Hello Regulatory Scientists,
Today, let’s explore the journey of Jardiance (empagliflozin) from receiving an FDA Complete Response Letter (CRL) to achieving approval. This case study provides valuable insights and lessons that can guide companies developing new drugs today.
Regulatory History and Initial Submission
Drug: Jardiance (empagliflozin) Mechanism of Action: Sodium-glucose co-transporter 2 (SGLT2) inhibitor, which helps lower blood sugar levels by preventing glucose reabsorption in the kidneys Indication: Type 2 diabetes mellitus Initial Submission Date: March 2013
The Complete Response Letter (CRL)
CRL Date: March 2014 CRL Concerns:
1. Manufacturing Issues: Concerns related to the quality and consistency of the drug’s manufacturing process.
2. Labeling Requirements: Need for revisions in the proposed labeling to better reflect the drug’s safety and efficacy profile.
3. Cardiovascular Safety: Request for additional data to better understand the drug’s cardiovascular safety profile.
Resubmission Strategy
Boehringer Ingelheim and Eli Lilly, the companies behind Jardiance, implemented a comprehensive strategy to address the FDA’s concerns:
1. Enhanced Manufacturing Processes: Implemented improvements in the manufacturing process to ensure consistency and quality.
2. Additional Cardiovascular Data: Conducted further analyses and submitted additional data to address the cardiovascular safety concerns.
3. Revised Labeling: Made necessary revisions to the proposed labeling to clearly communicate the drug’s benefits and risks.
4. Continuous FDA Engagement: Maintained open lines of communication with the FDA to ensure alignment on the resubmission strategy and clarify any outstanding questions.
Resubmission Date: July 2014
Outcome
Approval Date: August 2014 Jardiance was approved for the treatment of type 2 diabetes mellitus, with specific post-marketing requirements to further monitor cardiovascular outcomes.
Lessons Learned
The journey of Jardiance from CRL to approval highlights several key lessons for drug developers:
1. Rigorous Manufacturing Standards: Ensuring the quality and consistency of the manufacturing process is crucial to avoid regulatory setbacks.
2. Comprehensive Data Submission: Providing additional data, particularly related to safety concerns, is essential to address the FDA’s queries.
3. Clear and Accurate Labeling: Revising labeling to clearly communicate the drug’s benefits and risks is necessary for regulatory approval.
4. Effective Use of Advisory Committees: Leveraging advisory committees can provide valuable feedback and support the resubmission process.
5. Continuous FDA Engagement: Maintaining open and ongoing communication with the FDA helps align development efforts with regulatory expectations.
Relevance for Current Drug Developers
For companies developing drugs today, the Jardiance case underscores the importance of strategic planning and meticulous attention to detail in the regulatory process. Here are some takeaways to help avoid a CRL and achieve first-cycle approval:
1. Thorough Pre-Submission Preparation: Ensure that all aspects of your submission, including manufacturing processes and labeling, meet FDA standards.
2. Proactive Risk Management: Identify and address potential risks early in the development process to prevent issues from arising during FDA review.
3. Engage with the FDA Early and Often: Regular interactions with the FDA can provide valuable guidance and help steer the development process.
4. Utilize Advisory Committees: Seek feedback from advisory committees to validate data and address potential concerns.
5. Invest in Quality Data: Prioritize the collection of high-quality, detailed safety and efficacy data to support the submission.
By learning from the Jardiance resubmission experience, current drug developers can better navigate the regulatory landscape, avoid common pitfalls, and increase the likelihood of a successful first review cycle approval.
Stay diligent and strategic,
CERES Regulatory Services
