Drug sensitivity issues
Biotech drug formulations are often highly sensitive: they can react to one or more elements of their primary packaging and lose their stability, sometimes so much so that reformulation becomes necessary. That in turn means extra costs and delays in development when the patent clock is ticking.
Sensitivity has always been a problem for the pharmaceutical industry and is becoming even more so now that more and more drugs are biologics and highly concentrated. By some estimates, 20-30% of drug formulations now have sensitivity issues.
The problem can be caused by several means, notably: silicone oil sensitivity; interaction between the drug and the surface of the primary container, leading to protein aggregation; the particles generated by the rubber in the closure system; and surface delamination, especially in glass vials, causing visible flakes or glass lamellae.
To address these issues, Ompi has developed the EZ-fill® Alba platform. This was also designed to support drug development ‘from conception to injection’, with the aim of de-risking any switch from one container format to another.
The Alba range all comprise a sterile glass container platform, including vials, cartridges and syringes, with similar chemical and mechanical characteristics. They act in multiple ways to prevent the problems associated with sensitive drug formulations.
Alba technology: de-risking the development process throughout its lifecycle
First, all Alba products have an internal coating, based on the standard silicone oil, Dow Corning 360. This is cross-linked to form a chemical bond with the surface, which ensures that particle levels caused by silicone migration during container storage are significantly lower than with the mechanical bond formed by standard siliconization technologies.
In addition, the coating creates a barrier between the drug and the glass that makes it possible to reduce the amount of inorganic extractables significantly by comparison with a standard bulk container, or even with the glass container before being formed.
The strong chemical bond also leads to better stability during the time of functional performance, i.e. gliding and break-loose force. In addition, the homogeneity of the lubricant layer over the length of the barrel is maintained after long storage times.
With vials, for which the lubrication aspects of this technology are not relevant, the main added value of the Alba coating is its barrier effect against aggressive drugs, preventing delamination from occurring. Like the strength of the chemical bond, this has been comprehensively proven in tests.
Ompi also worked closely with rubber manufacturers when developing Alba because around 50% of particles are normally generated by an interaction between the rubber components and the drug. The collaboration focused on developing the lowest particle generation while ensuring that the same materials were available for all of the Alba platform container formats, i.e. vial stoppers, syringe plungers and cartridge plungers.
The final form of a drug is usually selected during clinical Phase II. At this time, the relatively simple early phase container, usually a vial, is replaced by a different container like a syringe or cartridge. This exposes the drug to new materials that may become a source of instability.
At best, a new stability study is needed; at worst, the drug may have to be reformulated. The 30 pharmaceutical industry experts Ompi interviewed when starting the Alba project in 2014 had different views on the extent of the problem but all recognized that it can have a significant impact on the drug development process.
The key benefit of the Alba platform is that all the containers show the same contact surface to the drug. This removes the uncertainties associated with new packaging materials when moving from Phase II to Phase III, de-risking the whole development process. The same benefits can be applied to marketed drugs when the packaging is changed or the drug is put into a different container format.
Alba is a turning point in the development of parenteral primary packaging
Alba represents the best-in-class solution for biologics and ophthalmic drugs. The drastic reduction in silicone oil particles and the extremely low propensity to delaminate address some of the key requirements of protein-based drugs and help keep them compliant with the latest regulatory guidelines.
Finally, the reduced variability of materials in contact with the drug throughout its life-cycle makes the Alba platform a perfect solution to de-risking the development process, saving on costs and securing a faster introduction to the market.