AGC Biologics’ Bothwell, Washington site is commercially manufacturing Provention Bio’s type 1 diabetes (T1D) monoclonal antibody Tzield (teplizumab).

Provention Bio said it selected AGC Bio to produce Tzield – the first authorized drug that can delay onset T1D –  after the contract development manufacturing organization (CDMO) supported the drug ahead of its approval by the US Food and Drug Administration (FDA) in November 2022.

Tepilzumab is manufactured in two main stages: the upstream process followed by the downstream process,” Kevin Ingham, general manager of AGC Bio’s Seattle campus, told BioProcess Insider.

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“The purpose of upstream is to cultivate a large amount of special cells that have been genetically engineered to express and secrete teplizumab.  Once there is enough teplizumab present in the cell culture, the downstream process begins by separating out teplizumab from all the other proteins and purifying it in the correct formulation for administration to the patient.”

While the specific number of batches has not been disclosed, Ingham said there is no need to scale-up staff at its Bothell plant to service the deal.

“We are already staffed and able to handle the work for this manufacturing line.  We expect to manufacture a handful of batches per year for the first year or two, and potentially grow as market needs adjust. But this is an extremely important product for the patient population so those batches matter,” said Ingham.

Moreover, the CDMO said it is supported by a global network and therefore has access to a secure supply chain to manufacture the product in a timely manner.

The journey towards authorization was not always straightforward and Provention landed itself with a complete response letter (CRL) from the FDA in July 2021, which cited concerns related to pharmacokinetic/pharmacodynamic (PK/PD) data and product quality. Additionally, the FDA also highlighted deficiencies identified at a fill/finish manufacturing facility used by Provention, though not specific to teplizumab, and said these needed to be resolved before approval.

The drug substance of teplizumab has been produced at AGC Bio’s Bothell facility since 2019 but when the CRL was issued Provention did not divulge where the drug product was being produced.