Supplementary Material
Benchmarking biopharmaceutical process development and manufacturing cost
contributions to R&D
Suzanne S. Farid1,*, Max Baron1, Christos Stamatis1, Wenhao Nie1, Jon Coffman2
1
The Advanced Centre for Biochemical Engineering, Department of Biochemical Engineering,
University College London, Gower Street, London WC1E 6BT.
2
Biopharmaceutical Development, AstraZeneca, 1 MedImmune Way, Gaithersburg, MD 20878,
USA
* Corresponding author
Prof. Suzanne S. Farid
s.farid@ucl.ac.uk
+44 20 7679 4415
https://orcid.org/0000-0001-8155-0538
www.linkedin.com/in/suzanne-farid-2aa61313/
In the paper, the costs of CMC activities are based on the number of projects at the current stage,
based on the assumption that typically early trial readouts allow the drug developer to plan for
future stages. This supplementary material highlights the impact on CMC and R&D budgets when
CMC activities are costed at-risk rather than being applied only to the projects that have
successfully transitioned to the next phase. To illustrate an example of this, if pre-clinical has 12.4
projects and Phase I has 8.6 projects, when considered at-risk the CMC costs for Phase I are
calculated for 12.4 projects. Comparatively, when CMC is not costed at-risk, these costs are
calculated for 8.6 projects.
To ensure a market success each year with an overall clinical success rate (Phase I to approval) of
~12% with CMC costed at-risk, the model predicted that a biopharmaceutical company needs to
allocate process development and manufacturing budgets in the order of ~$70 M for pre-clinical to
Phase II (early-phase) material preparation and ~$110 M for Phase III to regulatory review (late-
phase) material preparation. For lower overall clinical success rates of ~4%, which are more
indicative of diseases such as Alzheimer’s, these values increase to ~$240 M for early-phase and
~$360 M for late-phase material preparation; hence, the costs increase 3.3 fold. The costs for
process development and manufacturing per market success were predicted to represent 21–22% of
the R&D budget from pre-clinical trials to approval. Further key cost outputs from the work are
highlighted in Table S1.
Table S1. Summary of the key differences on CMC and R&D budget metrics when CMC is costed at-risk
versus not costed at-risk
CMC not costed CMC costed
at-risk at-risk
Average risk profile
Total CMC budget ($M) 127 182
Early-phase CMC budget ($M)
1
57 73
Late-phase CMC budget ($M)
2
71 109
Ratio of PD3 to manufacturing budget 1.54 1.77
Total out-of-pocket R&D budget ($M) 780 835
CMC % of total R&D 16% 22%
Total capitalised budget ($M) 1879 2004
Best-case risk profile
Total CMC budget ($M) 95 126
Early-phase1 CMC budget ($M) 24 28
Late-phase2 CMC budget ($M) 71 98
Ratio of PD3 to manufacturing budget 1.59 1.88
CMC budget change from Average risk profile × 0.74 × 0.69
Total out-of-pocket R&D budget ($M) 560 591
CMC % of total R&D 17% 21%
Total capitalised budget ($M) 1324 1395
Worst-case risk profile
Total CMC budget ($M) 329 600
Early-phase CMC budget ($M)
1
188 242
Late-phase2 CMC budget ($M) 141 358
Ratio of PD to manufacturing budget
3
1.31 1.78
CMC budget change from Average risk profile × 2.6 × 3.3
Total out-of-pocket R&D budget ($M) 2476 2747
CMC % of total R&D 13% 22%
Total capitalised budget ($M) 5987 6602
Note: All budgets here refer to the budgets needed to ensure a market success.
1
Pre-clinical to Phase II
2
Phase III to regulatory review
3
Process development
Figure S1
Figure S1 Cost evaluation of new biopharmaceutical product development with CMC costed at-risk.
The three risk scenarios are presented, average (a), best-case (b), and worst-case (c). Using the
phase transition probabilities the average numbers of projects required to achieve 1 market success
at each stage are calculated. The figure can be compared to Figure 3.
Figure S2
Figure S2 (a) Total out-of-pocket development cost distributions with CMC costed at-risk across
development stages presented under the three risk scenarios. Each scenario is annotated with the
percentage contribution from each stage along with the total out-of-pocket cost. (b) CMC out-of-
pocket cost distributions across development stages with CMC costed at-risk presented under the
three risk scenarios. Similarly, each scenario is annotated with the percentage contribution from
each stage along with the CMC out-of-pocket cost. (c) Early and late phase CMC budgets required
to ensure one market success under the three risk scenarios, with CMC costed at-risk. Each phase is
broken down to process development and manufacturing activities that form CMC, and annotated
with the total CMC budget. This figure can be compared to Figure 4.
