Biologics continue to gain ground as therapeutics, with 11 Biologic License Agreements approved in 2011 by FDA, and a staggering 900 or so products in the pipeline according to PhRMA, including 300 monoclonal antibodies, 298 vaccines, and 78 recombinant proteins other than mAbs (1). This year's survey suggests that the great rush to enter the biologics field has given way to a slow, steady rise in new entrants, but new entrants and old hands all face production challenges. To understand these challenges, Pharmaceutical Technology asked those involved in the production of biologics about the issues that concern them most, and about their choice of equipment for bioprocessing.
The largest group of respondents to this years survey worked at biotech companies, 38%, with 24% from innovator companies, and with a scattering of respondents from contract services companies or from academia or nonprofits. Half of the respondents (51%) said their companies produced only biologics, while the other half produced both large and small molecules. When asked what type of drugs they produced, 34% of respondents said they produced branded drugs, 21% said generic drugs, and another third, 33%, said they produced neither branded nor generic, and so presumably were producing biologics still in the development phase.Only a minority of companies were newcomers to the field—23% said their companies had started producing biologics within the past year, which is the same percentage as last year. Those just entering biologics production were more likely to be contract manufacturers: 33% of respondents who worked as contract manufacturers said they had started producing biologics within the past year, compared with only 10% of those from biotech companies.
Different products, different concerns
This years results indicate that some of the enthusiasm for biosimilars may be waning now that FDA has released its draft guidelines. The number of respondents who say that they are planning to make follow-on biologics is down slightly from 2011, 36% compared with 45% in 2011. Twenty five percent say they are not planning any follow-ons, compared with 21% last year, and 39% are uncertain if they will do so, compared with 34% in 2011.
For purification, those who produced protein-based products used chromatography with protein A (51%), chromatography with other resins (68%), and ion-exchange chromatography (70%). The proportion of those who used membrane-based filters, 64%, is increased somewhat over last year's reported 53%.
Those who produced nucleic acid-based therapies listed purification (35%), scale-up (25%) and stability (25%) as being their most pressing concerns. Fewer than 10% of respondents indicated that analytics or automation presented technical challenges during the manufacturing process. Of those making cell-based products, 38% indicated that process development continued to be a challenge, with scale-up (35%) and costs (33%) also of great concern. Adequate bioreactor volumes were a concern for only 18% of respondents, and cell viability a challenge for 19%.