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Phase-Appropriate Analytical Method Development and Qualification/Validation/Verification per ICH Q2 — U/HPLC-UV/Vis, Chiral HPLC, GC-FID/ECD, GC-MS, LC-MS, (q)NMR, ICP-MS, Dissolution are frequently used analytical technologies in the IPC and release testing of starting materials, process intermediates, DS and DP. For small molecule NCEs, these methods need to be developed and qualified/validated in phase-appropriate manner (R&D, GLP or early-phase/late-phase/commercial GMP), owing to the peculiarity of each small molecule project. As structural complexity increases with development candidates and certain molecular attributes make production and analysis challenging, clients are likely to face analytical and QC challenges. We have experience developing analytical methods for complex NCEs owing to our strong organic chemistry background and deep understanding for their chemical attributes.
In addition, compendial test methods (USP/EP/JP) are often verified for their suitability, including FT-IR/ATR, KF, pXRD, ROI, PSD, CU/BU, foreign insoluble matter, Aw/Microbial Content, Endotoxins, Sterility/CCIT etc. With over 10 years of hands-on wet-lab experience and collaboration with contract partners, we are well-versed in all relevant analytical and QC technologies, as well as ICH requirements, enabling us to efficiently execute method development, qualification, validation and verification activities.
Phase-Appropriate Process Control and Characterization — In-process monitoring (IPM) and in-process controls (IPC) are vital measures to meet the requirements of critical process parameters (CPP) and ensure that the GMP manufacturing process operates as designed and delivers consistent batch-to-batch results. Insufficient or inappropriate process characterization or control can lead to GMP manufacturing failure, financial loss, regulatory warnings and potentially impact the timeline of clinical studies.
To ensure manufacturing safety and quality, in-process samples can be tested in-line with the manufacturing process, or in a separate QC lab, with tests carefully designed in collaboration with process chemists, manufacturing and quality teams.
Phase-Appropriate Stability for DS, DP, SM and Intermediates — Stability testing, along with data trending, are essential tools for ensuring that both DS and DP meet acceptable standards for shelf life, expiry, and retest dates per ICH Q1A Stability Testing of New Drug Substances and Products. In-use stability testing for process intermediates is equally critical, as it ensures that process chemistry intermediates, raw materials, DP blends and intermediates can be safely stored both prior to and during the manufacturing process.
Stability-indicating methods are mandatory for assessing these materials under various storage conditions, including humidity, acidic or basic environments, oxidative stress, thermolysis and photolysis, per ICH Q1B and Q2. These methods help identify potential degradation pathways and ensure the materials maintain their chemical attributes throughout the product lifecycle.
Phase-Appropriate Mutagen Risk Assessment and Control — Mutagens as well as potential mutagenic/genotoxic impurities (pMIs) must be carefully identified with DEREK/SARAH in-silico analysis and monitored in all manufacturing processes of DS (DP under some circumstances), as outlined in ICH M7. These impurities are controlled at or below ppm level and require highly sensitive and specific analytical methodologies, such as HPLC-MS and GC-MS, which are capable of detecting/quantitating them even at the ppb level.
Additionally, a risk assessment including Mirabilis purging factor analysis or AMES testing should be conducted for each synthetic process to evaluate the potential presence of pMIs in DS. This assessment is crucial for mitigating risks, ensuring product quality throughout production and patient safety in early-phase clinical study. Lab testing, historical batch data analysis and spiking/purging study are required for late-phase clinical study or commercial projects to demonstrate that the pMI level in drug substances/products are under strict control.
Selection and Management of Contract Partners — Collaboration with Contract Partners is a critical process in ensuring the quality, compliance, and efficiency of outsourced operations for pharmaceutical and biotech companies. Careful evaluation of potential partners is based on their expertise, development/manufacturing capability, regulatory adherence, track record and stage of clinical study. Effective management throughout the collaboration ensures alignment with clients' goals, maintains regulatory compliance, and fosters a productive, long-term partnership.
A cost-efficient CRO with exceptional development capabilities and kilo-lab scalability is ideal for meeting the needs of pre-clinical or FIH/Ph1a projects. As clinical studies progress, a CDMO with higher production capabilities becomes necessary. When the project moves into commercialization, a CMO with large-scale manufacturing capabilities is essential to meet patient demand.
With extensive experience working with contract partners, we assist clients in performing vendor selection to identify the best contract partner for their projects, ensuring that their analytical and quality control capabilities align with the project’s specific requirements. We also offer expertise in authoring and reviewing critical documents, including RFPs, MSAs, and SOWs, to ensure that CMC development and manufacturing are executed in a phase-appropriate and regulatory-compliant manner. In addition, we provide support for technical transfers, conduct technical audits, and manage the entire technical development and manufacturing process. From the development inception, to engineering batch, to GMP/CTM batch production and release, we oversee every process detail and solve all the excursions (OOS/OOT, deviation, investigations etc.) to ensure seamless operation.
Author and Review CMC Regulatory Documents for IND/IMPD/CTA Filings — We author CTD Module 3 sections related to analytical development, quality control, and stability for both DS and DP. In addition, we conduct cross-functional reviews of all other sections within Module 3 to ensure consistency and regulatory compliance. When inquiries are received from regulatory agencies, we respond promptly by drafting clear, to-the-point, and well-supported RTQs to facilitate timely regulatory approval.
In addition, we author and review CQA documents including Specification & Justification, method validation protocols/reports, method bridging study reports, CoA/CoT, stability reports, forced degradation reports, reference standard qualification protocols/CoT, spiking/purging study reports, analytical risk assessment and gap analysis, SOP etc.
Structural Characterization of Pharmaceutical Materials — We perform structural characterization of drug substances and related substances using a comprehensive suite of analytical techniques, including 1D/2D NMR, FT-IR/ATR, LC-MS, UV/Vis spectroscopy, and elemental analysis. Please note that original electronic data—such as NMR FID files—must be provided by the clients or contract partners to support this work. Following characterization, we author a detailed Proof of Structure Report, which is required for CTD Module 3, Section 3.2.S.3.1 Structure Elucidation for IND or IMPD submissions.
We also recommend leveraging qNMR to determine potency of drug substances (for early-phase clinical study) and related substances. Compared to traditional LC-based methods, qNMR offers a more time-efficient and cost-effective alternative. For additional details, please refer to Publication 20.
On-site Support and In-plant/Wet-lab Services — We offer on-site support and face-to-face meetings upon request. Our team is available to travel to client offices for in-person collaboration as needed.
With over 20 years of hands-on wet lab experience, we are also equipped to provide in-plant and wet-lab services at client-designated facilities, subject to prior approval. This allows us to directly support technical activities and ensure seamless project execution on-site.
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