13 March Seminars

Counterfeiting pharmaceuticals can be a highly lucrative business as a fraudulent manufacturer avoids the costs of product development, commercialisation and rigor of regulatory conformance. At best, such criminal activity robs the legitimate pharmaceutical of hard earned revenue. Such activity is, however, highly dangerous as products with no proven efficacy or therapeutic effect, which may or may not contain an active may be supplied to vulnerable patients. Without regulatory oversight, fake pharmaceutical products may comprise toxic and/or degraded actives, excipients and auxiliaries as well as contaminants. According to the WHO, falsified medicines have caused fatalities, life changing disabilities, undermined vaccination programs, and contributed to antimicrobial resistance. If not curtailed counterfeiting will undermine confidence in the healthcare industry as a whole.

This presentation will highlight the key collaboration required between the pharmaceutical manufacturer and an expert pharmaceutical forensic partner to investigate these fraudulent products whilst demonstrating not only how counterfeited products can be identified but also how to potentially pinpoint their source or develop anti-counterfeiting measures.

Throughout the manufacturing process of a pharmaceutical product or medical device, there are any number of opportunities for microbial contamination to occur due to environmental factors, operator error, or sterility failures among others. Manufacturers therefore must rely on robust process validation and environmental monitoring to reduce the risk of contamination and identify when it does occur.

Traditional identification techniques have utilised time consuming and labour intensive methods such as selective medium subculturing, Gram staining, biochemical testing or morphological identification. Recently, however, rapid methods have been developed which have the ability to reduce turnaround time and provide greater testing accuracy.

Despite the issues inherent in adoption of new methods, rapid methods are an expanding area of microbiology and are now considered viable alternatives to more traditional methods. This seminar will focus on the validation of one rapid method in particular, MALDI-ToF (Matrix Assisted Laser Desorption Ionization-Time of Flight), which utilises mass spectrometry to identify microorganisms by measuring their unique protein fingerprints.

The production of Active Pharmaceutical Ingredients and solid dosage/formulation, are regulated by normatives intended to reduce the risk of contamination by foreing particles and cross contamination. The filters applied in the production processes, dedicated to product recovery, present few risks in these terms. The presentation goes through the latest regulations applied on this field.

When formulating and deconstructing tablets, accurately determining API particle metrics, coating thicknesses, distribution, and polymorphic form is critical. With the majority of APIs having a particle size below 30 µm, producing this information requires high spatial resolution (down to 1 µm) and high chemical specificity so different polymorphic forms are revealed. Maintaining the integrity of particle and granule domains is hugely desirable to ensure subsequent statistics from analyses are representative of the contents. Naturally cleaving the tablet surface, which is not mechanically altered, via microtoming or milling, achieves this and drastically simplifies the sample preparation process.
Here we present a series of case studies, highlighting the benefit of generating chemical images (from Raman spectral data) with topographic and morphology information. This benefits the spatial resolution and therefore accuracy of metrics derived from chemical image analysis as well as enabling correlation between physical and chemical tablet properties. Collecting Raman data over a complex surface also enables the analysis of coatings and API distribution from uncoated tablets and high spatial resolution analysis of powders.
Examples will include:
• Multi-API chemical/morphological correlation
• Small API domain size cleaved tablet analysis
• Pre-formulation granule blend analysis
• Coating thickness and uniformity

This presentation will compare the standards and systems in use in Europe with those in the USA.

The increasing use of and interest in innovative combination products - products combining a drug, device, and/or biologic - is raising significant challenges both for regulators and the industries they regulate.
Using specific case studies, this talk will present the challenges that Toxikon has overcome in drug stability studies as well as well in material characterization of drug/device products from a practical, analytical and regulatory point of view.

Extractable and Leachables studies will show an ever expanding number of organic and inorganic species migrating from the pharmaceutical packaging. In all the potential techniques used to provide either an extractables or leachables profile, the question that need to be addressed in the limit one must investigate to measure and understand the risk the packaging poses on the pharmaceutical product.  Applying an appropriate safety concern threshold and calculating an analytical evaluation threshold is vital in producing a scientifically robust study. It is therefore important to understand what safety concern threshold should be used, how best to calculate the analytical evaluation threshold and what other factors should be taken into consideration.

The current (2008) version of Annex 1 of the EU GMPs consists of 127 paragraphs spread over 16 pages. The draft of the new Annex 1 has been published by the European Commission and it is open to consultation up to 30 March 2018. With exactly 50 pages the new document has more than doubled. In this presentation I will give an overview of additional requirements, as well as changes to existing requirements.

An integral part of delivering a successful Data Integrity Program is the Hearts and Minds of the staff.
The session will deliver real life experience of delivering successful DI culture from DI programs delivered in 2017. including;-
1) How to build them
2) How to deliver and monitor them
3) When to present them