Particulate contamination is a critical quality attribute for any pharmaceutical. In this case study, our expert, Dr Peter Muehlschlegel describes the steps of an investigation into the occurrence of foreign particulate matter (FPM) in a lyophilised drug product. The composition of FPM was identified through the application of microscopy and spectroscopy techniques which helped to confirm the origin of the particles. The insight from this study then helped to de-risk the production process in relation to FPM.
Standards of producing pharmaceutical products are described within the various pharmacopeias, that include routine test methods for particulates such as:
• USP <787> Subvisible 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 / PharmEur 2.9.20.
• USP <1788> Methods for the Determination of Particulate Matter in Injections and Ophthalmic Solutions
Particulate Matter Analysis and Testing
Identification of particulate contaminants is the first step in the resolution of potentially critical contamination problems which might occur unexpectedly at multiple points along the supply chain for many industries. Once the source is known, however, action can be taken to control and prevent future contamination.
Particulate contamination investigations encompass the identification of microscopic particles, the isolation of different particulate phases of in-homogeneous production deposits and determination of the source(s) of the various contaminants. The impact of particles finding their way into valuable samples, such as pharmaceuticals and medical devices, for example, is wide-reaching; it can mean manufacturing processes inefficiencies, compromised product quality and delays in the delivery of product to patients.
Our particular contamination analysis team adopt a strategic approach to identifying contaminants which includes expertise in sampling and sample preparation, visual / physical examination, chemical identification and root cause analysis. Our approach is focused on delivering scientific evidence-based insight, which is essential to facilitate informed decision making and so mitigate the negative impact of particulate contamination on product quality (and safety) or production efficiency. Using microscopy techniques, contaminant particles are digitally imaged to provide forensic traceability. Following the initial microscopical assessment, analysis can be performed using Energy- Dispersive X-Ray Spectroscopy (EDX) on isolated particles using Scanning Electron Microscopy (SEM) or vibrational spectroscopy (Infra-Red or Raman), as appropriate. To characterise the size or shape of contaminating particles, photomicrography; image analysis and particle sizing are used to assess and quantify so that comparisons with “latent” or “suspect” contaminants can be made to increase the weight of evidence relating to potential sources.
Intertek offers both standardised and rapid deployment services for the identification and characterization of particulate contaminants and impurities using the following techniques:
Microscopy: Light (and Polarised Light):
- Confocal Raman Microscopy
- Attenuated Total Reflection Fourier-transform infrared spectroscopy (ATR-FTIR) Microscopy
- Transmission electron microscopy (TEM)
- Scanning Electron Microscopy (SEM, SEM/EDX)
- Molecular Spectroscopy: including Nuclear Magnetic Resonance Spectroscopy (NMR) and Raman Spectroscopy
- Surface analysis: X-ray photoelectron spectroscopy (XPS)
- Thermal analysis e.g. Differential scanning calorimetry (DSC
Examples of particulate contamination we have helped clients resolve typically involve:
- Extraneous particulates or fibers presenting as perhaps black specks within powder products or highly coloured material within a more lightly coloured product
- Residuals from cleaning and maintenance
- Particles observed upon dissolution or particles of different particle size and/or shape to the bulk of the material
- Metal abrasion and corrosion leading to extraneous metal particles from pipes, pumps and vessels
- Particles stemming from process equipment (e.g. PTFE particles from filters, joints or gaskets)
- Glass fragments caused by glass delamination or breakage
- Biological matter of microbiological origin
- Mineral particles where the manufacturing or geographic origin is important.
- Rubber, silicone or other polymeric particles or Teflon particles from filters, joints or gaskets
We have the capability to fully review analytical results and assess the findings of analytical studies focused on contamination incidents associated with production, engineering and the supply chain, providing the guidance you need to define corrective and preventive measures. Our broad experience in many industries such as the chemical, consumer products, pharmaceutical, medical device, polymer and coating sectors gives us the necessary know-how to effectively identify unknown contaminants and assist with locating their source, driving greater knowledge about supply chains, processes and products while working closely with our clients to implement necessary contamination control actions or validate legal action.
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A review and analysis of product recall for pharmaceutical drug product
Journal of Generic Medicines 0(0) 1–10, 2021
Abstract
The pharmaceutical industry’s primary concern is to provide high-quality drug products to the general public, so drug recalls play an important role in maintaining the quality system by removing defective products from the market. Pharmaceutical product recalls are increasing at an alarming rate as a result of increased inspection rates and the introduction of modernization and the digital world into the industry, raising concerns for regulatory agencies and public health to focus on more stringent regulations to control future recalls of defective drug products. This article will provide an overview of recall procedures, their impact on the pharmaceutical industry, and the various steps taken to reduce pharmaceutical recalls.
Particulate contamination is a critical quality attribute for any pharmaceutical. In this case study, our expert, Dr Peter Muehlschlegel describes the steps of an investigation into the occurrence of foreign particulate matter (FPM) in a lyophilised drug product. The composition of FPM was identified through the application of microscopy and spectroscopy techniques which helped to confirm the origin of the particles. The insight from this study then helped to de-risk the production process in relation to FPM.
Standards of producing pharmaceutical products are described within the various pharmacopeias, that include routine test methods for particulates such as:
• USP <787> Subvisible 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 / PharmEur 2.9.20.
• USP <1788> Methods for the Determination of Particulate Matter in Injections and Ophthalmic Solutions
Particulate Matter Analysis and Testing
Identification of particulate contaminants is the first step in the resolution of potentially critical contamination problems which might occur unexpectedly at multiple points along the supply chain for many industries. Once the source is known, however, action can be taken to control and prevent future contamination.
Particulate contamination investigations encompass the identification of microscopic particles, the isolation of different particulate phases of in-homogeneous production deposits and determination of the source(s) of the various contaminants. The impact of particles finding their way into valuable samples, such as pharmaceuticals and medical devices, for example, is wide-reaching; it can mean manufacturing processes inefficiencies, compromised product quality and delays in the delivery of product to patients.
Our particular contamination analysis team adopt a strategic approach to identifying contaminants which includes expertise in sampling and sample preparation, visual / physical examination, chemical identification and root cause analysis. Our approach is focused on delivering scientific evidence-based insight, which is essential to facilitate informed decision making and so mitigate the negative impact of particulate contamination on product quality (and safety) or production efficiency. Using microscopy techniques, contaminant particles are digitally imaged to provide forensic traceability. Following the initial microscopical assessment, analysis can be performed using Energy- Dispersive X-Ray Spectroscopy (EDX) on isolated particles using Scanning Electron Microscopy (SEM) or vibrational spectroscopy (Infra-Red or Raman), as appropriate. To characterise the size or shape of contaminating particles, photomicrography; image analysis and particle sizing are used to assess and quantify so that comparisons with “latent” or “suspect” contaminants can be made to increase the weight of evidence relating to potential sources.
Intertek offers both standardised and rapid deployment services for the identification and characterization of particulate contaminants and impurities using the following techniques:
Microscopy: Light (and Polarised Light):
Examples of particulate contamination we have helped clients resolve typically involve:
We have the capability to fully review analytical results and assess the findings of analytical studies focused on contamination incidents associated with production, engineering and the supply chain, providing the guidance you need to define corrective and preventive measures. Our broad experience in many industries such as the chemical, consumer products, pharmaceutical, medical device, polymer and coating sectors gives us the necessary know-how to effectively identify unknown contaminants and assist with locating their source, driving greater knowledge about supply chains, processes and products while working closely with our clients to implement necessary contamination control actions or validate legal action.
_________________________________________________________
A review and analysis of product recall for pharmaceutical drug product
Journal of Generic Medicines 0(0) 1–10, 2021
Abstract
The pharmaceutical industry’s primary concern is to provide high-quality drug products to the general public, so drug recalls play an important role in maintaining the quality system by removing defective products from the market. Pharmaceutical product recalls are increasing at an alarming rate as a result of increased inspection rates and the introduction of modernization and the digital world into the industry, raising concerns for regulatory agencies and public health to focus on more stringent regulations to control future recalls of defective drug products. This article will provide an overview of recall procedures, their impact on the pharmaceutical industry, and the various steps taken to reduce pharmaceutical recalls.