Our DPS team is highly skilled in the development and execution of analytical methods for drug products of biopharmaceuticals including standard monoclonal antibodies, recombinant proteins, fusion proteins, antibody-drug-conjugates, and vaccines, as well as viral-and cell-based therapies.

The service offerings comprise the complete array of development activities of analytical methods that may be required for a parenteral drug product, ranging from:

  • Developing and applying purity methods (size, charge based) such as SE-HPLC, RP-HPLC, iCE280 and CE-SDS 
  • Developing and applying identity methods
  • Developing and applying content (concentration) methods
  • Developing and applying bioassays (ELISA, cell-based, other)
  • Pharmacopeial testing methods including pH, osmolality, extractable volume, subvisible particles, visible particles, color, clarity, density 
  • Release and real-time and accelerated stability testing of drug products for GLP supplies or clinical GMP material 
  • Regulatory support for drug product sections IND/IMPD, BLA/MAA documentation
  • Trouble shooting
  • Addressing special topics and challenges, including identification of particulates, characterization of particles e.g. in the subvisible or submicron range, surfactant content and degradation, extractables/leachables and product characterization and comparability, peak identification
  • Design of adequate control strategy and specifications
 

Our DPS team has technical expertise in analytical development and quality control (QC). The analytical development and QC team offers specialized contract laboratory services including:

  • Drug product development (R&D) and GMP (QC) release & stability testing
  • Physical and chemical analytical laboratory services
  • Forensic chemistry including:
    • submicron and subvisible particle characterization 
    • particle identification
    • extractable and leachable characterization
    • excipient (e.g. surfactant) degradant characterization

Drug product QC release and stability testing is supported by analytical method development and cGMP drug product stability testing according to ICH guidelines. The drug product QC team can help to define shelf-life, specifications and develop a drug product control strategy for IND/IMPD or BLA/MAA, and design quality-by-design and breakthrough therapy submissions.

Our analytical team of experts is experienced to design appropriate analytical methods, ensuring a compliant method panel, understanding method capabilities including method validation, and performing release and stability testing. Our experts can support most challenging projects and understand requirements and typical requests from health authorities globally.

Our DPS team works closely with the drug substance sites and other analytical centers across the Lonza network enabling an integrated and high quality one-stop-shop from a single service provider.

All services are available as standalone services.

Are injection site reactions in monoclonal antibody therapies caused by polysorbate excipients?

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  • Analytical development (Physico-Chemical testing, including content, purity, identity)

    Our DPS team can provide comprehensive method development support for a full range of physico-chemical techniques, including chromatographic, electrophoretic and spectroscopic methods. Our team has extensive experience in method development and phase-appropriate analytical lifecycle strategies. Method development is performed in close consideration of the project needs for both formulation testing and eventual non-GMP and GMP release and stability testing using a common analytical platform.

  • Our experts have extensive experience with validation of methods and work closely with counterparts at Lonza drug substance sites to enable method validation and co-validation as appropriate. We consider phase-appropriateness for method development and a focus on relevant validation parameters.

  • Our experts can support the transfer of analytical methods. Method transfers can take the form of transfer of validated procedures under GMP, to non-GMP method implementation or transfer, depending on the program requirements and customer needs.

  • Our DPS team has a full service Quality Control (QC) department supporting GMP release and stability studies. Our DPS QC experts work proactively with our customers to plan and execute GMP activities to enable clinical testing. Additionally, non-GMP testing to support technical and toxicology studies is performed using the common analytical and instrument strategy with GMP testing.

  • The stability of surfactants, particularly that of polysorbates has been under significant regulatory scrutiny in the last years. This is because they have shown different degradation liabilities, whether by oxidation or hydrolysis, possibly enzymatic hydrolysis that can lead to deterioration of product quality, such as protein oxidation or (visible) particle formation;

    Our DPS experts have extensive experience with methods to quantify, characterize and control surfactant content and degradation products. From development, qualification and validation of methods for polysorbate quantification for non-GMP and GMP release and stability testing, to in-depth characterization of polysorbate degradation products as well as identification of degradation pathways and underlying causes, our DPS team have the capability to support any surfactant-related challenge.

  • Demonstrating bioactivity using a stage-appropriate validated bioassay is key for the progress and regulatory acceptance of the development program. Our DPS team can support development of both cell-based and ELISA methods. This includes method development and validation, support of formulation and process development studies by bioactivity testing, as well as supporting QC release and stability activities.

  • Parenteral preparations need to be evaluated for their potential to induce unwanted reactions in human, such as fever, that may be caused by pyrogens and endotoxins. Each batch of parenteral product would be tested for these contaminants, using a variety of potential assays (such as limulus amebocyte lysate (LAL), recombinant factor C, or the monocyte activation test MAT) specifically evaluated for each product matrix.

    Our laboratory is specifically design to address these testings in an adequate and safe environment, reflecting Biosafety Level (BSL) 2.

    As part of endotoxin testing, recovery of spiked reference endotoxins is key to assess method performance. However, some compounds or product matrices may impact endotoxin recovery, yielding lower recovery at a function of incubation time, putting final endotoxin results in question (“low endotoxin recovery (LER) or endotoxin masking”). Our experts can evaluate LER and endotoxin masking in specifically designed studies, and make suggestion for mitigation activities to overcome related hurdles.

  • Container closure integrity (CCI) is indispensable for ensuring product sterility and hence patient safety. Our DPS has extensive technical, regulatory and strategic experience in designing and executing container closure integrity studies. Lonza experts can provide clear guidance about CCI strategy, utilization of helium leak testing, as well as validation of the crimping parameters using residual force measurements combined with CCI testing. We are planning and performing testing according to USP 1207. We have also developed tailored, proprietary solutions to evaluate CCI using highly sensitive helium leakage pCCI testing for vials, syringes and cartridges and can evaluate specific requirements, such as the impact of stopper height on CCI, as per recent Annex 1 GMP requirements.

    We can support qualification of critical unit operations such as capping/crimping, evaluate container-closure systems and container-closure related issues such as fogging or glass delamination.

  • Control strategy and specification setting are among the most important topics for discussion with health authorities, and need sound justifications based on either prior knowledge or comprehensive analytical packages combined with preclinical and clinical data. Setting specifications wrongly can yield significant issues and challenges, both related to regulatory acceptance but also risk of product loss and thus, risking supply to patients.

    Our DPS experts have extensive experience in setting up analytical control strategies and specifications from early stage to commercial. From setting up shelf-life to challenging topics such as particle and polysorbate strategies, our DPS experts can provide in-depth guidance to help mitigate risk and ensure a successful program.

  • A drug product gets exposed to visible light and potentially ultraviolet radiation at several stages during its lifetime, from manufacturing and storage to administration. For some molecules, light exposure can be detrimental to their stability. Accordingly, careful evaluation of photostability is required, usually at early stages during product development.

    Our DPS team can perform photostability studies, ranging from ICH conditions to assessment of real-world light exposure during manufacturing and handling. Lonza’s experts can provide a comprehensive range of testing, including mass spectrometric based characterization of photodegraded samples and characterization of degradation pathways.

A case study: download our poster

This study provides a systematic CCI assessment of six prefilled syringes and systematically assesses the contribution of different sealing areas

Meet the expert

Dr. Atanas Koulov, Head Drug Product Analytical Development and Quality Control

Atanas Koulov brings eight years of industry experience in drug product analytical development and quality control release and stability testing, as well as characterization, investigations support and specification setting to Lonza. His previous roles include managing Roche’s Particle lab, activities for visible, subvisible and submicron particles, as well as responsibility for various programs in Analytical Development & QC of Drug Products. In addition to his roles at Roche, Atanas also worked as a Lab Head, Analytical Development at Novartis Biologics.

Atanas has published extensively in the field of protein aggregation and particles and is the immediate past chair of the AAPS Protein Aggregation & Biological Consequences Focus Group. He holds a Ph.D. in Biochemistry from the University of Notre Dame, IN (USA), earned his M.Sc. in Molecular Biology and Clinical Chemistry from Sofia University (BG) and worked as Postdoctoral Fellow at the Scripps Research Institute in San Diego, CA (USA).