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.
Who's who
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
Figure 1: What class(es) of biopharmaceutical does your company manufacture (multiple responses allowed)?
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The product produced by the largest group of survey participants (46%) was protein products other than monoclonal antibodies
(mAbs), little changed from last year's result of 51% (see Figure 1). Surprisingly, those who said they produced mAbs decreased
this year to only 34%, compared with 44% in 2011. There was a clear dichotomy in the types of companies producing mAbs: only
20% of respondents from companies with revenues of less than $500 million were producing mAbs, compared with 57% of those
from companies with revenues greater than $1 billion. Other classes of products manufactured by survey participants remained
little changed between 2011 and 2012. This year, 10% of respondents produced nucleic acid-based products, 33% produced vaccines,
and 16% produced cells for cell therapy.
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.
Figure 2: If you produce protein-based drugs, what are your current technical challenges (multiple responses allowed)?
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When producers of protein-based products, including both mAbs and proteins other than mAbs, were asked about their greatest
challenges during production, producing high enough protein yields and protein stability were of concern to 40% and 33% of
respondents, respectively, with purification (30%) and formulation (28%) also cited as areas of concern (see Figure 2). Other
aspects of protein production, such as creating efficient expression cassettes, creating working cell lines, viral contamination,
and achieving correct posttranslational modification were not of great concern to most respondents, garnering responses of
less than 15%. Perhaps not surprisingly, different concerns emerge if the responses are broken down according to the respondents'
job responsibilities. For instance, 56% of those who identify themselves as working in manufacturing say producing high enough
yields is a significant challenge, while only 27% of those in formulation perceive this to be a challenge. Those in formulation
are, of course, more sensitive to formulation issues (59%, compared with 29% of the sample at large) and drug delivery issues
(41%, compared with 15% of the sample at large).
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%.
