FY 2019 Report from the Director

Peter Marks smiling while sitting at desk.

Fiscal Year 2019 was an exciting time at CBER, as we continued to conduct important mission-oriented research and approved important new products that protect and improve public health. These included a novel gene therapy, vaccines, treatments for immune deficiencies, and tests for protection of the blood supply, among other products. We also conducted outreach to stakeholders and other public health agencies across the globe.

CBER approved Zolgensma, a gene therapy for pediatric patients less than two years of age with spinal muscular atrophy caused by a specific genetic mutation. We also approved three vaccines: Dengvaxia , to prevent dengue disease in individuals nine through 16 years of age with laboratory-confirmed previous dengue infection and living in endemic areas; Jynneos, to prevent smallpox and monkey pox disease in adults 18 years of age and older who are at high risk for either of these infections; and Vaxelis, to prevent diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B, and invasive disease due to Haemophilus influenza type b, for use in children from six weeks through four years of age.

In addition, we approved three treatments for primary immunodeficiency: XEMBIFY, indicated for patients 2 years of age and older; ASCENIV, indicated for adults and adolescents 12 to 17 years of age; CUTAQUIG, indicated for adults.

Our ongoing efforts to ensure the safety of the nation’s blood supply included approval of two assays that detect the genetic material of the Babesia species of protozoan parasites in whole blood specimens: the Procleix Babesia Assay and the cobas Babesia test for use on the cobas® 6800/8800 System. These assays enable screening of donated blood and living donors of organs and tissues.

These approvals are part of the overall success CBER had in FY 2019 in achieving or exceeding expectations of the Prescription Drug User Fee Act VI and Medical Device User Fee Amendments, as noted below.

In addition, CBER supported new product development by helping to manage and support the Complex Innovative Designs pilot program. This program enabled close collaboration with the Center for Drug Evaluation and Research to devise and disseminate a process for reviewing complex and innovative clinical trial designs. CBER also advanced work on the Biologics Effectiveness and Safety (BEST) post-market surveillance infrastructure, which significantly reduced the lag time to the identification of potential adverse events from approved products using claims data, electronic health records (EHR), and linked claims-EHR databases.

This report summarizes these and other achievements, which reflect our staff’s continued dedication to CBER’s mission and our ongoing commitment to improve public health globally.

Peter Marks, M.D., Ph.D.
Director
Center for Biologics Evaluation and Research

Approval of major, innovative, complex biologic products

In FY 2019, CBER product approvals reflected the center’s broad regulatory and research responsibilities, which contributed significantly to public health through treatment, prevention, and screening.

Office of Vaccines Research and Review

Jynneos (Smallpox and Monkeypox Vaccine, Live, Non-Replicating): Indicated for prevention of smallpox and monkeypox disease in adults 18 years of age and older determined to be at high risk for smallpox or monkeypox infection. (Sept. 24, 2019)
Dengvaxia (Dengue Tetravalent Vaccine, Live): Indicated for the prevention of dengue disease caused by dengue virus serotypes 1, 2, 3 and 4 and approved for use in individuals 9 through 16 years of age with laboratory-confirmed previous dengue infection and living in endemic areas. (May 1, 2019)
Vaxelis (Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Inactivated Poliovirus, Haemophilus b Conjugate [Meningococcal Protein Conjugate] and Hepatitis B [Recombinant] Vaccine): Indicated for active immunization to prevent diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B, and invasive disease due to Haemophilus influenzae type b. Vaxelis is approved for use as a 3-dose series in children from 6 weeks through 4 years of age (prior to the 5th birthday). (December 21, 2018)

Office of Tissues and Advanced Therapies

XEMBIFY (Immune Globulin Subcutaneous, Human-klhw, 20%): Indicated for the treatment of primary humoral immunodeficiency in patients 2 years of age and older. (July 3, 2019)
ZOLGENSMA (onasemnogene abeparvovec-xioi): Adeno-associated virus vector-based gene therapy indicated for pediatric patients less than two years of age with spinal muscular atrophy with bi-allelic mutations in the survival motor neuron 1 (SMN1) gene. (May 24, 2019)
ASCENIV (Immune Globulin Intravenous, Human-slra): Indicated for the treatment of primary humoral immunodeficiency in adults and adolescents 12 to 17 years of age. (April 1, 2019)
ESPEROCT (Antihemophilic Factor (Recombinant) GlycoPEGylated-exei): Extended half-life coagulation Factor VIII concentrate indicated for use in adults and children with hemophilia A for on-demand treatment and control of bleeding episodes, perioperative management of bleeding, and routine prophylaxis to reduce the frequency of bleeding episodes. (Feb. 19, 2019)
CUTAQUIG (Immune Globulin Subcutaneous [Human]): Indicated to treat primary humoral immunodeficiency. (Dec. 12, 2018)

Office of Blood Research and Review

Procleix Babesia Assay: Qualitative in vitro nucleic acid amplification test for the detection of RNA from Babesia species in whole blood specimens. It is intended for use in screening individual human donors, including volunteer donors of whole blood and blood components and in screening living donors of organ and tissue. It is also intended for use in screening cadaveric (non-heart-beating) donors for B. microti. (Jan. 24, 2019)
cobas® Babesia test for use on the cobas® 6800/8800 Systems: Qualitative in vitro nucleic acid screening test for the direct detection of Babesia (B. microti, B, duncani, B. divergens, and B. venatorum) DNA and RNA in whole blood samples from individual human donors, including donors of whole blood and blood components, and other living donors; also intended for use to screen organ and tissue donors when donor samples are obtained while the donor’s heart is still beating. (August 29, 2019)

Advancing access to safe and effective products

CBER continued to advance access to safe and effective products while achieving or exceeding expectations in its scientific and regulatory evaluation of new products. This includes the following accomplishments:

Prescription Drug User Fee Act VI (PDUFA)

As of June 30, 2019:

Received and filed five PDUFA BLA with two Standard review timelines and three PDUFA BLAs with Priority review designation. One of the BLAs with a Priority review designation has been approved. All others are within goal.

Of the five filed BLA PDUFA Original Applications CBER received in FY 2018, four have Standard review timelines, of which three have been approved and one has received a Complete Response decision. One BLA PDUFA Original Application has a Priority review designation and has been approved.

Generic Drug User Fee Amendments

As of June 30, 2019:

Received two ANDA applications during FY 2019. Of the two, one ANDA has been filed and the other has been designated as refused to receive. The filed ANDA is pending within goal.

Medical Device User Fee Amendments (MDUFA)

As of June 30, 2019, CBER had:

Reached all performance goals for 510(k) submissions, Real-Time PMA Supplements, and the PMA 180 Day Supplements. Those still under review are pending within the MDUFA goals.

Exceeded its performance target for FY 2019 510(k) submissions (95% within 90 FDA days), issuing a MDUFA decision on 100% of submissions received within 90 FDA days.

Exceeded its performance target for Real-Time PMA Supplements (95% within 90 FDA days).

Was meeting the FY 2019 95% within 180 FDA days performance target for PMA 180 Day Supplements.

Achieved or exceeded all MDUFA review performance goals for FY 2019. As of June 30, 2019, there were seventeen 510(k) applications with a MDUFA IV decision; 100% were acted on within goal. These within-goal actions include clearing seventeen 510(k) applications.

Reached a decision on one FY 2019 MDUFA IV PMA Real-Time Supplement.

Approved four of the five filed BLA PDUFA Original Applications received in FY 2018, three of which were approved and one of which received a complete response decision. One BLA PDUFA Original Application with a Priority schedule review designation was also approved.

Received and filed five PDUFA Biologics License Applications (BLAs) with two Standard review timelines and three PDUFA BLAs with Priority review timelines. One BLA with a Priority review timeline has been approved and all others were within goal.

21st Century Cures deliverables

CBER helped to manage and support the Complex Innovative Designs (CID) pilot program, working closely with the Center for Drug Evaluation and Research (CDER) to devise and disseminate a process for reviewing complex and innovative clinical trial designs. As part of this effort, CBER led the development of a draft guidance document, “Interacting with the FDA on Complex and Innovative Clinical Trial Designs for Drugs and Biological Products,” a 21st Century Cures deliverable (see Guidances section).

Patient-Focused Drug Development Guidance Workshop (Oct. 15-16, 2018) This workshop was designed to inform development of patient-focused drug development guidance as require by the 21st Century Cures Act of 2016 and as part of commitments made by FDA under the 6th authorization of PDUFA.

Expanded use of vaccines

Expanded use of Gardasil 9 (vaccine for all nine human papillomavirus types) to include women and men 27 through 45 years of age (October 5, 2018)

Approved Afluria Quadrivalent to include children 6 through 35 months of age for the prevention of seasonal influenza. (October 4, 2018)

Increasing efficiency of influenza reference reagent production

Increased the efficiency of influenza reference reagent production by: 1) improving the quality of candidate vaccine viruses; 2) accelerating production of sheep antiserum; 3) providing data to support use of alternative sera; 4) improving the product circular; 5) establishing a process for customer feedback.

Advancing Product Development & Ensuring Product Safety

Advancing Product Development

As part of its effort to facilitate the development and approval of safe and effective products, CBER works to identify stakeholder priorities and incorporate improved approaches to both research and regulatory science.

Established the CBER Advanced Technologies Team (CATT) to address the need for a maximally efficient, agile, flexible pharmaceutical manufacturing sector that reliably produces high quality biologics. CATT aims to achieve this vision by promoting dialogue, education, and input among CBER staff and between CBER and prospective innovators and developers of advanced manufacturing technology intended to be implemented in CBER-regulated products. The goal of this program is to promote a more robust manufacturing process with fewer interruptions in production, fewer product failures, and greater assurance that the biologic products will meet clinical performance expectations. CBER awarded several grants to support research projects to study and recommend improvements for the advanced manufacturing of biological products.
Established the Tissue Reference Group Rapid Inquiry Program (TRIP) to help the human cell, tissue, and cellular and tissue-based product (HCT/P) industry to obtain a rapid, preliminary, informal, non-binding assessment from FDA regarding how specific HCT/Ps are regulated. TRIP is a temporary program of the Tissue Reference Group that was established to respond in a very timely manner to each inquiry that contains enough detail for evaluation.
Signed a Memorandum of Understanding with the US Department of Defense (DoD) in November 2018 to ensure that products prioritized by DoD as important to the health of those involved in national defense receive the highest level of attention from the agency, on par with breakthrough designated therapies. CBER has met quarterly with DoD to better understand DoD’s priority product development areas and to ensure the agency is adequately resourced to enable the efficient development of safe and effective products. (Nov. 2018)
- OBRR granted a variance to the Department of the Army that allows cold storage of platelets for up to 14 days for the treatment of active bleeding when conventional platelets are unavailable or their use not practical. (August 2019)
Provided key leadership in the execution of a pilot training program on advanced therapies held by Northeastern University in Seoul, South Korea. The program was organized by the Asia-Pacific Economic Cooperation Regulatory Harmonization Steering Committee, which CBER chairs, in support of global regulatory convergence and harmonization in the emerging product area of advanced therapies. (July 30 – Aug. 1, 2019)
Contributed to agency efforts to enable patients to engage with FDA through various initiatives organized by the Patient Affairs Staff (PAS) in the Office of the Commissioner:
- Participated in planning meetings and provided input and feedback on the pilot plan to launch a Cross-Center Patient Inquiry Webform and the FDA/National Organization for Rare Disorders (NORD) disease listening session pilot.
- Attended FDA/NORD patient-led rare disease listening sessions organized by the Patient Affairs Staff (PAS).
- Attended Patient Engagement Collaborative (PEC) meetings and contributed input to priority topics to be considered by the PEC.
- CBER/OTAT and PAS worked together to organize the first FDA/NORD FDA-led rare disease listening session with patients, at which the topics were gene therapy and hemophilia.

Ensuring product safety: Regulatory actions

Part of advancing product development at CBER is ensuring the safety and effectiveness of new therapies. That includes, when necessary, taking action against products being unlawfully marketed and that pose a potential significant risk to patient safety, and informing the public of product safety issues. In FY 2019, FDA exercised its authority to address the problem of stem cell clinics offering unapproved therapies to consumers. Among the actions taken were the following:

FDA sent a warning letter dated August 28, 2019, to Stemell, Inc. (Stemell), of San Juan Capistrano, California, and its president and Chief Executive Officer, Peyman Taeidi, Ph.D., for manufacturing and distributing unapproved products derived from umbilical cord blood and umbilical cord and for significant deviations from current good tissue practice (CGTP) and current good manufacturing practice (CGMP) requirements. Stemell’s unapproved products derived from umbilical cord blood and umbilical cord were StemL UCB-Plus and StemL UCT-Plus.
The US Southern District of Florida issued an order on June 3, 2019 preventing US Stem Cell Clinic LLC, of Weston, Florida, and US Stem Cell Inc., of Sunrise, Florida, and their Chief Scientific Officer Kristin Comella, PhD, from manufacturing or distributing stromal vascular fraction products (adipose-tissue-derived stem cell products) until they come into compliance with the law. The court granted the government’s motion for summary judgment after concluding that the companies adulterated and misbranded stem cell drug products made from patients’ adipose tissue.
CBER sent an untitled letter dated May 28, 2019, to R3 Stem Cell, LLC of Scottsdale, Arizona, its more than 50 affiliate centers or clinics, and its chief executive officer, David Greene, MD, in response to the company’s offering unapproved stem cell products to treat a variety of diseases and conditions, such as Lyme disease, diabetes, Parkinson’s disease, stroke, kidney failure and amyotrophic lateral sclerosis.
FDA sent a warning letter dated October 31, 2018, to StemGenex Biologics Laboratories, LLC, for manufacturing and distributing unapproved products derived from adipose tissue, which are further processed into stromal vascular fraction (SVF), and for significant deviations from current good manufacturing practice. The company’s SVF products are administered in a variety of ways, including intravenously, inhalation via nebulizer, catheterization of the bladder, and intrathecally, and intended to treat a variety of diseases and conditions, including Alzheimer’s disease, multiple sclerosis, muscular dystrophy, Parkinson’s disease, and rheumatoid arthritis.
CBER issued 60 letters to separate manufacturers and health care providers across the country, notifying them that it has come to the attention of CBER that they appear to be offering unapproved stem cell products to treat a variety of diseases or conditions. The letters also inform the manufacturers and health care providers that FDA is currently applying a risk-based approach to enforcement, accounting for how products are being administered and the diseases and conditions for their use and remind them that the 36-month period during which FDA intends to exercise enforcement discretion will end in November 2020.
FDA advised consumers to be cautious about establishments that offer infusions of plasma obtained from young human donors with the claim that the infused plasma will treat a variety of conditions ranging from normal aging to memory loss. The advisory noted that there have been no well-controlled studies that show clinical benefit from administering plasma from young donors.
The Food and Drug Administration (FDA) informed blood establishments of recent reports of platelet contamination with Acinetobacter species bacteria. Bacterial contamination of platelets with this organism has caused septic transfusion reactions. Until the recent cases, Acinetobacter sp. had not been frequently identified as a contaminant in platelets.
FDA informed health care providers and patients of the potential risk of serious or life-threatening infections with the use of fecal microbiota for transplantation. (June 13, 2019)
FDA informed all stakeholders of additional protections needed for any investigational use of fecal microbiota for transplantation (FMT) based on the previous FDA communication on the potential risk of serious or life-threatening infections with the use of FMT. (June 18, 2018)

Ensuring product safety: Public meetings and projects

Office of Vaccines Research and Review

Convened the Vaccines and Related Biological Products Advisory Committee to select the influenza viruses for the composition of the influenza vaccine for the 2019-2020 U.S. influenza season. The viruses are selected based on the committee’s review and evaluation of influenza surveillance data collected from around the world. (March 6 and 22, 2019)
Participated in eight meetings sponsored by the World Health Organization that advised developing country national regulatory authorities on vaccine evaluation. This included participation in an Expert Committee on Biological Standardization (ECBS) and Global Advisory Committee on Vaccine Safety (GACVS) meetings.
Initiated two new virus spiking studies in collaboration with industry and 14 other laboratories to evaluate the sensitivity of virus detection using different next generation sequencing (NGS) platforms. One study will use the five reference virus stocks developed in CBER’s Office of Vaccines, Research and Review for standardization of NGS, which represents potential safety concerns in vaccines.
Participated in eight of the federal Influenza Risk Management Meetings (FRMM) to improve the annual seasonal influenza vaccine virus selection process.
Identification and Use of Biomarkers to Advance Development of Preventive Vaccines; Public Workshop (Sept. 16-17, 2019)
Exchanged information with stakeholders from industry, academia, and government about the scientific, clinical, and regulatory challenges encountered in the identification, characterization, and qualification of biomarkers for use in the development of preventive vaccines for infectious diseases indications.

Office of Tissues and Advanced Therapies

Developing Alpha-1 Antitrypsin Therapeutics; Public Workshop (Sept. 16, 2019)
The purpose of the public workshop was to foster the development of therapeutic products for the treatment of alpha-1 antitrypsin deficiency (AAT deficiency).
22nd U.S. - Japan Cellular and Gene Therapy conference on Adeno-associated Virus-Mediated Gene Therapy (March 7, 2019)
This conference included discussions of the most recent advances, key achievements, and emerging issues in the AAV-mediated gene therapy and regulatory consideration for clinical development of AAV-based vectors.
Quantitation of AAV-Based Gene Therapy Products (Dec. 07, 2018)
The purpose of the public workshop was to discuss best practices when measuring the concentration of AAV vectors and to provide FDA perspective on qualifying such assays. The public workshop brought together academia, industry, and other stakeholders involved in research, development, and regulation of AAV-Based gene therapy products.
Product Development in Hemophilia (Dec. 6, 2018)
OTAT collaborated with FDA’s Oncology Center of Excellence and the Center for Drug Evaluation and Research to present a public workshop on the development and regulation of novel hemophilia products.

Office of Blood Research and Review

Perspectives on In Vitro Diagnostic Devices Regulated by the Office of Blood Research and Review A public workshop to provide an overview of key elements of regulatory submission for these devices and to facilitate education and communication between manufacturers and sponsors of these devices and the divisions in CBER that regulate them. (July 15-16, 2019)
Blood Products Advisory Committee meeting (Includes links to videos of sessions) Two open sessions on consecutive days to 1) discuss and make recommendations on strategies to reduce the risk of Zika virus (ZIKV) transmission by blood and blood components; 2) discuss blood donation policies regarding men who have sex with men. (March 20-21, 2019)
Pathogen Reduction Technologies for Blood Safety A public workshop that included experts from academic institutions, industry, and government agencies, aimed at fostering the development and implementation of pathogen reduction technologies for blood components intended for transfusion. A conference report was subsequently published. (Nov. 29-30, 2018)

Office of Biostatistics and Epidemiology

OBE enhanced the Biologics Effectiveness and Safety (BEST) post-market surveillance infrastructure, which formerly consisted of mostly administrative claims data, restrictive pre-configured analytical tools, and a data lag of at least nine months. The newly enhanced system, which is part of the Sentinel initiative, comprises large-scale claims data, electronic health records (EHR), and linked claims-EHR databases with a data lag of approximately three months. Flexible analytic capabilities expedite both simple queries and complex observational studies of many biologic products. The system enables queries and surveillance studies of vaccines, blood-derived products, and blood components in multiple data sources. The linked claims-EHR database supports complex outcomes validation, such as pregnancy outcomes.
OBE conducted a vaccine study as a test case through the BEST System (see above). This study aimed to replicate a previous study by the Vaccine Safety Datalink (VSD) (Klein et al. Pediatrics 2010) that examined the databases and analytic capabilities of the new system. The objectives of this study included: 1) characterizing the capabilities of the newly commenced BEST Initiative; 2) becoming familiar with the operational components of the new system; 3) determining the new system’s ability to reproduce existing evidence for the increased risk of febrile seizures in children receiving the first dose of measles-mumps-rubella-varicella (MMRV) vaccine, compared to that of MMR and varicella vaccines separately but on the same day. The results of the OBE study fulfilled the objectives and demonstrated the ability of the BEST Initiative data network to run a complex study protocol at multiple sites using a distributed data network and the Observational Medical Outcomes Partnership Common Data Model (organizing disparate data sources into the same database design using a common format).
The Transfusion-Transmitted Infections Monitoring System (TTIMS) collected and validated data for over 23 million donations at participating blood establishments as of December 31, 2018. Data analyses were approved for the following:
- Donor and donation prevalence for HIV, HBV, and HCV.
- Classical incidence analysis among repeat donors for the TTIMS study period for HIV, HBV and HCV (September 2015 - December 2018).
- Incidence modeling for first time TTIMS donors for HIV, based on 1) evaluation of donor HIV antibodies, using LAg avidity assays that characterize “recent” HIV infection; 2) viral load testing.
OBE and the Centers for Medicare and Medicaid Services (CMS) developed capabilities for routine and time-sensitive assessments of the safety of vaccines for people 65 years of age and older. OBE, CMS, and the Centers for Disease Control and Prevention conducted near real-time surveillance and self-controlled, end-of-the-season analyses for the risk of Guillain-Barré syndrome (GBS) after influenza vaccination, which demonstrated the capability to rapidly assess safety signals generated by other data sources. A Rapid Cycle Analysis in the Vaccine Safety Datalink, led by the CDC found safety signals in the 2018-2019 influenza season for an increased risk of GBS following high-dose influenza vaccinations and Shingrix vaccinations. CBER, CDC, and CMS formed working groups in February 2019 to refine these safety signals in CMS data.

Mission-Related Research

CBER research is essential for supporting development of safe and effective new products and to the fulfillment of our mission of ensuring that products we regulate are safe, pure, potent, and effective. The following examples represent the broad scope of our research and illustrates the extraordinary expertise of our scientists.

Influenza candidate vaccine viruses improved by amino acid substitution in hemagglutinin
CBER developed two candidate vaccine viruses (CVVs) that may be used as the starting material for production of inactivated influenza vaccines. These CVVs protected laboratory animals against a highly pathogenic strain of Influenza A (H7N9), a potentially pandemic virus.
TCPro simulates immune system response to biotherapeutic drugs
CBER developed a mathematical tool that predicts whether the body will produce antibodies that block the activity of biotherapeutic protein drugs. The computational tool, called TCPro, simulates the response of the immune system’s CD4+ T cells to specific biotherapeutic drugs.
FDA identifies biomarker for immune response to FVIII products used to treat hemophilia A
CBER developed a technique for determining whether immune system cells called dendritic cells appear primed to trigger the production of antibodies against Factor VIII (FVIII) products used to treat hemophilia A. The technique might enable scientists to use the presence of such primed dendritic cells as biomarkers for potential immune reactions that would block the therapeutic effects of FVIII.
Luciferase Immunoprecipitation System (LIPS) assay is a rapid, simple, and sensitive test to detect antibody response to respiratory syncytial virus
CBER developed a simple, rapid, and sensitive test that identifies individuals who have made antibodies against respiratory syncytial virus (RSV), the most common cause of serious lower respiratory tract infection in infants and young children worldwide. RSV also affects many elderly individuals, especially those with underlying heart or lung disease, accounting for nearly as many hospitalizations as influenza. The assay could be a valuable tool for assessing the efficacy of RSV vaccines during clinical trials, since it can help to identify individuals infected with RSV following a winter season.
Cell analysis technique identifies subpopulations of stimulated mesenchymal stromal cells with in vitro immunosuppressive activity
CBER developed a strategy that may improve identification of batches of mesenchymal stromal cells (MSC) that can suppressive immune system activity. This ability of MSCs could make them useful for treating certain diseases, such as Crohn’s disease (chronic inflammation of the intestine) and multiple sclerosis (loss of nerve cell function due to immune reactions against nerve cells). The new technique, called functionally-relevant morphological profiling (FRMP), enabled the CBER scientists to predict how much a population of stimulated MSCs would be able to suppress key types of immune cells.
FDA poliovirus assay is faster and more versatile than current assays used in vaccine development and environmental surveillance
CBER developed a poliovirus assay that is faster and more versatile than those now used to monitor polio vaccine production, assess patient responses to polio vaccines during clinical trials, and do environmental surveillance of vaccine poliovirus. The assay is also the first to measure the amount of several different strains simultaneously in a mixture of polioviruses. The ability to identify and determine the quantity of several different viruses simultaneously enables the assay to rapidly process the large number of fecal samples collected from subjects during clinical trials, which is more time-consuming using current techniques.
FDA scientists discover key chemical steps in formation of microparticles carrying abnormal hemoglobin in sickle cell disease
CBER identified chemical reactions inside the red blood cells from a transgenic mouse mode with sickle cell disease (SCD) that help trigger the release of microparticles (MPs), small packets of the highly reactive form of SCD hemoglobin (Hb), called HbS, that contribute to some of the symptoms of this disease. The FDA scientists also reported for the first time a link between the abnormal chemical environment of SCD red blood cells and the destruction of HbS by a cellular structure called the proteasome. The findings of the study suggest new strategies using hydroxyurea (an FDA approved drug), that would lessen the intensity of the symptoms of this disease by blocking specific abnormal chemical reactions that occur in the red blood cells of SCD patients.

CBER Guidance for Industry

CBER produces Guidance documents to inform stakeholders of the center’s current interpretation of its regulations and ways that regulated industry can remain in compliance. The center also collaborates with other FDA centers on joint guidances that cover issues with intra-agency regulatory implications.

Office of Blood Research and Review

Bacterial Risk Control Strategies for Blood Collections Establishments and Transfusion Services to Enhance the Safety and Availability of Platelets for Transfusion; Guidance for Industry (Sept. 2019)
Provides recommendations to control the risk of bacterial contamination of room-temperature-stored platelets intended for transfusion that apply to all platelet products stored at room temperature in plasma or additive solutions; also provides licensed blood establishments with recommendations on how to report implementation of manufacturing and labeling changes under Title 21 of the Code of Federal Regulations (CFR) 601.12.
Testing for Biotin Interference in In Vitro Diagnostic Devices; Draft Guidance for Industry
(June 2019)
Provides recommendations on testing for interference by biotin on the performance of in vitro diagnostic devices; intended to help device developers and clinicians understand how FDA recommends biotin interference testing be performed, and how the results of the testing should be communicated to end-users, including clinical laboratories and clinicians.
Recommendations for Reducing the Risk of Transfusion-Transmitted Babesiosis; Guidance for Industry (May 2019)
Provides recommendations for donor screening, donation testing, donor deferral and product management to reduce the risk of transfusion-transmitted babesiosis.
Labeling of Red Blood Cell Units with Historical Antigen Typing Results; Guidance for Industry
(Dec. 2018)
Provides establishments that collect blood and blood components for transfusion, with recommendations for labeling Red Blood Cell (RBC) units with non-ABO/Rh(D) antigen typing results obtained from previous donations (historical antigen typing results); provides recommendations to transfusion services for managing RBC units labeled with historical antigen typing results; provides licensed blood establishments that choose to implement labeling of RBC units with historical antigen typing results instructions regarding how to report the manufacturing and labeling changes under 21 CFR 601.12.
Considerations for the Development of Dried Plasma Products Intended for Transfusion; Draft Guidance for Industry
(Oct. 2018)
Guidance to assist manufacturers, sponsors, and applicants developing dried plasma products intended for transfusion to facilitate the availability of safe and effective dried plasma products in the US: 1) considerations for the successful development and licensing of dried plasma products and for the approval of devices used to manufacture dried plasma; 2) recommendations on optimal sources of input plasma; 3) manufacturing and product quality, including product characterization; 4) packaging and reconstitution; 5) clinical studies; 6) device submissions.

Office of Tissues and Advanced Therapies

Expedited Programs for Regenerative Medicine Therapies for Serious Conditions; Guidance for Industry
(Feb. 2019)
Provides sponsors engaged in the development of regenerative medicine therapies for serious or life-threatening diseases or conditions with recommendations on the expedited development and review of these therapies, including as provided under section 506(g) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), as added by section 3033 of the 21stCentury Cures Act (Cures Act).
Evaluation of Devices Used with Regenerative Medicine Advanced Therapies; Guidance for Industry
(Feb. 2019)
Provides manufacturers, applicants, and sponsors engaged in the development of regenerative medicine therapies, with FDA’s current thinking regarding evaluation of devices used in the recovery, isolation, or delivery of regenerative medicine advanced therapies.

Office of Biostatistics and Epidemiology

Interacting with the FDA on Complex and Innovative Clinical Trial Designs For Drugs and Biological Products (September 2019)

Discusses the use of novel trial designs in the development and regulatory review of drugs and biological products, how sponsors may obtain feedback on technical issues related to modeling and simulation, and the types of quantitative and qualitative information that should be submitted for review.

CBER guidances in cooperation with other centers