Foreign Particles in Parenterals:

Although considerable effort is devoted to ensuring cleanliness – i.e., the absence of visible particles – in the production and control of parenterals, as much as 0.1% to 3% of all batches produced are wasted and discarded as rejects due to contamination which, in turn, results in lower yields. Manufacturers failing to meet the functional specifications sometimes have to block or possibly even destroy entire batches. Returns, products rejected by the end customer, cause even greater damage. The Single Particle Explorer rapidly provides you with the relevant information required forthe detection, enumeration, and identification of foreign particles, in turn, facilitating timely and objective decisions regarding contamination sources.

SPE applications for a parenteral examiner:

Forensic examiners must work with several instruments to find distingtive features which enable them to compare known materials with samples data. In the industrial forensics lab a similar approach is taken to find the origin of a trace sample. The time to perform this task is typically a critical issue.

The SPE-ls raman.ID + metal.ID combines in one instrument: optical, vibrational and elemental spectroscopy. Delivering information on color, size, shape, chemical structure and elemental composition. In one measurement allowing extremely fast and efficient root cause search. Resulting in fully automated root cause reporting of your parenteral reject following the CFR Part 11.

Monitoring of the chemical composition of foreign particulate matter, following a sampling plan the SPE provides an extremely powerful tool which aids in the quality of design of your products. The ease of use of the system ensures high yield and quality with minimal efforts.

Benefits for this application:

extrinsic sources of contamination:

intrinsic sources of contamination:

Today's modern biopharmaceuticals pose a significant challenge to manufacturers and developers due to their complex nature. The SPE raman.ID 0.5 biopharma makes small variations in formulations, and thereby reliably identifies protein particles. Highly sensitive analytical results are particularly important in silicone compatibility studies in biopharmaceutical formulations.

Identify find and Eliminate Sources of Foreign Particulate Matter

Over 90% of all foreign particulate matter can be reliably identified using combined (LIBS )metal.ID)/raman.ID technologies. metal.ID can also distinguish different types of glass and rubber stoppers. Furthermore, hundreds of individual inorganic (metal.ID) and organic (raman.ID) particles can be easily searched, identified and tracked back to their originating sources using the automated database.

Packaging is one of the primary sources of particulate contamination in parenterals. Controlling the cleanliness levels of syringes, stoppers and their containers is a very useful method to detect and minimize rejects. Single Particle Explorer CSS (SPE CSS) performs standard container cleanliness control and closure systems analysis prior to filling. The fully automated system is also easily validated to work according to the membrane counting method described in the USP <788>.

Integrated Sampling, Fast Counting:

TheSingle Particle Explorer was designed specifically for the routine counting and identification of foreign particles in parenterals. Its integrated sampling solution, which eliminates the risk of cross-contamination, makes vacuum filtration of the parenterals under examination a matter of minutes and saves the user invaluable analysis time. All particles on the membrane larger than 10µm are counted and documented within just 1 minute, in strict compliance with international pharmacopoeia. Although as simple as a particle counter, this tool provides far more detailed information thanks to the particle size and shape analysis.

Standardized Reject Analysis:

The SPE uses highly sensitive vibrational spectroscopic methods to identify particulate contamination sources. Any user can learn how to determine a particle's chemical compositions based on individual Raman fingerprints after only one day of training.The particles are detected and subsequently identified using the integrated database. Corrective and Preventive Action (CAPA), which is mandatory when dealing with customers in the USA and Japan, can easily be integrated into the standard quality control system.

Trend Analyses Become Affordable:

Fully automated foreign particle characterization provides statistical sample analysis. Trend Analyses, which would normally take several months using traditional methods, can now be performed in a matter of hours requiring minimal human and technological resources. Valuable stability information accelerates the development of sensitive biopharmaceuticals. Quality improvements in parenteral production and filling help ensure larger production volumes as well as maximum customer satisfaction.

Qualified Measurement System:

The SPE is manufactured according to ISO 9001:2008 standards for optimal use in a cGMP environment. All data is stored in compliance with CFR Part 11. Customizable IQ/OQ/PQ documentation can be quickly integrated into your documentation environment. In addition, rap.ID will gladly assist you in your method development and validation efforts, should you so require.

Publications:

LANKERS, M., VALET, O., (2010), Quantification of Protein Agglomeration in Differently Siliconized Syringes, PDA Annual Meeting Orlando 2010

VALET, O., LANKERS, M., (2008), Automated Imaging Analysis coupled with Raman Identification of 0.5-5000 µm Particles – Particle Explorer, PSA 2008

LANKERS, M., VALET O., (2008), Differentiation between foreign particulate matter and silicone oil induced protein aggregation in drug solutions by automated Ramanspectroscopy, Microscopy and Microanalysis, 14 (Suppl. 2), Conference 2008

VALET, O., LANKERS, M., (2008), Higher Yield and Quality through Particle Identification, Journal of the IEST, October 2008

LANKERS, M., VALET, O., (2007), Improved Quality through Particle Identification . PDA Journal of GMP and Validation in Japan, 9: 82-89, 2007

DAS, T., (2007), Early Stage Protein Formulation Development and Use of High Throughput Screening Methods, AAPS NBC , San Diego 2007

VALET, O., (2006), Automatische Partikelidentifikation - Aufklärung von Mikrometer Kontaminationen ab 500nm, rap-ID Particle Systems GmbH

RÖSCH, P., et. al., (2005) Chemotaxonomic Identification of Single Bacteria by Micro-Raman Spectroscopy: Application to Clean-Room-Relevant Biological Contaminations, Applied and Environmental Microbiology, March 2005

VALET, O., LANKERS, M., (2005) Automated Raman Spectroscopy of ambient Aerosols with Airborne Particle Explorer, AAAR 2005

LANKERS, M., (2003), Higher Productivity through Particle Identification - Manufacturing of Parenterals, Annual Meeting der PDA 2003

VALET, O., (2002), Made to Measure, Cleanroom Technology, Polygon Media

LANKERS, M., (2002), Determining particle composition: Consider the path to the source, Cleanrooms, PennWell

VALET, O., (2001), Woher stammen Partikel, Reinraumtechnik, GIT-Verlag

VALET, O., (2001), Schnelle Materialbestimmung von Mikropartikeln, Laborzeitschrift, GIT-Verlag

LEWANS, M., (2001), Fingerprinting particles "automatically” , CleanRooms Magazine, 9