Supporting an ANDA submission for a complex, generic drug-device product

A Canadian-based mid-size pharma company was developing a complex generic formulation of a "ready-to-use" injectable drug-device combination product. The product was intended to treat opioid overdoses. The sponsor recognised their generic drug’s potential for the US market. Commercialising the drug for the US required a submission to the US Food and Drug Administration (FDA). The sponsor sought support from ICON Regulatory Affairs to prepare for the FDA abbreviated new drug application (ANDA) submissions process. This process involves several phases including pre-submission, initial submission and FDA review. During the review phase the FDA can seek clarification and further information which require prompt responses.

ICON Regulatory Affairs team began by conducting a gap assessment of the available information, to build a regulatory strategy for the FDA submission. The dossier and device component information were complex. Unlike the reference product which required assembly prior to administration, the proposed product was “ready-to-use”. 

Specific issues were identified as crucial to a successful ANDA submission: 

• Reference product selection and availability
• Qualitative and quantitative similarity to the reference product
• Differences between the proposed and reference product
• Eligibility for a 505(j) ANDA pathway
• Eligibility for a waiver from submitting an in vivo bioequivalence (BE) study
• Reliability testing requirements of the drug-device combination product
• Comparative (threshold) analyses data reliability and need for a human factor study
• Additional product-specific CMC and labelling requirements

Failing to comply with these requirements could result in unfavourable FDA outcomes such as refusal to receive the submission or a denial of the ANDA application.

ICON Regulatory Affairs reviewed data from the FDA’s databases and the sponsor’s proposed product information. Based on this and supplemental information identified during the gap analysis, ICON developed a detailed regulatory strategy. ICON supported the sponsor for the FDA presubmission meeting by advising on the questions to ask, how the sponsor should represent their position and the rationale for the product. ICON ensured that the submissions dossier was acceptable, approvable and would avoid the FDA’s refuse-to-receive determination. Our support continued throughout the ANDA review to ensure prompt communications and timely responses to FDA queries. 

The sponsor availed of the following services from ICON:

• Acting as the sponsor’s US agent
• Medical device and CMC regulatory support
• Document authoring and reviewing
• Structured product labelling
• eCTD publishing and project management
• Priority review designation
• Maintaining establishment licenses and NDC codes

The FDA approved the sponsor’s ANDA application, enabling them to market their ready-to-inject treatment in the US. This life-saving treatment can be given to opioid overdose patients before emergency medical assistance is available. The sponsor was very appreciative of our support, as evidenced by their ongoing relationship with ICON for submissions for US marketing authorisation of other products and lifecycle maintenance of FDA-approved products.