Preclinical Survey

Despite leading global innovation, the United States is rapidly losing its competitive edge to countries such as China, Australia, and those in Europe. Lengthening IND clearance timelines are driving U.S. companies to conduct clinical trials outside the country, meaning American patients are not fully benefiting from American biotech innovation.

The enclosed survey, developed by MassBio in collaboration with the Biotech Consortium to Accelerate Innovation (BCAI), is designed to capture insights on these challenges to ensure that American patients gain early access to breakthrough therapies.

Your company’s input will help inform discussions aimed at addressing critical issues in the U.S. regulatory process. The survey focuses on preclinical and early clinical trial phases, where inconsistent standards, limited incorporation of patient perspectives on benefit/risk, and excessive requirements affecting IND clearance timelines are contributing to delays, increased costs, and reduced investment in groundbreaking therapies.

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* 1. What is your approximate number of US-based FTE and full-time consultants, if applicable:

Less than 20

21 - 50

51 - 125

126 - 250

More than 250

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* 2. What is your therapeutic disease area(s):

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* 3. What is your approximate number of US-based pipeline projects?

1 - 5

6 - 10

> 10

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* 4. What is your approximate number of US-based preclinical projects (i.e. lead stage)?

1 - 5

6 - 10

> 10

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* 5. What is your approximate number of US-based clinical programs (Dossier prep/phase 1/phase 2):

1 - 2

3 - 5

> 5

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* 6. What is your approximate number of non-US-based clinical programs (Dossier prep/phase 1/phase 2):

1-2

3 - 5

> 5

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* 7. If early phase regulatory submissions and review criteria were the same or equivalent across jurisdictions, please rank in order of priority which regions you would select to conduct First-in-Human clinical trials?

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* 8. Based on the current state of the regulatory environment in the US regarding early phase trials, please rank in order of priority which regions you are currently selecting or considering conducting First-in-Human clinical trials?

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* 9. Have you been hesitant to conduct First-in-Human clinical trials in US due to the regulatory framework/requirements?

Yes

Not relevant (please specify)

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* 10. Considering recent changes and proposed plans at the FDA, how likely are you to conduct First-in-Human clinical trials in US?

More likely

Less likely

No change

Not relevant (please specify)

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* 11. Have your submissions been held to the guidance of the 1/10 of the human equivalent dose from the NOAEL (10X lower) applied as the maximum clinical dose and not as the maximum safe starting dose?

Yes

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* 12. Do you support that the guidance of the 1/10 of the human equivalent dose from the NOAEL (10X lower) should be only applied for the maximum safe starting dose but not as the maximum clinical dose and that human safety data should be leading?

Yes

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* 13. If a unique and restructured IND pathway for First-in-Human clinical trials was developed using biotech and pharma input, patient perspectives about benefits/risks, and global best-in-class practices were implemented; rank order of importance the following criteria (1 being the highest):

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* 14. If a unique and restructured IND pathway based on the above input were rolled out, how comfortable would you be piloting your programs through this process?

Highly likely, if the new process significantly addressed the current issues with early phase review

More likely to take a ‘wait and see’ approach

Would not consider it, as the company already has invested in and has a well-established regulatory infrastructure outside the U.S.

Prefer the current regulatory framework/requirements for early phase trials

Other (please specify)

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* 15. What are the top 3 reasons why you are hesitant to conduct First-in-Human clinical trials in the US due to regulatory framework/requirements?

Risk of full or partial clinical hold

Risk of not understanding the pre-IND FDA feedback about the content and format of initial IND submission and ability to effectively remediate

Cost of delay both from timeline and financial to address clinical full or partial clinical hold comments

Lack of clearly defined preclinical data requirements for the IND submission

Lack of understanding about the benefit/risk in rare diseases to inform benefit/risk for IND “may proceed” decision

Not hesitant at all

Other reason (please explain)

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* 16. Over the past 5 years what percent of your FDA meetings (i.e., pre-IND, INTERACT) did the sponsor receive?

Written responses only - -what %

Face-to-face meeting with FDA meeting minutes -- what % (could have written responses as well)

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* 17. What was your satisfaction level with the written responses only and/or FDA meeting minutes providing clear and understandable guidance?

Most responses were clear and implementable

Several responses were ambiguous

The responses provided confusion, and it was unclear about how to proceed

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* 18. What was your satisfaction level with the face-to-face meeting and meeting minutes providing clear and understandable guidance?

Most responses were clear and implementable

Several responses were ambiguous

The responses provided confusion, and it unclear about how to proceed

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* 19. To support acceleration of Early Phase Development for Rare Diseases by the FDA, please select what you would consider as resources (e.g., white paper, updated or new guidance, educational materials) to be developed by FDA that would increase the likelihood of conducting First-in-Human clinical trials in the US:

Incorporate patient perspectives about the burden of their serious and life-threatening rare condition and what is their tolerance of risk and acceptance of uncertainty for early phase clinical trials as part of initial IND submission

Improve and harmonize the expectations about the nonclinical data content included in INDs with other OUS regions

Improve communications through pre-submission meetings, IND submission, and during Phase 1

Further guidance or white papers about preclinical data package requirements and regulatory expectations, including a graduated or novel approach

Other (please specify)

Thank you for completing the survey!