Regulatory Focus™ > News Articles > FDA Form 483 for Botox Competitor's Manufacturer Could Delay BLA Approval

FDA Form 483 for Botox Competitor's Manufacturer Could Delay BLA Approval

Posted 29 January 2018 | By Zachary Brennan 

FDA Form 483 for Botox Competitor's Manufacturer Could Delay BLA Approval

The US Food and Drug Administration (FDA) last week posted a Form 483 with 10 observations for South Korea-based contract manufacturer Daewoong Pharmaceutical Co., which is manufacturing a Botox competitor (injectable 900 kDa purified botulinum toxin type A complex) for the company Evolus, which on Monday downgraded its plans for an IPO from $75 million to $65 million.

Evolus said in its S-1 filing that FDA conducted a cGMP and pre-approval inspection of Daewoong's manufacturing facility in South Korea from 8 November to 17 November 2017, which resulted in the Form 483. FDA has issued a Prescription Drug User Fee Act date of 15 May 2018 for completion of its review of Evolus' Biologics License Application. 

"The Form 483 includes observations relating to the need for adherence to and improved procedures, processes and documentation relating to investigations of and corrective actions for non-compliance with specifications for batches and components, environmental monitoring, drug substance testing, computer system access, material handling and staff training. Daewoong timely responded to the FDA with a plan for implementing corrective actions related to these observations and is awaiting a response from the FDA," Evolus said.

The top three observations in the 483 were related to failing to review unexplained discrepancies and the failure of a batch or any of its components, ensuring that all specifications, sampling plans and test procedure were scientifically sound and deficiencies in asceptic processing.

Daewoog has told Evolus, "it believes that its responses to the Form 483 will satisfy the requirements of the FDA and that no significant further actions will be necessary" but Evolus warns that FDA "may not be satisfied with such response, and it may require Daewoong to take additional corrective actions or other measures, require re-inspection, or decline to approve the facility. If any of these scenarios were to occur, we and Daewoong may be required to expend significant time and resources, which could cause delays and adversely affect our results of operations."

Daewoong's Botox rival for Allergan's product, which brought in $2.8 billion in 2016, was first sold in South Korea in 2014 and is now available in about 60 countries, according to Bloomberg.

Bernstein biotech analyst Ronny Gal said in an investor note on Monday that the 483 "does not contain any of the killer issues (honor code violations, physical facility problems, actually releasing dangerous products, not listening to FDA/making good on prior commitments). Instead they had large number (10) observations which address procedures, processes and validations. If this was a well-established facility, these would have been 'intermediate' problems; as this is a new facility and some gaps are to be expected, we would argue this is more on the mild side. That said, (i) this may still delay approval given the inherent riskiness of botulinum toxin and (ii) competitors will ostensibly share this letter with physicians as counter-detailing tool."

Form 483


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