IPEC e-newsletter - Excipients Insight August 2017 - 11-08-17

 

Inside this issue

     

Biologic drugs pose excipient challenges - and opportunities

There has been a massive increase in the proportion of large-molecule biologic drugs coming though pharmaceutical pipelines – providing big benefits for patients but also challenges for formulation scientists.

The higher level of structural complexity makes them some of the most challenging molecules to formulate, thanks to physical factors such as higher viscosity as well as other factors such as a shift towards less frequent dosing and longer storage times and the move towards combining drugs and medical devices.

The formulation and handling of biologic drugs pose unique challenges that are generally not experienced with small molecules. For instance, they are generally more susceptible to physical and chemical degradation that can have a dramatic impact on their safety and efficacy.

"Pharmaceuticals continue to evolve from traditional proteins and peptides to more complex molecules such as antibody drug conjugates and cell-based therapies," according to Kate Denton of Albumedix Limited, who serves on the IPEC Europe Quality & Regulatory Affairs Committee.

"This causes many challenges for formulation of these newer more complex drugs, in the context of both stabilisation and bioavailability," she told Excipients Insight. In fact, it has become apparent that standard formulation technologies are often no longer adequate and more advanced formulation strategies are required for this new generation of therapies.

It is estimated that somewhere between 5% and 15% of all drugs require advanced formulation agents that are not typically provided by the standard 'toolkit' of excipients used for formulation development, namely sugars, amino acids, detergents and surfactants. Now, added to these well-established excipients is an increasing range of more advanced formulants such as cyclodextrins, polymers and complex polysaccharides. Although many of these agents are effective stabilisers, their use requires careful consideration in terms of local toxicity and potential immunogenicity. However, human albumin demonstrates a number of benefits as an effective stabiliser with a low toxicity and immunogenicity profile. Biotechnologically-derived novel excipients, such as the recombinant form of human albumin, are valuable additions to the advanced excipients portfolio.

"Novel excipients generated by biotechnology such as recombinant human albumin can help address some of these challenges as they can be tailored more towards drug manufacturers' needs," says Denton. But they can be tough to bring to market, due to the lack of an independent regulatory review procedure or formal mechanism for demonstrating their acceptability. Therefore, pharma manufacturers are sometimes reluctant to use them and add an additional 'unknown' element to their drug development projects.

However, the regulatory environment for excipients is improving with the implementation of internationally-recognised schemes such as EXCiPACT, increased GMP guidance and global efforts for harmonised standards in recent years. Together with an efficient master file system which in many regions allows a novel excipient manufacturer to provide extensive product details while protecting their confidential manufacturing information, the perceived regulatory hurdle for use of novel excipients is decreasing.

 

 

 

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