Stability data issue holds up Adventrx cancer drug
pharmafile | March 3, 2010 | News story | Manufacturing and Production, Sales and Marketing | Adventrx, Cancer, vinorelbine
US drugmaker Adventrx Pharmaceuticals has had the marketing application for its cancer drug ANX-530 (vinorelbine emulsion) rejected by the US Food and Drug Administration on the grounds that it had not provided enough testing data.
The development, which could delay the registration programme for ANX-530 for several months, raises important questions about the way the agency is interpreting the current requirements for stability data, according to Adventrx’ chief executive Brian Culley.
Once a New Drug Application (NDA) is submitted in the US, the FDA has a preliminary period of 60 days to decide whether the dossier can be accepted for full review. In this case the agency deemed that Adventrx application was not sufficiently complete, and issued what is known as a ‘refusal-to-file’ letter.
The agency says in the letter that “data included in the initial submission from the intended commercial manufacturing site was insufficient to support a commercially-viable expiration dating period”.
Put simply, that means that the stability testing – a standard practice in pharma designed to show how long a batch maintains its quality over a minimum of 12 months and sometimes as long as several years – is deemed inadequate.
At the heart of the issue is that in 2008 Adventrx hired a new contract manufacturer for commercial production of ANX-530, swapping from the CMO that made the product used in its bioequivalency study for the drug.
The FDA is concerned that stability data on ANX-530 was generated on batches made by the first CMO, not the second, and considers that this makes the chemistry, manufacturing and controls (CMC) section of the file deficient.
“We continue to believe that ANX-530 is an important and approvable drug,” said Culley on a conference call, pointing out that International Conference on Harmonization (ICH) guidelines do not insist that stability testing is site-specific.
Adventrx maintains that according to ICH it is acceptable to include stability data from batches made at the first CMO, alongside additional data showing equivalence between material made at the two production sites.
However, Culley said there have been other cases where the FDA has issued refusal to file letters tied to stability data, suggesting that the agency may have changed its interpretation of the ICH guidance to require 12 months, real-time data from the commercial production facility.
If that is the case, refilling of the dossier could be delayed for six to seven months while Adventrx generates the stability data from batches made at the commercial plant, said Culley.
Adventrx’ emulsion formulation of vinorelbine is designed to reduce the side effects associated with currently-available formulations of the drug, particularly injection site reactions which occur in around a third of patients.
Vinorelbine is approved to treat advanced non-small cell lung cancer (NSCLC) and breast cancer and has a worldwide market of around $200 million a year.
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