3 Best Practices for Analytical Balance to Ensure Accurate Weighing in Drug R&D

Weighing is one of the most fundamental and frequent operations in drug development, with its accuracy being critical across all stages. Deviations in weighing can lead to invalid experimental data, resulting in wasted resources, project delays, potential regulatory penalties, and even risks to medication safety. Therefore, the accuracy and standardization of analytical balances’ weighing operations must be highly prioritized and ensured through strict management and standardized procedures.

Based on issues identified in FDA inspections and relevant regulatory requirements, this article outlines the following key points for weighing operations during the preclinical research stage:

• Selecting Appropriate Analytical Balances: Suitable balances should be selected based on actual weighing needs, comprehensively considering maximum capacity, division value (precision), and overall equipment performance.

• Standardizing the Balance Laboratory Environment: Balances should be placed in a dedicated weighing room to avoid cross-contamination. The installation location must be reasonable, taking into account environmental factors such as air currents, temperature/humidity fluctuations, Electromagnetic interference, and vibration.

• Improving Personnel Operational Standardization: Operators should possess good laboratory literacy and operational skills, and select appropriate weighing methods for different sample properties. For special samples, corresponding procedures should be established.

Common Balance Weighing Issues Identified in FDA Inspections 

In common perception, weighing is a simple operation—take the sample, place it on the balance, and record the reading. But is the weighing process really that simple? By reviewing FDA Warning Letters and Form 483 inspection reports issued to various companies since 2021, we found that issues related to weighing can be primarily categorized into three areas: equipment, environment, and personnel operation. The following are some typical cases for reference.

Table 1. Common analytical balance weighing issues identified in FDA inspections

3 Best Practices for Analytical Balance Weighing

Selecting an Appropriate Analytical Balance

The balance is the core equipment in weighing operations. Its selection should focus on two key parameters: maximum capacity and division value. Generally, a larger maximum capacity corresponds to a larger division value. The relationship between the two must be balanced in practice.

Maximum Capacity: Must be greater than or equal to the mass of the object being weighed to prevent overload, which can damage the equipment or distort data.

Division value: Should meet the precision required by the experiment. "Accurately weighed" means the weight taken should be accurate to one-thousandth of the taken weight, while "weighed" means one-hundredth^[4]. For instance, to accurately weigh a 10 mg sample, a balance with a division value of 0.01 mg should be selected.

Ensure equipment performance is reliable by completing calibration and adjustment before use.

Calibration: To ensure weighing results have metrological traceability, electronic balances should be calibrated according to relevant industry standards ^{[5, 6]}. The calibration report should include measurement uncertainty information. The calibration interval should be determined based on actual usage frequency and risk assessment. Recalibration is required after initial installation, relocation, or repairs that could affect weighing performance ^{[7, 8]}.

Adjustment: Adjustment of an electronic balance refers to the process of adjusting its display using external or internal weights. External adjustment uses external standard weights, while internal adjustment uses the balance's built-in weights. The internal adjustment function can reduce the frequency of daily external checks but still requires periodic external adjustment to verify the accuracy of the built-in weights ^[7-9]. It is recommended to perform an adjustment at the beginning of each day before first use. Additionally, adjustment should be performed promptly when numerical drift occurs, weighing results are abnormal, or after cleaning and leveling.

At WuXi AppTec DMPK, analytical balances undergo calibration after initial installation, relocation, or major repairs, followed by periodic annual calibration. The balances are equipped with built-in weights, enabling daily automatic internal adjustment. Furthermore, manual adjustment is performed every day. The adjustment range shall cover the actual weighing requirements.

Standardizing the Balance Laboratory Environment

The placement environment of the balance decisively influences its weighing accuracy. The following are key aspects requiring attention in environmental control:

Table 2. Environmental requirements and measures affecting weighing accuracy

WuXi AppTec DMPK's weighing rooms are equipped with a professional ViewLink temperature and humidity monitoring system, enabling real-time monitoring and helping to dynamically regulate the room environment.

Improving Personnel Operational Standardization

Strengthening Analytical Balance Training Management

Even with optimal equipment and environmental conditions, personnel operation remains a key variable affecting weighing accuracy. Systematic training and assessment systems should be established to ensure laboratory personnel possess the necessary theoretical knowledge and standardized operational skills, continuously improving laboratory literacy.

Standardizing Balance Usage Procedures

• Appropriate Equipment Selection: Select a suitable balance based on the minimum sample weight, the balance's maximum capacity, and precision requirements.

• Adequate Warm-Up: The electromagnetic force compensation sensor of an electronic balance is significantly affected by temperature. Sufficient warm-up time is needed to reach thermal equilibrium. If power is disconnected, a warm-up time of no less than 30 minutes is recommended.

• Pre-Use Check: Confirm the balance is within its calibration validity period, the level indicator bubble is centered, daily adjustment has been performed, and the weighing range falls within the adjusted range.

• Post-use Handling: Remove samples promptly, tare the balance to zero, and avoid long-term load on the sensor, causing fatigue drift.

Appropriate Selection of Weighing Methods

Suitable weighing methods should be selected based on sample properties and experimental purpose ^[7-9].

Table 3. Three main weighing methods

Handling Special Samples in Analytical Balance Weighing

Warm or Cool Samples ^[9]

Temperature differences between the sample and the weighing room cause air currents, leading to reading errors. Allow samples to equilibrate to room temperature before weighing; generally, refrigerated samples require about 30 minutes.

Electrically charged Samples ^[7-9]

Fine powders in low-humidity environments are prone to generating static electricity, causing weighing inaccuracies and transfer losses. Recommendations include using anti-static devices, controlling humidity to not less than 40%, or using anti-static containers.

Hygroscopic Samples ^[7-9]

These readily absorb moisture from the air, causing continuous weight increase. Control environmental humidity, use small-mouth or stoppered containers, minimize exposure time, and aim to complete the reading within 1 minute.

Volatile Samples ^[7-9]

For substances like low-boiling-point liquids that evaporate easily, use sealed or small-mouth containers, operate quickly, and complete the reading within 1 minute to prevent mass loss due to volatilization.

Corrosive Samples ^{[7, 9]}

For substances like acids, use corrosion-resistant containers, and operate carefully to prevent spills that could corrode the balance or contaminate the environment.

Highly Potent Samples

For highly potent samples (e.g., OEB 5), operate under engineering controls such as negative pressure isolators to ensure personnel safety and prevent cross-contamination.

Personnel operation is the most flexible and uncertain factor in the weighing process. Standardized operations, systematic training, and accurate responses to special situations are the fundamental guarantees for ensuring that weighing data is accurate, complete, and traceable.

Final Words

The accuracy of weighing data is the cornerstone for ensuring experimental reliability and data validity. We consistently place weighing quality in a key position, having built a systematic weighing assurance system:

• Precision Equipment and Real-time Monitoring: Equipped with high-performance weighing devices and temperature/humidity monitoring systems to ensure a consistently stable weighing environment.

• Professional Team and Standardized Operations: Possess an experienced weighing team that strictly executes standardized operating procedures to minimize human error.

• Compliance Management and Regulatory Submission Support: Strictly adhere to various regulations and guidelines, establishing a comprehensive weighing quality management system to meet the submission requirements of different regulatory agencies.

• Safe Weighing of Special Samples: Equipped with negative pressure isolators and weighing hoods to ensure the safe and accurate weighing of highly potent samples and unstable substances.

• Data Integrity and Traceability: Utilize the Mosaic system to achieve automatic collection and transmission of weighing data, ensuring data is accurate, real-time, and traceable.

• Dedicated Space and Consumables Management: Establish dedicated weighing rooms and comprehensively use single-use consumables to effectively avoid cross-contamination risks.

WuXi AppTec DMPK, by constructing a comprehensive, multi-dimensional weighing quality assurance system, provides accurate and reliable weighing data support for all stages of drug development, continuously empowering innovative drug discovery.

Authors: Huili Wang, Dandan Zhao, Lingling Zhang

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Committed to accelerating drug discovery and development, we offer a full range of discovery screening, preclinical development, clinical drug metabolism, and pharmacokinetic (DMPK) platforms and services. With research facilities in the United States (New Jersey) and China (Shanghai, Suzhou, Nanjing, and Nantong), 1,000+ scientists, and over fifteen years of experience in Investigational New Drug (IND) application, our DMPK team at WuXi AppTec are serving 1,600+ global clients, and have successfully supported 1,700+ IND applications.