Because life sciences companies hope to never end up on clinical hold, preparing for such a call from the U.S. Food and Drug Administration (FDA) is often not on the to-do list. But there can be significant advantages to advance preparation. Following are some tips for life sciences companies on navigating that first call with FDA and the actions that follow:
- Full or Partial Hold? Believe it or not, many companies can walk away from a clinical hold notification call from FDA without knowing whether an ongoing trial is on full or partial clinical hold. In a partial clinical hold, some portion of the trial is allowed to continue during the pendency of the hold, such as allowing already enrolled patients to continue receiving treatment but preventing new patients from enrolling in the trial during the hold. For trials with enrolled patients, knowing if dosing can continue in the enrolled population without interruption can be critical to preventing disruption in the data set for those already enrolled patients. For companies that forget to clarify a full vs. partial hold on the initial call, it is possible to follow up with FDA thereafter but there can be response delays getting additional information from FDA, which can affect dosing timelines.
- CMC or Clinical Concerns? Companies can receive clinical holds both for chemistry, manufacturing and controls (CMC) concerns with investigational drugs as well as for clinical concerns, such as with unexpected serious adverse events that may be treatment-related. In order to quickly plan a hold resolution strategy, it is important to know whether FDA’s imposition of a clinical hold is in response to CMC vs. clinical concerns. Where the concerns may be CMC in nature, if there is enough clinical supply of investigational product free of the concerns FDA has raised, this can be a factor in support of a partial clinical hold that would allow continued dosing and enrollment using the unaffected clinical batches.
- FDA’s Specific Concerns? First-time recipients of clinical holds may not realize it, but FDA has 30 calendar days to provide a detailed listing of the reasons it has imposed a clinical hold. This fact alone places pressure on the recipient of the initial call from FDA to learn as much as possible during that brief interaction in order to inform the company’s communication and “next steps” strategies.
- Who Needs to Know? Upon learning about a clinical hold, companies need to quickly mobilize a communication strategy, not only to communicate with their clinical site investigators but also with co-development or collaboration partners or other parties they may be required by contract to notify of clinical holds. Additionally, for public companies, timely disclosure of clinical holds to investors may be required depending on the circumstances, so it is critical for companies to bring in their in-house and outside counsel immediately to carefully assess such disclosure obligations and strategy. If a company has an impending quarterly or annual SEC filing or is scheduled to speak at an investor or medical conference at the time it receives the clinical hold, careful consideration should be given as to what additional information, if any, regarding the hold (and the clinical program more generally) should be included. In the event that a public disclosure to investors is necessary, drafting the public disclosure can be challenging due to the uncertainty and potential development delays that a clinical hold can cause, particularly given that the specific details as to the reasons for the clinical hold may not be provided for up to 30 days by FDA. This is, again, why learning as much information as possible on the initial call from FDA is critically important.
- Additional Considerations? Prior to public disclosure, a clinical hold may be considered material non-public information under the federal securities laws, so companies should consider whether it is necessary to close their trading windows or restrict particular individuals from trading in the company’s stock. If the company is in the midst of an offering when it receives the clinical hold, it most likely will need to disclose the hold to the underwriters and in its offering materials. Similarly, if a company is in the midst of a corporate transaction when it receives the hold, it likely will need to disclose the hold to the potential counterparty under NDA and provide information and/or documentation regarding the hold in the due diligence process.
The Goodwin FDA, Corporate, and Securities teams work closely with private and public life sciences companies on clinical hold communication, response, and remediation plans. Given the number of factors and considerations at play, navigating clinical holds requires a well-coordinated plan across the regulatory, clinical, corporate, and securities functions within a company. Contact Goodwin FDA team members Julie Tibbets or Caroline H. Bullerjahn for any questions about clinical holds.