Advanced Therapies

Analytical services for the new frontier of pharmaceutical development: gene therapies, cell therapies and next-generation nucleic acid therapeutics.

Advanced therapies represent the most innovative frontier of pharmaceutical and medical development. Under this designation — encompassed in European regulation by the concept of advanced therapy medicinal products (ATMPs) — are grouped those therapeutic products that use genes, cells or tissues as active substance, with the aim of treating, preventing or diagnosing disease through mechanisms of action fundamentally different from those of conventional medicines.

Unlike small molecule drugs or even conventional biologics, advanced therapies intervene directly in the genetic or cellular mechanisms of disease: they correct defective genes, introduce functional genetic material into target cells, modify the patient’s own cells to equip them with new therapeutic capabilities, or use RNA as a tool to transiently modulate gene expression. This transformative potential is accompanied by analytical demands of unprecedented complexity in the history of pharmaceutical development.

The regulatory framework for advanced therapies is specific and constantly evolving: in Europe, Regulation (EC) No 1394/2007 governs ATMPs and establishes specific quality, safety and efficacy requirements. The EMA and FDA have also published numerous specific guidelines for the different types of advanced therapies, including guidance on gene therapy, cell therapy and mRNA vaccines. AMSbiopharma provides specialised analytical services to support the development of these therapies under the scientific rigour and regulatory compliance that their complexity demands.

Advanced therapies present one of the most demanding and specific quality regulatory frameworks in the pharmaceutical landscape. The analytical services applicable to these modalities may be conducted under Good Laboratory Practice (GLP) for support of preclinical and clinical studies, under Good Manufacturing Practice (GMP) for CMC characterisation and quality control services for the drug substance and the product, or in non-regulated environments for exploratory research and development studies. Given the specificity of quality requirements in this area, we recommend contacting our team to define the most appropriate regulatory strategy for your project.

Types of advanced therapies

Advanced therapies comprise several main categories with specific characteristics and analytical challenges:

Gene therapy medicinal products (GTMPs) are products containing a recombinant nucleic acid — DNA or RNA — or a genetically modified microorganism, administered with the aim of regulating, repairing, replacing, adding or silencing a gene sequence. They may use viral vectors — such as adeno-associated vectors (AAV), lentiviruses or adenoviruses — or non-viral vectors, including lipid nanoparticles (LNPs) for the delivery of mRNA or DNA plasmids.

Cell therapy medicinal products use living cells — autologous, from the patient, or allogeneic, from a donor — as active substance. They include tissue-engineered medicines and, most notably, therapies using genetically modified cells such as CAR-T cells, in which patient T-lymphocytes are modified to express chimeric antigen receptors capable of recognising and destroying tumour cells.

Therapeutic mRNA medicines use messenger RNA strands that, upon introduction into the patient’s cells, direct the transient production of a protein of therapeutic interest. This modality experienced unprecedented momentum with the development of mRNA vaccines against SARS-CoV-2, and is now being actively explored in oncology, rare diseases and other indications.

Analytical complexity of advanced therapies

The analytical characterisation of advanced therapies faces unique challenges arising from the biological nature of their active components. Viral vectors such as AAV are complex biological particles whose characterisation requires titre determination, capsid integrity assessment, confirmation of the identity and purity of the encapsidated genome, quantification of the ratio of full to empty particles, and control of process-related impurities.

Plasmid DNA — used both directly as the drug substance in some gene therapies and as starting material for the production of viral vectors and mRNA — requires rigorous characterisation of its isoforms (supercoiled, open circular and linear) and control of impurities related to the fermentation and purification process.

mRNA therapies require confirmation of the integrity and identity of the RNA strand, assessment of stability against nuclease degradation, control of 5’ cap and poly-A tail modifications, and evaluation of the potential immunogenicity of the product.

An evolving regulatory landscape

The regulation of advanced therapies is in continuous development, with the EMA and FDA regularly publishing new guidelines and updating existing ones to address the specific challenges of these modalities. This regulatory dynamism requires development teams and analytical laboratories to remain permanently up to date and to be capable of adapting their analytical strategies to the most recent requirements. AMSbiopharma closely follows this regulatory evolution and adapts its services to ensure that the analytical data generated for our clients’ advanced therapy programmes meet the most demanding standards of current regulation.

Our catalog of services include

Metabolomics applications

Pharmacokinetic (PK/PD) Analysis / NON GLP

Accurate quantification of drug concentrations in biological matrices is the foundation of every pharmacokinetic programme. Our PK bioanalytical services support pharmacokinetic and preclinical toxicokinetic studies, providing the quantitative data required to characterise drug exposure throughout the development process.

We develop and validate bioanalytical methods for a wide range of biological matrices, including plasma, serum, whole blood, urine, cerebrospinal fluid (CSF), tissue homogenates, and dried blood spots (DBS). Full method development and validation are performed in accordance with ICH M10, covering specificity, selectivity, sensitivity, linearity, accuracy, precision, matrix effects, stability, and dilution integrity.

PK/PD data are delivered in formats compatible with leading pharmacokinetic and pharmacometric modelling software, enabling seamless integration into the sponsor’s development workflows. All studies are conducted under controlled documentation systems aligned with applicable regulatory requirements.

Key analytical capabilities

  • Full ICH M10-compliant bioanalytical method development and validation for regulated studies 
  • Bioanalysis of plasma, serum, urine, CSF, tissue homogenates, and alternative biological matrices 
  • PK/PD data support for dose selection, exposure assessment, and regulatory submissions 
  • Applicable to small molecules, therapeutic peptides, biologics, oligonucleotides, and gene therapy vectors

Drug Metabolism and Pharmacokinetics (DMPK) studies provide a mechanistic understanding of how a compound is absorbed, distributed, metabolised, and excreted (ADME). This information is essential for predicting in vivo behaviour, optimising compound properties, and assessing the potential for drug–drug interactions (DDIs).

AMSbiopharma provides comprehensive DMPK bioanalytical support using both preclinical species and human-derived matrices. Our services include metabolic stability studies in hepatic matrices, metabolite profiling and identification by high-resolution mass spectrometry (HRMS), plasma protein binding, and blood-to-plasma partitioning. Metabolite identification studies are performed to standards suitable for regulatory submissions.

Our team delivers early-stage ADME screening to support lead selection and optimisation, as well as comprehensive, regulatory-grade metabolite profiling studies to support clinical development programmes.

Key analytical capabilities:

  • Metabolic stability screening in liver microsomes, hepatocytes, and S9 fractions

  • Metabolite profiling and structural identification by high-resolution mass spectrometry (HRMS)

  • Plasma protein binding and blood-to-plasma ratio determination

  • Support for reactive metabolite risk assessment and drug–drug interaction (DDI) studies

Stability studies provide the analytical data required to establish shelf life, define storage conditions, and support regulatory submissions. A well-designed stability programme supported by validated stability-indicating analytical methods is a regulatory requirement under ICH Q1 for all drug substances and drug products.

AMSbiopharma supports ICH Q1-compliant stability programmes with validated stability-indicating methods for the determination of assay, degradation products, related substances, and other critical quality attributes. Our team manages sample receipt, analytical testing, and data management throughout the study. Analytical testing is performed using HPLC-UV, HPLC-MS/MS, and GC-MS/MS, as appropriate for the product and analytical requirements.

Key analytical capabilities:

  • Design, execution, and analytical support for ICH Q1-compliant stability studies

  • Validated stability-indicating methods using HPLC-UV, HPLC-MS/MS, and GC-MS/MS

  • Data management compliant with 21 CFR Part 11 and EU GMP Annex 11

Appearance is a fundamental quality attribute of pharmaceutical products and a mandatory release test for all dosage forms. Deviations in colour, clarity, or particulate matter from predefined specifications may indicate product degradation, contamination, or manufacturing process failure.

AMSbiopharma performs validated appearance testing for colour, clarity, and particulate matter using calibrated visual and instrumental methods in accordance with applicable pharmacopoeial specifications and regulatory requirements.

Key analytical capabilities:

  • Visual and instrumental appearance testing in accordance with Ph. Eur. and USP

  • Colour assessment against pharmacopoeial reference standards

  • Clarity testing for solution-based pharmaceutical products

  • Particulate matter testing, including sub-visible particle analysis

  • Applicable to parenteral, oral liquid, and semi-solid dosage forms

  • Supporting documentation for batch release and stability studies

Assay and dosage unit uniformity are fundamental quality control requirements for all pharmaceutical products, providing quantitative evidence that each batch contains the intended amount of drug substance, uniformly distributed throughout the dosage units.

AMSbiopharma employs validated analytical methods across a broad range of analytical platforms, including UV/Vis spectrophotometry, HPLC and UHPLC with multiple detection techniques, GC, GC/MS, and LC/MS, selecting the most appropriate technology for each product. All methods are developed and validated in accordance with the Ph. Eur., USP, and ICH Q2(R2) guidelines.

Key analytical capabilities:

  • Validated assay methods using UV/Vis, HPLC/UHPLC, GC, GC/MS, and LC/MS

  • Content uniformity testing in accordance with Ph. Eur. 2.9.40 and USP <905>

  • Applicable to solid, liquid, semi-solid, and parenteral dosage forms

  • Method development and validation in accordance with Ph. Eur., USP, and ICH Q2(R2)

  • Analytical support for method development, validation, and routine batch release testing

  • Complete documentation to support regulatory submissions

Physical and physicochemical characterization provides critical quality attribute (CQA) data for pharmaceutical products. For liquid and semi-solid dosage forms, parameters such as pH, viscosity, and osmolality are critical determinants of product stability, while for parenteral products, they are essential to ensure physiological compatibility.

AMSbiopharma offers a comprehensive range of validated physicochemical testing services, covering the full spectrum of analytical parameters required for pharmaceutical development and quality control. All analyses are performed using calibrated and qualified instrumentation to ensure reliable, reproducible, and regulatory-compliant results.

Key analytical capabilities:

  • pH measurement across a wide range of pharmaceutical dosage forms

  • Viscosity determination using calibrated instrumentation

  • Density and relative density determination using validated methods

  • Refractive index measurement for identity confirmation and concentration determination

  • Osmolality determination by the freezing-point depression method for parenteral products

The detection of anti-drug antibodies (ADAs) is the cornerstone of immunogenicity assessment programmes. A well-designed and properly validated ADA assay must detect anti-drug antibodies with sufficient sensitivity and drug tolerance to generate clinically meaningful data while maintaining the specificity required to accurately distinguish true positive responses.

AMSbiopharma develops and validates binding ADA assays using the tiered testing approach recommended by the EMA and the FDA, comprising screening, confirmatory, and antibody titre assays. Assay formats are selected according to the characteristics of the therapeutic molecule, and assay cut points are established using the statistical approaches recommended in current regulatory guidance.

Key analytical capabilities:

  • Tiered ADA testing strategy: screening, confirmatory, and antibody titre assays

  • Applicable to monoclonal antibodies (mAbs), bispecific antibodies, therapeutic peptides, and advanced therapy medicinal products (ATMPs)

  • Full assay validation covering sensitivity, drug tolerance, and specificity

  • Documentation aligned with EMA and FDA immunogenicity guidelines

The bioanalysis of therapeutic oligonucleotides and gene therapy vectors in biological matrices requires analytical approaches with significantly greater complexity and sensitivity than those used for conventional small-molecule drugs. The structural similarity between the active therapeutic and endogenous nucleic acid species places exceptional demands on method sensitivity, specificity, and selectivity.

AMSbiopharma provides validated PK/PD bioanalytical services for oligonucleotide therapeutics, supporting preclinical and translational development programmes with robust quantitative data generated using state-of-the-art bioanalytical methodologies.

Key analytical capabilities:

  • Validated bioanalysis of antisense oligonucleotides (ASOs), RNA interference (RNAi) therapeutics, mRNA therapeutics, and viral DNA/RNA in biological matrices

  • Bioanalytical capabilities for plasma, serum, tissue, and cerebrospinal fluid (CSF)

  • ICH M10-compliant method development and validation

  • Analytical support for tissue distribution and biodistribution studies

Reliable quantification of nucleic acid species and the assessment of gene expression changes in biological matrices are critical analytical requirements for the development of gene therapies and RNA-based therapeutics.

AMSbiopharma provides validated bioanalytical services for the quantification of DNA and RNA targets in biological matrices, including the assessment of gene expression changes relevant to pharmacodynamic monitoring and safety evaluation. Method development and validation are performed in accordance with applicable regulatory guidelines, ensuring robust, reproducible, and regulatory-ready data.

Key analytical capabilities:

  • Quantification of DNA and RNA targets in plasma, tissue, and other biological matrices

  • Gene expression analysis to support pharmacodynamic biomarker programmes

  • Method development and validation in accordance with applicable regulatory guidelines

  • Analytical support for preclinical development programmes

  • Applicable to RNA therapeutics and gene therapy vector programmes

  • Comprehensive documentation to support regulatory submissions

Genetic biomarkers play an increasingly important role in modern drug development, providing mechanistic and predictive insights that support patient stratification, pharmacodynamic monitoring, and precision medicine approaches.

AMSbiopharma provides validated analytical services for the detection and quantification of genetic biomarkers in biological samples. Our methods are developed for regulatory use in both preclinical and clinical studies, with biomarker strategies aligned with current regulatory qualification guidelines.

Key analytical capabilities:

  • Detection and quantification of genetic biomarkers in biological samples

  • Biomarker strategies aligned with regulatory expectations and qualification frameworks

  • Applicable to oncology, rare diseases, and gene therapy programmes

  • Method development for preclinical studies

Plasmid DNA is a critical component of the drug substance used in the manufacture of gene therapies and DNA vaccines. Plasmid quality, integrity, and isoform distribution are critical quality attributes (CQAs) that must be characterised and controlled throughout the manufacturing process. Regulatory authorities require comprehensive plasmid characterization data as part of the CMC package for gene therapy products.

AMSbiopharma provides validated analytical services for plasmid DNA isoform analysis, enabling the accurate quantification and relative distribution of supercoiled, open circular, and linear plasmid isoforms in both drug substance and drug product samples.

Key analytical capabilities:

  • Quantification and relative distribution of plasmid DNA isoforms (supercoiled, open circular, and linear)

  • Analytical support for in-process quality control and drug substance testing

  • Method development to support CMC development and process optimisation

  • Applicable to gene therapy vectors and DNA vaccine development programmes

  • Method development with appropriate sensitivity and specificity

Inflammatory biomarkers are among the most widely evaluated endpoints in pharmaceutical development, providing critical mechanistic, pharmacodynamic, and safety data across immunology, oncology, autoimmune, metabolic, and central nervous system (CNS) diseases.

AMSbiopharma offers both targeted quantification of specific inflammatory biomarkers and broad inflammatory profiling approaches. Targeted assays provide the precision and validation status required for regulatory-grade pharmacodynamic data, while broad-panel approaches enable comprehensive inflammatory profiling to support biomarker discovery programmes.

Key analytical capabilities:

  • Targeted quantification of individual cytokines, chemokines, and acute-phase proteins

  • Broad-panel inflammatory profiling for biomarker discovery

  • Development and validation of analytical methods for plasma, serum, and tissue matrices

  • Applicable to immunology, oncology, autoimmune diseases, and metabolic disorders

Vascular and angiogenesis biomarkers play a central role in oncology, cardiovascular diseases, and ophthalmology. Key mediators such as vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and angiopoietins are widely used as pharmacodynamic endpoints in anti-angiogenic therapy programmes.

AMSbiopharma provides validated analytical services for the quantification of vascular proteins and angiogenic mediators in biological matrices, supporting mechanistic studies, target engagement assessment, and pharmacodynamic evaluations throughout drug development.

Key analytical capabilities:

  • Quantification of VEGF, PDGF, angiopoietins, and related vascular biomarkers

  • Method development and validation for plasma, serum, tissue, and other biological matrices

  • Analytical support for pharmacodynamic monitoring in anti-angiogenic therapy programmes

  • Applicable to oncology, cardiovascular diseases, and ophthalmology

Systemic disease biomarkers provide essential diagnostic, prognostic, and pharmacodynamic insights across a broad range of therapeutic areas.

AMSbiopharma provides validated analytical services for the quantification of proteins, enzymes, metabolites, and other disease-associated molecular targets in biological samples. Our methods generate high-quality data suitable for regulatory biomarker submissions and support companion diagnostic (CDx) development programmes.

Key analytical capabilities:

  • Quantification of disease-associated proteins, enzymes, and metabolites

  • Applicable across multiple therapeutic areas and disease indications

  • Development and validation of analytical methods for pharmacodynamic monitoring in clinical trials

  • Data packages aligned with FDA and EMA biomarker guidance

Oncology biomarkers are central to the design of modern clinical trials, enabling patient stratification based on predictive biomarker status, pharmacodynamic monitoring of target engagement, and the development of companion diagnostics (CDx).

AMSbiopharma provides bioanalytical services for the quantification of tumour-associated proteins, circulating biomarkers, pharmacodynamic endpoints, and response biomarkers in plasma, serum, tumour tissue, and liquid biopsy samples.

Key analytical capabilities:

  • Quantification of circulating tumour biomarkers and pharmacodynamic endpoints

  • Validated analytical methods for plasma, serum, tumour tissue, and liquid biopsy samples

  • Analysis of patient stratification biomarkers for oncology clinical trials

  • Applicable to immuno-oncology, targeted therapies, and antibody-drug conjugate (ADC) development programmes

Extractables and leachables (E&L) represent a critical safety consideration for pharmaceutical products in contact with primary packaging components, container closure systems, drug delivery devices, and manufacturing process contact materials. Leachable compounds migrating from these materials into the drug product may pose potential risks to patient safety and product quality.

AMSbiopharma provides comprehensive Extractables and Leachables (E&L) analytical services aligned with ICH Q3E, including extractables studies to characterise the extractable profile of packaging and process contact materials, leachables studies performed on drug products under appropriate storage conditions, and the preparation of Analytical Evaluation Reports (AERs) to support regulatory submissions.

Analytical studies are performed using HPLC-UV, LC-MS/MS, and GC-MS platforms to ensure broad chemical coverage, applying risk-based approaches that prioritise compounds of greatest toxicological and regulatory relevance.

Key analytical capabilities:

  • Extractables studies for packaging materials, container closure systems, and manufacturing process contact materials

  • Leachables studies in drug products under defined storage conditions

  • HPLC-UV, LC-MS/MS, and GC-MS analytical platforms providing broad chemical coverage

  • Analytical Evaluation Reports (AERs) prepared in accordance with ICH Q3E

Analytical characterization of vaccines encompasses testing to evaluate antigen identity, purity, and content, adjuvant characterization, excipient analysis, process-related impurity profiling, and container closure system integrity. For recombinant vaccine antigens, structural characterization by mass spectrometry, glycosylation analysis, and higher-order structure (HOS) assessment provide critical quality attribute data.

AMSbiopharma provides validated analytical services for vaccine component characterization and quality control, applying validated methods aligned with WHO, EMA, and FDA guidelines, as well as applicable pharmacopoeial requirements.

Key analytical capabilities:

  • Antigen identity confirmation and structural characterization by mass spectrometry

  • Antigen content determination using validated quantitative methods

  • Adjuvant characterization and quantification

  • Process-related impurity profiling

  • Support for CMC development and regulatory submissions to the WHO, EMA, and FDA

Untargeted metabolomics enables the simultaneous, unbiased profiling of hundreds of metabolites across multiple biochemical classes in a single analytical run, without prior selection of target analytes. This approach is particularly valuable during the discovery phase, where metabolic profiling data can reveal altered metabolic pathways and identify potential biomarker candidates for further investigation.

AMSbiopharma employs high-resolution mass spectrometry (HRMS) platforms operating in both positive and negative ionisation modes, combined with advanced data processing workflows for peak detection, alignment, normalisation, and metabolite annotation against reference databases. Statistical analyses are performed to identify significantly altered metabolites and metabolic pathways across study groups.

All analytical runs include a comprehensive set of quality control (QC) samples and reference standards to continuously monitor analytical performance and ensure the generation of reliable, high-quality data.

Key analytical capabilities:

  • HRMS-based metabolic profiling in positive and negative ionisation modes

  • Simultaneous detection of hundreds of metabolites across multiple biochemical classes

  • Database-driven metabolite annotation and metabolic pathway mapping

  • Comprehensive quality control strategy to ensure data quality and analytical robustness

  • Applicable to plasma, urine, and tissue samples

Targeted quantitative metabolomics provides accurate, validated quantification of defined metabolite panels, delivering the data quality required for clinical biomarker programmes, pharmacodynamic monitoring studies, and regulatory submissions.

AMSbiopharma offers targeted quantitative metabolomics services using validated LC-MS/MS methods for the simultaneous quantification of predefined metabolite panels. Method development and validation are performed in accordance with applicable regulatory guidelines, covering sensitivity, specificity, linearity, accuracy, precision, and stability.

Our metabolite panels cover the major metabolic pathways—including amino acid, lipid, energy, nucleotide, and one-carbon metabolism—with the flexibility to design custom panels tailored to specific programme requirements.

Key analytical capabilities:

  • Validated LC-MS/MS methods for the simultaneous quantification of multiple metabolites

  • Custom metabolite panel development tailored to specific programme requirements

Our method development services begin with a comprehensive understanding of the analytical challenge: the physicochemical properties of the analyte, matrix complexity, regulatory context, and performance requirements. Based on this foundation, we design analytical methods optimized for sensitivity, specificity, accuracy, and robustness.

Method validation is performed in accordance with applicable regulatory guidelines — ICH Q2(R2) for quantitative pharmaceutical methods and ICH M10 for regulated bioanalytical methods — covering all required validation parameters: specificity, linearity, range, accuracy, precision, detection and quantification limits, robustness, and stability. Complete validation reports are prepared in a regulatory-ready format.

Method transfer services ensure that validated methods perform consistently in receiving laboratories, through an interlaboratory comparability exercise demonstrating equivalent performance. Transfer documentation complies with applicable regulatory requirements.

Key analytical capabilities:

  • Method development for HPLC, UHPLC, GC, LC-MS/MS, HRMS, and other analytical platforms

  • Full validation in accordance with ICH Q2(R2), ICH M10, and applicable specific guidelines

  • Validation for small molecules, peptides, biologics, and oligonucleotides

  • Method transfer with interlaboratory comparability and regulatory documentation

  • Phase-appropriate validation strategies for early- and late-stage development programs

Accurate molecular weight determination of intact or reduced protein therapeutics by mass spectrometry provides fundamental identity data, confirming primary structure integrity and the presence of any modifications that alter the molecular mass.

AMSbiopharma applies high-resolution mass spectrometry for intact protein and middle-up analysis, with online desalting or deglycosylation performed where appropriate. Charge state deconvolution software generates accurate average and monoisotopic molecular masses for protein species, while isoform distributions are quantified based on relative signal abundance.

Key analytical capabilities:

  • Intact protein molecular weight determination by high-resolution mass spectrometry

  • Middle-up analysis of antibody fragments (Fc, Fab, scFv)

  • Glycoform distribution mapping by intact mass spectrometry

  • Charge state deconvolution for accurate molecular mass determination

  • Applicable to mAbs, Fc fusion proteins, ADCs, bispecific antibodies, and other biologics

Glycosylation is one of the most critical quality attributes of biological therapeutics, with a direct impact on pharmacokinetics, effector function, immunogenicity, and clinical efficacy. The glycosylation profile must be fully characterized for regulatory submissions and monitored as part of routine quality control.

AMSbiopharma provides comprehensive glycan characterization services at both the released glycan and glycopeptide levels. Released N-glycan analysis by HPLC with fluorescence detection or LC-MS/MS provides quantitative data on glycan composition. Glycopeptide analysis by LC-MS/MS provides site-specific glycosylation information.

Key analytical capabilities:

  • Released N-glycan profiling by HPLC with fluorescence detection

  • Glycan identification and relative quantification by LC-MS/MS

  • Site-specific glycosylation analysis through glycopeptide mapping

  • O-glycosylation characterization for relevant biological classes

  • Applicable to mAbs, Fc fusion proteins, therapeutic enzymes, and biosimilars

  • Validated methods for CMC submissions and routine quality control

Accurate and selective quantification of specific proteins in complex biological matrices is a critical analytical requirement in bioanalytical, pharmacodynamic, and quality control applications. The method of choice depends on the context: immunoassay-based approaches provide high sensitivity for low-abundance targets in complex matrices, whereas mass spectrometry-based methods offer greater specificity and multiplexing capabilities.

AMSbiopharma provides validated protein-specific quantification services using ligand-binding assay (LBA) and LC-MS/MS-based approaches. Stable isotope-labelled peptide internal standards ensure accurate and reproducible quantification with appropriate correction for matrix effects.

Key analytical capabilities:

  • Validated LC-MS/MS-based protein-specific quantification using stable isotope-labelled standards

  • Protein quantification by ligand-binding assay (LBA) for high sensitivity

  • Applicable to bioanalytical, pharmacodynamic, and quality control applications

  • Protein quantification capabilities

  • Applicable to plasma, serum, tissue, and pharmaceutical matrices

Exact mass measurement by high-resolution mass spectrometry provides the most definitive identity confirmation available for therapeutic oligonucleotides, delivering a precise molecular formula that confirms the number and identity of constituent nucleotides, backbone modifications, and any other chemical modifications incorporated into the active substance.

AMSbiopharma offers validated exact mass measurement services for therapeutic oligonucleotides using UHPLC coupled to high-resolution mass spectrometry under ion-pair chromatography conditions. Charge-state deconvolution software provides deconvoluted average and monoisotopic masses.

Key analytical capabilities:

  • Exact mass determination with sub-ppm accuracy for therapeutic oligonucleotides

  • Coverage of ASOs, siRNA, aptamers, and highly modified species

  • High-resolution UHPLC-MS with ion-pair chromatography

  • Charge-state deconvolution for intact oligonucleotide mass determination

  • Applicable to phosphorothioate species, 2′ modifications, and other backbone modifications

  • Identity confirmation data for CMC regulatory submissions

Purity assessment is a critical batch release and stability monitoring assay for therapeutic oligonucleotides, ensuring that the active substance meets its purity specification and that process-related impurities — including truncated sequences (n-1, n-2), deletion sequences, extended sequences (n+1), and other synthetic by-products — are within acceptance criteria.

AMSbiopharma provides validated UHPLC-based analytical services for purity determination and impurity identification, applying ion-pair reversed-phase chromatography with UV detection for quantification and mass spectrometry detection for impurity identification.

Key analytical capabilities:

  • Purity determination by validated UHPLC-UV using ion-pair chromatography

  • Chromatographic resolution of n-1, n-2, and n+1 sequence impurities

  • Impurity identification by LC-MS for structural characterization

  • Applicable to ASOs, siRNA, aptamers, and modified oligonucleotides

  • Support for CMC development.

Sequence confirmation provides definitive identity verification for therapeutic oligonucleotides, ensuring that the active substance contains the intended nucleotide sequence and that all chemical modifications are present at the correct positions. It is a mandatory component of the identity characterization package for regulatory submissions.

AMSbiopharma provides validated sequence confirmation services using tandem mass spectrometry (MS/MS)-based approaches, generating fragment ion series that confirm the nucleotide sequence and localize chemical modifications throughout the entire length of the oligonucleotide.

Key analytical capabilities:

  • MS/MS-based sequence confirmation with comprehensive sequence ion coverage

  • Identification and localization of backbone and base modifications

  • Confirmation of phosphorothioate linkages, 2′ modifications, and other backbone features

  • Regulatory-grade sequence identity data for CMC submissions

  • Support for short and long oligonucleotides

Stability and degradation analysis for therapeutic oligonucleotides provides essential information for shelf-life determination, storage condition specification, and understanding of degradation pathways. ICH Q1-compliant stability programs require validated stability-indicating analytical methods capable of detecting the full range of degradation products.

AMSbiopharma provides validated analytical services for stability and degradation assessment, applying UHPLC and LC-MS/MS platforms to detect, quantify, and identify degradation products.

Key analytical capabilities:

  • Validated stability-indicating UHPLC methods for formal ICH Q1-compliant stability studies

  • Detection and quantification of degradation products

  • Identification of degradation products and pathway elucidation by LC-MS/MS

  • Applicable to active substance and drug product stability programs

  • Coverage of hydrolytic, oxidative, and depurination degradation pathways

Microbial enumeration testing of non-sterile pharmaceutical products is a fundamental requirement for ensuring product quality and patient safety. Determination of the Total Aerobic Microbial Count (TAMC) and the Total Yeast and Mould Count (TYMC) provides the quantitative evidence required to demonstrate compliance with the microbiological acceptance criteria established in the applicable pharmacopoeial specifications, confirming that the microbial bioburden remains within acceptable limits throughout the product’s shelf life.

AMSbiopharma performs validated TAMC and TYMC testing in accordance with Ph. Eur. 2.6.12/2.6.13 and USP <61>/<62>, including the method suitability studies required for each product type and matrix. All testing is carried out under controlled laboratory conditions by qualified personnel following documented procedures aligned with Good Manufacturing Practice (GMP) principles.

Method validation includes assessment of method suitability for each product type, incorporating the recovery studies required by Ph. Eur. 2.6.12/2.6.13 and USP <61>/<62>. Test results are provided with comprehensive supporting documentation suitable for batch release and stability programmes.

Key analytical capabilities:

  • Total Aerobic Microbial Count (TAMC) in accordance with Ph. Eur. 2.6.12 and USP <61>

  • Total Yeast and Mould Count (TYMC) in accordance with Ph. Eur. 2.6.13 and USP <62>

  • Testing of active pharmaceutical ingredients (APIs), drug products, excipients, and raw materials

Microbiological testing of water is a critical component of the quality assurance system in pharmaceutical manufacturing facilities. The microbiological quality of water used during manufacturing—including Purified Water (PW), Water for Injection (WFI), and Highly Purified Water (HPW)—is a critical quality attribute that must be routinely monitored in accordance with the requirements of the Ph. Eur., the USP, and applicable GMP guidelines.

AMSbiopharma provides microbiological testing services for pharmaceutical water using methods compliant with applicable pharmacopoeial and regulatory requirements. Our services include microbial enumeration testing (TAMC/TYMC) and the detection of specified microorganisms, in accordance with the water quality specifications established by the Ph. Eur. and the USP for each pharmaceutical water grade.

Key analytical capabilities:

  • Microbiological testing of Purified Water (PW), Water for Injection (WFI), and Highly Purified Water (HPW)

  • TAMC/TYMC determination and detection of specified microorganisms in pharmaceutical water in accordance with Ph. Eur. and USP requirements

Antimicrobial preservatives are critical formulation components in many multidose pharmaceutical products, including ophthalmic, parenteral, oral, and topical preparations. Demonstrating preservative efficacy—its ability to prevent microbial proliferation and maintain the microbiological integrity of the product throughout its intended storage and in-use period—is a mandatory regulatory requirement that must be assessed using Antimicrobial Preservative Effectiveness Testing (AET) in accordance with applicable pharmacopoeial methods.

AMSbiopharma performs Antimicrobial Preservative Effectiveness Testing (AET) in compliance with Ph. Eur. 5.1.3 and USP <51>, using the pharmacopoeia-required challenge panel of bacteria, yeasts, and moulds, and applying the acceptance criteria established for each product category. All studies are conducted using certified reference strains under controlled laboratory conditions, with comprehensive documentation suitable for inclusion in regulatory submissions.

Key analytical capabilities:

  • Antimicrobial Preservative Effectiveness Testing (AET) in accordance with Ph. Eur. 5.1.3 and USP <51>

The quantification of biological indicators and specific microorganisms is an essential component of a wide range of pharmaceutical microbiology applications, including sterilisation process qualification and validation, pre-sterilisation bioburden determination, and the monitoring of manufacturing processes where control of specific microorganisms is critical to product quality and patient safety.

AMSbiopharma provides biological indicator quantification and microorganism enumeration services using validated methods tailored to each specific application. Biological indicators are microorganisms with a defined and characterised resistance to the sterilisation process under evaluation—typically Geobacillus stearothermophilus spores for steam sterilisation and Bacillus atrophaeus spores for ethylene oxide sterilisation. Their quantification before and after the sterilisation process provides documented evidence of sterilisation process effectiveness.

Key analytical capabilities:

  • Pre-sterilisation bioburden determination in accordance with Ph. Eur. 2.6.12 and ISO 11737-1

  • Enumeration of specific microorganisms in product and process samples

Bacterial endotoxins are lipopolysaccharides (LPS) found in the outer membrane of Gram-negative bacteria. When introduced into the body through parenteral products, they can trigger severe pyrogenic reactions and, in extreme cases, septic shock. Consequently, bacterial endotoxin testing is a critical quality attribute for all parenteral pharmaceutical products and a mandatory requirement for batch release.

Key analytical capabilities:

  • Bacterial Endotoxins Testing (BET) using the Limulus Amebocyte Lysate (LAL) method in accordance with Ph. Eur. 2.6.14 and USP <85>