FDA Details Authorized Treatment Pathways and Collection Requirements for Administration of COVID-19 Convalescent Plasma

As the number of infections from severe acute respiratory syndrome coronavirus 2 (“SARS‑CoV‑2”), the virus that causes COVID-19, continues to rise globally, interest in effective treatment options remains a concerted focus internationally. One potential treatment option that holds promise is the use of convalescent plasma. The FDA’s recently released “Investigational COVID-19 Convalescent Plasma, Guidance for Industry” (“FDA Guidance”) for health care providers and investigators establishes a process to study whether convalescent plasma collected from recovered COVID-19 patients might be an effective treatment approach. Although the FDA Guidance outlines clear and efficient processes for gaining access to COVID-19 convalescent plasma for patient treatment purposes, health care entities and their providers should also ensure that they comply with applicable Institutional Review Board requirements and entity-specific policies and procedures regarding the use of expanded access treatments before embarking on one of the FDA Guidance treatment options.

Convalescent Plasma and Its Potential for Treatment of COVID-19

People who have recovered (or convalesced) from a virus-caused disease develop antibodies (also known as immunoglobulin) to the disease in their blood. These antibodies are capable of fighting the virus that causes the disease. When the blood is processed, blood cells separate from the liquid plasma which retains antibodies to the virus. The remaining antibody-rich plasma is referred to as convalescent plasma. In other coronavirus-based diseases such as Severe Acute Respiratory Syndrome and Middle East Respiratory Syndrome, transfusing individuals with convalescent plasma has been shown to shorten the duration of the illness, reduce morbidity or prevent death. However, this must be counterbalanced by the understanding that convalescent plasma may not always be effective in treating viral infections, such as when a similar approach was tried with limited success to treat Ebola, a filovirus.

Despite the risk of potential lack of therapeutic effect, the United States and other countries have hopes that COVID-19 convalescent plasma transfusions may result in similar benefits to patients suffering from severe or life-threatening effects of the SARS-CoV-2 virus. Preliminary research from China into the efficacy of COVID-19 convalescent plasma for patients suffering from severe or life-threatening cases shows some indication that convalescent plasma may help treat COVID-19. However, convalescent plasma has not yet been shown to be safe and effective as a treatment for COVID-19 and is not an FDA-approved treatment. To facilitate studies of this treatment in the United States, the FDA Guidance identifies the appropriate regulatory pathways through which convalescent plasma treatments may be investigated and administered in the United States.

FDA Provides Three Authorized Pathways for Administration and Study of Investigational Convalescent Plasma

Despite preliminary research findings, COVID-19 convalescent plasma has not yet been approved for use by the FDA and, thus, is still regulated as an investigational product. Therefore, the administration of COVID-19 convalescent plasma must be authorized under an investigational new drug application (“IND”). There are three IND pathways (collectively, “Pathway(s)”) discussed in the FDA Guidance:

Traditional IND regulatory pathway (“Clinical Trial”);
Expanded use access IND (“Expanded Access”); or
Single-patient emergency investigational new drug application (“Single Patient eIND”).

Each FDA-detailed Pathway has specific eligibility criteria for patients and process requirements.

The Clinical Trials Pathway is appropriate for patients who meet the eligibility criteria for participation in randomized clinical trials and must follow the traditional IND requirements.[1] This Pathway will only be available to physicians and patients that have access an active randomized clinical trial investigating COVID-19 convalescent plasma.
The Expanded Access Pathway is only available to patients with serious or immediately life-threatening COVID-19 who are not eligible for randomized clinical trials or who are otherwise unable to participate in the Clinical Trial Pathway.[2] Such patients must participate through an expanded access protocol that is already in place. The FDA is currently working with the Mayo Clinic and other academic and federal partners to facilitate a nationwide National Expanded Access Treatment Protocol (“National EA Protocol”). Physicians and acute care facilities must sign up for the National EA Protocol for their patients to be eligible to participate and patients must meet specific inclusion criteria to receive the treatment.
The Single Patient eIND Pathway is available to patients who are otherwise unable to participate in either the Clinical Trial or Expanded Access Pathways. If an individual patient has a serious or immediately life-threatening COVID-19 infection, the patient’s physician may request FDA authorization to use an investigational drug to treat the patient if regulatory criteria are met.[3] To obtain authorization from the FDA under this Pathway the provider must include a brief clinical history of the patient and determine that the probable risk to the person from the investigational drug is not greater than the probable risk from the disease or condition.[4]

Collecting and Sourcing COVID-19 Convalescent Plasma

For participation in any Pathway, the health care provider must also include information about the intended source of COVID-19 convalescent plasma. Under IND regulations, an investigational drug – in this case, COVID-19 convalescent plasma – must meet certain chemistry, manufacturing, quality, purity and strength requirements. To demonstrate that the COVID-19 convalescent plasma adheres to these requirements, health care providers and acute care facilities must obtain COVID-19 convalescent plasma from an FDA-registered blood establishment that follows donor eligibility criteria. In addition to meeting regulatory blood donor[5] and plasma donor[6] eligibility requirements, the FDA-registered blood establishment must also ensure that the COVID-19 convalescent plasma donor also demonstrates:

Laboratory documented COVID-19 via nasopharyngeal swab or positive serological test for SARS-CoV-2 antibodies after recovery, using a test that has been appropriately qualified and validated;
Complete resolution of symptoms for a specified amount of time;
Negative for HLA antibodies; and
Presence of SARS-CoV-2 neutralizing antibody titers, if available.

Practical Takeaways

If you are a health care provider or entity interested in administering COVID-19 convalescent plasma to your patients, you should:

Determine whether your institution has access to one or more of the Pathways, and, if so, complete any necessary registrations, submissions and/or contracts;
Identify whether you have adequate access to a FDA-registered blood establishment that meets the COVID-19 convalescent plasma donor eligibility criteria required by the FDA;
Discuss the potential treatment pathway with your entity’s Institutional Review Board; and
Review your entity’s policies and procedures related to expanded access treatments, including applicable informed consent forms.

For all Pathways, there are specific requirements that must be met, including the provision of information to the FDA. The FDA has committed to an expeditious review of all requests in order to facilitate these treatment responses to the COVID-19 pandemic.

Hall Render is actively tracking all FDA guidance related to the COVID-19 pandemic and regulation of COVID-19 convalescent plasma. For guidance on obtaining FDA authorization to administer COVID-19 convalescent plasma or related issues please contact:

If you have any questions on the issues discussed in or related to this article, please contact:

Melissa Markey at (248) 740-7505 or mmarkey@wp.hallrender.com;
Amy Poe at (919) 228-2404 or apoe@wp.hallrender.com;
Andrew Harrison at (414) 721-0467 or aharrison@wp.hallrender.com;
Kathryn Costanza at (303) 801-3534 or kcostanza@wp.hallrender.com; or
Your regular Hall Render attorney.

Resources

[1] See generally 21 C.F.R. Part 312.

[2] 21 C.F.R. § 312.305.

[3] 21 C.F.R. § 312.310.

[4] 21 C.F.R. § 312.310(a).

[5] 21 C.F.R. §§ 630.10; 630.15.

[6] 21 C.F.R. § 630.15(b).

Hall Render’s attorneys and professionals continue to maintain the most up-to-date information and resources at our COVID-19 Resource page, through our 24/7 COVID‑19 Hotline at (317) 429-3900 or by contacting your regular Hall Render attorney.

Hall Render blog posts and articles are intended for informational purposes only. For ethical reasons, Hall Render attorneys cannot—outside of an attorney-client relationship—answer specific questions that would be legal advice.