Visual Inspection

Our Services
Visual Inspection

Method Introduction

Visual inspection aims to determine the absence or presence of visible particles within parenteral products.

Visual inspection is performed by trained human operators using their naked eyes. The European Pharmacopoeia and the Japanese Pharmacopoeia specify inspection conditions, such as light source, handling procedure, inspection time, and background, whereas the United States Pharmacopoeia (USP) does not give instructions.

Especially during formulation development, where visual inspection is mainly used to detect proteinaceous particles, a ranking of the extent of visible particle formation can be beneficial to differentiate between formulations with only a few visible particles and those with a high number of visible particles. Within the “Deutscher Arzneimittel Codex” (DAC), a scale and procedure is described, which ranks the presence of visible particles in scores from 0 (no particles visible within 5 s) to 10 (particles visible immediately and clearly in significant quantities within 5 s). In many cases, company- or project-specific scores are developed to rate the formation of visible particles during formulation development.

Applications

During formulation development, a visual inspection is performed to judge if particles are formed within formulations, for example, during forced degradation or stability studies. For this application, a small number of vials/containers are usually inspected, and a rating of the extent of visible particle formation can help differentiate between formulations.

The main challenge of visible inspection is the probabilistic nature of the test, even when performed under standardized conditions.

The lower particle size detection limit and the outcome of visual inspection depend on various factors, such as the examination settings (light source and background, auxiliary equipment), the operator (training, eyesight, fatigue, concentration), primary packaging (vial type and size, filling volume), formulation properties (viscosity) and particle properties (concentration, refractive index, shape). Depending on the listed factors, particles larger than 50-100 µm can usually be detected as visible.

Quality and Biosafety Level

We provide all our analytical services with the highest quality standards. Experienced scientists carry out each project, and a scientific reviewer comprehensively checks every report or data presentation.

We offer this technology with the following quality and biosafety levels:

R&D level

We offer this method under R&D. Our GRP system assures the highest-quality research standards.

Up to biosafety level 2

This method can be applied to nucleic acids, viruses, cells, viral vectors, including lentiviruses and more.

Analytical Method Development, Qualification and Validation

For common sample types, we can often apply standardized methods with little setup effort. However, when needed, our experienced analytical experts create or optimize custom methods tailored to your active pharmaceutical ingredient, product type and development phase.

Method Development

Our method development approach tailors sample preparation, method settings and data analysis to the needs of your project and sample.

We include representative samples and, where available, suitable reference standards and stressed/degraded materials, allowing our analytical scientists to design a highly suitable, stability-indicating, robust and repeatable method. Upon request, we will compile a detailed description of the method for your records.

Method Qualification

Method qualification is the initial assessment of an analytical procedure’s performance to show its suitability for its intended purpose.

During method qualification, our analytical scientists perform documented testing demonstrating that the analytical procedure meets criteria in several categories. Criteria may include factors such as repeatability, specificity and robustness. We compile a qualification plan and report, including all relevant data.

Method Validation

Under GMP conditions, method validation confirms that an analytical procedure’s performance suits its intended purpose. Depending on the method’s scope, a broad range of method characteristics, such as specificity, accuracy, precision, limit of detection/limit of quantification (LOD/LOQ), linearity and range, is considered.

During method validation, our analytical scientists perform documented testing demonstrating that the analytical procedure consistently produces a result that meets the predetermined acceptance criteria. We compile a validation plan and report that includes all relevant data.

Depending on the development phase, a fit-for-purpose validation approach can be offered, adjusting the validation required efforts in a phase-appropriate way to meet the method’s needs.

Method Verification

Compendial method verification confirms that a compendial method (e.g., from Ph. Eur. or USP) is suitable and reliable for its intended purpose under the specific conditions of the laboratory.

Unlike full method validation, compendial method verification is often considered a partial validation since the method has already undergone extensive testing and validation during its inclusion in the compendium. The extent of method verification depends on the type of method.

During method verification, our analytical scientists perform documented testing demonstrating that the developed analytical method performs adequately for the specific product or matrix being tested and within the specific laboratory where the method will be employed.

Talk to Our Experts or Request a Quote

Our expert team is ready to answer your questions and guide you to the services best suited to your program’s modality, stage and challenge. If your needs are well-defined, we’ll begin the quotation process.

Description

Related Services

Particle Characterization – Overview Analytical ultracentrifugation (SV-AUC / SE-AUC) Asymmetrical flow field-flow fractionation (AF4) Backgrounded membrane imaging (BMI) Dynamic light scattering (DLS) Electrical sensing zone (ESZ) / microfluidic resistive pulse sensing (MRPS) Fourier-transform infrared (FTIR) microscopy Hollow fiber flow-field-flow fractionation (HF5) Imaging flow cytometry (IFC) Light microscopy (LM) Light obscuration (LO) Mass photometry (MP) Micro-flow imaging (MFI) Nanoparticle tracking analysis (NTA) Nephelometry / turbidity Quantitative laser diffraction (qLD) Resonant mass measurement (RMM) Scanning electron microscopy coupled energy-dispersive x-ray spectroscopy (SEM-EDX) Semi-automated visual inspection (SAVI) Total holographic characterization (THC) Transmission electron microscopy (TEM)

Visual Inspection FAQs

  • The Deutscher Arzneimittel Codex (DAC) outlines a systematic approach to visual inspection to ensure that biopharmaceutical products meet strict quality standards. Key instructions include:

    • Assessment of Appearance: The product should be examined for clarity, uniformity, and the absence of visible particulate matter or discoloration. For lyophilized products, the cake’s consistency, structure, and integrity are evaluated.
    • Standardized Conditions: Inspections must be conducted under controlled lighting and against appropriate backgrounds to accurately reveal deviations or anomalies.
    • Documentation: Any observed irregularities—such as undissolved particles, unexpected coloration, or structural defects—must be thoroughly documented and trigger further investigation.
    • Trained Personnel: Qualified staff should conduct visual inspections following standardized protocols to ensure consistency and reliability in detecting potential quality issues.

  • The European Pharmacopoeia sets clear criteria for the visual inspection of biopharmaceutical products to ensure they meet quality standards before release. These general criteria include:

    • Clarity and Transparency: When appropriate, the solution should be clear and free from turbidity. Any particulate matter or haze is unacceptable for reconstituted products.
    • Absence of Particulates: Products must not contain visible particulate matter, precipitates, or aggregates that could indicate instability or contamination.
    • Uniformity of Appearance: The color and overall appearance should be consistent with the product specifications. Irregularities may signal degradation or manufacturing issues.
    • Integrity of the Container: The container and closure system should be intact, ensuring the product has not been compromised during storage or handling.
    • Lyophilized Product Specifics: For lyophilized drugs, the cake should exhibit a uniform structure without signs of collapse, shrinkage, or melting. The reconstituted product must also meet the clarity and particulate standards.

  • The European and Japanese Pharmacopoeias both establish robust visual inspection standards for biopharmaceuticals yet diverge in methodology and emphasis. Key differences include:

    • Assessment Focus: The European Pharmacopoeia emphasizes clarity, uniformity, and the absence of particulates, with specific guidance on the appearance of solutions and lyophilized cakes. In contrast, the Japanese Pharmacopoeia may place greater emphasis on detailed color matching and the precise description of any deviations from the expected appearance.
    • Inspection Environment and Protocols: While both require controlled lighting and backgrounds, the Japanese Pharmacopoeia tends to be more prescriptive regarding the environmental conditions and inspection procedures. This includes stringent guidelines on lighting, magnification, and the methodical documentation of even minor visual discrepancies.
    • Container and Closure Evaluation: Both standards assess container integrity; however, the Japanese guidelines often extend to a more detailed evaluation of the container system, ensuring that micro-particulates or any signs of compromise are meticulously recorded.

    Overall, although both pharmacopeias aim to ensure product quality and safety, the Japanese Pharmacopoeia typically adopts a more detailed and prescriptive visual inspection approach throughout drug development than the broader criteria of the European Pharmacopoeia.