Alternative Procedures for Blood and Blood Components During the COVID-19 Public Health Emergency Guidance for Industry U.S. Department of Health and Human Services Food and Drug Administration Center for Biologics Evaluation and Research April 2020 Contains Nonbinding Recommendations Preface Public Comment This guidance is being issued to address the Coronavirus Disease 2019 (COVID-19) public health emergency. This guidance is being implemented without prior public comment because the Food and Drug Administration (FDA or Agency) has determined that prior public participation for this guidance is not feasible or appropriate (see section 701(h)(1)(C)(i) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) and 21 CFR 10.115(g)(2)). This guidance document is being implemented immediately, but it remains subject to comment in accordance with the Agency’s good guidance practices. Comments may be submitted at any time for Agency consideration. Submit written comments to the Dockets Management Staff (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. Submit electronic comments to https://www.regulations.gov. All comments should be identified with the docket number FDA-2020-D-1137 and complete title of the guidance in the request. Additional Copies Additional copies are available from the FDA webpage titled “Coronavirus Disease 2019 (COVID-19),” available at https://www.fda.gov/emergency-preparedness-and- response/mcm-issues/covid-19-related-guidance-documents-industry-fda-staff-and-other- stakeholders, and from the FDA webpage titled “Search for FDA Guidance Documents” available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents. Additional copies of this guidance are also available from the Office of Communication, Outreach and Development (OCOD), 10903 New Hampshire Ave., Bldg. 71, Rm. 3128, Silver Spring, MD 20993-0002, or by calling 1-800-835-4709 or 240-402-8010, or email ocod@fda.hhs.gov, or from the Internet at https://www.fda.gov/vaccines-blood- biologics/guidance-compliance-regulatory-information-biologics/biologics-guidances. Questions For questions on the content of this guidance, contact OCOD at the phone numbers or email address listed above. Contains Nonbinding Recommendations Table of Contents I. INTRODUCTION ................................................................................................................... 1 II. BACKGROUND ...................................................................................................................... 2 III. NOTICE OF EXCEPTIONS OR ALTERNATIVES .......................................................... 3 IV. RECOMMENDATIONS ........................................................................................................ 4 V. IMPLEMENTATION ............................................................................................................. 4 Contains Nonbinding Recommendations Alternative Procedures for Blood and Blood Components During the COVID-19 Public Health Emergency Guidance for Industry This guidance represents the current thinking of the Food and Drug Administration (FDA or Agency) on this topic. It does not establish any rights for any person and is not binding on FDA or the public. You can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations. To discuss an alternative approach, contact the FDA staff responsible for this guidance as listed on the title page. I. INTRODUCTION The Food and Drug Administration (FDA or Agency) plays a critical role in protecting the United States (U.S.) from threats including emerging infectious diseases, such as the Coronavirus Disease 2019 (COVID-19) pandemic. FDA is committed to providing timely guidance to support response efforts to this pandemic. FDA is issuing this guidance to provide a notice of exceptions and alternatives to certain requirements in Title 21 of the Code of Federal Regulations (CFR) regarding blood and blood components. This notice of exception or alternatives to certain requirements is being issued under 21 CFR 640.120(b) to respond to a national public health need and address the urgent and immediate need for blood and blood components. We expect that the alternative procedures will improve availability of blood and blood components while helping to ensure adequate protections for donor health and maintaining a safe blood supply for patients. The alternative procedures are intended to remain in effect only for the duration of the public health emergency related to COVID-19 declared by the Department of Health and Human Services (HHS), including any renewals made by the Secretary in accordance with section 319(a)(2) of the Public Health Service Act (PHS Act). FDA intends to provide further notification when the alternative procedures are no longer in effect. Given this public health emergency, and as discussed in the Notice published in the Federal Register of March 25, 2020, titled “Process for Making Available Guidance Documents Related to Coronavirus Disease 2019,” available at https://www.govinfo.gov/content/pkg/FR-2020-03- 25/pdf/2020-06222.pdf, this guidance is being implemented without prior public comment 1 Contains Nonbinding Recommendations because FDA has determined that prior public participation for this guidance is not feasible or appropriate (see section 701(h)(1)(C)(i) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) and 21 CFR 10.115(g)(2)). This guidance document is being implemented immediately, but it remains subject to comment in accordance with the Agency’s good guidance practices. In general, FDA’s guidance documents, including this guidance, do not establish legally enforceable responsibilities. Instead, guidances describe the Agency’s current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word should in Agency guidance means that something is suggested or recommended, but not required. II. BACKGROUND There is currently an outbreak of respiratory disease caused by a novel coronavirus. The virus has been named “SARS-CoV-2” and the disease it causes has been named “Coronavirus Disease 2019” (COVID-19). On January 31, 2020, HHS issued a declaration of a public health emergency related to COVID-19 and mobilized the Operating Divisions of HHS. 1 In addition, on March 13, 2020, the President declared a national emergency in response to COVID-19. 2 SARS-CoV-2 has demonstrated the capability to spread rapidly from person to person, leading to significant impacts on healthcare systems and causing societal disruption. Respiratory viruses, in general, are not known to be transmitted by blood transfusion. There have been no reported cases of transfusion-transmitted coronavirus, including SARS-CoV-2, worldwide. However, the COVID-19 pandemic has caused unprecedented challenges to the U.S. blood supply, including collections of blood and blood components for transfusion and collections of Source Plasma for further manufacture into plasma derivatives. As the COVID-19 pandemic affects communities, blood establishments and plasma donation centers across the nation have experienced a dramatic reduction in collections. Blood establishments have issued urgent appeals for blood donation and FDA has issued a public statement on the importance of maintaining the nation’s blood supply during the COVID-19 pandemic. 3 FDA’s information to blood establishments regarding COVID-19 is available at: https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/updated-information-blood- establishments-regarding-novel-coronavirus-outbreak. 1 Secretary of Health and Human Services Alex M Azar, Determination that a Public Health Emergency Exists. Jan. 31, 2020. (Accessible at https://www.phe.gov/emergency/news/healthactions/phe/Pages/2019-nCoV.aspx). 2 President Donald J. Trump, Proclamation on Declaring a National Emergency Concerning the Novel Coronavirus Disease (COVID-19). Mar. 13, 2020. (Accessible at https://www.whitehouse.gov/presidential- actions/proclamation-declaring-national-emergency-concerning-novel-coronavirus-disease-covid-19-outbreak/). 3 FDA Statement, Coronavirus (COVID-19) Update: Blood Donations (Accessible at https://www.fda.gov/news- events/press-announcements/coronavirus-covid-19-update-blood-donations). 2 Contains Nonbinding Recommendations III. NOTICE OF EXCEPTIONS OR ALTERNATIVES To address the urgent and immediate need for blood and blood components in the U.S. during the COVID-19 public health emergency, effective immediately, the Director, Center for Biologics Evaluation and Research (CBER), is issuing the following exceptions or alternatives under 21 CFR 640.120(b) to the following requirements regarding blood and blood components, including Source Plasma. The alternative procedures are intended to remain in effect only for the duration of the public health emergency related to COVID-19 declared by HHS, including any renewals made by the HHS Secretary in accordance with section 319(a)(2) of the PHS Act, or until FDA provides further notification. 1. 21 CFR 630.30(a)(2) and 21 CFR 630.30(b)(1): To release donations for transfusion or further manufacturing when the review of records, required after donation under 21 CFR 630.30(a)(2), identifies the donation as unsuitable because of failure to follow procedures to ensure that the donation would not adversely affect the health of the donor (i.e., 21 CFR 630.10 (f)(2) for blood pressure; 21 CFR 630.10 (f)(4) for pulse; 21 CFR 630.10 (f)(5) for weight; and 21 CFR 630.15(a)(1) for donation frequency), and the donation is otherwise suitable under 21 CFR 630.30(a). By issuing this alternative procedure, FDA is continuing to require that blood establishments determine donor eligibility consistent with 21 CFR 630.10 and 21 CFR 630.15 and not collect blood from a donor found to be ineligible prior to collection. However, in the event that an error occurred during the eligibility determination, we are allowing release of blood components collected from certain ineligible donors, because of the urgent need for blood components during the pandemic. The alternative procedures do not apply to donations found unsuitable because of screening test results or risk factors for relevant transfusion- transmitted infections (RTTI) or other factors that would affect safety of the blood or blood component. Therefore, we expect an increase in available blood and blood components, while maintaining the health of blood donors and safety of blood and blood components. 2. 21 CFR 640.69(f): To release Source Plasma donated by paid donors and determined to be suitable for further manufacturing into injectable products after a quarantine hold of 45 calendar days, instead of 60 calendar days, provided all other donor eligibility and donation suitability requirements are met. By issuing this alternative procedure, FDA is permitting release of Source Plasma from quarantine hold fifteen days sooner than required under the regulation to address the urgent need for Source Plasma during the pandemic. The requirement for quarantine hold is intended to permit the retrieval of a Source Plasma donation in the event it is later determined to be unsuitable because of RTTI screening test results or the donor is deferred for other factors. Reducing the timeframe for the quarantine hold during the pandemic is expected to increase the availability of Source Plasma without compromising the safety of the Source Plasma and plasma-derived products because blood establishments must continue to comply with the requirements for donation suitability in 21 CFR 630.30, and additional 3 Contains Nonbinding Recommendations restrictions on distribution in 21 CFR 640.69(e). In accordance with 21 CFR 640.69(e), Source Plasma must not be distributed for further manufacturer into injectable products until the paid donor has a record on two occasions in the past six months of meeting the eligibility requirements under 21 CFR 630.10 and negative test results for all relevant transfusion- transmitted infections. FDA intends at a later date to consider whether permanent changes to the applicable regulations would be appropriate. 3. 21 CFR 630.10(c)(2): To clarify a donor’s response or obtain omitted information required to determine donor eligibility and component suitability within 72 hours of the time of collection, instead of within 24 hours of the time of collection. 21 CFR 630.10 (c)(2) authorizes blood establishments to clarify donor records after collection in the event that, upon review, establishments find that a donor’s responses to the donor questions were incomplete. Under this regulation, establishments may clarify a donor’s response or obtain omitted information within 24 hours of collection. This clarification applies only to responses to donor questions. It does not apply to information establishments are required to obtain as part of the physical assessment of donors required in 21 CFR 630.10(f). In addition, blood establishments must continue to comply with donation suitability requirements in 21 CFR 630.30. By issuing this alternative procedure and permitting blood establishments to clarify a donor’s response to questions within 72 hours of collection, we expect an increase in available blood and blood components, while maintaining the health of blood donors and safety of blood and blood components. FDA intends at a later date to consider whether permanent changes to the applicable regulations would be appropriate. IV. RECOMMENDATIONS Blood establishments may adopt the above-listed alternative procedures to improve availability and reduce shortages of blood and blood components, including Source Plasma, during the public health emergency related to COVID-19. If, based upon the available scientific evidence, including epidemiologic evidence, the risk to the safety of the blood supply or the risk to donors’ health significantly changes, the Director of CBER may update the above-listed alternative procedures as warranted. FDA intends to provide further notification when the alternative procedures are no longer in effect. V. IMPLEMENTATION A. Reporting Changes to an Approved Application 1. Licensed blood establishments that intend to implement any of these exceptions and alternative procedures must submit a Changes Being Effected (CBE) Supplement under 21 CFR 601.12(c)(5) (see 21 CFR 601.12(a)(3)). The blood 4 Contains Nonbinding Recommendations and blood components made using the change may be distributed immediately upon receipt of the supplement by FDA. You may include multiple alternative procedures in the same supplement. Include the following information in your CBE Supplement: a. Form FDA 356h “Application to Market a New or Abbreviated New Drug, or Biologic for Human Use”. b. Cover letter describing the contents of the supplement. c. Specific description(s) of the alternative procedure(s) that will be implemented during the COVID-19 pandemic and the applicable regulation(s). d. The blood components that will be collected or manufactured under the alternative procedure(s). e. A list of facilities that will be implementing the alternative procedure(s). f. A description of processes you will follow (e.g. revision of blood establishment computer software) to implement the alternate procedure(s). 2. Unlicensed blood establishments are not required to report this change to FDA. B. Requests for Other Alternative Procedures Licensed and unlicensed blood establishments must submit requests for alternative procedures other than those described in this guidance document under 21 CFR 640.120 (a). 5