The traditional manufacturing process is via extracellular expression in yeast, which still constitutes the bulk of production capacities.

However, achieving high expression yields in P. pastoris requires utilizing the yeast's methanotrophic metabolism alongside methanol fed-batch regimes, which demands not only precise control of the pH deadband in the fermenter but also leads to the accumulation of large quantities of methanol in the upstream biomanufacturing suites.

This poses high operational risks and also requires stringent FM/ATEX regulations of Div 1/Zone 1 classification. Afterwards, in DSP suites, pH remains critical in almost all the unit operations designed to achieve the pure product at the end of the pipeline.

传统的制造工艺是通过酵母中的细胞外表达，这一直是构成生产能力的大部分。

然而，要在毕赤酵母中实现高表达产量，需要利用酵母的甲烷营养代谢以及甲醇补料分批生产，这不仅需要精确控制发酵罐中的 pH 范围，还会导致上游生物制造过程中大量 甲醇 的积累。

这会带来很高的运营风险，并且还需要严格的 FM/ATEX 1 区的法规要求。 在下游生产过程中，pH 值保持非常重要的作用在整个纯产品的生产管线。