How to Successfully Respond to an FDA Information Request (IR)

How to Successfully Respond to an FDA Information Request (IR)

You’ve submitted a new drug application (NDA) or a biologics license application (BLA) for your new drug candidate. Congratulations! Now the long wait begins. Or not.

The US Food & Drug Administration (FDA) strives to review and act on applications within ten months for standard review or six months for priority review, but that doesn’t mean you won’t hear from them in the interim. In fact, it’s common for the FDA to issue an Information Request (IR) during its review cycle. When that happens, it’s critical that you respond quickly and effectively to get your vaccine or therapeutic approved in a timely way.

How and Why You Might Receive an IR

The FDA issues an IR when the application reviewers need additional information or clarification on your NDA or BLA.  The review team can issue an IR at any point in the review cycle for any section of your drug or biologic application.

IRs are issued while the application review is in progress, not upon its completion, and the review team considers your IR response during its normal review cycle. That’s good news for your approval timeline because it means the review clock—the timeline for your review—doesn’t stop when the IR goes out. But since the process keeps moving, you must respond promptly, thoroughly, and strategically to the IR. Though it’s not common, if your response is significant enough to be considered a major amendment to the application and received within the last three months of the review cycle, it could push the agency’s action due date out by three months.

When it comes to temperature-sensitive vaccines or therapeutics, various issues related to the cold chain can trigger an IR. In Modality Solutions’ experience helping pharmaceutical and biotech companies respond to FDA notifications, the following are among the most common cold chain-related issues an IR might cover.

• Confirmation of the drug product’s quality, stability, and safety after shipment. Temperature-sensitive drugs can encounter five hazards in transit: temperature, vibration, shock, pressure, and humidity. Increasingly, regulators expect a pharmaceutical or biotech company to provide DATA on tests performed evaluating environmental hazards and their effects on a drug product at the outer edge of its operating space. Using transport simulation like the type conducted in Modality Solutions’ Transport Simulation Lab is the fastest and most reliable way. Suppose an application doesn’t include transport simulation data to demonstrate that the drug’s quality, stability, and safety have been maintained in transit. In that case, regulators may issue an IR requesting simulation data or asking for a rationale to justify why stimulation testing wasn’t conducted.
• Proper performance qualification (PQ). When you transport a controlled-temperature drug product across a complex supply chain, you need to demonstrate that your cold chain process and packaging will perform sufficiently in the real world. Sometimes, an NDA or BLA fails to provide adequate documentation and DATA that the company has appropriately conducted the PQ in terms of procedure and testing levels. When that happens, it’s likely to trigger an IR.

How to Respond to an IR Successfully

To keep your NDA or BLA moving through the filing process smoothly, you need to respond to an IR quickly and effectively. A strategic approach typically follows these best practices:

• Don’t panic. IRs are a common occurrence in the NDA and BLA review process.
• Respond promptly. Unlike a Form 483 which you must respond to within 15 days, an IR doesn’t have a specific response due date. But the agency has issued an IR because it needs additional information to complete your review. To avoid holding up the process, reply as quickly as feasible.
• Only submit the requested information. Avoid offering additional details that weren’t requested, which could invite further questions or more IRs.
• Take a lesson from previous filings. If your organization has responded to IRs in the past, what’s worked and what hasn’t? Experienced cold chain specialists like Modality Solutions also can offer guidance based on their successful dealings with regulators.

Case in Point: Crafting A Successful Response

When a Modality Solutions client received an IR after filing a BLA for its antibody-drug conjugate (ADC), our engineers leveraged their experience with 250+ regulatory interactions to help the company respond. The ADC comprises a linker, a toxin, and a monoclonal antibody, and the latter can be considered its own drug product. The client had tested the ADC as a whole using transport simulation and had conducted a PQ on the antibody but had not performed transport simulation testing on the antibody separately. During the review cycle, the agency issued the following IR. The text has been redacted to protect the client’s anonymity.

“Insufficient information and data were provided in [REDACTED report] and [REDACTED report], [REDACTED vendor] to support an evaluation of [REDACTED product] shipping validation from [REDACTED location 1] to [REDACTED location 2]. Provide information and data to support an evaluation of the potential impact of commercial shipment of [REDACTED product] through each intended commercial shipping lane on product quality (e.g., biochemical stability). Data should include the evaluation of samples collected from the same [REDACTED product] lot prior to and after exposure to commercial shipping and handling conditions. If you intend to leverage data generated from simulated shipping studies, provide a detailed justification for how the type, sequence and duration of simulated shipping condition exposure are representative or worst-case relative to the seasonal temperatures, shipping route(s) and mode(s) of transportation expected during commercial shipment from [REDACTED vendor] to [REDACTED manufacturer]     .”

Modality Solutions quickly designed a transport simulation protocol for the mAb, conducted transport simulation testing in our Transport Simulation Laboratory, and provided the test results and other documentation the client needed to craft an IR response. The response was considered successful, the review cycle kept moving forward, and the client received full approval for its ADC.

Responding quickly and effectively to an IR is vital to keeping your NDA or BLA review process moving forward. Modality Solutions has extensive experience helping pharmaceutical and biotech companies respond successfully to IRs, with exceptional outcomes. Schedule a free consultation to learn how our proven approach can help you successfully file your drug product.