Regulation of the pharmaceutical development process is important to ensure that drug products are consistently safe and effective. There are written guidelines for pharmaceutical validation, which ensure that drug compounds are handled and tested properly. There are also separate guidelines for the bioanalytical methods used in the development and testing of new drug compounds. The goal is to standardize and improve the consistency of pharmaceutical studies and that data that are used for drug approval. Examples of analytical methods include ligand binding assays and chromatographic methods (liquid chromatography, gas chromatography, and mass spectrometry). Both the FDA (U.S. Food and Drug Administration) and EMA (European Medicines Agency) regularly update their bioanalytical method validation guidelines, but their focuses are slightly different. The FDA outlines reporting guidelines in more detail, while the EMA focuses more closely on the conduction of experiments. The validation guidelines are unified under ICH (International Council for Harmonisation of Technical requirements for pharmaceuticals for human use).
We have come a long way from the days of blood letting, trephination, and snake oil salesmen peddling cure-all tonics. The oversight and regulation of organizations such as the European Medicines Agency and the Federal Drug Administration (FDA) have significantly improved the quality and safety of our medical and pharmaceutical products. Of course, our medical understanding has deepened dramatically, our science has become more sophisticated, and we have developed tools to perform large scale drug discovery and screening. With this deeper understanding of chemistry and drug development we have realized the importance of preserving the chemical molecules via proper storage conditions.
The ICH guidelines for stability lay out the requirements for identifying and maintaining drug efficacy by understanding the pathways of degradation. The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) was founded in 1990. The European Commission, FDA from the USA, and the Ministry of Health, Labour, and Welfare (MHLW), which later became the Pharmaceuticals and Medical Devices Agency (PMDA) in Japan are all founding members. Since that time, many other regulatory authorities from around the world have joined the ICH. The stated mission of the ICH is to “achieve greater harmonisation worldwide to ensure that safe, effective, and high quality medicines are developed and registered in the most resource-efficient manner.”
When one scales up production using a classic magnetic separation system, one finds that the separation time increases quickly with an increase in production volume. An increase in separation time means that material losses are higher and aggregation problems become a serious problem. By using homogenous separation time, one finds that the magnetic separation process is shorter and the separation time can be easily estimated. In homogeneous systems material loss and bead aggregation is minimized.
In non-homogenous magnetic separators, monitoring the entire separation process is difficult to impossible. As a result, errors in the magnetic separation process, such as using the wrong magnetic beads or using buffers with the wrong properties are not detected until the final QC testing stage.
When magnetic bead reagents are produced in quantity, often you cannot know if you have the correct properties of the beads until the final quality control step. But if these properties are wrong, finding out the properties at the end of the magnetic separation process for production does not allow you to salvage the lot. Knowing magnetic bead properties, such as size, magnetic charge and surface charge, is critical in order to have excellent reproducibility in the final product (e.g. IVD kits).
When using biomagnetic separation, in order to ensure the consistency of the resulting product and the process itself, there must be some sort of validation procedure. Validation should be consistent within a given lot, from lot to lot and also when the process is scaled up. The validation procedure should optimally be related to the conditions of magnetic bead separation and not be dependent on any specific device that generates the magnetic field.
Biomagnetic separation used to take place in academic labs, but recently it has become a very industrial application. As processes are scaled up and volumes increase, the investment required for each batch is larger, but the expected economic return is also larger.
Because biomaterial is expensive, fragile, complex and sometimes rare, biotech companies spend a great deal of time and resources to develop and refine biomaterial production processes. Quality control and standard operating procedure demand that production managers make sure that all technicians and operators know and follow the exact procedures from batch to batch.
Consistent lot-to-lot results are achieved with biomagnetic technology only when magnetic bead separation is performed in defined and homogeneous conditions. When homogeneity is realized, separation is reproducible and scalable.
Of course, as in most industries, product consistency is key to the success of the Life Sciences industry. With magnetic bead separation, not only should working conditions be constant over time, but conditions should also be consistent from lot to lot, regardless of the time between production runs. One thing that should always be considered is the quality of the magnet used in the biomagnetic separation devices.