Optimising the Development of Protein Formulations

Pharma IQ

The pharmaceutical industry constantly sees the need to develop a marketable and safe protein drugs for mainstream human use as an important issue. However, there are many challenges which surround such a vision and make protein formulation particularly problematic.

Perhaps one of the largest of these barriers that needs to be overcome in order to make sure that protein drugs can become marketable is that surrounding the most effective way to deliver them at the bedside.

At the moment, the primary way to deliver proteins into the body continues to be via syringe into the bloodstream. However, there are other methods, such as nasal, oral and pulmonary administration. One of the issues with these is commercial, as all of the positives seen can be a result of just luck as opposed to a consistent set of results.

On top of the financial implications of the drug delivery however, there are challenges with the actual administration itself. Unlike small chemical drugs, proteins form higher ordered, more complicated structures, which means that in order to make sure they remain safe for patient use, the preservation of their fragile makeup is vital.

This was a point discussed by Sven Fokjaer and Daniel Oetzen, who said that proteins are susceptible to a number of external factors such as pH, temperature and surfaces, as well as a number of external contaminants which can affect their stability. For these reasons, they suggest that the use of an oral delivery of the drug is not ideal, because proteins will be open to contaminants and other problems in the intestinal tract.

"Protein structure is flexible and sensitive to external conditions, which means that production, formulation and handling of proteins needs special attention in optimising efficacy and safety, including minimised immune responses," the authors said.

As well as the issue surrounding the problems of drug delivery in terms of these proteins however, there are obviously challenges which come to the fore in terms of the production of the protein medication itself.  Merck Research Laboratories released a report entitled Addressing New Analytical Challenges in Protein Formulation Development, in which Henryk Mach said that the development of new ways to create protein drugs had been very slow over the past few years. 

"Relatively little progress has been made in the development of analytical methods that would address specific needs encountered during the development of these new drugs," the report from the pharmaceutical company stated, before adding that adaptation rather than innovation when it comes to methodology and instrumentation has been seen as the key for protein drug production.

The ways in which this is done includes atomic force microscopy  visualise proteinacious sub-visible particles, the use of fluorescent types of dye that allow pharmacists to see protein aggregates, particle tracking analysis and a development of high-pressure liquid chromatography (HPLC) to let it measure viscosity. The report said that these techniques allow the manufacturers of drugs to have a better insight into protein formulation than in the past, but also help to reduce outlay by decreasing the number of samples needed to see results.

There will also be other issues which need addressing, especially when it comes to safety, both at the benchside and the bedside, with calls for regulation seeking to ensure that conditions are conducive to protein stability being an important consideration.

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