Final Summary of the PPTA-FDA Liaison Meeting: October 7, 2021
The following is a final summary of the PPTA-FDA Liaison Meeting held virtually on October 7, 2021.
Welcome, Introductions & Meeting Guidelines
PPTA’s Senior Director, Advocacy and Regulatory Policy, opened the meeting with introductory remarks. PPTA Chief Legal Officer and Vice President, Global Initiatives, advised the participants on the meeting guidelines and the antitrust statement. PPTA President and CEO welcomed all participants and invited everyone to attend the Global Plasma Summit next month.
PPTA’s current priorities were presented to FDA. The priorities included remedies for current donation concerns caused by COVID-19 and the prohibiting of Mexican nationals from crossing the US border to donate, donor health projects, conflicts between federal records retention requirements and state biometrics privacy acts, advocating for the inclusion of plasma derived pharmaceuticals within the Mutual Recognition Agreement, inventory hold, concern about the potential elimination of the HBsAg blood donor test, and improving communication with OBRR staff. PPTA also shared their restructuring activities which will take effect in 2022.
FDA shared their initiatives with PPTA. Their initiatives included expediting the development and availability of COVID-19 vaccines, initiating the implementation of the bespoke gene therapy program, improving compliance with the tissue regulations (HCT/Ps), moving forward research informing blood donation policies (including policies on MSM donations), advancing blood component pathogen reduction research, addressing gene therapy human resource and infrastructure needs, and ensuring workforce resilience during the remainder of the pandemic.
In response to FDA’s initiatives, PPTA emphasized that blood donation policies should be separate from plasma donation policies because behavioral risks and fractionation are different between the two industries. PPTA also appreciated FDA’s challenges from the pandemic and shared that centers were also having workforce challenges.
FDA Remote Inspections
PPTA provided a presentation on how COVID-19 changed both surveillance inspections and center licensure inspections to remote or desk audit inspection. There were multiple pros to the new inspection process including the ability to have new centers licensed during the inspection, remote inspections maintaining safety for both the FDA and the firm it inspects, reductions in time from submission to licensure, more consistent document preparation and submission and firm can support the inspection with fewer resources. However, there were a few cons such as lack of communication from FDA regarding review status, inability to resolve questions or comments quickly, fewer opportunities for communication between the firms and FDA, inability to download large document files to a centralized location and lack of consistency in timelines, reviewers, and document management. PPTA also showed that data comparing days from collection start to FDA licensure from 2016-2018 and 2019-2021 that showed a statistically significant reduction in the latter dates compared to the former. PPTA asked FDA to continue the desk audit and hybrid approach for both pre-license inspections and routine surveillance inspections but enhance communication.
FDA responded by asking for more clarification on the data as 2019 preceded the change from inspections to no inspections PPTA stated that the companies were asked to send in data for all facility approvals that did not include a physical , which included collection start dates in 2019. FDA mentioned that it initiated a change in submissions earlier this year by requesting that the supplement not be sent until the facility was operational for 90 days, which allowed the immediate request for records and facilitated FDA’s reviews. By their data, in June 2020 it took 214 days to licensure and by May 2021, it reduced to 71 days. PPTA acknowledged that the process change by FDA prevented the comparison of the submission to licensure dates. PPTA data represented date of opening to licensure.
For surveillance inspections, FDA stated that the 704(a)(4) records request (Form FDA 4003) in advance of the inspection is not a substitute for the inspection but can increase the interval between when an inspector visits the center and can shorten the inspector’s time onsite. Their reviewers and investigators are also frustrated by communication difficulties. FDA is looking for other ways to integrate the records request and interactive communications by using platforms, such as Microsoft Teams and Zoom, to share screens reviewing records, but still needs to find a uniform secure way to send/share records and data. FDA also stated they will have dialogue during the document review/hybrid inspection process and will advise when the process is closed and will follow up in writing.
PPTA asked FDA/CBER who can they contact for general questions, questions related to review or progress updates. FDA/CBER stated that firms can contact their assigned Regulatory Program Manager (RPM) as they are moving away from single calls to be more consistent in their advice and to document the process. For general questions unrelated to a firm’s specific submission, FDA/CBER stated firms can contact CBER/OBRR Blood and Plasma Inquiry Box or they can set up a formal meeting .
FDA/CBER asked PPTA to share examples of inconsistencies focusing on after the RPM program was put into place so they can discuss internally and can consider other improvements.
Donation Suitability Requirements
PPTA discussed the April 2020 Guidance that allows Source Plasma donations to be used when the review of records required after donation identifies that the donation was unsuitable because of blood pressure, pulse, weight, donation frequency or if the donation was otherwise suitable under 21 CFR 630.30(a). PPTA asked FDA in the presentation to make these changes permanent and to expand the guidance to include all requirements found in 21 CFR 630.10, 21 CFR 630.15 and 21 CFR 640.65 that do not have an impact on the safety or quality of the product.
FDA responded that they continue to accept individual requests for 21 CFR 640.120 alternative procedures as they recognize that errors are made. The reasons and causes for errors will be investigated. The guidance mentioned in the CBER guidance agenda is being drafted, and FDA will look forward to PPTA’s comments.
PPTA stated that missing the initial syphilis test is the cause for many of the errors as there are many reasons that may include not drawing the sample but also shipment and laboratory mistakes. Unlike other tests that are amenable to using back-up samples, the test requirements for syphilis testing allow less flexibility.
Donor Registration/Presence of a Physician Substitute: When is a donor a donor requiring medical supervision?
PPTA provided a presentation asking FDA when is a donor “a donor” requiring onsite medical supervision? A company was cited for not having a physician substitute on site when a donor completed their donor eligibility screening on the kiosk, although the questions on the kiosk are the same questions a donor could choose to complete at home/outside the center using new technology. PPTA asked FDA what their current considerations were related to onsite presence of the medical staff in light of the adoption of electronic software advances into the donation process and how do they view onsite and offsite medical oversight for defined aspects of the donor eligibility process using technology.
FDA responded that this was a very general presentation. They stated that donor eligibility is in the regulations, specifically 21 CFR 630.5 for medical oversight. They stated that since each center would have different processes, they suggested that the centers contact FDA by using their Regulatory Process Manager, the inquiry box or request a meeting with FDA to submit and ask any specific questions they have or to discuss what they would like to change.
PPTA provided a presentation with the rates of nontreponemal and treponemal syphilis tests. This presentation was in response to a request from FDA at the 2020 Liaison Meeting. PPTA also emphasized that syphilis poses no concern regarding the safety, purity, potency, identity, strength or quality of source plasma or the finished product provided to patients, no transmissions of syphilis were ever reported with plasma-derived therapies and that current testing scenario denotes donor monitoring with no relevance for product safety.
FDA responded by thanking PPTA for the data and understands PPTA’s position regarding source plasma and the final product. FDA believes that the testing is beneficial to donors and public health, especially first-time donors. As research with blood donation policies are in FDA’s current initiatives, they will take this information and talk more internally.
Fractionation of Domestic Plasma from the United Kingdom (U.K.) to Manufacture Human Normal Immunoglobulins (Igs): FDA’s Current Considerations of Variant Creutzfeldt-Jakob Disease (vCJD)/Prion Safety of U.K. Plasma
PPTA provided a presentation on the April 2021 UK MHRA Assessment Report. The report concludes that the risk of vCJD cases from UK plasma was negligible and that UK-sourced plasma is acceptably safe for manufacture of Immunoglobulins. PPTA asked FDA how they viewed the UK decision, if there are plans to re-evaluate their risk assessment and donor deferral policies (in the 2020 Guidance) and what are their current considerations regarding technical requirements specifically for manufacturing of plasma from this geographical region.
FDA responded that the April 2020 Guidance reflects their current thinking and there are no immediate plans to revise it. However, FDA periodically reviews its recommendations on blood donation policies based on new information and will take any new evidence and data into consideration.
IQPP Standards Program Update
PPTA provided a presentation on the PPTA’s Standards Program, emphasizing both the IQPP and QSEAL voluntary standards.
PPTA restated that plasma donations have been declining since the start of the pandemic and that every donor and donation are important to ensure patients’ access to plasma protein therapies.
PPTA is thankful to the FDA for their willingness to continue to have this liaison meeting as stakeholder communications are important.
Cyndi Tolman, ADMA BioCenters
Kaitlin Kesterberg, ADMA Biologics, Inc
Alina Frantescu, Biotest
Jennifer Duven, BPL Plasma
Chaaya Ganorkar, Bio Products Laboratory
Emmanuelle Lecomte Brisset, CSL Behring
Kelly Hyatt, CSL Plasma
Eva Quinley, CSL Plasma
Erica Radojewski, Emergent BioSolutions
Tiffany Ramsey, GCAM, Inc.
Kelly Smith, Grifols, Inc.
James Knowles, Grifols, Inc.
Michael Messick, ImmunoTek
Nelli Cherny, KEDPlasma
Michele Battle, Octapharma Plasma
Ron Kraiss, The Interstate Companies
Julio Padilla Gil, Scantibodies Laboratory
Jorge Escasan, Scantibodies Laboratory
Roger Brinser, Takeda
Barbara Glantschnig, Takeda
Celia Witten, MD, PhD, CBER Deputy Director
Diane Maloney, JD, OD, Associate Director for Policy
Sherry Lard, PhD, Associate Director for Quality Assurance
Nicole Verdun, MD, Director
Anne Eder, MD, PhD, Deputy Director
Jennifer Scharpf, MPH, Associate Director for Policy and Communications
Janet Goldberg, JD, MPH, Regulatory Counsel
Hira Nakhasi, PhD, Director, Division of Emerging & Transfusion Transmitted Diseases (DETTD)
Orieji Illoh, MD, Director, Division of Blood Components and Devices (DBCD)
Wendy Paul, MD, Deputy Director, DBCD
Richard McBride, Chief, Blood DBCD, Plasma Branch (BPB)
Mahmood Farshid, MD, Deputy Director, DPPT
Dorothy Scott, MD, Chief, Plasma Derivatives Branch (PBD)
Scott Brubaker, Director, Division of Human Tissues (DHT)
Anne Rowzee, PhD, Associate Director for Policy
Susan Rogerson, Division of Inspections and Surveillance/Acting Program Surveillance Branch Chief
Susan Turcovski, Deputy Program Director, Office of Biological Products Operations (OBPO)
Pauline Cottrell, Consumer Safety Officer, Manufacturers Assistance & Technical Training Branch (MATTB)
Amy Efantis, President & CEO
Josh Penrod, Senior Vice President, Source & International Affairs
Mary Gustafson, Vice President, Global Regulatory Policy
John Delacourt, Chief Legal Officer and Vice President, Global Initiatives
Dominika Misztela, Senior Director, Regulatory Policy Europe
Bill Speir, Senior Director, Advocacy and Regulatory Policy
Larisa Cervenakova, Medical Director
Sonia Balboni, Director, Source & Standards
George Schreiber, Director, Epidemiology
Michelle Fransen, Project Manager, Health Initiatives
Michelle Mason, Coordinator, Regulatory Policy