USP Chapter 41 Updates and Breakdown


By: Fred Algieri Jr., Atlantic Scale Company

USP Chapter 41 has updated their testing requirements to determine the suitability of balances. Here is a quick reference on the important aspects and updates:

Chapter 41 is a REQUIREMENT for QC analysis measurements.

There are two required tests in Chapter 41, Accuracy and Repeatability. Both tests have tolerances of 0.10%.

The Accuracy requirement is applicable between 5% and 100%.

Calibration weights being used in the Accuracy check must have an accuracy of NMT 1/3 of the balance tolerance for that respective test point. This can be the tolerance of the nominal value of the weight or it can be the uncertainty of measurement for the weight when applying the actual weight value from the certificate.

The Repeatability test consists of 10 replicate weighings. The resulting standard deviation is to be used in the following calculation:

(2 × SD) ÷ Desired Minimum Sample Weight ≤ 0.10%

The coverage factor is now 2. Previously it was 3.

The denominator in the calculation is now stated as the “Desired Minimum Sample Weight”, not the weight applied as previously stated.

There is also now a “standard deviation floor” of 0.41d (d being the scale interval or the readability of the unit). This means if the determined standard deviation from the replicate test is less than the 0.41d value then the 0.41d value will need to be used in the assessment calculation.

The 0.41d (standard deviation floor) limits the low end measuring range to the below:

  • 8.2 mg minimum sample weight (lowest possible) 5-place (0.00001 g) analytical balances
  • 82 mg minimum sample weight (lowest possible) 4-place (0.0001 g) semi-analytical balances
  • 820 mg minimum sample weight (lowest possible) 3-place (0.001 g) toploading balances
  • 8.2 g minimum sample weight (lowest possible) 2-place (0.01 g) toploading balances

Again, the above values are the lowest possible minimum weights. The determined standard deviation needs to be at or lower than the 0.41d value to obtain the above results. This usually requires a very good environment. Most test results for on-site repeatability testing is as follows:

  • 10 mg – 20 mg minimum sample weight (commonly determined) 5-place (0.00001 g) analytical balances
  • 100 mg – 200 mg minimum sample weight (commonly determined) 4-place (0.0001 g) semi-analytical balances
  • 1 g – 2 g minimum sample weight (commonly determined) 3-place (0.001 g) toploading balances
  • 10 g – 20 g minimum sample weight (commonly determined) 2-place (0.01 g) toploading balances

Successful repeatability testing mostly depends on the balance quality, the controlled environment it is in, and also the balance operator’s dexterity and experience in performing the repeatability test.

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Pneumatic Blending

Pneumatic blending offers numerous advantages over mechanical mixing. It incorporates a series of controlled compressed gas (or air) pulses into the bottom of a conical hopper to mix dissimilar materials into a homogeneous blend. As the compressed gas expands back to atmospheric pressure, it drives the material at the bottom of the bin upward through the material bed above, causing the blending action. Continue reading

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Productivity in Upstream Processes

By Ken Clapp, Upstream Product Manager, GE Healthcare

Although keeping a better-faster-cheaper mindset, the bioprocessing industry cannot sacrifice quality. Over the past few decades, tremendous improvements have been made, including the industrialization of Chinese hamster ovary (CHO) cells and biologics titers.

Less than 20 years ago, single-use bioreactors were not part of our biomanufacturing vernacular. Such systems have become synonymous with offering improved product quality, faster turnaround times, and cost-effective operations. Single-use bioreactors continue to find new processes in product development and manufacturing worldwide. The convergence of this technology, the higher titers, and better product specificity fostered an environment to reassess the conventional ways of biologics manufacturing. Continue reading

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Designing for Operational Excellence

Kristina Pumphrey, PE – CRB
Associate / Operational Improvement Specialist

It seems counterintuitive to wait until a facility is in operation to apply Lean/ Six Sigma techniques to improve operational efficiency.  There are many decisions made during design that affect operations.  The facility layout affects travel paths and the distance traveled to move material and personnel throughout the facility.  When developing the layout it is important to look at adjacencies and frequencies of operations in order to optimize the layout and ensure there is no excessive movement.  Equipment sizing sets the batch size and expected throughput in the facility.  Small batch sizes help to make the process more responsive to product demands and tend to reduce inventories.   Large batch sizes help to minimize non-value adding activities such as set ups, cleaning, quality testing, etc.  Weighing the pros and cons of these items can help to optimize batch sizes and assist in minimizing product lead times. Room air classifications have a large impact on energy consumption in the facility.  Reducing room sizes and downgrading air classification can reduce airflow and energy consumption in the facility.  Continue reading

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PharmaSystems to Exhibit Two Innovative Systems at INTERPHEX

PharmaSystems Inc. will be exhibiting two very innovative systems at the 2016 Interphex. An RDS (Rapid Decon System) from Franz Ziel GmbH and an RWM 120 vial and ampoule washer from ROTA Verpackungstechnik GmbH will be on display at booth no. 3743. Both systems are designed and manufactured in Germany. Continue reading

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ACG Worldwide presents Innovative Packaging and Track & Trace Solutions at INTERPHEX 2016

With over fifty years of industry expertise, ACG Worldwide is an integrated processing, manufacturing and packaging solutions provider to the global pharmaceutical industry. The company has emerged as one of the world’s largest and most respected business enterprises providing a complete range of pharma solutions like empty hard capsules, packaging films, capsule filling machines, fluid bed processors, tablet presses & tooling, tablet coaters, blister packing & cartoning machines, and vision inspection & serialization solutions. Sensing the alarmingly increasing demands of the consumers, ACG Worldwide has always provided the best of the technologies in the industry. Continue reading

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Maximizing On-Target Yields during The Production of APIs

Maximizing on-target yields during the production of active pharmaceutical ingredients (APIs) is a crucial goal for efficient pharmaceutical manufacturing.  Meeting that goal can have a significant impact on your bottom line.  On-target optimization depends on achieving the tightest particle size distributions (PSDs) possible.  Of course, consistently achieving uniform particle size is important for any number of applications.  Yet when it comes to APIs, it can mean the difference between success and failure. Continue reading

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