The United States Food and Drug Administration (FDA) issued a new guidance for industry related to the Coronavirus Disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2). FDA issued the guidance, titled “Development and Licensure of Vaccines to Prevent COVID-19”, on June 30, 2020 without prior public comment typically associated with draft guidances. Therefore, the guidance document is being implemented immediately.
The guidance document outlines a series of recommendations intended to assist sponsors in the clinical development and licensure of vaccines for the prevention of COVID-19. The guidance reflects the Agency’s current thinking on the issue and is intended to remain in effect for the duration of the public health emergency.
FDA provides key considerations for COVID-19 vaccines in the following major categories. A few key considerations are summarized below:
- Chemistry, Manufacturing, and Controls (CMC)
- General considerations include:
- “COVID-19 vaccines licensed in the United States must meet the statutory and regulatory requirements for vaccine development and approval”¹
- “COVID-19 vaccine development may be accelerated based on knowledge gained from similar products manufactured with the same well-characterized platform technology to the extent legally scientifically permissible.”
- General considerations include:
- Nonclinical Data
- General considerations include:
- “Data from studies in animal models administered certain vaccine constructs against other coronaviruses have raised concerns of a theoretical risk for COVID-19 vaccine-associated enhanced respiratory diseases (ERD).”
- Toxicity Studies recommendations include:
- “In some cases, it may not be necessary to perform nonclinical safety studies prior to FIH [first in-human] clinical trials because adequate information to characterize product safety may be available from other sources. For example, if the COVID-19 vaccine candidate is made using a platform technology utilized to manufacture a licensed vaccine or other previously studied investigational vaccines and is sufficiently characterized, it may be possible to use toxicology data (e.g., data from repeat dose toxicity studies, biodistribution studies) and clinical data accrued with other products using the same platform to support FIH clinical trials for that COVID-19 vaccine candidate.”
- General considerations include:
- Clinical Trials
- General considerations include:
- Conducting clinical trials in the setting of a public health emergency presents operational challenges. FDA has issued guidance to provide general considerations to assist sponsors in assuring the safety of trial participants, maintaining compliance with good clinical practice (GCP), and minimizing risks to trial integrity for the duration of the COVID-19 public health emergency.
- Trial Populations considerations include:
- “FDA strongly encourages the enrollment of populations most affected by COVID-19, specifically racial and ethnic minorities.”
- “Evaluation of vaccine safety and efficacy in late phase clinical development I adults should include adequate representation of elderly individuals and individuals with medical comorbidities.”
- Trial Design considerations include:
- “Protocols for adaptive trials should include pre-specified criteria for adding or removing vaccine candidates or dosing regimens, and protocols for seamless trials should include pre-specified criteria (e.g., safety and immunogenicity data) for advancing from one phase of the study to the next.”
- “Follow-up of study participants for COVID-19 outcomes (in particular, for severe COVID-19 disease manifestations) should continue as long as feasible, ideally at least one to two years, to assess duration of protection and potential for vaccine-associated ERD as immune responses to the vaccine wane.”
- “Efficacy trials should include contingency plans for continued follow up and analysis of safety and effectiveness outcomes in the event that a safe and effective vaccine becomes available (e.g., as demonstrated in a planned interim analysis or as demonstrated in another clinical trial). In that case, discussion with the agency may be necessary to address ethical arguments to break the blind and offer vaccine to placebo recipients.”
- Efficacy considerations include:
- “As it is possible that a COVID-19 vaccine might be much more effective in preventing severe versus mild COVID-19, sponsors should consider powering efficacy trials for formal hypothesis testing on a severe COVID-19 endpoint.”
- Statistical considerations include:
- “To ensure that a widely deployed COVID-19 vaccine is effective, the primary efficacy endpoint point estimate for a placebo-controlled efficacy trial should be at least 50%, and the statistical success criterion should be that the lower bound of the appropriately alpha-adjusted confidence interval around the primary efficacy endpoint point estimate is >30%.”
- General considerations include:
- Post-Licensure Safety Evaluation
- General considerations include:
- “For COVID-19 vaccines, it is likely that during the early postmarketing period, a large population might be vaccinated in a relatively short timeframe. Thus, FDA recommends early planning of pharmacovigilance activities before licensure.”
- General considerations include:
- Diagnostic and Serological Assays
FDA reiterates several times throughout the guidance document that sponsor should engage in early communications with the appropriate office at each stage of development. Pearl Pathways routinely communicates with FDA on behalf of our clients and has direct experience supporting COVID-19 related products and research. If you require support for your COVID-19 related drug, device, or diagnostic, contact us today to schedule a free consultation.
¹ FDA Guidance for Industry: Development and Licensure of Vaccines to Prevent COVID-19