Innovations for Exceptionally Low-Cost Monoclonal Antibody (mAb) Manufacturing - Frequently Asked Questions (FAQs)Frequently Asked Questions
Eligibility
Who is eligible for grants?
This initiative is open to nonprofit organizations, for-profit companies, international organizations, government agencies and academic institutions. We particularly encourage applications involving projects led by women / in collaboration with women-led organizations, or applications from / in collaboration with institutions based in low- and middle-income countries. Only individuals who are applying through a legally recognized corporate entity are eligible.
Upon registration, applicants must provide information about the tax status of their organization as different terms and conditions may apply under the applicable tax laws. You should confirm your organization's tax status with the appropriate advisor or entity within your organization such as your grants or contracts department, finance, or office of sponsored research. Either funder may request additional information regarding your tax status. For information about tax statuses, you may check with your own advisors and review information on the applicable tax requirements.
Application Process
What must my application include?
Please refer to the Application Instructions document.
Am I able to edit my proposal once submitted?
Yes, you may edit your proposal up until the specified deadline.
What amount of indirect cost is available?
Details of the foundation indirect cost policy guidelines can be found here: Bill & Melinda Gates Foundation's indirect cost policy. For Option A of this joint Grand Challenges call, LifeArc may have additional or different indirect cost policies, for example for this funding call LifeArc permits indirect costs up to 15% for LMIC-based applicants.
Review Process
How does the review process work?
Please refer to the Rules and Guidelines document.
Can I get a list of potential reviewers who might be assigned to my application?
No. We do not make public the roster of reviewers.
Can I request that my application not be reviewed by a specific individual?
No. However, we will ask reviewers to self-identify conflicts of interest and will not assign reviewers with conflicts.
Will I receive specific feedback on my application if it is not selected?
Due to the rapid proposal and review timelines applicable to this RFP, applicants with proposals that are not selected for award may receive a notification of decline without specific feedback.
Award Information
Are grant awards made directly to individuals?
No. All awards are made to the organization where the individual holds their primary appointment. Institutions must agree to the terms and conditions governing each grant award prior to award activation.
How much money will each grant provide?
Option A: The funders will consider several proposals for awards of up to $750,000 USD for each project, with a grant term of up to 18 months. Each organization will make coordinated but independent award decisions. Application budgets should be commensurate with the scope of work proposed.
Option B: Potential funding and grant terms will be evaluated on a per-project basis. The funding and timeline are intentionally open given that the work is exploratory at this time. Application budgets should be commensurate with the scope of work being proposed.
Technical Support
I forgot my password. How do I reset my password?
You can request to update your password within the application site. If you continue to have issues, please reach out to [email protected].
How will I know if my application was submitted?
Once an application is submitted, an email confirmation will be sent.
I'm having trouble uploading my application file. What should I do?
If you are having issues submitting your application, we would encourage you to submit from a different browser. If the issue persists, please email the specifics of your problem to [email protected].
How often do you intend to update the Frequently Asked Questions, and do you plan to provide answers to all questions submitted?
We will periodically post answers to questions as they are submitted, but do not have a specific schedule. We will provide answers on this page that are of relevance and of general interest to potential applicants. For answers to specific questions that are not covered here, please email [email protected]
FAQ shared on both webinars:
What does a successful proposal look like for this RFP?
Please refer to the RFP rules and guidelines document for what is in and out of scope for this RFP. A successful proposal can be focused on a specific step of manufacturing or an integrated process, and applicants should outline how they would drive the cost down to $10 per gram. We are not expecting a very detailed cost analysis at this stage, though this will be expected of the six grantees selected. At this stage, applicants need to describe their idea, and considering the cost components, outline how they think the cost objectives could be achieved.
What alternative technologies exist for mAbs purification?
The workhorse for the mAbs purification today is still protein A absorption and elution. It's an expensive resin. Meanwhile, several alternatives are emerging. For example, precipitation could be an alternative. For human serum albumin, which is produced at a much lower cost compared to antibodies, plasma goes through a precipitation step where you can recover the human serum albumin. So that makes it a much more condensed process. That is just one example, but there could be alternative methods for the mAbs purification to be much more efficient.
What support can be expected beyond funding? Is there an opportunity to collaborate with other organizations or experts?
Technical consultation will be available to awardees and will be provided by staff at the Gates Foundation and LifeArc, as well as partners. At the application stage we encourage collaboration amongst applicants if you think collaborating with other investigators will help you strengthen your proposal.
Is it possible to submit more than one project?
Yes. But the email address and PI should be distinct for each submission.
Are single domain antibodies (VHH) and animal-derived polyclonal Ab products considered as mAbs in this call?
No. These products and production platforms have great utility for infectious disease, but they're outside the scope of this funding call. We are interested in full length human IgG.
Does the call only concern specific targets i.e. malaria, RSV, HIV or is it possible to submit projects on other targets?
We want to encourage applicants with strong data from mAb candidates, even if they target different pathogens or areas. Our focus at the Gates Foundation and LifeArc is on monoclonal antibodies for infectious diseases, with the malaria mAb (MAM01) providing a way to standardize across different projects. That might be tackling a part of the production process, or an end-to-end, and we aim to conduct rigorous comparisons across projects. While we emphasize the use of MAM01 for standardization, we welcome strong applications with compelling data and mAb candidates and production platforms. Our goal is to foster innovation while maintaining consistency across funded projects.
Are technologies that improve the efficacy of approved antibodies in scope?
No, they are out of scope. We recognize that increased potency can lead to dose sparing and can lead to reduced costs. But technologies in this space are out of scope for this call. We are focused on bioprocessing innovations to support low-cost manufacturing.
Are novel technologies for discrete stages (e.g., novel resins for downstream chromatography) eligible for grants?
Applicants can target a discrete part of the mAb production pathway and do not need to apply with a full end to end solution, but if this is the case, we are looking for proposals that propose a way to integrate a novel technology or novel approach in an end-to-end system. Applicants should also highlight what a rigorous techno-economic cost assessment might look like at the end, given the data produced.
Are variable domains of heavy chain antibodies of Camelidae and derivatives of these Abs also considered as monoclonal antibodies?
No, we are pursuing manufacturing of human full length IgGs.
Is this a one-time grant opportunity for this cause?
Currently our focus is on the open RFP opportunities, but we may explore additional opportunities in the future. The best way to keep up to date on challenges is to sign up for email notifications on our Grand Challenges website.
Q&A from Dec 2nd Webinar:
Does including a fusion protein that can be cleaved off the antibody count as "changing" the existing molecule or coding sequence? Basically, does the end mAb need to be solely MAM01 or does it need to be the original unchanged MAM01 sequence throughout the entire purification process?
We welcome unique ideas and encourage out-of-the-box thinking in the applications submitted. We have a thorough review process in place that will help in making determinations. The idea with MAM01 is to be able to standardize across, but we are open to any innovative thinking at this time.
Can we request the grant as a consortium in one proposal?
Yes, we welcome and encourage collaboration. When creating an application, there is an option in the system for applicants to add collaborators to work on a joint proposal and submit. In this case, one organization would be the primary recipient of an award, and that awardee could potentially sub-grant to others, or collaborate informally, as it makes sense.
Is a grant considered non-dilutive funding?
Yes, the grants are non-dilutive. They are not equity investments.
Does the grant include clinical trial and/or non-clinical?
No, trials should not be included.
You mentioned WHO report on mAbs - can we ask for the reference?
The report is here: Guidelines on the nonclinical and clinical evaluation of monoclonal antibodies and related products intended for the prevention or treatment of infectious diseases
If we use MAM01 as a model, what are the licensing restrictions of this mAb?
We'll provide the published sequence and the selected grantees will be able to use that for now. There will be permission granted to use this for the purpose of this RFP grant.
Q&A from Dec 3rd Webinar:
For Option A, does the cost of goods of $10 need to be demonstrated by modelling or can we show an increase in manufacturing yield and project cost of goods improvement?
We anticipate that funded projects will generate lab data to show proposed results. At the application stage, data will strengthen your application, and the more data you have, the stronger the application will be. If you have a concept and can clearly outline the potential, that will be evaluated, but there must be at least some references to published data or your own data to say that your solution may be achievable.
Are both options limited to the disease areas indicated in the slide or can any mAb be used for showing proof of principle?
It's ok to expand further than the diseases listed. We are open to other areas of focus as well, for example cancer antibodies or autoimmune antibodies, if you have data to support your idea.
Is improvement in cost of labor considered 'moving the needle'?
Not by itself. By going to continuous processing and with high productivity intensified processing, the labor component has already come down very significantly. Unfortunately, while that has come down, what has remained high cost is the materials component. By making some of these process improvements, we predominantly reduced the cost of labor, but we marginally changed the cost of raw materials. Labor can't be the only factor that'll move the needle, applicants need to think about the materials as well.
Will the mAb be produced at GMP levels?
Not for now. For applications down the line, we'll be looking for GMP material, but today for your cost modeling, if you have process development data or you will generate the process development data that is all non-GMP at this point, that's fine. However, the process should be GMP-like in the future, meaning, make sure that it can meet the regulatory requirements, because if you come up with a process that is very unlikely to gain regulatory approval, that's not a good process because then we'll have trouble. So, think about specifications, which are very important for human proteins here. There will be a lot of requirements about the impurities, etc. So just make sure that GMP ability is possible in the future, but you don't have to produce it at GMP now.
For the model mAb, would mAb material be provided? If so, would this be in the form of drug substance, cell culture fluid, intermediate pools, etc.?
No, in this case, only the sequence for the antibody will be provided. Therefore, the expression and the upstream must be done by the collaborators. Let's say somebody wants to work only on the downstream - down the line, maybe there are opportunities to collaborate where somebody else is doing the work on expression and the cell culture or fermentation to provide the feed for the downstream. To be clear, neither the Gates Foundation nor LifeArc can provide these materials directly to you. You have to generate the materials.
Does Option B need to include a grant amount requested in the application?
Yes, there is a high-level budget document to fill out for both options.
Do the technology sponsors get to own any IP generated under the grant terms or is the IP owned by the Gates Foundation or LifeArc?
Grantees own IP resulting in Gates Foundation funded grants. The Gates Foundation does, however, require that grant outputs be made widely available to the intended beneficiaries. Please review the Rules and Guidelines document for additional information, including our sample terms and conditions.
At LifeArc, recipients of funding will similarly retain and own all the arising IP. But when we put the funding agreement in place, there will be certain rights in the funding agreement that ensure that the arising IP is used to fulfill our charitable objectives. LifeArc is a medical research charity, and we need to ensure that there's the maximum public benefit from the research that we fund, so it's very similar situation between LifeArc and the Gates Foundation in that regard.
Are there any product quality attributes that we are constrained to with MAM01?
The reason we said MAM01 is we understand a lot of the characteristics of that antibody internally. Glycosylation is an important point that we will be looking at; glycosylation has an impact on the mechanism of action, etc. As you are thinking about different expression systems, you need to think whether that will make a suitable antibody for human application - that is the only requirement. At this stage of application, it can be theoretical where you can cite some of the other data as to what kind of glycosylation has been observed, for example. However, down the line, once the grantees are confirmed, we'll be assessing the quality of the product as well to make sure that expression system does provide appropriate quality material for human applications.
For any economic modelling, we have to assume many parameters like upstream titer, the scale of production, etc., as well as labor/material cost, which varies from country to country, affecting the final COGS largely. How will you evaluate that model?
The proposed techno-economic assessment will likely include a range/mean of current labour and material costs from well-established geographical regions which will be applied to assess a project output.
Will standards (e.g., purified mAb) be available for use in analytics?
We can't provide any materials in general. Labs will need to be set up to carry out the projects. Our organizations do not have the ability to provide applicants with materials.
What if it is a novel chassis and glycosylation is different?
We are looking for innovative approaches consistent with the goal of low-cost, full-length human IgG; expression systems that result in mAbs with modified/non-mammalian glycosylation or lacking glycosylation are in scope if data are available showing feasible path for establishing safety, efficacy and addressing regulatory issues.
Will you consider approaches that use non-glycosylating hosts (bacteria) - if they are still focused on technical advances that drastically lower cost?
Yes, if data are available showing feasible path for establishing safety, efficacy and addressing regulatory issues.