Analytical Platform

• Characterization of APIs and comparative testing
• Development and validation of analytical methods
• Impurities testing
• Genotoxic impurities studies
• Stability study according to ICH (International Council Harmonization)
• Drug Substances and Drug product GMP testing
• Pharmacopoeia (USP/NF, EP, JP, BP) raw material GMP testing
• Extractable & Leachable studies
• Investigative analysis
• Qualification of reference standards

Our services include

• Method development
• Method optimization
• Method feasibility
• Method qualification
• Method validation
• Method verification or method suitability

Analytical method performance is critical to ensure the quality, safety and efficacy of pharmaceutical products. Currently, there are several approaches for method development with two most commonly used being the One Factor At Time (OFAT) and Analytical Quality by Design (AQbD).

The AQbD approach enables to explore multiple parameters and settings to provide a broad knowledge about the impact of the studied factors on method performance. This knowledge is used to establish the Method Operable Design Region (MODR) which corresponds to the multi-dimensional combination of variables that have been verified to meet the method performance criteria. The outcome of this approach is a fit-for-purpose, well-designed, understood, and robust method that reliably delivers the expected performance throughout its lifecycle.

Whenever a method is used for stability and release purposes, a validation should be performed. The validation data are assessed by our statistical experts to demonstrate specificity, linearity, accuracy and precision as per ICH Q2 guidelines.

SEQENS offers comprehensive support for impurities testing and contaminant investigations from residual solvents or elemental impurities to process-related impurities or degradant related issues.

Drug substances produced by chemical syntheses contain impurities which must be controlled to ensure the desired product quality. Generation and depletion of impurities, which are formed during chemical syntheses or due to limited stability of intermediates should be investigated in a Fate & Purge study, designed to ensure clearance of impurities and knowledge of carry-over and tolerable levels. Our analysts have a strong experience in impurity control strategy from IND through to commercial stages, with a long track-record in the design and execution of impurity fate and purge studies.  Our expertise is supported by in-silico method to predict purge factor based on the chemistry route.

We offer rapid method development and alternative analyses such as LC/MS (TQ, QTOF), GC-MS (SQ, TQ) and NMR which are required for impurity identification and quantitation, and to scientifically support study conclusions. In addition, we have developed in silico simulation tools to predict degradation pattern and support analytical forced degradation studies to ensure the reliable and short lead times.

Since metal residues do not provide any therapeutic benefit to the patient, and product risk should be commensurate with the level of product benefit, the specification of a pharmaceutical substance or the drug product may need to include a limit and validated method for metal residues to guarantee acceptable product quality.

The solvents are not completely removed by practical manufacturing techniques. Appropriate selection of the solvent for the synthesis of drug substance may enhance the yield, or determine characteristics such as crystal form, purity and solubility. Therefore, the solvent may sometimes be a critical parameter in the synthetic process. Since there is no therapeutic benefit from residual solvents, all residual solvents should be removed to the extent possible to meet product specification.

Our expertise and instrumentation enable our analyst to perform residual solvent testing according to pharmacopeia (EP, USP) or to develop and validate customized methods.

Pharmaceutical Ingredient that might often require the use of reactive raw materials that have the potential to interact with human DNA to cause mutations and cancer, even at the lowest levels. Therefore, genotoxic impurities should be avoided and if not possible, reduced below a defined threshold.

Analysis of genotoxic impurities can be very challenging because they must be controlled at levels significantly lower than 0.01–0.03 %. Such levels require more sensitive and selective analytical instrumentation due to a higher number of other organic impurities that may be present at lower concentration ranges. The relatively large amount of API may also interfere with low-level impurities.

We have vast experience in the development of highly sensitive methods to demonstrate control of potential GTIs using best in class technologies such as GC-MSMS and LC-MSMS.

• Conditions include: -80°C; -20°C; 5°C; 25°C/60%RH; 30°C/65%RH; 40°C/75%RH
• ICH Photostability Testing Capability
• Stress studies, accelerated and long-term stability studies.

Our stability teams have developed a broaden experience in testing raw materials, intermediates, Active Pharmaceutical Ingredients, alternative salt and polymorph forms.

The materials are tested against specification for identity, potency, impurities and physical properties under strict cGMP compliance.

The testing programs are customized with our customers to streamline laboratory documentation and reporting to ensure quality-focused data deliverable together with strong commitment on short turnaround time.

Based on our analyst expertise in drug substances batch testing and release, we have extended our offering to support our customers in testing their drug product.

The methodologies available with the Seqens’Lab are:

• Chromatography (GC, HPLC, TLC)
• Spectroscopy (FTIR, UV)
• Karl Fischer (volumetric and coulometric)
• Autotitration (acid-base, redox, complexometric)
• Viscosity and rheology
• Thermal analysis (DSC / TGA / Melting Point)
• Loss On Drying, Gravimetric Analyses
• Polarimetry, refractometry

We are testing raw materials in accordance with EP, USP/NF, BP or JP methodologies and monographs, or according to any client-supplied or vendor-defined methods to support raw materials release or to perform vendor qualification.

Our analysts have acquired a broad expertise in impurity identification to perform extractable and leachable testing, supported by the best-in-class analytical technologies.

We have developed controlled extraction techniques (reflux, Soxhlet, sonification, incubation and/or agitation in controlled temperature conditions) to generate an extractable profile that will meet the intended use of the components being evaluated.

With the support of our partner Harmonic Pharma within the Seqens’Lab we can predict based on computational toxicological profiling any potential toxicological concerns of any extractables identified.

We can then ensure a successful development and full GMP-compliant validation method to monitor leachable in your intermediates or drug products.

We have established the following methodology to analyze extraction solutions by LC/MS (TQ and QTOF), GC/MS (SQ and TQ) and ICP-MS.

Our analysts perform identification of degradation products found during stability testing and the impurities found during Active Pharmaceutical Ingredients (API) and drug product testing. Structural elucidation and chemical characterization of compounds are carried out routinely.

Our spectroscopy expertise combined with chromatography and in-house synthetic chemistry knowledge can help determine the likely source of impurities. We also have the instrumentation and synthetic capabilities to isolate or manufacture samples of impurities.

The product must be as pure as possible to ensure its safety in patients.

Reference standards are used to help ensure the identity, potency, quality and purity of drug products and drug substances.  This is accomplished by analyzing the substance against its qualified reference standard, so the accuracy of reference materials is essential to the manufacture of quality APIs.

We regularly synthesize and qualify materials as reference standards for a variety of projects, such as the following:

• quantitative determination,
• Detection of impurities,
• Raw materials release,
• In-process monitoring,
• Retention time reference marker.
• Stability studies.

Reference-standard materials that are synthesized and supplied by the sponsoring client or through another third-party are always evaluated by Seqens in order to ensure the integrity of the substance, regardless of what testing already took place.  The reference standard must be of the highest purity possible and may require further purification to be considered one.