Seqens provides GMP testing on Active Pharmaceutical Ingredients (API) and excipients. We have an extensive team focused on the development and clinical phase appropriate validation of sensitive and specific analytical methods. Our analysts work closely with our chemists to develop In Process Control, isolated intermediate, and finish product release and stability indicating methods.
Our in-deep technical expertise in analytical science combined with the most advanced analytical instrumentation ensures fast and reliable execution of analytical programs that range from routine tests to highly complex developments.
Our core expertise includes:
- Characterization of Active Pharmaceutical Ingredients and comparative testing
- Development and validation of analytical methods
- Impurities testing
- Genotoxic impurities studies
- Stability study according to ICH (International Harmonization Council)
- 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
Characterization of Active Pharmaceutical ingredients
Our physical Characterization Testing Capabilities includes a full set of advanced technologies:
XRPD characterization and testing (Empyrean Serie III, Malvern-Panalytical):
Particle Size Determination (Mastersizer 3000, Zetasizer Pro Red, Alpine e200 LS, Hosokawa):
Morphological analysis (Morpho 4-ID with Raman, Malvern-Panalytical):
Surface Area (BELSORP-mini X, 2S):
Microscopy (TM-1000, Hitachi and Nikkon Eclipse):
Dynamic Vapor Sorption (DVS Intrinsic, SMS):
Differential Scanning Calorimetry (DSC3, Mettler):
Thermogravimetric Analysis (TGA/DSC3+, Mettler):
Hot-Stage microscopy (FP-80, Mettler):
Density and Flow properties (Tap density, Vankel and PF1, Sotax):
Our chemical characterization testing Capabilities include several spectroscopic technologies:
NMR (Bruker Avance III 400 Mhz equipped with a probe BBO400 Z108618_0277 / 5mm):
Fourier Transform Infrared & Near-Infrared Absorption Spectroscopy:
Ultraviolet-Visible Absorption Spectroscopy:
Development and validation of analytical methods
Seqens offers a large range of laboratory techniques to support your needs for expert testing consultation, method development or validation protocol design. We support our customers at various stages of the clinical development and we have a proven track record of success on full development and validation studies, optimization of existing methods and transfer of validated methods.
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).
In the OFAT protocol, only one parameter is varied, and its effect on response is evaluated whilst other remain constant. When no more improvements are attained from changing this factor, another parameter is then explored. This approach is not very comprehensive, and the separations are often sub-optimal in terms of resolution, peak shape and robustness.
Our analysts have developed the Analytical Quality by Design approach (Fusion QbD) to automate the entire method development process, reduce development time and ensure the development of robust methods. The AQbD approach enable 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.
Residual Solvents testing
Residual solvents in pharmaceuticals are defined as organic volatile chemicals that are used or produced in the manufacture of drug substances or excipients, or in the preparation of drug products. 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 pharmacopeia (EP, USP) or to develop and validate customized methods.
Metal residues in pharmaceutical substances or drug products may originate from several sources like metal catalysts and metal reagents used during the synthesis of the active pharmaceutical substance and the excipients, manufacturing equipment and piping, bulk packaging, the environment, cleaning solvents etc. Since metal residues do not provide any therapeutic benefit to the patient, and product risk should 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.
Our expertise and instrumentation within our site in Canada enable our analysts to offer a wide range of assays for metals testing, as well as other customer specifications.
Genotoxic impurities studies
The primary concern related to genotoxic impurities stems from synthesis of an Active 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.
ICH Stability studies
ICH compliant stability studies are performed to support regulatory CMC programs and process development. Our stability teams work alongside our development analysts, routinely running multiple stability studies:
- 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.
Drug Substances and Drug Product GMP testing
To support the clinical trial material and commercial product release, Seqens offers its comprehensive capabilities to test in-process materials and drug substance. 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.
Pharmacopoeia (USP/NF, EP, JP, BP) raw material GMP testing
Seqens has a wide range of chemistry expertise and state-of-the-art instruments required to perform all types of raw materials testing, including qualification of compendial methods, as well as development, qualification and validation of new methods.
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.
Extractable & Leachable studies
During the drug development process, it is important to evaluate the potential for various chemicals to migrate from container closure or manufacturing systems into pharmaceuticals. Regulatory agencies require extractable and leachable testing to identify any risks of product adulteration.
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 extensive knowledge and experience allow us to approach investigative analysis proactively and efficiently
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.
Qualification of reference standards
While the Active Pharmaceutical Ingredient (API) manufacturing industry continues to grow and evolve, with the goal of developing new drugs extracted from natural products or synthetically produced drug substances, one things remains unwavering: 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.
Surface: 40, 000 m²
Lab surface: 2, 000 m²
- 6 kilo-labs
- 2 cGMP pilot plants with 11 multipurpose reactors from 100 L to 2, 800 L (total capacity of 12 m³)
- Temperature range: -15/+150°C (hastelloy reactor: -80/+200°C)
- 3 finishing rooms (agitated filter dryers, filters, dryers, milling and sieving equipments)
- Crystallization expertise and technologiesd(salt, co-crystal and polymorph screenings, process development)
- Process Safety expertise and tecnologies
- Flow chemistry for fine chemicals
- Potent API process development
- Genotoxic Impurities
- Issue Management
- Generic A.P.I Solid state expertise
Last inspection: ANSM October 2018
Number of scientists: 110
Other: Ecosystem Pharma with integrated services