) — PGI assessment with DEREK Nexus/Sarah in silico classification, control at TTC ≤1.5 μg/day for >10-year lifetime exposure), Polymorph Confirmation Report (XRPD diffractogram with overlay vs. RLD polymorph, DSC thermogram), Particle Size Distribution Report (laser diffraction, Malvern Mastersizer, D10/D50/D90 with span (D90-D10)/D50), BSE/TSE-Free Statement, Non-GMO Statement, Allergen Statement, ISO 9001:2015 Certificate, ISO 22000 Certificate, HACCP Certificate, FDA Facility Registration, HALAL Certificate, KOSHER Certificate, and Complete Lot Traceability from raw material batch records through synthesis batch records, purification records, packaging records, and shipping documentation. Free sample available for qualified B2B buyers. MOQ: 10 grams (Research Grade), 100 grams (Pharma API Grade), 1 kg (GMP Grade). All documents provided in English. DMF Letter of Authorization available upon signed Confidentiality Disclosure Agreement and Quality Agreement.