Regulatory Submission Review

Background

ECI was engaged by a global biopharmaceutical manufacturer of medicinal products, some of which are provided along with a device constituent making these products fall under the definition of a drug-device combination product per the US and EU regulations. The firm intended to supplement one of its products’ Biologics License Application (BLA) to obtain approval from the Food and Drug Administration (FDA) for the release of a new configuration into the US marketplace.

Objective

The objective of the engagement was to perform an independent, mock FDA review of the client’s supplement Biologics License Application (sBLA), specifically:

• To identify potential risks in terms of requests for information (RFI) that may be issued by FDA on the device constituent.

• Propose revisions to the application as well as recommendations to mitigate risks including robust justifications or identify data for the client to proactively collect in anticipation of a deficiency.

ECI Engagement

ECI assigned a Principal Regulatory Consultant, who was a former FDA reviewer, with many years of review at the device center and who served as an independent consultant reviewer at the FDA drug center for drug data integrity and current good manufacturing practice (CGMP) compliance.  

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During this independent review, ECI received the project background information including the historical FDA communication regarding the pending sBLA. Our ECI consultant pursued any information available on the submission of competitive combination products, device and performance standard requirements, and guidance.

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Submission feedback was categorized as either major or minor issues for the device constituent.  There were several proposed revisions to the performance testing summary and re-organization for alignment with FDA guidance and readability. Potential requests for information were discussed with the client’s team to proactively prepare responses to comprehensively address potential FDA inquiries efficiently.

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In addition to reviewing the submission content on the device constituent, ECI performed a data analysis using the client’s available drug stability study results. These results included the product configuration currently marketed in the US. The goal was to identify sources of variance across sets if any, to determine appropriateness of batch pooling and determine if the current marketed product configuration could be exploited for the estimation of the subject product expiration date. Data sets for the subject product configuration remained limited at the time of the analysis. The results of the analysis were discussed with the client’s team, along with the potential for FDA to request additional data, if an unsupported (longer) expiration date was proposed.

Results

The ECI mock FDA submission review allowed identification of potential areas of concern on the device constituent. Collaboration with the client resulted in modifications to their submission content to mitigate the risk prior to filing with the FDA. The stability data analysis helped the client to understand the potential risk, i.e., delay to product approval, when proposing a drug expiration date beyond what their data supports. This feedback enables the client to make an informed decision when presenting the drug expiration date or shelf life to the FDA. To date, the firm is pending FDA feedback on its sBLA and continues to collect additional results from its drug stability studies to further support its proposed product expiration date.