Foreign Particles Control and Identification in Inhalable Drug Products, Medical Devices, and Prefillable Syringes in regards to the QbD Paradigm

Markus Lankers

Rap.ID Particle Systems GmbH
Köpenicker Str. 325 Haus 40 C, DE- 12555 Berlin, Germany
Tel: +49. 30 6576 3440   Fax: +49. 30 6576 3441

Biography

Dr. Markus Lankers is one of the co-founders of rap-ID Particle Systems GmbH a company that develops manufactures and sales rapid particle identification and
siliconization measurement systems. Within rap.ID Dr. Lankers is responsible for research and development of specific solution of particulate analysis. Prior to this
position he worked as scientist in different development departments with Schering AG, Berlin, Germany. He has published and presented work in the field of analytical
methods for particle analysis and spectroscopic analysis.

He helped to establish the Visual Inspection of Parenterals Interest Group in Europe and to setup the first company independent Vis. Inspection trainings course. He served as program cochair for Scientific Conference on Visual Inspection of Partenterals 2001-2007 in Europe and USA.

Abstract

Foreign Particles (FP) in Parenterals, injectables and medical devices are insoluble material. The size range depends on the application, e.g. in an inhalable drug particles are small enough to be inhaled or swallowed by the patient. In any case, product quality control is directly attributed to foreign particulate matter control. The Quality by Design (QbD) initiative enables developers and manufacturers to set limits or manufacturing approaches based on scientific data. Therefore, the manufacturer is able to change parts of the production or packaging processes based on solid analysis results regarding particle impact or changes.

Studies show that the application of a Design Space for the control of foreign particulate matter during the development phase of a dry powder inhaler product is advantageous. The goal is to minimize the amount of foreign particles during the entire lifetime of a product. First, all components influencing the particle load of a delivered dose should be identified. The following are components of the formulation: Actives, Excipients and the primary packaging materials. To locate the major contributor of particle contamination each component must be separately evaluated.
An integrated measurement device is used to quickly evaluate the amount and chemical composition of foreign particles with integrated Raman spectroscopy at a throughput rate of up to 1000 per hour.

Foreign Particulate control and detection in primary packaging can also be used for reject minimization control and high quality parenteral production.

The release of foreign particles from a surface is dependent on several surface characteristics, such as smoothness, electrical charge and the geometry of primary packaging material. These variables influence the cleaning characteristics of each material, and therefore cleanliness testing procedures. To obtain reliable and reproducible parameters the pharmaceutical industry could benefit from a recent approach used by the automotive industry for the qualification of cleanliness parts testing called ISO 16232.

This guideline implements breakthrough methods and tests that reliably extract foreign particles from a part, container or device. There are several steps needed to qualify the particle extraction procedure described in ISO 16232. After a successful qualification, a standard operation protocol can be determined. This validated procedure makes it possible to control cleanliness levels and compare cleanliness levels in different production facilities over time.

Cleanliness testing procedures are able to enumerate and identify a significant number of particles.  This gives the pharmaceutical manufacturer enough data to control and perform immediate root cause analysis regarding quality primary packaging material parameters, devices or products such as implants. The determination of out of specification containers before filling avoids rejects or even recalls and saves precious product.