Authorized by the 21st Century Cures Act , Food and Drug Administration’s (FDA) Oncology Center for Excellence (OCE) was established in January 2017. OCE was established to facilitate the development and clinical review of oncology products by uniting scientific experts across the FDA’s product centers to conduct expedited review of drugs, biologics, and devices. In May 2019 OCE launched Project Orbis, a framework for concurrent marketing application submission and review of oncology products among international partners. This leverage of the regulatory partnerships between international agencies provides patients with a high unmet medical need faster access to innovative cancer therapies across multiple countries. Project Orbis Partners (POPs) began with Australia and Canada and have expanded to include Brazil, Israel, Singapore, Switzerland, and the UK. Additionally, in 2023 the European Medicines Agency (EMA) expressed interest in participating as an observer.
Advantages of Project Orbis:
- Global Collaboration: Project Orbis allows regulatory agencies from different countries to collaborate, streamlining the drug approval process by reducing overlapping Health Authority comments.
- Faster Approvals: By reviewing and approving oncology drugs simultaneously across multiple countries, Project Orbis accelerates the availability of treatments to patients globally. This speed can be critical for patients with limited treatment options.
- Harmonized Standards: Participating agencies align their review criteria, making it easier for drug developers to navigate the regulatory landscape across multiple countries. This consistency benefits both patients and pharmaceutical companies.
- Expanded Clinical Trial Opportunities: Project Orbis encourages global clinical trials, allowing researchers to collect data from diverse patient populations. This can lead to more robust evidence supporting drug efficacy and safety.
The first step for participation in Project Orbis is for applicants to determine which of the three Types of Project Orbis submissions to pursue: A, B, or C. This typically requires discussion with FDA’s OCE who will communicate with the POPs. The three types of Orbis submissions are:
- Type A: Marketing applications are submitted to POPs within 30 days of submission to FDA.
- Type B: Marketing applications are submitted to POPs with a >30-day delay or a regulatory action >3 months of the regulatory action taken by the FDA, with the possibility of concurrent or overlapping review.
- Type C: Marketing applications are submitted with a >30-day delay or a regulatory action >3 months of the regulatory action taken by the FDA, with no concurrent or overlapping review.
Companies interested in pursuing Project Orbis will need to determine additional strategy requirements to submit an NDA / BLA under Project Orbis. While many development activities remain the same as a typical registration application, companies pursuing a global marketing strategy should pay particular attention to regional requirements for POPs so they are fully prepared. Regulatory strategy should include pre-submission meetings, determining CMC content beyond that detailed in ICH (International Council for Harmonisation) M4Q Guideline and the associated M4Q Q&A Guideline, as well as regional expedited pathway flexibility such as EMA Priority Medicines (PRIME) or FDA Manual of Policies and Procedures (MAPP) 5015.13 Quality Assessment for Products in Expedited Programs. Brazil, in particular, has RDCs (Resolution of the Collegiate Board) requiring information different from ICH M4Q.
Companies should be aware that a Product Quality Assessment Aid (PQAAid) will be required for a Project Orbis marketing application. The PQAAid is an Office of Pharmaceutical Quality-specific iteration of the Assessment Aid (AAid) which summarizes relevant quality information to assist regulatory reviewing tasks for NDA/BLA original applications. In the context of Project Orbis, the AAid and PQAAid provide a medium for sharing applicant data summaries and reviewer assessments across regulatory organizations.
Companies will interact with Health Authorities (HA) separately for pre-submission meetings and applications will be submitted separately to FDA and POPs. Each HA will maintain their own review timelines, milestones, communication with applicants, and expected response times. Collaborative review may occur between HAs, especially under the Type A procedure, which may streamline some review comments from HAs to avoid repetitive questions.
It is critical for companies to map out HA review timelines, including anticipated information requests (IRs) and timing requirements for response to questions, so teams are prepared for an influx of queries and potential overlap preparing multiple responses at the same time. Prior to HA questions, teams must prepare for the high volume of activity from concurrent review of several marketing applications. Applicants need to be prepared with rapid response teams to manage questions related to quality, nonclinical and clinical development for information requests from several authorities arriving within the same timeframe, some with defined timeframes (Israel, Brazil, Switzerland, Australia), some with turnaround times as rapid as 48 hours (e.g. Canada), others arriving without defined timelines or response (e.g. US).
FDA provided a Project Orbis update at a November 2023 Pharmaceutical Quality Symposium sponsored by the Small Business and Industry Assistance (SBIA) program at FDA’s Center for Drug Evaluation and Research (CDER). R. Angelo de Claro, Division Director for CDER Office of Oncologic Diseases (OOD) highlighted that project ORBIS has grown continually since its inception. A total of 369 applications have been submitted to the program since its inception, representing a significant jump from the 27 submitted in 2020.
De Claro highlighted that Project Orbis in the first 3.5 years included 80 unique “projects”; 33% were for new molecular entities, and the remainder were either new indications or new dosage forms for pediatric populations. He noted that Project Orbis comprises 40% of the FDA’s oncology division workload and an average of three countries were involved per application.
One of the program’s benefits is that it enables FDA’s oncology review staff to share their expertise with other HA regulators. The oncology division has a full-time staff of 280 people comprised of oncologists, analysts, statisticians, clinical pharmacologists, nonclinical and project managers organized into 18 disease-specific areas.
As mentioned above, planning and strategy are key to success with Project Orbis. De Claro noted some logistical challenges posed by the simultaneous review of applications by multiple authorities, including coordinating reviews across multiple time zones, applicants submitting/managing concurrent applications, translation requirements, and operational considerations such as different review clocks. Careful consideration and planning requiring management of resources, communication plans, and tracking tools will drive whether a company is successful when undertaking Project Orbis.
Syner-G consultants who attended the June 2024 DIA Global Annual meeting noted many conference sessions highlighted Project Orbis as an example of successful collaboration between international health authorities to provide lifesaving drugs to patients. Dr. De Claro shared OCE success with Project Orbis, Dr. Tamy Kim, OCE’s Director for Regulatory Affairs and Regulatory Policy, cited 521 applications under Project Orbis, of which 96% were approved. Dr. Julie Tierney, CBER’s deputy center director for strategy, policy and legislation expressed the CBER goal to utilize global collaboration similar to Project Orbis. Indeed, in January 2024, FDA announced a pilot program called Collaboration on Gene Therapies Global Pilot (CoGenT Global). Inspired by Project Orbis, the initiative, conducted in collaboration with FDA’s global regulatory partners including the World Health Organization and ICH members, which includes the EU, Japan, Canada, and Switzerland, is intended to explore the potential for concurrent, collaborative review of gene therapy applications.
Syner-G BioPharma Group has experience with Project Orbis submissions and the PQAAid. The regulatory team has experience with Project Orbis programs and can be a strategic partner for applicants interested in submitting their NDA or BLA under Project Orbis. Additionally, Syner-G provides depth of experience across many global marketing applications and different product modalities. Additionally, we have strong project management capabilities with proven tools to manage a high volume of information with tight timelines. Additionally we have a strong and nimble Regulatory Operations team who can adeptly coordinate global electronic submissions across regions for timely submissions.
