Congratulations to Moderna for receiving full U.S. FDA approval for their landmark SPIKEVAX COVID-19 vaccine. Moderna’s pioneering work in developing their messenger RNA (mRNA) vaccine has played a pivotal role in mitigating this global health crisis. We are proud to support Moderna with Clinical Quality Evaluations for their COVID Clinical Programs.
Learn more about Beaufort’s full range of Clinical Quality Oversight services and how we help sponsors demonstrate to the FDA that their trial meets the highest scientific and regulatory standards.
Moderna Receives Full U.S. FDA Approval for COVID-19 Vaccine SPIKEVAX
January 31, 2022
Approval based on a comprehensive submission package including efficacy and safety data approximately six months after second dose
SPIKEVAX has received approval by regulators in more than 70 countries, including Canada, Japan, the European Union, the UK, Israel
807 million doses of Moderna’s COVID-19 vaccine shipped globally in 2021; approximately 25% of those doses shipped to low- and middle-income countries
CAMBRIDGE, MA / ACCESSWIRE / January 31, 2022 /Moderna, Inc. (Nasdaq:MRNA), a biotechnology company pioneering messenger RNA (mRNA) therapeutics and vaccines, today announced the U.S. Food and Drug Administration (FDA) has approved the Biologics License Application (BLA) for SPIKEVAX (COVID-19 Vaccine, mRNA) to prevent COVID-19 in individuals 18 years of age and older.
“Our COVID-19 vaccine has been administered to hundreds of millions of people around the world, protecting people from COVID-19 infection, hospitalization and death. The totality of real-world data and the full BLA for Spikevax in the United States reaffirms the importance of vaccination against this virus. This is a momentous milestone in Moderna’s history as it is our first product to achieve licensure in the U.S.,” said Stéphane Bancel, Chief Executive Officer of Moderna. “The full licensure of Spikevax in the U.S. now joins that in Canada, Japan, the European Union, the UK, Israel, and other countries, where the adolescent indication is also approved. We are grateful to the U.S. FDA for their thorough review of our application. We are humbled by the role that Spikevax is playing to help end this pandemic.”
The FDA based its decision on the totality of scientific evidence shared by the Company in its submission package, which included follow-up data from the Phase 3 COVE study showing high efficacy and favorable safety approximately six months after the second dose. Moderna also submitted manufacturing and facilities data required by the FDA for licensure. SPIKEVAX has received approval by regulators in more than 70 countries.
Moderna’s COVID-19 vaccine was available under Emergency Use Authorization (EUA) in the U.S. from December 18, 2020. Under an EUA, the FDA has the authority to allow medical products to be used in an emergency to diagnose, treat, or prevent serious or life-threatening diseases or conditions during a declared public health emergency when there are no adequate, approved, and available alternatives. A booster dose of the Moderna COVID-19 vaccine at the 50 µg dose level is authorized for emergency use in the U.S. under EUA for adults 18 years and older. A third dose of the Moderna COVID-19 vaccine at the 100 µg dose level is authorized for emergency use in immunocompromised individuals 18 years of age or older in the United States who have undergone solid organ transplantation, or who are diagnosed with conditions that are considered to have an equivalent level of immunocompromise.
SPIKEVAX (COVID-19 Vaccine, mRNA) is a vaccine indicated for active immunization to prevent coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in individuals 18 years of age and older.
IMPORTANT SAFETY INFORMATION
Do not administer to individuals with a known history of severe allergic reaction (e.g., anaphylaxis) to any component of the vaccine.
Appropriate medical treatment to manage immediate allergic reactions must be immediately available in the event an acute anaphylactic reaction occurs following administration of the vaccine.
Postmarketing data demonstrate increased risks of myocarditis and pericarditis, particularly within 7 days following the second dose. The observed risk is higher among males under 40 years of age than among females and older males. The observed risk is highest in males 18 through 24 years of age.
Syncope (fainting) may occur in association with administration of injectable vaccines. Procedures should be in place to avoid injury from fainting.
Immunocompromised persons, including individuals receiving immunosuppressive therapy, may have a diminished response to the vaccine.
The vaccine may not protect all vaccine recipients.
Adverse reactions reported in clinical trials following administration of the vaccine include pain at the injection site, fatigue, headache, myalgia, arthralgia, chills, nausea/vomiting, axillary swelling/tenderness, fever, swelling at the injection site, and erythema at the injection site, and rash.
The vaccination provider is responsible for mandatory reporting of certain adverse events to the Vaccine Adverse Event Reporting System (VAERS) online at https://vaers.hhs.gov/reportevent.html or by calling 1-800-822-7967.
In 10 years since its inception, Moderna has transformed from a research-stage company advancing programs in the field of messenger RNA (mRNA), to an enterprise with a diverse clinical portfolio of vaccines and therapeutics across seven modalities, a broad intellectual property portfolio in areas including mRNA and lipid nanoparticle formulation, and an integrated manufacturing plant that allows for both clinical and commercial production at scale and at unprecedented speed. Moderna maintains alliances with a broad range of domestic and overseas government and commercial collaborators, which has allowed for the pursuit of both groundbreaking science and rapid scaling of manufacturing. Most recently, Moderna’s capabilities have come together to allow the approval of one of the earliest and most effective vaccines against the COVID-19 pandemic.
Moderna’s mRNA platform builds on continuous advances in basic and applied mRNA science, delivery technology and manufacturing, and has allowed the development of therapeutics and vaccines for infectious diseases, immuno-oncology, rare diseases, cardiovascular diseases and auto-immune diseases. Moderna has been named a top biopharmaceutical employer by Science for the past seven years. To learn more, visit www.modernatx.com.
Forward Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including regarding: the Company’s development of a vaccine against COVID-19 (mRNA-1273, or Spikevax); the ability of Spikevax to protect against COVID-19 and prevent infection, hospitalization and death; and the safety profile for Spikevax. The forward-looking statements in this press release are neither promises nor guarantees, and you should not place undue reliance on these forward-looking statements because they involve known and unknown risks, uncertainties, and other factors, many of which are beyond Moderna’s control and which could cause actual results to differ materially from those expressed or implied by these forward-looking statements. These risks, uncertainties, and other factors include those other risks and uncertainties described under the heading “Risk Factors” in Moderna’s most recent Annual Report on Form 10-K filed with the U.S. Securities and Exchange Commission (SEC) and in subsequent filings made by Moderna with the SEC, which are available on the SEC’s website at www.sec.gov. Except as required by law, Moderna disclaims any intention or responsibility for updating or revising any forward-looking statements contained in this press release in the event of new information, future developments or otherwise. These forward-looking statements are based on Moderna’s current expectations and speak only as of the date hereof.
The long-awaited Medical Device Coordination Group (MDCG) Guidance on Clinical Evidence is now available. The 31-page document, MDC 2022-2, outlines how clinical evidence is to be demonstrated pursuant to the requirements of the IVDR.
What does this mean for study sponsors and manufacturers? In short, the need for continuous oversight of clinical data and performance evaluation throughout the IVD’s entire lifecycle from pre-market release to post-market surveillance and follow-up.
The guidance, which also includes more than 5 pages of definitions, details the specific principles and procedures to follow over the entire lifetime of a product, with dedicated sections across the following areas:
General principles of Clinical Evidence
Performance evaluation process
The role of risk management in performance evaluation
Performance Evaluation Plan (PEP)
Scientific Validity, Analytical Performance and Clinical Performance
Performance Evaluation Report (PER)
Continuous update of the performance evaluation
The last point on continuous performance evaluation reflects the overarching approach manufacturers must adopt, as stated in the excerpt below:
“Scientific developments and improvements in state-of-the-art should be reviewed and assessed by the manufacturer on a regular basis as part of their continuous and pro-active postmarket surveillance activities. Therefore, manufacturers must instate a procedure for planned monitoring of scientific developments and changes in medical practice relevant to the IVD(s). Any relevant new information, developments and progress in the scientific field should trigger reassessments of the existing clinical evidence thus ensuring safety and performance through a continuous performance evaluation process.”
This guidance document also includes an appendix on the methodological principle for generating clinical evidence as well as the required frequency for updating reports. All of which reinforces the critical need for a systematic approach to short and long-term study planning – and the benefit of having Beaufort’s highly-skilled IVDR team by your side.
As we move closer to the May 2022 deadline where all IVD products marketed in the EU must meet the new IVDR regulations, it is imperative for manufacturers to begin the process of implementing the mandated requirements. To help manufacturers navigate this complex landscape, Karin Hughes, PhD, Senior Vice President, Regulatory & Quality, delivered a presentation during the 14th Annual IVD Clinical & Regulatory Affairs Conference in October, 2020. This webinar, Ensuring Compliance with IVDR Clinical Requirements, covers considerations and best practices across the following topics:
Developing clinical evidence reflective of a European population
Establishment of scientific, clinical, & analytical validity
Implementation of a risk based post market surveillance system
Confirming the IVD test adheres to “state of the art” definition
Beaufort can support all facets of your IVDR implementation. Our team of IVDR subject matter experts have an in-depth understanding of the complex details, regulatory expectations and new mandatory requirements. We provide the strategic and technical guidance to develop an appropriate project plan, as well as assist with the implementation of any stage of the IVDR certification process.
IVD Sponsors and CROs are tasked with identifying new processes and systems to facilitate clinical trial monitoring and management remotely due to COVID-19 restrictions. This requires developing and implementing plans to continue subject enrollment, sample collection and testing, efficient data collection and monitoring without the benefit of in-person, on-site review. The use of technology and innovation are critical to perform these clinical study tasks remotely and keep projects on track. During this webinar, Beaufort will review a case study that details the required planning and implementation of best practices to conduct monitoring visits remotely, including:
Factors in the Sponsor/CRO Assessments/Decision-making processes:
Which sites are equipped to participate in monitoring visits performed remotely?
Which types of visits can be performed remotely and related key considerations?
What technologies & processes can be used to remotely review source documents & site binder documents?
How to effectively communicate with the Principal Investigator and site staff without being on site?
Required updates to study documentation
Risks and Mitigations
Application of lessons learned to future clinical trials
During times of increased urgency for market-ready products, including the development of COVID-19 vaccines and therapeutics, the value of comprehensive Quality Oversight (QO) becomes even greater. This is underscored by the FDA’s mandate for all sponsors to validate the work of their CRO’s and ensure the integrity of their clinical trial data and rigor of the scientific process. This is where the Beaufort team can help.
Beaufort’s QO team are true innovators of this critically-needed service. Our comprehensive QO solutions provide an independent perspective that helps sponsors keep their commitment to developing products in accordance with the highest regulatory standards. As all businesses are adapting to the impact of the pandemic, Beaufort has continued to take the lead as our specialized teams are providing both remote and on-site QO services for a Phase 3 COVID-19 vaccine clinical trial.
Pioneering Innovation in Quality Oversight
Beaufort is proud to be the first to develop an independent Quality Oversight program to help sponsors objectively assess and improve CRO and site performance. We have worked with leading global sponsors and delivered a quantifiable approach to assessing data, processes and performance while optimizing the effectiveness and efficiency of their trials.
See how a global pharmaceutical company in need of Quality Oversight for a pivotal Phase 3 trial benefited from our services. Read
The Value of Independent Quality Oversight
Why should you outsource your QO needs to Beaufort? Our dedicated QO team are experts in critically assessing and providing unbiased feedback that results in opportunities for early process improvement and cost and time savings. We also provide:
Third-party assurance to regulatory agencies of your commitment to CRO oversight
Independent assessments that eliminate any inherent biases that may exist
Improved efficiencies and risk mitigation through co-monitoring
Better adherence to trial plans to reduce non-regulatory compliance
Communication and questions were the theme on November 28 at FDA’s Public Workshop on Troponin Assays — all about the opportunities and quandaries associated with high sensitivity and not so high negative predictive value. Consistent with this, slide decks were short and most of the time was spent in five different panel discussions. Below is a list of topics covered and a few notable points from each. Also, here’s a link an FDA page with recorded proceedings listed in sections – Part 1 through Part 4 – under Webcast Archive and Slides.
We’ll be watching for next statements and next steps from FDA, and we’re ready to work with clients who have pending matters in each of these areas.
Cut-Off Determination/Reference Interval Studies
Which subjects to enroll
How to analyze the data
What to do with outliers
Clinical Trial Design
Precision around each assay’s unique cut-off
Rapid rule out of MI
Informed consent challenges
Pre-Analytical and Analytical Considerations for Clinical Trials
Lab-to-lab and analyzer differences
Clinical Trials for Point of Care Devices
Sample matrix performance differences – whole blood vs plasma
Fresh vs transported samples
Use of Existing Clinical Data to Support Claims
Beaufort, a leading diagnostic CRO and Regulatory consultancy, is experienced in assisting clients with Troponin assay goals. We work with both clients and sponsors in developing assays and managing every stage of your clinical trial. Contact us to learn more about how we can support your Troponin and other clinical, regulatory, quality and staffing needs.
Lucy Gibney, MD, is Medical Director at Beaufort where she provides clients with a breadth of experience in medical, scientific and clinical leadership. Lucy advises operations staff in all aspects of medical management of clinical trials, while serving as a medical expert during the project delivery lifecycle.
Beaufort Solution: Beaufort helped the company resolve ASR compliance issues with the pre-IDE submission and crafted an appropriate pre-IDE submission and project plan. Prior to mediating the pre-IDE meeting with the FDA, Beaufort helped the company develop a presentation and assisted with a dress rehearsal.
Beaufort Solution: After identifying pathways to a Class II device classification, Beaufort prepared a strategic regulatory plan for the test kit, enabling the company to satisfy regulatory requirements in a cost-effective manner. Beaufort drafted a pre-IDE filing, including a clinical trial plan, and provided coaching to the client as it prepared for its pre-IDE meeting with the FDA. After successful meetings with FDA officials, the company relies on Beaufort for continued support as necessary, including assisting with preclinical and clinical trial activities.
Beaufort Solution: These actions included a review and revision of its Quality Document System, a review of its Computer System Validation (CSV) Plan, and performing Vendor Audit Assessments. Beaufort performed an in-depth review of the company’s current document system, including meetings with all key stakeholders. This review led us to suggest several alternative document structures. The final project deliverables included an SOP Assessment Report, complete Document Index, revised SOPs, Flow Diagrams, Glossary of Terms and Definitions and an SOP Writing Style Guide.
Beaufort Solution: Beaufort conducted these audits on behalf of the company, which allowed the company to make informed decisions as a clinical trial sponsor. This client has since requested Beaufort’s additional support in developing a Quality System and assisting with its 510(k) submissions.
Beaufort Solution: The client sought assurance that clinical data was valid and could support a PMA submission. Lacking sufficient internal resources, the client selected Beaufort to conduct the assessments. Beaufort planned and audited two clinical sites and worked with the client to gain historical information regarding site staff and data collection. Beaufort recommended performing an audit of the sponsor’s trial master file prior to auditing clinical sites, thus ensuring that the sponsor held required regulatory documents for each site. Beaufort provided audit reports and held subsequent discussions with the client, enabling it to make informed decisions regarding the integrity of data associated with the clinical trial. The output of these audits provided the client assurance that its required study files were in order for potential FDA inspection following the submission of the PMA.
Beaufort Solution: Realizing it had insufficient internal resources, the Quality Assurance division sought assistance in transitioning from a paper-based document system to a software-based document control system. Beaufort performed an initial review of its system to identify any existing gaps. This effort included a review of approximately 670 SOPs and 350 forms for content including obsolete references; document relevance; assignment of appropriate ownership/responsibility; and potential for SOP deletion, modification, or combination. In addition, Beaufort worked closely with functional areas to gain an understanding of the numerous processes and how they were potentially linked. This assignment led to a follow-on SOP project.
Beaufort Solution: The company’s products range from early detection and prevention of diseases to diagnosis, treatment and treatment monitoring, and this was the first time it had turned to outside resources to fill its needs. Beaufort developed a turnkey clinical trial management plan, beginning with site identification/qualification and essential document development for three separate clinical trials. In parallel, Beaufort performed a formal Risk Analysis Plan to ensure the project team was aware of the potential risks involved in performing three clinical trials within the very short time frame required by the client. The plan identified potential risks, mitigating factors and planned corrective actions if identified risks occurred. Beaufort initiated site identifications/qualifications and prepared the project operations.
Beaufort Solution: The company needed a clear regulatory strategy for bringing its project to market in the shortest possible time frame. In addition, the client needed clinical trial management and data entry to support a 510(k) submission to the FDA. Beaufort provided ongoing regulatory consultation and conducted the clinical trials, including site identification/qualification, clinical study and regulatory document preparation, IRB submissions, site monitoring and data entry in support of the company’s first 510(k) submission to the FDA.
Beaufort Solution: Beaufort provided clinical trial management support, including clinical trial and regulatory document preparation, IRB submissions, and clinical trial monitoring support. This support enabled the company to make its first successful 510(k) submission to FDA.
Beaufort Solution: The company’s previous interactions with FDA highlighted a need for assistance in finalizing its clinical trial protocol, subsequent clinical trial management, and preparing for a pre-IDE meeting with FDA. Beaufort developed a comprehensive clinical trial protocol that provided the statistical power to support the intended uses. Beaufort prepared the company for interactions with FDA and meetings with the agency. Following these meetings, FDA supported the clinical plan which enabled the trials to move ahead and Beaufort located, qualified, and coordinated clinical trial sites for a highly time-sensitive trial.
Beaufort Solution: Maintaining frequent contact with the client to stay abreast of ever-changing needs, Beaufort presents pre-screened and highly qualified candidates to the client’s management. This arrangement gives the client the ability to move forward with its field monitoring, knowing that its CRA pool can be supplemented with Beaufort field monitors across a wide spectrum of therapeutic areas and geographic locations. Beaufort’s flexibility, knowledge of monitoring practices, and our ability to deliver qualified CRAs in specific regions of the country has enhanced the client’s monitoring program and reduced travel costs.
Beaufort Solution: This was this division’s first use of an outside vendor to manage clinical trials in support of an FDA submission. Working closely with the client to obtain a full understanding of its processes, Beaufort created systems to manage the trials, combining the client’s operational procedures with our suggestions for system improvements. Clinical trial management included site and investigator qualification, IRB submissions, training, and site monitoring. Beaufort served as a conduit between the sponsors and the clinical sites during the trial for communications and trouble-shooting to ensure necessary processes, documentation, and data collection were in compliance with GCPs.
Beaufort Solution: The lack of internal expertise and infrastructure threatened this client’s ability to successfully achieve its business objectives. Beaufort was initially brought in for regulatory support, but as the project progressed, the client realized it needed assistance with clinical trial management as well. Beaufort created a collaborative environment to carry out the many responsibilities with the various partners in order to achieve the necessary results, including 510(k) clearance of this client’s medical device.
Beaufort Solution: Beaufort designed an IND strategy that addressed the challenges facing an oncology vaccine, while taking into consideration the problems faced by other companies with similar compounds. Beaufort provided CMC support for the client’s manufacturing efforts. In addition, Beaufort consulted on and prepared the pre-IND package for the FDA. The client received such a clear positive response to the package that a meeting with the agency was deemed unnecessary. This process facilitated the near-term development of its compound and led the way for the international Phase II program.
Beaufort Solution: Division management had a clear plan for the scope of its product but lacked the regulatory expertise necessary to devise the most time-efficient and cost-effective approach for launching a new product. The company engaged Beaufort to develop a comprehensive regulatory strategy focusing on all aspects of the new technology, including biomarker targets and methodology. Beaufort provided a complete regulatory strategy that classified the device for the company including identification of potential predicate devices and assessed the possible pathways for the product, as well as timelines, associated tasks, and costs for each type of submission. The company is using this strategy to plan its current product development. In follow-up to the initial Regulatory Strategy for 510(k) submission, the company tasked Beaufort with providing a Regulatory Opinion. Specifically, the company provided 14 questions regarding its top priority and most controversial products due to the biomarker detection and Beaufort provided comprehensive answers to all of the questions.
Beaufort Solution: In-house clinical trial plans and previous 510(k) submissions had been rejected by the FDA. The company engaged Beaufort to redefine the intended use of the assay and provide guidance regarding effective interactions with FDA. Beaufort redefined the intended use to specify the results of the product and to enable FDA to focus on the potential positive uses of the product. After previous applications, literature, and data were reviewed, Beaufort redesigned a clinical trial protocol that would support the new intended use of the assay, providing appropriate focus on the actual functionality of the product. This done, the client was positioned to move forward in their plans for the product.
Beaufort Solution: The company wanted a comprehensive regulatory perspective encompassing the various potential pathways for converting ASRs into diagnostic kits, as well as assistance in creating the pre-IDE information packages for each product. Working with the company’s internal resources, Beaufort completed this assignment, and, in addition, reviewed relevant literature and created a pre-IDE information package which included a high level clinical trial protocol for FDA review.
Beaufort Solution: Before engaging Beaufort, the company had been advised that it would be unable to register a major product in the United States. Beaufort worked with senior management to consider regulatory alternatives including a switch to cGMP-compliant manufacturing. As a part of the process, Beaufort provided a thorough review of all documents related to the company’s products, inspected its plant and other operations, and trained employees regarding regulatory process and criteria for submissions. As a result, the client passed a Health Canada regulatory inspection, won approval for its product in Canada, and is on the road to full cGMP compliance with an IND pending with FDA.
Beaufort Solution: Founded by an academic physician, a chemist, and a business person, the company had a clear vision regarding its business objectives but lacked the expertise necessary to navigate the FDA regulatory maze. As a result, its initial in-house orphan disease application was rejected by FDA. Realizing its need for experienced guidance, the company engaged Beaufort to develop a comprehensive regulatory strategy taking the compound’s history into consideration. Beaufort prepared a new orphan drug application, which was cleared in one review cycle. Beaufort also provided ready-to-use information for investor and academic presentations. Since engaging Beaufort, the company has increased fundraising, cleared an additional orphan drug application, and is proceeding with a sound regulatory strategy.
Beaufort Solution: Beaufort addressed numerous gaps with the client’s design control system to establish root causes, corrective and preventive action (CAPA) plans, and effectiveness verification checks. Specific gap-closure activities included procedure generation, training, Design History File (DHF) creation, and records review related to all aspects of design controls. Work involved interfacing with and engaging numerous site personnel having limited knowledge of regulatory regulations. The project was further challenged with aggressive business priorities that competed with the same personnel and involved multiple sites. Beaufort was instrumental in closing these gaps through a unique blend of hands-on involvement, training through mentoring, and great flexibility. Our collaboration and work with this client ensured it was capable of meeting regulatory and corporate requirements without impacting business objectives.