About X5 Scientific
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At X5 Scientific, we are dedicated to reshaping the landscape of laboratory quality assurance and management. Our journey began in 2022 with a clear mission: to empower scientific organizations and laboratories in their pursuit of excellence.
Comprehensive Quality Assurance Solutions
We understand that quality assurance and efficient lab management is pivotal in the pharmaceutical industry. That's why, over the years, we have developed cutting-edge solutions and strategies to help labs achieve and maintain the highest standards of quality.
"From ISO compliance consulting to state-of-the-art sample management software, our services are designed to streamline operations, enhance efficiency, and elevate the overall performance of your lab."
Quality Laboratory Services
We collaborate with you to develop tailored solutions that ensure your lab's compliance with ISO and other quality standards.
Our Services
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From small research facilities to large-scale testing centers, we have consistently delivered results that have set new benchmarks in lab performance.
Useful Data. Made Simple. Wireless Monitoring Solutions
Ensure patient safety and operational excellence with our scalable wireless solutions, designed to maintain optimal environmental conditions and prevent costly damage. Our proprietary temperature monitoring safeguards protect sensitive products, while advanced water and leak detection systems prevent downtime by safeguarding critical equipment.
With seamless ESG compliance and enhanced HSE reporting, you'll not only safeguard patients but also achieve the highest standards of safety and regulatory performance.
With seamless ESG compliance and enhanced HSE reporting, you'll not only safeguard patients but also achieve the highest standards of safety and regulatory performance.
Cutting-Edge Certified Challenge Sets
Choosing the right partner is essential in early stage pharmaceutical development. Let X5 be your guide to discovering the nuances of particle types, potential risks, and precision-driven inspection processes, on your way to market.
Whether you're new to the field or seeking to deepen your understanding, our comprehensive FAQ serves as a valuable guide; helping you grasp the essentials and challenges associated with particulate matter in the pharmaceutical industry.
Whether you're new to the field or seeking to deepen your understanding, our comprehensive FAQ serves as a valuable guide; helping you grasp the essentials and challenges associated with particulate matter in the pharmaceutical industry.
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The U.S. Pharmacopeia General Chapter 788 Particulate Matter for Injections defines particulate matter as “extraneous mobile undissolved particles, other than air bubbles, unintentionally present in solutions.
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The U.S. Pharmacopeia General Chapter 787 Subvisible Particulate Matter in Therapeutic Protein Injections classifies particulate matter into three categories.
Extrinsic – unexpected foreign material such as hairs, insects, or dirt/debris.
Intrinsic – particles stemming from materials used in the manufacturing process or environment.
Inherent – particles originating or precipitating from the formulation, such as protein agglomerates, salts, or precipitates. -
The U.S. Pharmacopeia General Chapter 1 Injections expects all sterile injectable drug products intended for human use to be free and clear of particulate matter. The ultimate risk of particles in injectable drugs is harm coming to the patient. However, particles in injectable drug products also imply a need for manufacturing process controls. Therefore, investigations should be performed to determine the source of particulates found in drug products.
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No formal chapter or guidance exists that prescribes how to choose the types of particulate matter you use for your challenge sets. However, the U.S. FDA and regulatory experts advise companies to select representative material types used in their manufacturing process. Companies building new facilities or manufacturing lines should select representative material types they expect to find as particles in their drug products. In addition, other materials should be chosen for extraneous particles that could also find their way into manufactured drug products, although not intended to.
Some common material types are glass particles, metal shavings, naturally derived fibers such as cotton or cellulose, synthetic fibers from clothing or gowning, human hair, Teflon, and polymeric materials such as polyethylene or polypropylene. -
The U.S. Pharmacopeia General Information Chapter 1790 advises that defect unit rates in challenge kits be 10% of the total kit size. Within the industry, it is generally accepted that defect units should comprise at most 20% of the total challenge kit size. No official chapter or guidance also prescribes a specific total challenge kit size.
To adequately challenge and qualify inspectors, companies may select a kit size that considers the following:
· The number of representative defect types to be included in the kit.
· The size ranges of defects for the defect units.
· The budget or any budget limitations for contracting the creation of their challenge kits.
· The number of challenge kits required for your manufacturing process and finished products.
In 2023, the Parenteral Drug Association conducted a visual inspection survey and found the composition of test kits used to qualify inspectors to be the following.
We commonly find challenge kits created in the total unit range of 150 – 350 units and at a 10% – 16% defect rate. -
The frequency of requalifying inspectors is a critical consideration for this industry, especially in the pharmaceutical sector, where stringent quality standards are paramount.
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Challenge kits should be updated annually to include defect units from new materials added to the manufacturing process. Companies should also add defect units created from the particulate matter they characterize as part of the 100% visual inspection or AQL inspection processes.
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The most common particles found during the visual inspection are lint and fibers, product-related particles, glass, rubber or elastomeric particles, and metal.
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Most companies use prepared standards for routine challenges; however, many companies also use production defects for routine challenge purposes.
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In 2023, most respondents to the PDA Visual Inspection Survey used the following AQL values:
· Critical: 0 – 0.1%
· Major and Particles: 0.4 – 0.65%
· Minor: 2.5 – 4.0% -
The following references are a good primer for information about the visual inspection process and challenge kits for visual inspectors.
USP 790 Visible Particulates in Injections
USP 1790 Visual Inspection of Injections
European Pharmacopeia (EP) Particulate Contamination: Sub-visible Particles; Method 2.9.20, 6.0, 1, 302, 2011.
Generalized Methodology for Evaluation of Parenteral Inspection Procedures. Julius Z. Knapp and Harold K. Kushner, PDA J Pharm Sci and Tech 1980, 34 14-61.
Particulate matter in parenteral products: a review. Borchert SJ, Abe A, Aldrich DS, Fox LE, Freeman J, White RD. PDA J Pharma Sci and Tech 1986, 40 212.
Automated Particulate Inspection Systems: Strategies and Implications. Julius Z. Knapp and Lee R. Abramson, PDA J Pharm Sci and Tech 1990, 44 74-107.
Considerations for Design and Use of Container Challenge Sets for Qualification and Validation of Visible Particulate Inspection. James A. Melchore and Dan Berdovich, PDA J Pharm Sci and Tech 2012, 66 273-284. -
Most companies use ANSI/ASQ Z1.4 as their sampling plan; however, many companies also use ISO 2859.
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It is generally accepted that you should create your challenge kits once your inspection method is standardized.
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Before you select the number and size of particles for your defect units, you must be aware of the three detection zones based on Knapp’s definition.
Reject Zone: >70% probability of detection – units in this category are generally considered defective.
Accept Zone: 30-70% probability of detection – units below the threshold of reliable and accepted as good.
Gray Zone: 30% probability of detection – units generally accepted as good.
Generally, it is advisable to include particle sizes starting at the expected threshold between the Gray and Reject Zones. An example of this is 100µm, 150µm to 250µm, and 300µm, and include 500µm and greater. Remember that fiber defects have a unique probability of detection range, so different size ranges are required to compensate for this.
You should create multiple units for your challenge kit at each particle size in the Gray and Reject Zone threshold ranges. An example is 80µm to 250µm.