Covering four core modules: API quality studies, solid dosage form (SR/CR) quality studies, genotoxic impurity method development & validation, and elemental impurity method development & validation. Equipped with LC-MS/MS, GC-MS/MS, and ICP-MS analytical instruments, providing pharmaceutical analysis CRO services fully compliant with ICH Q2/Q3/M7/Q3D guidelines.
Pharmaceutical analysis is not conventional "assay and related substances" testing. In drug registration filings, the selection and validation quality of analytical methods directly impact review outcomes — with genotoxic impurities and elemental impurities being the two highest-frequency CDE deficiency areas in recent years.
Establish a lifecycle quality control system for APIs based on ICH Q3A/Q3B and CDE's technical guidelines for API preparation and structure confirmation.
The challenge in solid dosage form quality studies lies in developing methods that possess both discriminatory power and in vivo-in vitro relevance. For SR/CR formulations, the discriminatory requirement for dissolution methods is particularly stringent — conventional QC dissolution methods often lack the ability to distinguish formulation/process changes.
ICH M7(R2) has been the most closely watched impurity control guideline in drug registration over the past five years and the CDE deficiency area with the highest query density. GTI analytical method development faces three major challenges: structural diversity precludes universal methods, extremely low limits (typically ppm/ppb level) demand ultra-high sensitivity, and severe matrix interference.
ICH Q3D classifies elemental impurities into Class 1 (As/Pb/Cd/Hg), Class 2A/2B, Class 3, and unclassified elements, requiring PDE values and control strategies determined by route of administration, daily intake, and treatment duration. Requirements are more stringent for injectable and inhalation products.
Different impurities require different analytical platforms and method strategies. Taikomed is equipped with comprehensive chromatography-mass spectrometry and elemental analysis platforms for full-spectrum impurity coverage.
| Analytical Platform | Applicable Impurity Types | Typical LOQ | Applicable ICH Guidelines |
|---|---|---|---|
| HPLC-UV/DAD | Related substances, assay, dissolution | 0.05%–0.1% | ICH Q2 / Q3A / Q3B |
| LC-MS/MS | Genotoxic impurities (nitrosamines, sulfonate esters, aromatic amines, etc.), degradation impurity identification | 0.01–1 ppm | ICH M7 / Q3A |
| GC-MS/MS | Volatile genotoxic impurities (alkyl halides, epoxides), residual solvents | 0.01–1 ppm | ICH M7 / Q3C |
| ICP-MS | Elemental impurities Class 1/2A (As/Cd/Hg/Pb/Co/Ni/V, etc.) | 0.1–10 ppb | ICH Q3D |
| ICP-OES | Elemental impurities Class 2B/3 (Fe/Zn/Cu/Li/Sb/Ba, etc.) | 0.01–1 ppm | ICH Q3D |
| GC-HS | Residual solvents Class 1/2/3 | 1–50 ppm | ICH Q3C |
LC-MS/MS + GC-MS/MS + derivatization triple technical approach, covering all structural classes — nitrosamines, sulfonate esters, alkyl halides, aromatic amines, hydrazines — with LOQ down to 0.01 ppm.
ICP-MS + ICP-OES dual platform, customized control strategies for all Class 1/2A/2B/3 elements based on route of administration and PDE values.
Not a simple adaptation of generic solid dosage form methods — customized discriminatory dissolution methods tailored to the release mechanism (matrix erosion / membrane-controlled / osmotic pump).
The team possesses in-depth understanding of CDE review focus areas for genotoxic impurities and elemental impurities, proactively avoiding common deficiency issues at the method development stage.
Seamless interfacing between the pharmaceutical analysis team and the synthesis technology team — impurity source tracing → structure identification → process optimization forms a closed loop, drastically shortening problem resolution cycles.
Upon completion of analytical method development and validation, directly output filing documentation conforming to CTD 3.2.S.4 / 3.2.P.5 format requirements, reducing the client's documentation integration workload.
The specialty pharmaceutical analysis platform is deeply integrated with Taikomed's other core technical capabilities.
Synthesis provides targeted impurity reference standard synthesis; analysis provides impurity structural identification and quantitative method development
Release profile method development, discriminatory power verification, and IVIVC analysis are core capabilities for SR/CR formulation quality studies
Liposome encapsulation efficiency, particle size/zeta potential, in vitro release — nano-formulation-specific analytical method support
Per ICH M7, the LOQ of a GTI analytical method should not exceed 10% of the impurity's acceptable intake (AI). For example, if NDMA's AI is 96 ng/day and the maximum daily dose is 320 mg, the limit in the drug product is 0.3 ppm, and the method LOQ should reach approximately 0.03 ppm. Our LC-MS/MS methods typically achieve an LOQ of 0.01–0.05 ppm for common nitrosamine GTIs.
Yes. Since 2020, CDE has explicitly required an ICH Q3D-based elemental impurity risk assessment report in generic drug filings. We provide not only method development and validation but also a complete risk assessment dossier — including potential elemental source identification, measured vs. PDE value comparison, and control strategy justification — directly supporting CTD submissions.
In addition to conventional linearity, precision, and accuracy validation, SR/CR dissolution methods must undergo discriminatory power verification — the method must be capable of distinguishing dissolution behavior differences resulting from formulation and process parameter changes. Furthermore, if a client plans to apply for a biowaiver (BCS-based or SR/CR multi-strength waiver), in vivo-in vitro correlation (IVIVC/IVIVR) of the dissolution method is essential data that must be established.
Individual analytical method development typically requires 4–8 weeks (including validation); full API quality studies (method validation + stability sample testing) typically 4–6 months; genotoxic impurity method development + validation typically 6–10 weeks. Specific timelines depend on product complexity and the number of methods — we provide detailed Gantt charts and milestone plans.
Whether it is genotoxic impurity method development, elemental impurity risk assessment, or SR/CR dissolution method discriminatory power verification — our analysis team can deliver a technical proposal in the shortest possible time.
Contact Pharma Analysis Team →