Editors' (re)View: The fate of interchangeability studies; CDMOs and CRLs
FDA says interchangeability studies may soon be obsolete
In 2022, I spoke with Dr. Sarfaraz K. Niazi, adjunct professor of Biopharmaceutical Sciences at the College of Pharmacy, University of Illinois in Chicago regarding the highly anticipated loss of exclusivity status for blockbuster Humira.
Niazi, a patent law practitioner with more than 100 U.S. patents in the biotech field, has developed a biosimilar to Humira, as well as two other biosims that have FDA approval. When we spoke, Niazi briefly mentioned his plans to lobby against interchangeability studies required by the agency.
A few weeks ago, his intention materialized when the FDA announced a new draft guidance aimed at providing updated considerations for biosimilar developers on interchangeability study requirements.
For drugmakers, interchangeability status is a big win. It means their product can automatically replace the original biologic at the pharmacy, helping them grab a bigger market share without extra marketing to doctors, helping to boost sales and widen reach.
Plus, the interchangeability label adds credibility and also allows drugmakers to price their biosims higher than non-interchangeable biosimilars. It also strengthens drugmaker's bargaining power with insurers and formulary committees since their product is seen as a direct, fully swappable alternative to the original biologic.
Back in 2019, the guidelines were created before the FDA had checked out any applications for interchangeable biosimilars under section 351(k) of the Public Health Service Act. Since then, the FDA has found that data from approved biosimilars show that switching between a biosimilar and its original product, whether once or multiple times, doesn't really pose significant safety or efficacy risks.
But the new draft guidance, "Considerations for Demonstrating Interchangeability with a Reference Product: Update," suggests that applicants might not always need to run extensive switching studies to prove interchangeability. Instead, they can provide a detailed assessment demonstrating that the comparative analytical and clinical data in their application or supplement meet the required switching standards under section 351(k)(4)(B) of the PHS Act.
While pharma organizations, such as the the Biosimilars Council, a division of the Association for Accessible Medicines, have “applauded” the updated draft guidance, the jury is still out on what individual drugmakers will have to say regarding the change.
The FDA has now opened a public comment period until September 20, 2024, and is inviting feedback from everyone interested to help refine the draft guidance before it becomes final. This is a chance for stakeholders to express their support, raise concerns or suggest improvements for the interchangeability demonstration process. — Andrea Corona
A rough week for pharma CDMOs
This week, we read about two FDA rejections based on issues at third-party manufacturing facilities.
On Tuesday, AbbVie revealed that it was handed a second complete response letter for its blockbuster-hopeful treatment of motor fluctuations in advanced Parkinson's disease. According to AbbVie, the CRL noted observations that were identified during inspection of a CDMO listed in the company's NDA for foscarbidopa/foslevodopa.
Just days later, Daiichi Sankyo and Merck & Co. came forward and said the FDA had issued a CRL for their jointly developed ADC, patritumab deruxtecan (HER3-DXd) — again, in response to findings from an inspection of a third-party manufacturing facility.
Neither press release identified the specific CDMOs, nor the nature of the inspection issues.
Quality and manufacturing issues, such as CGMP violations, process validation issues and contamination problems, are a leading cause of CRLs. According to Pink Sheet data, of the 238 CRLs were issued between 2017 and 2023, 30% were issued due to quality/manufacturing issues (second only to clinical deficiencies, which was the driving behind 45% of CRLs).
With the pharma industry relying so heavily on CDMOs, regulatory setbacks based on third-party facilities are probably inevitable, especially as more and more CDMOs focus on the toughest (and also the most popular) areas of pharma, such as cell and gene therapies or sterile injectables.
But there are currently over 500 pharma CDMOs in the world, all jockeying to carve out a unique niche for themselves in key sectors of the modern drug industry — so quality records continue to be a crucial distinguishing factor.
Unfortunately, CRLs aren’t public, so details are scarce — but this is a good reminder that manufacturing quality is an area still in need of attention. —Karen Langhauser
