Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

Real Time Release Testing - Challenges and Opportunities for the Pharmaceutical Industry

Dr. Tina Lübbehüsen (Abschlußjahr: 2014)

Summary
Language: English
In the traditional approach finished product specifications are often set based on a relatively small number of batches believed to be acceptable. Limits for the acceptance of the results of analytical procedures are set and these acceptance criteria must be met by future batches in order to conform with the specification. In case of manufacturing variability there is little flexibility to account for any changes occurring, often resulting in out of specification results or deviations. Specifications are tight as they serve to assure consistency of the manufacturing process, and over time regulatory authorities may urge applicants to further tighten existing limits. Each batch has to be tested against and show compliance with the product specification prior to being released. In the advanced approach, when applying real time release testing (RTRT) as introduced in the context of ICH Q8, quality is not assured by end-product testing but by understanding and controlling manufacturing variables by process analytical technology, multivariate models or combinations thereof.
RTRT itself does not improve the product quality, though in many instances it may be able to provide higher assurance concerning the product quality. When taken as an enabler for implementation of further QbD elements, due to increased product knowledge, it can contribute to an on-going improvement though. It allows for generating valuable process data, consequently further increasing understanding, e.g. via monitoring of critical process parameters and critical quality attributes, these data will become valuable for annual product review. The quality of a product can be measured during the manufacturing process, batch data thus is available earlier and allocation of batches can be handled faster without awaiting quality control results.
For successful implementation of RTRT a company’s pharmaceutical quality system must support the operation of the control strategy and thus RTRT, the focus on quality systems and risk management is increased. RTRT is strongly linked with GMP – and approval of RTRT by regulatory authorities will not only be based on the submission dossier but also GMP compliance at the actual site.
The concept of RTRT may presently still be unfamiliar or not accepted by third countries, thus globally operating companies may need to implement both RTRT as well as traditional testing to cater all requirements.
Pages: 42