Foreign particle contamination, particularly in injectable products, poses a significant risk to patient safety and regulatory compliance. Effective identification of these contaminants not only safeguards product integrity but also provides manufacturers with critical insights to mitigate risks and enhance quality control.
At Particle Analytical, we specialize in foreign particle identification using Raman spectroscopy integrated within a confocal microscope. This cutting-edge technology combines high-resolution imaging with molecular-level analysis, delivering precise and non-destructive identification of contaminants in drug products.
Methodology and Techniques
Analytical Equipment
| Equipment | Software |
|---|---|
| Raman Microscope, inVia confocal with with 532 and 785 nm lasers and 5X, 20X, 50X and 100X objectives | Wire 5.6 software with a reference libraries for material identification |
Sample Preparation
We can accommodate a wide range of sample types, including solutions, solid materials and medical devices. Our approach is tailored to each sample’s specific requirements:
- Filtration: For liquid samples, filtration through sterile 0.2 µm membranes is used to capture potential contaminants
- Direct Analysis: Solid samples are analyzed directly using the Raman confocal microscope without additional preparation steps.
- Controlled Handling: All preparation occurs within Laminar Air Flow (LAF) cabinets to maintain sample integrity.
- Imaging: For filtered samples, the filter surface is fully imaged using montaging to locate foreign particles of interest.
Raman Spectroscopy and Optical Microscopy
Once a particle is isolated, the Raman confocal microscope provides:
- Optical Imaging: High-resolution imaging to capture the particle’s morphology, color, and other physical characteristics.
- Chemical Analysis: Raman spectroscopy uses a 532 nm or 785 nm laser to analyze molecular vibrations, producing a unique spectral fingerprint for accurate material identification. Library searches with advanced algorithms verify the particle’s composition.
Case study: High-Density Polyethylene Contamination
In this case study, a placebo drug product solution containing a visually observed unknown particle was analyzed to demonstrate the process of particle identification using Raman microscopy under GMP.
Optical Imaging
The sample was first filtered, and the filter’s surface was imaged both before and after filtration. This process revealed a reddish, irregularly shaped particle (Figure1).
Raman Spectroscopy
Subsequent analysis using Raman spectroscopy, spectra were collected from the particle, using 785 nm, point focused laser. A library search was performed to identify the potential material of the foreign particle. The resulting Raman spectra, along with the best match from the library search, are presented in Figure 2.
It can be observed that the highest quality score obtained for this search is 0.823, indicating that the analyzed spectrum slightly differs from the spectra in the library. This discrepancy is attributed to the different excitation laser used to collect the spectrum in the library. The higher Raman peak intensities observed in the Raman shift area >2500 cm⁻¹, relative to the intensities in the <1800 cm⁻¹ region, are characteristic of spectra obtained using a shorter wavelength (i.e., <785 nm) laser.
The library search indicates that the particle’s Raman spectra most closely match that of high-density polyethylene materials. The top 5 best match results are listed in Table 2.
| Renishaw library detail | Material Index | Name | Quality score |
|---|---|---|---|
| 60001-1-602-2_Raman-Complete-1 | 7422 | D-995 FILM, Polyolefins = High density polyethylene | 0.823 |
| 60001-1-602-2_Raman-Complete-1 | 7378 | Polyethylene high density | 0.763 |
| 60001-1-602-2_Raman-Complete-1 | 7373 | Linear low-density polyethylene | 0.743 |
| 60001-1-602-2_Raman-Complete-1 | 7320 | Polyethylene | 0.679 |
| 60001-1-602-2_Raman-Complete-1 | 291 | 1-octadecanol | 0.651 |
Bridging Science and Business Value
The ability to accurately identify and analyze foreign particles in drug products is essential for maintaining product safety and quality. This study demonstrates that the combination of optical microscopy and Raman spectroscopy provides a powerful and reliable tool for identifying foreign particles at the microscopic level.
Our integrated approach to foreign particle identification offers:
- High Sensitivity: Raman spectroscopy can detect particles, providing precise identification based on molecular composition.
- Non-Destructive Analysis: Unlike other analytical methods (e.g. SEM/EDX, HPLC, MS, solution NMR), Raman spectroscopy does not alter the sample, enabling further analysis if needed.
- Versatility: This technique is adaptable for use with a wide range of pharmaceutical products, including solutions, powders, tablets, and medical devices.
- Regulatory Compliance: Alignment with global standards ensures product safety and market readiness.
Combining these technologies ensures comprehensive particle identification and analysis. This is particularly valuable for pharmaceutical manufacturers maintaining high standards of product safety and quality. Non-destructive methods for analyzing particles in complex drug products offer significant advantages in drug development and quality control – contributing to better patient outcomes and regulatory compliance.
This approach can also be applied to similar tasks in complex samples such as drug product solutions.
Business Benefits
By integrating our services into your quality control processes, you can realize the following benefits:
- Risk Mitigation: Early detection of contaminants prevents costly recalls and potential harm to patients.
- Quality Assurance: Reliable quality control ensures product integrity and compliance.
- Cost Efficiency: Minimize downtime and streamline troubleshooting with precise analysis.
- Rapid Results: Quickly address manufacturing issues to avoid operational delays and costs.
Conclusion
Identifying and analyzing foreign particles in drug products is paramount for maintaining product quality and ensuring patient safety. Our approach of optical imaging and Raman spectroscopy provides a reliable, efficient, and non-destructive method for detecting and identifying contaminants in pharmaceutical products.
This case study has demonstrated how the combination of these technologies can quickly and accurately identify a polypropylene particle in a placebo drug product solution, showcasing their effectiveness in particle analysis. For any questions, please do not hesitate to contact us.
