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34 BioPharm International ® Manufacturing and Facilities 2022 eBook www.biopharminternational.com OUTSOURCING current or future anticipated capacity needs)? What is the financial capacity? Is it sufficient to carry idle manufacturing capacity until the pipeline matures to fill this capacity? Is there enough activity to maintain a workforce en- gaged and in a sufficiently-trained state? Are the process and analy tical technolog y used rapidly evolving and requiring frequently up- dated equipment, methods, training, etc.? An organization must a lso determ ine whet her there is a budget to maintain state-of-the-art manufacturing technology. If the decision is to partially or fully outsource the activity based on the assessment of these various fac- tors, the choice then becomes what CDMO to work with. In many sectors of bioprocessing technology, there are usually many contract service providers to choose from, and some larger CDMOs offer services across a disparate range of technologies and platforms. Cell and gene therapies The area of cell and gene therapies (CGTs) is an in- teresting case to consider for "make versus buy" de- cisions. The field is immature but evolving rapidly. While products have been developed since 2000, approvals have only started in earnest since 2017. Even with six product approvals in 2021 (10), the peak of such approvals is yet to come (10, 11). The under- standing of how the products work is currently weak (e.g., dosing as well as the adeno-associated virus empty/full capsids issue [10]), which manifests in a general sentiment around chemistry, manufactur- ing, and control (CMC) challenges for these programs. As this continues to rapidly evolve, it will have a profound ef fect on t he choice of ma nufact ur ing and analytical technology (10). This complexity and state of product understanding also put a premium on the quality of any partnership with a CDMO (i.e., capability, experience, and reliability). Costs and control Concerns about perceived high costs of CGT manufac- turing and the level of control over the CMC program are frequently evoked, as many programs are currently outsourced to CDMOs as developers build up their own internal capabilities. There is also a strong sentiment around the lack of available capacity, which is more spe- cifically related to slot availability and turnaround time. For example, a requested turnaround time of six to nine months from an order to batch completion, as opposed to a proposed 12- to 18-month turnaround time, which may not be coherent with overall program timelines. The costs of work ing with a CDMO in the CGT area can sometimes appear to be high but may, in fact, not be so different from the comparative costs of doing this internally. In general, even for large pharmaceutical companies using a sufficiently plat- formed process and operating in an efficient man- ner, the cost for manufacturing biopharmaceutical drug substance batches (e.g., mAbs) is often in the millions of euros per batch, and approximately 50–70% of this cost is for the associated drug product batch. The key drivers for these costs are facility utilization (asset costs and depreciation, utilities, etc.), people, and raw materials. The economic efficiency of the process can be quoted as X$ per Z gram of DS (or X$/ DP vial), with the process deemed to be more efficient with higher yields, and the X$/Zg or vial can be bench- marked across similar drug categories (e.g., for mAbs). This approach is typically applied more rigorously for commercial supply of biopharmaceuticals, whereas in the clinical supply phase costs are more typically on a per-batch basis with sometimes no guarantee of fixed yields as the process may be under development and Figure 1. Key decision criteria for make vs buy (perform internally or outsource) in biopharmaceutical product development. • Large and promising product pipeline • Financial capacity • In-house CMC (Dev, Mfg, Reg) expertise • Smaller / focused product pipeline • More limited financial capacity • Lack of in-house expertise • Short/medium term capacity issues • Need for additional expertise • Retain specific / key products internally "Make" (develop and manufacture internally) "Buy" (outsource) Hybrid (selective / focused outsourcing) Key questions: • Expertise: o Do you have the necessary expertise / capabilities in-house? o Can you translate the technology to GMP mode, scale it up, and support regulatory activities? • Capacity and technology: o Do you have the technology and the necessary scale to develop and produce the product at the required volumes? o Is this capacity available now, or in a couple of years' time? • Economics: o Is your product pipeline well-developed? o Do you have the financial capacity to carry idle capacity until your pipeline matures? o Do you have enough activity to maintain in a trained state? o Is the technology you work with rapidly evolving? Points to consider: FIGURE 1. Key decision criteria for "make versus buy" (performing internally or outsource) in biopharmaceutical product development. FIGURE COURTESY OF THE AUTHOR