Most pharmaceutical companies know little about how to make biopharmaceuticals on a large scale and so they need to develop in-house expertise as well as outsource several steps in their production chain, advises the head of chemistry and production at Genzyme Pharmaceuticals.
Mimoun Ayoub took some time off at the Controlled Release Society's annual meeting in Vienna to speak to In-PharmaTechnologist.com about ways drugmakers can save time and money in the manufacturing of biologics.
Biopharmaceuticals, and protein-based drugs in particular, are becoming increasingly popular because of their potency, high specificity and lack of accumulation and toxicity.
But their low stability, poor bioavailability and challenging delivery means that only around ten per cent of them progress further than Phase I.
Therefore, the last thing companies need is a problematic synthesis, yet this is exactly what happens often because they lack the know-how in designing large scale manufacturing processes for these molecules.
"To make biologics you need knowledge to optimise the process, scale it, manufacture and validate," Ayoub said.
"It makes no sense to outsource the critical steps which require expertise and regulation, what you do is ensure you have the skills for them in-house."
On the other hand, fast steps requiring high volumes should be outsourced to custom manufacturers that handle production more cost-effectively thanks to their capacity and specialisation.
So for example, preparative high performance liquid chromatography (HPLC) is a bottleneck contributing substantially to the cost of protein-based drugs, so it should be handled in-house, something also important for validation. However, the production of crude peptides and intermediates on a large scale can be outsourced.
Likewise with phospholipids that make micelles and liposomes and do not have high solubility, one requires high dilution and this is the most limiting step in terms of cost, handled in-house. Synthetic lipids, analogues, segments and derivatives can be obtained from external providers.
"Always try to have a single supplier instead of three or four, it makes it easier to control the process and its cost," Ayoub said.
"You should choose that partner based on their affinity with the chemistry you need, some specialise in hazardous chemicals, others in phospholipids and others in amino acids."
Ayoub's company is the custom manufacturing branch of Genzyme Corporation, providing companies with production-scale quantities of biologic active pharmaceutical ingredients (APIs), intermediates and critical excipients.
He works at Genzyme's good manufacturing practice (GMP) facility at Liestal, Switzerland which has an Fmoc/solid-phase synthesis capacity for peptides up to 150L, solution-phase synthesis capacity for peptides up to 2,500L and can make up to 50Kg batches of phospholipids, the only company making such volumes.
There, Ayoub is responsible for maintaining manufacturing processes that deliver the highest possible crude purity of API.
In May Genzyme entered a partnership with Brookwood Pharmaceuticals to offer the drug industry customised solutions for parenteral formulations by combining expertise in design for peptide delivery, peptide synthesis, and drug delivery technologies.
With approximately one-fourth of new drugs coming on the market being biopharmaceuticals and annual sales projected to surpass $52bn (€41bn) by 2010, Ayoub believes it is imperative drug companies have a manufacturing strategy to deal with the increasing demand.