Visible Particle Contamination in Parenterals

In the last number of years, visible foreign particulate matter, FPM, became the number one reason for recalls in the pharmaceutical industry. Therefore the attention and demands of the authorities has increased, with a special focus on root cause investigation of the particle contamination. Compendial chapters have been changed and specified accordingly. FDA inspectors like to see the staged investigation cycle approach.

rap.ID provides knowledge on particle control

rap.ID has established training programs in the US and in Europe to train the life cycle as well as the investigation stages. In our laboratories we follow this approach and we also provide services on USP <1790> and USP <790>. rap.ID develops methods and aids in implementing a defect library of visible investigation rejects supported by means of micro imaging.

services on USP and USP Visible Particle Contamination in Parenterals
 
micro imaging as seen with in situ microscopy  - visible particle reject floating in a vial

Fast and efficient investigations

FDA and other authorities demand for a thorough investigation on particulate contamination. Within hours rap.ID´s particulate matter experts provide you with a reliable comprehensible CMC report on the Foreign Particulate Matter visible reject. Subvisible particle identification down to 2 µm by means of micro Raman and micro LIBS can reveal systemic contamination issues in your pharmaceutical filling environment and processes and differentiate from single incidents.

 

Thorough documentation and sterile manufacturing experience

From the documentation of the particulate, prior to opening the container, to the comparison of spectra from your reference samples with the particulate´s spectroscopic signature, rap.ID documents and delivers GMP compliant information on all necessary steps and information for your particle contamination root cause investigation.

in situ Documentation Micro-photographic images

In-Situ Documentation

Micro-photographic images of your particle without opening the container, therby preserving the samples integrity:

  • Video microscope and the
  • Inverted microscope high resolution imaging and recording
PLM - polarized light microcopy high quality images

Polarized Light Microscopy (PLM)

PLM delivers high quality images and useful information for the  fibers origin and group of defects

Spectroscopy: SPE Raman and LIBS

  • Raman and LIBS delivers molecular structure and chemical elements of the contamination particles material.
  • Fingerprint spectra is compared with generic material in the Raman library, which has over  5,000 entries. Due to  the comparison on the sponsor specific databases, you are able to locate the contamination source in your production processes.
raman and LIBS spectra Raman and LIBS delivers molecular structure and chemical elements of the contamination particles material

Spectroscopy: ATR and FTIR

Depending on the results from Raman and LIBS the particle will be further characterized by ATR and FTIR. rap.ID has IR libraries with 10,000 entries to match unknown contaminants and previously unidentified mixtures.

 

ATR and FTIR spectroscopy Depending on the results from Raman and LIBS the particle will be further characterized by ATR and FTIR
SEM / EDS spectroscopy SEM / EDS Spectroscopy for metallic and inorganic particles, and heterogeneous particle materials

Spectroscopy: SEM / EDS

Depending on the results from Raman and LIBS the particulate can be additionally characterized by our Scanning Electron Microscope with the Electron Diffraction Spectroscopy unit. This works great for metallic and inorganic particles, and heterogeneous particle materials such as a rubber stopper.

Examples of Thorough Root-Cause investigations of visible Particles in Injectables and Parenterals

 

Compendial Methods

 

Methods and testing procedures established under GMP