January was a busy month for the US Food and Drug Administration’s precision medicine efforts, as the agency produced guidance on ASO drugs for patients with debilitating or life-threatening genetic disorders and guidance on manufacturing considerations for certain cellular and gene therapy products during the COVID-19 pandemic.
The agency first issued a draft guidance to facilitate the development of individualized antisense oligonucleotide (ASO) drugs for patients with severely debilitating or life-threatening genetic disorders (ASO Guidance). The Food and Drug Administration (FDA) also issued a guidance, with immediate effect, on manufacturing considerations for licensed and investigational cellular and gene therapy products during the COVID-19 public health emergency (Manufacturing Guidance). Sponsors investigating or marketing these products should pay special attention to the discussion in these documents, as FDA outlines its approach to COVID-19 and development considerations with respect to these personalized therapies.
The Manufacturing Guidance supplements FDA’s June 2020 guidance on Good Manufacturing Practice Considerations for Responding to COVID-19 Infection in Employees in Drug and Biological Products Manufacturing. However, because cell and gene therapy (CGT) manufacturers may face special challenges, FDA recommends that CGT manufacturers perform risk assessments to identify, evaluate, and mitigate factors that may allow for the transmission of SARS-CoV-2 through CGT products. Any plans should take into account FDA’s view that allogeneic products may be associated with a higher risk of infection compared to autologous products.
FDA specifically recommends the following:
As always, any adopted risk assessment and mitigation strategies must be documented and approved by the manufacturer’s quality unit, should include scientific justification and literature references, and should be submitted to FDA.
Turning away from the current COVID-19 crisis, FDA indicated that it is also looking ahead to the continued advancement of personalized therapies, issuing the ASO Guidance to assist sponsor investigators in the development of individualized ASO products for severely debilitating or life-threatening genetic diseases that are tailored to a patient’s specific genetic variant. As noted by FDA, the ASO Guidance is targeted to academic investigators, who may be less familiar with FDA’s requirements and less experienced in interacting with FDA.
While the specific impetus for this guidance is unclear, assumedly FDA is receiving more inquiries regarding individualized ASO drugs from investigators, patients, or those acting on their behalf. Regardless of the reason, healthcare institutions where ASO products are used should familiarize themselves with FDA’s requirements and processes to ensure that any use of an investigational ASO product accords with FDA’s regulations. It will also be important that manufacturers supporting the use of ASO products or that later intend to work with ASO product investigators ensure that programs comply with FDA’s regulations via contractual agreements and, as appropriate, due diligence.
For these programs, FDA recommends the following:
The ASO Guidance is likely a first step in the development of individualized therapies. As stated by FDA, the agency is “optimistic that development of [ASO] individualized drug products may spur gene sequencing that leads to the development of additional individualized drug products.” Accordingly, through the ASO Guidance, FDA aims to determine the most effective and efficient way to bring personalized drugs to patients, while ensuring the right risk-benefit balance.
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