Pharma & Biopharma

Bioprocessing is the use of living cells, biological materials, or their components to develop and manufacture products such as biopharmaceuticals, vaccines, enzymes, and biofuels. This multidisciplinary field combines biology, engineering, and technology to transform raw materials into high-value products through controlled biological processes. 

Key stages of bioprocessing include upstream processing (cell cultivation and fermentation), downstream processing (purification and recovery), and formulation of the final product. Advanced techniques such as bioreactor systems, chromatography, and filtration ensure efficiency, scalability, and compliance with regulatory standards. Bioprocessing is critical for producing safe, effective, and high-quality biologics that meet the growing demands of healthcare and industry. 

Cell culture is a method to study the behavior of cells in a controlled environment, free of systematic variations. Different types have been adapted and developed based on the purpose of the investigation, such as interactions of drugs and other chemicals with cells, production of vaccines and proteins, and advanced analysis using the C2MAP System and Cell Culture Profiling Ver. 3. To care for optimal conditions, the composition of the media is checked regularly; therefore different chemical compounds and parameters are controlled, and different techniques and applications are used, including solutions such as CELL POCKET.

Proteins are a versatile group of macromolecules; peptides are smaller in size with a limited number of building stones. Both consist out of a chain of amino acids, their structure is determined not only by the amino acids, but also by interactions between them, forming a secondary and tertiary structure which is important for the activity of the molecule and its chemical and physical characteristic.  
Proteins are present in all cells, functioning e.g. as enzymes, as transmitters or as biomarkers. Understanding about conditions and mechanism of their expression or absence is crucial for further development of biopharmaceuticals for a targeted therapy of diseases. 

Monoclonal antibodies (mAbs) have emerged as revolutionary therapeutic agents for an array of human diseases. In addition to their large mass and complex structure, mAbs are varied in their origin, makeup, effector function and delivery, and therefore require thorough formulation development, including characterization, quantitation and preservation. 
More and more special designed Antibody drug conjugates (ADCs) are under development as targeted therapy for treating cancer.  ADCs combine the targeting capabilities of monoclonal antibodies with the cancer-killing ability of cytotoxic drugs. 

nSMOL (nano-surface and molecular orientation limited proteolysis) is Shimadzu’s proprietary, innovative technique that enables selective proteolysis of the Fab region of monoclonal antibodies. The nSMOL Antibody BA Kit is a ready-to-use reagent kit for collecting monoclonal antibodies from blood or other biological samples using immunoglobulin collection resin, and then performing selective proteolysis of the Fab region of these antibodies via trypsin-immobilized nanoparticles. Variable region-derived peptides produced by limited proteolysis can then be quantified via MRM measurements utilizing a high-performance LCMS-8050/8060 triple quadrupole liquid chromatograph mass spectrometer.

• Faster, Less Expensive Method Development

 Dramatically improves response and quantitative repeatability. No capture antibodies or ligands are required.

• nSMOL Proteolysis

 Selective collection of Fab peptides. Limits contamination from excessive peptides or trypsin.

• Performance

 Highly sensitive and accurate essays are possible for a variety of antibodies

• Highly Versatile

 Applicable to a wide variety of pharmaceutical antibodies.

• Simple Workflow

 This kit enables highly reproducible data and avoids the troublesome steps of denaturing, reduction, and alkylation normally associated with protein digestion. There is also no need for solid phase extraction after reaction. After nSMOL preparation, samples can be injected directly into the LCMS.

Host cell proteins (HCPs) are process related impurities expressed by host cells during the production of biopharmaceuticals. The purification process eliminates the majority, but residual HCPs remain in the distributed products. 
Regulatory authorities require that these impurities must be analyzed and purified to reduce the HCPs to an acceptance level. This is evaluated case by case and depend on a lot of factors, such as dose, frequency of drug administration, type of drug and severity of the disease. 
The analytic is not simple as the HCP mixture contains a large number of protein species, unique to the host and not related to the biopharmaceutical. 

Post-translational modifications (PTMs) are chemical changes that occur in proteins after their synthesis, significantly influencing their structure, function, stability, and activity. Common PTMs include phosphorylation, glycosylation, acetylation, methylation, ubiquitination, and disulfide bond formation. These modifications play vital roles in cellular processes such as signal transduction, immune responses, and protein regulation.
Analyzing PTMs is essential for understanding protein function and developing therapeutic applications, particularly in biopharmaceuticals. Advanced techniques like mass spectrometry (MS), high-performance liquid chromatography (HPLC), and antibody-based assays are used to identify, quantify, and characterize PTMs. Precise analysis enables researchers to study disease mechanisms, optimize drug development, and ensure the quality of protein-based therapeutics.

Many protein-based biopharmaceutical products, typified by antibody drugs, are synthesized in cultured cells derived from eukaryotes such as CHO (Chinese hamster ovary) cells. For this reason, there are inevitably many post-translational modifications to the biosynthesized proteins. Among these, modifications of glycans have gained attention as items for evaluating the quality of biopharmaceuticals since they are associated with the adjustment of protein functions, as well as with the unwanted development of antigenicity depending on their structure. 

Glycan characterization is important in the process of protein drug development, from early stage candidate selection to late stage regulatory submission. Glycan variants of a glycoprotein product must be adequately analyzed and controlled to ensure product quality. The inherent complexity of protein glycosylation poses an analytical challenge.
 

The main dogma of molecular biology states that DNA is transcribed into RNA, which then is translated into the amino acid sequence of an expressed protein. Knowledge about the DNA structure and sequence is important to gain a better understanding of genes, protein expression, and the complex regulatory mechanisms in cells. Analysing the nucleic base sequence and structure-determining elements of DNA and RNA is often the starting point, supported by advanced analytical technologies such as the MALDI-8030, OAD-TOF System, RF-6000, UV-1900i Plus, and LabSolutions Insight Biologics.

Diagnosis of gene defects as a cause of rare diseases and their treatments are the driving force for the development of new-generation medications, such as gene therapy. After synthesis of the special DNA or RNA pieces, the verification of their structure and sequence are key tasks to cover, where instruments like the MALDI-8030, OAD-TOF System, and LabSolutions Insight Biologics can be integrated naturally into the workflow.

Modern vaccines based on mRNA and their production once more underline the importance of having state-of-the-art techniques and solutions for fast and precise analysis, including spectroscopic support from the RF-6000 and UV-1900i Plus, alongside data analysis capabilities provided by LabSolutions Insight Biologics.

Ensuring the quality and safety of pharmaceutical products begins with rigorous raw material testing. In pharmaceutical manufacturing, raw materials such as active pharmaceutical ingredients (APIs), excipients, and packaging components play a critical role in determining the efficacy and stability of the final product. Comprehensive testing of these materials is essential to meet regulatory standards, prevent contamination, and guarantee consistency across production batches.
Raw material testing involves evaluating physical, chemical, and microbiological properties using advanced analytical techniques. This process helps identify impurities, confirm compliance with pharmacopeial specifications, and verify supplier certifications. By implementing stringent testing protocols, pharmaceutical companies safeguard patient health and maintain the integrity of their production processes.
Explore how our expertise in raw material testing supports the foundation of high-quality pharmaceutical manufacturing.

Residual solvent analysis is a crucial step in ensuring the safety and quality of Active Pharmaceutical Ingredients (APIs). Residual solvents are organic chemicals used during API synthesis that may remain in trace amounts after production. If not properly controlled, these solvents can pose risks to patient health or impact the stability of pharmaceutical products.
Using techniques such as gas chromatography (GC), residual solvent analysis identifies and quantifies these solvents to ensure compliance with regulatory limits, such as those outlined in ICH Guideline Q3C. This process helps manufacturers eliminate harmful levels of solvents, ensuring that APIs meet strict safety standards and are suitable for therapeutic use.

Impurity analysis is a critical aspect of pharmaceutical development and manufacturing, aimed at identifying, quantifying, and controlling unwanted substances that may arise during synthesis, storage, or packaging. These impurities, including degradation products, residual solvents, and trace contaminants, can impact drug efficacy, stability, and patient safety.
Genotoxic impurities are critical components of pharmaceutical development and manufacturing, focusing on the detection, identification, and control of impurities with the potential to damage genetic material. These impurities, which may arise during synthesis, degradation, or from raw materials, pose serious safety risks even at trace levels, making their control essential to protect patient health. 

Sophisticated analytical techniques, such as high-performance liquid chromatography (HPLC), gas chromatography (GC), and mass spectrometry (MS), are employed to detect and quantify genotoxic impurities with high sensitivity and precision. Compliance with regulatory guidelines, such as ICH M7, ensures the effective management of these impurities throughout the drug lifecycle. By prioritizing genotoxic impurity analysis, pharmaceutical manufacturers can uphold product safety, meet stringent regulatory requirements, and minimize risks to public health.

Nitrosamines are chemical compounds that have raised significant concerns due to their potential carcinogenic properties. Found in various industries, including pharmaceuticals, food, cosmetics, and water treatment, their presence can result from chemical reactions or contamination during manufacturing processes. Accurate nitrosamine analysis is essential to safeguard public health, ensure regulatory compliance, and maintain product integrity.
Modern analytical techniques, such as gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS), enable precise detection and quantification of nitrosamines even at trace levels. These methods support diverse applications, from pharmaceutical quality control to environmental monitoring and food safety testing.
Explore our application examples to learn how advanced nitrosamine analysis solutions can address challenges across industries, ensuring safety and reliability in your products and processes.

Quality control (QC) is a cornerstone of pharmaceutical production, ensuring that every product meets stringent standards for safety, efficacy, and consistency. Through systematic testing and monitoring at every stage of manufacturing, QC verifies that raw materials, intermediates, and final products comply with regulatory requirements and industry specifications.
Advanced analytical techniques, such as chromatography, spectroscopy, and microbiological testing, play a vital role in detecting impurities, confirming active ingredient concentrations, and assessing product stability. Additionally, QC processes validate packaging integrity and ensure batch-to-batch uniformity. By prioritizing quality control, pharmaceutical manufacturers safeguard patient health, enhance product reliability, and maintain compliance with global regulatory frameworks such as GMP (Good Manufacturing Practices).

Pharmaceutical formulation is the process of designing and producing drug products with the desired therapeutic efficacy, stability, and patient acceptability. This involves combining active pharmaceutical ingredients (APIs) with excipients to create a final product in the form of tablets, capsules, injections, or other dosage forms. Ensuring the accuracy of the formulation is critical to achieving consistent content uniformity and maintaining product quality.
Analytical techniques such as high-performance liquid chromatography (HPLC), UV-Vis spectroscopy, and dissolution testing are essential for confirming the API content, verifying excipient compatibility, and ensuring batch-to-batch consistency. Final product testing focuses on key parameters like potency, purity, stability, and bioavailability to meet regulatory requirements and ensure patient safety. By integrating robust formulation practices with precise analytical methods, pharmaceutical manufacturers can deliver high-quality, reliable medicines to the market.
 

Cleaning validation is a critical process in pharmaceutical manufacturing that ensures equipment and facilities are thoroughly cleaned to prevent cross-contamination, maintain product integrity, and comply with regulatory standards. As pharmaceutical production involves handling various active ingredients, excipients, and chemicals, residues left behind can compromise product quality and pose risks to patient safety.
The cleaning validation process involves establishing scientifically proven cleaning procedures, testing for residual contaminants, and setting acceptable limits for residues such as active pharmaceutical ingredients (APIs), cleaning agents, and microbial contaminants. Analytical methods like high-performance liquid chromatography (HPLC), total organic carbon (TOC) analysis, and swab testing are commonly used to verify cleaning effectiveness.
By implementing robust cleaning validation protocols, pharmaceutical manufacturers can ensure consistent product quality, meet Good Manufacturing Practices (GMP) requirements, and uphold patient safety. Explore our solutions to learn more about advanced tools and techniques for cleaning validation in pharmaceutical production.