Editor’s (re)View: Atara Biotherapeutics learns that relying on a third-party manufacturer can be an Achilles’ heel
It’s been a rough couple of weeks for Atara Biotherapeutics. Last week, the company was hit with a Complete Response Letter (CRL) from the FDA — issued following a pre-license inspection — which identified deficiencies at a third-party manufacturing facility. This week, Atara announced that the regulator has put a clinical hold on its two active Investigational New Drug (IND) applications.
When it comes to the clinical hold on Ebvallo, Atara’s monotherapy treatment for adult and pediatric patients two years of age and older with Epstein-Barr virus positive post-transplant lymphoproliferative disease, the company said it is “directly linked” to inadequately addressed GMP compliance issues identified at the third-party manufacturing site, which was referenced in the CRL.
The good news for Atara: the CRL did not raise any concerns about the efficacy, safety, or the manufacturing process in the company’s Biologics License Application for Ebvallo, and the company is working with the third-party manufacturer to address the FDA’s feedback.
The bad news for Atara: the regulatory actions are a major setback for the company and while Atara’s ATA3219 allogeneic CD19-targeted CAR-T therapy for the treatment of non-Hodgkin’s lymphoma and systemic lupus erythematosus is manufactured at a separate, fully compliant GMP-certified facility, the starting materials used in its production are affected by the compliance issues at the same third-party facility cited in the CRL.
Atara is the latest example of a company whose drug candidate application has been rejected by the FDA due to issues with a third-party manufacturer. The reality is that such companies rely on third-party manufacturing, which can leave them vulnerable.
It’s worth noting that out of a total of 238 CRLs issued between 2017 and 2023, 30% involved quality/manufacturing issues — particularly problems with manufacturing processes, facility inspections, or chemical, manufacturing and controls (CMC).
Paul Josephs, CEO of Minnesota-based Lifecore Biomedical, told Pharma Manufacturing that on the regulatory front he proactively thinks about “those things that can cripple” his contract development and manufacturing organization. Josephs said the company routinely conducts self-audits to “identify our own weaknesses” upfront for potential quality or production issues that could be flagged by regulators.
“You get a bad audit with the FDA or any regulatory agency and it could have a direct impact on your current and future revenue, as well as peoples’ confidence in doing business with you,” Josephs warned.
The biopharma industry’s reliance on third-party manufacturers is a business necessity these days, but it also can be an Achilles’ heel. This week, it hurt Atara.
In a Jan. 21 note to investors, a Seeking Alpha analyst wrote that the CMC issues identified by the FDA were “seemingly resolvable” but how long that takes “depends on the seriousness of the problem.” Based on Atara’s press release, the analyst said they are “hoping for an eventual approval” of Ebvallo by the end of 2025 or early 2026.
