Drug Development Solutions

Foreign Particulate MatterThe presence of Foreign Particulate Matter (FPM) in pharmaceutical and biopharmaceutical products affects their quality and safety, leading to loss of batches, plant shutdowns, product recalls or regulatory action. FPM contamination still remains as one of the leading causes for product recalls1.Manufacturers of pharmaceutical and biopharmaceutical products are required to demonstrate a thorough understanding of their processes which includes carrying out appropriate investigations to determine the identity and origin of any contamination that may occur.

Particle Counting

The size and count of particulate matter are critical factors when considering the potential risk to patients. Therefore, Particulate Matter Testing forms a part of the regulatory requirement to ensure that unintended and non-therapeutic particulates in products do not exceed established limits.

Particulate matter can be classed as being visible (>100µm) or sub-visible (1-100µm). We support the following routine tests for both visible and sub-visible particles:

• USP <787> Sub-visible Particulate Matter in Therapeutic Protein Injections

• USP <788> Particulate Matter in Injections • USP <789> Particulate Matter in Ophthalmic Solutions • USP <790> Visible particulates in Injection • USP <1788> Methods for the Determination of Particulate

Matter in Injections and Ophthalmic Solutions

All sample preparation is performed in Class 5 laminar flow cabinets and our staff are trained in aseptic and sterile handling techniques to minimise contamination.

Particle Characterisation

Identification of particulate matter contamination and determination of the source of origin is essential for root cause analysis investigations. With many years experience in both pharmaceutical and forensic analysis, our staff have in-depth knowledge and expertise in a wide range of foreign particulate types and their likely origins.

We are, therefore, able to design and carry out such investigations in the most timely and cost effective manner thus minimising disruptions and delays to the manufacturing process.

1 https://www.fda.gov/Drugs/DrugSafety/DrugRecalls/default.htm

Science for a safer world

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For further information on how LGC can assist with Foreign Particulate Matter,

please contact us:

lgcgroup.com/enquiries

+44(0)1638 720500

Our technical capabilities and expertise include:

• Isolation of FPM (as small as 25 µm) from a variety of matrices (API, raw materials, tablets, solutions, suspensions, creams) using appropriate techniques e.g. filtration, micro-extraction, pipetting and centrifugation.

• Microscopy for information on particle appearance, size, morphology, crystallinity, homogeneity and physical behaviour.

• Fourier Transform Infra-Red (FT-IR) Spectroscopy and Microscopy for determination of chemical composition. FT-IR mapping can identify components of a heterogeneous mixture without having to isolate each component. Our extensive spectral libraries (with over 260,000 spectra) allows for identification of the component.

• Scanning Electron Microscopy/Energy Dispersive X-ray (SEM/EDX) analysis for elemental composition e.g. determination of the alloy type or grade of stainless steel for metallic contamination.

• Powder X-ray Diffraction (PXRD) for identification of crystalline particulates (e.g. minerals, organic powders). PXRD can also be used to determine crystallinity and differentiate between polymorphs.

• Mass spectrometry (GC-MS, LC-MS) for structural elucidation.

• Inorganic trace analysis using ICP-OES and ICP-MS.

We routinely analyse reference materials (i.e. suspected sources of contamination) and compare them with the FPM in order to determine its origin. We can also build a searchable reference library consisting of typical materials your product might come into contact with for quick comparison and identification.

Depending on the nature of the particulate matter and the process or product matrix we will tailor our work package to provide the most efficient and cost-effective solution for you.

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Isolation

Microscopic Examination

Spectroscopy / Microspectroscopy

(FT-IR) Elemental Analysis

(SEM / EDX) Supplementary

Techniques(PXRD, MS, ICP)

Comparison to Reference and

Spectral Libraries

Technical and Quality Reviewed

Report

Figure 1. Typical approach taken for Foreign Particulate Matter identification.