One pivotal aspect of this process involves conducting tests to ensure the absence of visible particulate matter in parenteral products. This particulate matter, consisting of unwanted foreign particles suspended in a liquid, can pose health risks to the patient if not detected and managed appropriately. In this article, we delve into the reasons behind the importance of testing for particulate matter in parenterals.
Why is it important to test for particulate matter?
The presence of particulate matter in parenteral products, such as injectable drugs, can have dire consequences for patient health. Particles, both from visible and sub-visible, can introduce contaminants that lead to adverse reactions or sepsis when introduced into the bloodstream. Another possible hazardous effect could be the occlusion of small veins or arteries, stopping the patient’s blood from flowing into affected organs. For this reason, all main pharmacopoeias require a test for visible particulate matter for parenteral products.
Understanding the sources of particulate contamination is crucial for preventing its occurrence. Particles can originate from various sources, including the manufacturing environment, packaging materials and the drug formulation itself. Airborne particles, equipment surfaces and even personnel can introduce contaminants. Contamination can also arise during the manufacturing process, such as when vials or ampoules are filled and sealed.
At eyetec, we’ve helped many clients in developing their Particle Source Risk Assessment, describing all possible particle sources for a given process and their associated risks. Having this risk assessment done is currently a regulatory expectation both in the US and Europe – under the recent Annex 1 update. Read more about the updated annex 1.
How is particulate matter tested in parenterals?
The testing for particulate matter is described in all major pharmacopoeia (USP, JP and Ph.Eur.) and quite harmonized. The reference method for Visual Inspection uses the black and white background apparel, with specifications for light intensity and inspection time. Automated inspection systems utilize advanced camera technology and software algorithms to enhance accuracy and consistency in identifying even the tiniest particles.
Manual Visual Inspection in the pharmaceutical industry is a manufacturing step in the production of parenteral products, such as injectable drugs and vaccines. It involves human operators carefully examining each unit (e.g., vials, ampoules, syringes) for visible defects, contaminants, particles, fibers or container damages that may have occurred during the manufacturing process. The inspection is conducted in a controlled environment to minimize external sources of error. The Visual Inspection booth should have uniform, glare-free and shadow-free lighting, including diffused white and polarized light, against a black-and-white background to enhance defect visibility. The product is also shaken or inverted to ensure that any particles present are visible.
Automated Visual Inspection (AVI) is a technologically advanced method used in the pharmaceutical industry for the inspection of vials, ampoules, syringes and other parenteral products. It involves the use of specialized machines equipped with high-resolution cameras, advanced image processing software and artificial intelligence algorithms to conduct precise and rapid inspections. AVI systems can detect a wide range of defects, including particles, cosmetic flaws, container defects and container closure integrity issues.
Regulations governing particle testing in the pharmaceutical industry
The pharmaceutical industry is subject to strict regulations to ensure product quality and patient safety. The United States Pharmacopeia (USP), European Pharmacopoeia (EP) and Japanese Pharmacopoeia (JP) set standards for particle testing in pharmaceutical products, including limits for the number and size of particles allowed in injectable products. Regulatory bodies such as the FDA and EMA require pharmaceutical companies to conduct particle testing as part of their manufacturing process (100% of containers) and again at Quality Control, as part of release testing on a smaller number of samples.
After 100% Visual Inspection in production, acceptance sampling is also mandatory for the EU and the US. It implies that a large sample of the accepted containers is again inspected and the outcome of this second inspection is evaluated against predetermined acceptance criteria, based on ISO or ANSI AQL standards.
eyetec’s Visual Inspection services
eyetec offers specialized services for visual inspection of parenterals. We support clients worldwide optimizing their Visual Inspection process, be it manual, semi-automated or automated. The daily contacts we have with pharmaceutical manufacturers, regulators and equipment builders allow us to provide sound advice to our clients performing Visual Inspection.
Additionally, particle identification can help in determining the particle origin and source. Identification methods provide valuable data for assessing product quality and potential risks associated with particle contamination. Infrared (Raman / FTIR) spectroscopy and (ultra)microscopy are most often utilized to determine particle composition and origin.
eyetec also provides Visual inspection test sets (such as our Particle Test Samples - PTS). Visual Inspection test sets are used to assess and validate the performance of Visual Inspection systems and operators in the pharmaceutical and other industries such as the cosmetics industry. These sets typically consist of standardized samples that simulate various types of defects and foreign matter that might be encountered in real products. By using these test sets, companies can ensure the accuracy, consistency and reliability of their visual inspection processes. Find out more about Visual Inspection test sets here.
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