Outputs: We will provide a training to LATAM in Biotherapeutics and Advanced Therapies.  The training will begin with asynchronous learning modules for biotherapeutics and advanced therapies, which will provide basic information to ensure participants are all on the same page.  Following this asynchronous training, synchronous webinar style training will be provided.  Over a two week time frame 8 hours of webinar based lectures will be provided to participants.  These webinars will occur on Tuesdays and Thursdays and consist of 2 45 minute lectures and 2 15 minute break-out sessions, respectively.  Following the synchronous webinars, in person case-study based trainings will occur in late 2021.  The first goal of this training is to develop an online training module in Biotherapeutics and Advanced therapies specific to Latin America, followed by webinar based lectures, and then to follow-up with an in person training of case studies.  We have used online training in the past to train on the foundational concepts (e.g. what a protein or cell is) needed to understand more advanced concepts (e.g. Biosimilars).  Thus, the online training will allow us to get all participants at the same level, trackf participant progress and success, thus allowing us to focus the in-person training on specific areas of concern highlighted from the online training.  Participants will have access to the online training for 6 months after the in-person training as well allowing for key concepts to be emphasized and learned, which will be monitored by course coordinator.  The webinars will build on this foundational knowledge taught online by presenting lectures on specific in-depth topics related to biotherapeutics and advanced therapies.  These webinars will allow for interaction between the faculty and participants.  Webinars will be taped for review after the live event as well.  Lastly, if possible, in person training will be conducted, which will consist of case studies and didactic lectures to support those case studies.  For case studies, a faculty expert presents the case study and small groups of participants work together to address specific questions.  For example, the participants may perform a mock review of a specific product type and have to recommend approval or not based on the concepts learnt through the online content, webinar, and case study presentation.  We know that a hybrid learning model, online and in person, is the most effective modality of teaching learners. 

The specific outputs for this project will consist of 1.) Training program in Biotherapeutics, 2.) Training program in Advanced Therapies, and 3.) Project report.  The training programs will consist of asynchronous online modules, synchronous webinars (recorded for future viewing), and an in-person case-study based program.  The agendas for each aspect of the training will be developed using the approved Asia-Pacific Economic Cooperation (APEC) Life Science Innovation Forum (LSIF) Regulatory Harmonization Steering Committee (RHSC) core curriculums for Biotherapeutics and Advanced Therapies, experts from industry, governments and academia will be recruited to develop and deliver the content. 

A project report will be provided in the form of a project summary.  This report will also encapsulate important discussions (virtual or in person) and summaries from project activities.  The Project Report will be approximately 3-5 pages and include a summary of the events, key discussions, as well as results from a participant satisfaction survey based on previous participant satisfaction surveys used in past trainings.  The asynchronous learning has check your knowledge sections (short quizzes) and other quantitative information (eg number of log ins for a participant and length on time spent reviewing course content) that will be used in a report; in additional a report of the outcome of the training and summary participant evaluations will be provided.  The project report will be produced by Northeastern University and published by APEC.

CoE in Biotherapeutics:

The first pilot held at Biopharmacuetical Analysis Training Laboratory (BATL) on Northeastern’s Innovation Campus at Burlington, MA took place from September 13-16, 2016. In this case, 11 participants from 11 travel eligible APEC economies (Chile, Peru, Indonesia, Vietnam, Chinese Taipei, Philippines, Malaysia, Papua New Guinea, Mexico, Thailand and Russia) were trained over these four days. The curriculum was developed in collaboration with the advisory committee (regulators, industry and academic experts) and composed of three parts: (1) Introduction to Biologics, (2) Comparability throughout the life cycle, and (3) Clinical considerations for the assessment for Biosimilars. Introduction to Biologics was developed as an online training module for participants to complete prior to arriving on site for further training. Comparability throughout the life cycle and Clinical considerations for the assessment for Biosimilars was delivered on the ground in Burlington and consisted of a mix of lectures, hands-on (experiential learning) lab work, case studies and group work. 

The overall training was a success with all participants saying their overall satisfaction was good or excellent. The majority of the students (5) said the materials presented were at an appropriate level for them, and all eleven said they attended to obtain up-to-date information about the current regulatory and technical issues. Participants said the most useful sessions were the case studies, hands-on, and lectures; they also said they would like the training time to be extended, have an increase of academic involvement and to provide more information prior to the training itself.  Lessons learned in this training were implemented into a second pilot in Seoul, Republic of Korea, in November 2016. 

Based on these successful pilots, BATL became an APEC Center of Regulatory Excellence in Biotherapeutics in 2017 through an official memorandum of understanding (MOU) with APEC for a 5 year term.  BATL held its first official CoE training at its Burlington facility in 2017, with regulators from various APEC economies in attendance, and has been offering this training annually at the Burlington lab.  Additionally, training has been brought to locations around the world to reach a broader group of regulators, which includes hands-on experience remotely to the lab and data in Burlington.  These trainings are 2 or 3 days long and are lecture-based, use case studies and remote access to the lab to put a real-life perspective on the learning.  The trainings done at on-site locations use a technology that allows participants to use the instruments in Burlington remotely to run data and do analysis as they would if the instruments were there. 

CoE in Advanced Therapies (Cell/Gene Therapies):

Built on the success of our CoE in Biotherapeutics BATL became an APEC RHSC Center of Regulatory Excellence in Advanced Therapies in 2019 (5 year MOU) after completing a successful pilot in Seoul, Republic of Korea. 

An important part of all of our training programs includes a hands-on experience in the lab.  When we execute trainings online or in economies we usually achieve this through remotely logging into Northeastern’s lab in Burlington, Massachusetts.  In this training program we will deploy, for the first time, a mixed reality hands-on experience for participants.

The concepts taught will help reduce the regulatory burden in the region and ensure high quality, safe and effective drugs get to patients in a timely fashion.  The training entails five key components to ensure capacity is built: (1) didactic lectures, (2) small group discussions, (3) case studies, (4) laboratory/data training, and (5) post-training follow-up.  These diverse activities give the appropriate background to participants, gives them an opportunity to put into practice what they learned and understand where the data is coming from that they review in drug dossiers.  The post-training follow-up allows us to monitor what was retained and to re-emphasize key points (usually a teleconference meeting with small groups of participants).  Participants will leave with an understanding of innovative new technologies, thus expediting regulatory review in respective economies. 

Mixed Reality-Hands-on Lab Experience

· The use of Microsoft HoloLens mixed reality headsets can be used to enhance the engagement and authenticity of laboratory science activities.

· The HoloLens would be worn only by the lab instructor. No special hardware needs to be purchased for students, facilitating scale up at no cost to the University or the students.

· A key feature of HoloLens is that it supports videoconferencing via Teams, allowing remote students to see exactly what the instructor in the lab is seeing and doing from the instructor’s point of view.

· Teams can be connected with other cloud based data analysis tools to support the full spectrum of laboratory course learning objectives.

There are several critical learning objectives that laboratory experiences seek to impart, and the HoloLens (alone or coupled with cloud services) can support each of these learning objects.  Specifically: learning experimental design, good laboratory procedures, reliability and reproducibility of results, and data analysis and interpretation are all central goals of these experiential learning experiences.

Experiential design, laboratory procedures, and reliability learning goals.  Using Microsoft HoloLens’ remote assist feature allows an instructor to “screen share” what he or she is doing in the lab with remote students using regular laptops or mobile devices. This allows a lab instructor to conduct laboratory experiments and/or demonstrations in their on-campus lab and broadcast that experience live. The HoloLens’ remote assist feature also allows the instructor to annotate the live experience with 3D holographic annotation tools, for example to point or direct learners’ attention to specific objects or features of the physical environment.

Using interactive screen sharing, the instructor could then stop at critical decision points in the lab procedure to gauge remote students’ understanding. For instance, the instructor my ask remote students to explain the rationale for a step in the lab procedure, specify what should be done next, identify safety or reliability issues, or predict outcomes of a procedural task. This interactive input could be provided verbally, or a student could be called upon to click and point (using their own mouse and the HoloLens’ remote assist annotation tools) to specific elements of the lab equipment or material. The instructor wearing the HoloLens would see the student point to the exact location in their field of view and could then confirm, query, or correct the student. Other techniques include polling the entire class or embedding quizzes within the Teams environment.

Like other Teams meetings, these live laboratory sessions can be recorded and archived for asynchronous viewing by students. Faculty may also elect to create pre-recorded videos using the HoloLens and invite students to view them at their convenience.

Data analysis and interpretation learning goals. To complement the live HoloLens laboratory procedure experience, data analysis can be done during the HoloLens sessions or afterwards using the cloud.  Data collected during experiments conducted live via the HoloLens could be copied into the cloud where data analysis software is also located.  Learners can access individual or team copies of the data and analyze it with the instructor’s guidance or on their own.  If the data analysis happens during the HoloLens session, data could be analyzed and adjustments to experiments made in real time.

For example, Agilent has put their data analysis software in the cloud (AWS) and instructors can drag experimental dataset(s) into that work environment.  Then, each student in the class can log in their cloud account and analyze data in real time together.  This analysis can be done through a Team meeting with the instructor sharing his or her screen to demonstrate the analysis techniques while students manipulate their own datasets.  The two Liquid Chromatography Mass Spectrometers (LC-MS) and liquid handler at BATL also have these kinds of cloud-based data analysis capabilities.

Summary.  With these techniques, remote students can be engaged in interactive laboratory experiences led by their instructor who is physically present in Northeastern’s teaching or research laboratories. In addition to facilitating a greater faculty-student interaction, this also provides students with baseline familiarity with our lab facilities and equipment so that when they return to campus they are not starting from scratch.  Combining the Hololens with cloud-based data analysis, either collaboratively via Teams or individually by students on their own time, enables our instructors to provide high quality laboratory-based instruction to remote students targeting the most critical learning objectives of experimental design, good laboratory procedures, reliability and reproducibility of results, and data analysis and interpretation.

Outcomes: Outcomes will be specifically measured by participant feedback on a satisfaction survey, based on previously used surveys.  This survey will consist of questions with rating options from very satisfied to very unsatisfied, as well as open ended feedback questions.  In addition, discussion will be collected as part of the evaluation process.  In addition, an outcome will be monitoring if economies present at the training implement their learnings from the training.  Or, the extent to which regulatory convergence is reached within the participating economies after the events the predominant project outcome.  We can monitor this outcome by listing the agenda in the RHSC meeting after the events are complete as a method to track and report the achievement, outcome. 

With the current COVID19 pandemic, training programs on how to approve safe, effective, and high-quality drugs is more important than ever.  Proper training will allow us to ensure that patients receive quality medicines even in a time when there is major pressure to find anything to treat COVID19.  We must ensure only those medicines that work and are the proper quality hit the market, otherwise we run the risk of sub-standard medicines hitting the market making the situation worse.  This training will ensure that the regulators in LATAM are ready and able to ensure only medicines of the proper quality hit the market, in particular biotherapeutics and advanced therapies, which are two classes of drugs aggressively being pursued for the treatment of COVID19. 

In addition, this training will emphasize the science-based, risk-based, approach to approving drugs, which will support regulatory convergence in the region.  In the long-run, this grass roots training effort could impact policies that benefit the region, getting drugs to patients more quickly and cheaply while not compromising quality, safety or efficacy. 

Lastly, the foundation of this training could be used in other APEC regions, thus broadly support the mission towards global regulatory convergence.  The LATAM specific parts of the training would be changed to the region the course was being used in.

2.     Beneficiaries: Who are the direct project participants and users of the outputs? Describe their qualifications, level of expertise, roles/level of responsibility, gender, economies represented, government departments, APEC fora involvement etc. Explain how they will use and benefit from the project. Who else will benefit from the project and how? [½ to ¾ page]

Government officials in the way of regulators and inspectors will be invited to attend the training, which are members of the domestic drug approval authorities under the Ministry of Health in most economies.  The training will be geared towards mid-level regulators, with 5-7 years of experience.  Participants will be recruited using the normal APEC processes, as well as by reaching out to cluster development agencies in many of the APEC economies.      

Direct beneficiaries are the regulators whom attend the training.  They will be able to apply what they learn to their daily jobs and their review of drug dossiers.

Long-term or indirect beneficiaries are patients.  The goal of regulatory convergence is to reduce the regulatory burden getting quality drugs to patients safely and quickly, saving lives and reducing costs.