Pharmaceutical quality control solutions designed in accordance with GxP standards

Sartorius brings innovative solutions for quality control – from microbial contamination detection to optimization of key quality attributes and document protection. Find out how these solutions can enhance your daily practices and ensure the highest standards across all stages of research and production.

1. Quality Control in Microbiology Labs

The primary goal of quality control in a microbiological laboratory is to identify viable microorganisms in the air, raw materials, water, and finished products at every stage of the production process. Safe handling of lab equipment and consumables reduces the risk of false positive and negative results, ensuring batch release with a safety guarantee.

Monitoring and eliminating microbial contaminants from lab and production environments is crucial to ensuring pharmaceutical product quality. Sartorius supports the contamination control strategy (CCS) with consumables and hardware for:

• Microbial quantification (USP <61>, <62>, <1231>, Ph.Eur. 2.6.12, JP 4.05)
• Sterility testing by growth-based methods (USP <71>, EP 2.6.1, JP 4.06)
• Rapid PCR-based sterility testing (EP 5.1.6, EP 2.6.27)
• Airborne microbial monitoring (EN ISO 17141, EU GMP Annex 1)
• Mycoplasma detection by rapid PCR method (EP 2.6.7)

Bioburden Assessment

Routine bioburden assessment for microbial quantification on surfaces or in liquids is a crucial part of microbiology. Membrane filtration is the preferred method for microbial quantification, although filter transfer to media can introduce contamination and false positives.

Microsart^® membrane filters, combined with a pre-filled agar media plate and sterile filter units, allow contact-free membrane transfer and reduce secondary contamination risk for simple, reliable microbial quantification.

Rapid Sterility Testing by PCR

Alternative sterility testing methods provide near-real-time results, creating an opportunity for proactive corrective actions, enhancing testing quality for small volumes and new cell therapies that cannot be filtered, such as ATMP or CAR-T cells. While still a reference method, the validation of rapid methods increases patient safety by reducing the need for prophylactic medications and antibiotics. Common bacterial and fungal contaminants are present in most labs and production sites. Microsart® ATMP Sterile Release is specifically designed for institutions and companies working with bacterial and fungal cultures, according to EP 5.1.6, EP 2.6.27, and USP <1223>.

The Microsart^® ATMP Sterile Release Kit combines Microsart^® ATMP Bacteria and Microsart^® ATMP Fungi PCR tests for detecting bacterial and fungal contamination within three hours.

Rapid Mycoplasma Detection by PCR

Mycoplasma are small bacteria capable of self-replication and can cause issues in cell cultures. Routine quality control and testing of cell substrates in biological product manufacturing are required for the master cell bank (MCB) and working cell bank (WCB).

Alternative nucleic acid amplification techniques (NAT) can provide faster results than traditional methods, with a detection threshold of 10 CFU/mL viable but non-cultivable (VBNC) mycoplasma. Mycoplasma can remain undetected for up to 28 days after culture by traditional methods, risking false-negative results.

Microsart^® AMP mycoplasma kit is specially designed for quick and easy mycoplasma detection, validated in accordance with EP 2.6.7 for ATMP, reducing the testing time from several weeks to 3 hours.

Microbial air monitoring

Airborne microorganisms pose a potential contamination risk to products and raw materials. Successful microbiological air quality testing requires establishing, implementing, and maintaining a formal biocontamination control system. Sartorius air samplers are used for air quality monitoring in the pharmaceutical, biotech, and food industries and for environmental and workplace safety measurements.

MD8 Airscan^® air sampler provides continuous air monitoring using a single gelatin membrane filter for at least 8 hours. The agar-free gelatin membrane filters do not dry out during long sampling periods, nor do they affect microbial growth, ensuring absolute microbial and virus retention rates. They are fully water-soluble, allowing microbes from a single sample to be cultivated on various media.

Sterility testing

Before the distribution and sale of products labeled as sterile, the international pharmacopoeia requires sterility testing and a certificate of sterility for each batch of the product. Sterility testing is part of the validation process and routine batch checks. Membrane filtration is used for aqueous, alcoholic, or oil-based preparations, as well as preparations that are soluble in aqueous and oily solvents. To ensure accurate results, the testing environment must be aseptic.

Sterisart^® universal pump offers a range of closed and compatible units for sterility testing. These units protect samples from secondary contamination and laboratory personnel from risks associated with needle handling. The pump is designed for use in clean rooms and laminar flow hoods, in compliance with 21 CFR Part 11 and EU Annex 11.

2. Sample Preparation - The foundation of reliable Physicochemical Quality Control

Sample preparation is a critical step in regulated quality control (QC) and GxP laboratories, where analytical result accuracy and reliability are non-negotiable. Sample preparation directly impacts success in detecting and quantifying analytes, making it essential to use tools that ensure consistency, precision, and the ability to detect the lowest contaminant levels, all while ensuring the highest repeatability.

Laboratory water preparation system

Ultrapure water is used as a solvent for the preparation of solutions, reagents, and buffers in analytical methods such as HPLC, GC, and MS, as well as in other processes that require high-purity conditions, such as molecular biology and cell culture experiments.

The Arium^® Mini Extend ultrapure water system purifies tap water into Type I ultrapure water at a flow rate of up to 1 liter per minute, meeting ASTM, NCCLS, ISO, and USP standards.

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Ultra-micro laboratory balances

Cubis^® II ultra-micro balance with a readability of 0.1 µg a maximum capacity of 2.1 g, provide precision weighing with features that support regulatory compliance with 21 CFR Part 11 and EU Annex 11. Software with up to 60 optional applications grouped into QApp packages with possibilities of subsequent upgrades of hardware and software will adapt future laboratory needs:

• 45 weighing modules adapted to customer needs and requirements
• user management, audit trail i alibi memory
• draft shields - 7 different options with unique features and a user-oriented design
• advanced connectivity for ELN/LIMS system integration
• complete elimination of electrostatic charge
• stable and reliable performance over the entire weighing range, resulting in a low minimum sample weight

Syringe Filters

Syringe filters are essential for sample clarification and sterilization, ensuring the removal of particles, microorganisms, and contaminants that could compromise analytical testing. These filters are crucial for maintaining the sterility of solutions and preserving instrument integrity, thus ensuring consistent and repeatable results. Using high-quality syringe filters reduces contamination risks, leakage, and variability in filtration, which is key for regulatory compliance and product safety assurance.

Minisart^® Syringe Filters are available with pore sizes of 0.2 μm or 0.45 μm and feature specialized membranes for HPLC sample filtration:

• regenerated cellulose membrane optimized for aqueous solutions and solvents, including DMSO, amides, ketones, esters, and ethers
• NY membrane for alkaline solutions
• PTFE membrane for aggressive chemicals

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Electronic Pipette

Ergonomically designed pipettes with easy-to-handle tips minimize errors and prevent muscle fatigue during repetitive tasks, ensuring accurate volume measurements. The tip design provides a secure fit and easy release, essential for maintaining sample purity and achieving consistent results.

Picus^® 2 electronic pipette, equipped with a multiwell plate tracking device, automatic mixing, and electronic tip ejection, ensures reproducible results with effortless pipetting.

• single-channel models with a volume range of 0.2 to 10,000 µL
• multichannel models with a volume range of 0.2 µL to 1,200 µL
• Sartorius Pipetting App for pipetting with the latest features, customizable protocols, and guided workflows

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3. Biologics Analytical Quality Control

All medicinal products must be tested using robust, GxP-qualified, and validated methods. Since biologics are more complex than small-molecule drugs, simplifying the testing process is important. Octet^® analytical platform allows easy method implementation within testing processes, along with a comprehensive GxP protocol that meets the regulatory requirements of 21 CFR Part 11, including installation qualification (IQ), operational qualification (OQ), and performance qualification (PQ). The Octet^® platform is ideal for regulated Quality Control (QC) environments.

The Octet^® BLI platform is suitable for method development and validation for batch release, as well as for in-process ligand binding, concentration, and impurity analysis in both upstream and downstream processes (host cell proteins (HCP) and residual Protein A (RPA)). Octet^® instruments are routinely used for potency analysis of drug-target and drug-Fc receptor (FcyRI, FcyRIIa, FcRIII, and FcRn) interactions, as well as for developing stability indication methods that assess changes in activity through stress and forced degradation.

The Octet^® platform easily adapts to different experimental designs (DOE) for the rapid development of robust potency measurement methods, providing relative affinity constants or response signals for potency measurements and comparability studies.

• Quantification of titer and proteins
• Contamination analysis
• Fc receptor binding analysis
• Ligand binding potency analysis
• Quantification of viral capsids

Protein Quantification

Traditional protein concentration techniques, such as HPLC and ELISA, have been replaced by more robust Octet^® BLI assays in upstream and downstream processes. The Octet^® platform enables accurate and rapid protein concentration and potency measurement assays:

• full plate analysis (96 samples)
• IgG titer results in just two minutes
• testing of crude and contaminated samples
• automation for high-throughput analysis

Contamination Testing

Monitor and quickly detect potential contaminants, such as host cell proteins (HCP) and residual Protein A, with greater precision and robustness compared to traditional ELISA assays. The Octet^® Residual Protein A kit is ready for HCP detection based on residual Protein A and CHO, native Protein A detection, as well as non-native Protein A constructs, including MabSelect SuRe™. The Octet^® RPA Kit supports accurate Protein A quantification down to 100 pg/mL, allowing analysis of 96 samples in less than two hours on the Octet RH96 system.

The HCP Detection Kit, utilizing Anti-CHO antibodies (Cygnus Technologies), can detect as little as 0.5 ng/mL HCP with a coefficient of variation of 5-10%.

Fc Receptor Binding Assays

Antibodies are often used for binding to Fc gamma receptors. The safety and efficacy of monoclonal antibodies can be greatly influenced by their binding to targets and Fc gamma receptors.

The Octet^® analytical platform provides a sensitive, high-throughput Fc receptor binding assay method, enabling rapid and flexible assay development.

Ligand Binding Assays

Reproducible ligand binding assays can be used for developing methods for accurate drug potency assessment. These methods can be used to evaluate and monitor:

• manufacturing variability between batches
• drug binding response
• biomolecular interaction affinity
• binding kinetics

Comprehensive and Personalized Solutions for Your Laboratory

Are you interested in more efficient solutions to enhance quality control in your laboratory? Our team of experts is ready to assist with questions, provide additional information and arrange consultations - contact us at sartorius@sartorius.hr or via our contact form.

The article was downloaded and translated from the official Sartorius website.