Over the past few decades, the FDA has sped up the development of drugs addressing serious conditions and unmet medical needs through special designations.

Speeding up access to drugs for serious diseases benefits everyone, especially when they represent the first available treatment or offer significant advantages over existing options. To achieve this, the FDA has developed 4 key pathways - each offering key incentives to bring these drugs to market as quickly as possible:

1. Fast Track

2. Accelerated Approval

3. Priority Review

4. Breakthrough Therapy

1. Fast track

In the 1980s, as the AIDS pandemic intensified, there was an urgent demand for new treatments to tackle the escalating health crisis. In response, the FDA launched the Fast Track program, aimed at accelerating the development and review of drugs for serious conditions with unmet medical needs.

Eligibility

✅Treats a serious condition

✅No existing treatment available OR significant improvement over current therapies

Key Incentives

1. Skipping Phase 3: Approval can be granted if the Phase 2 data looks promising, bypassing the need for longer, costlier Phase 3 trials.

2. Rolling FDA Review: This allows companies to submit sections of their NDA (New Drug Application) or BLA (Biologics License Application) as they’re completed, allowing the FDA to begin reviewing earlier instead of waiting for the entire application to be completed to be reviewed for approval.

3. Frequent FDA Communication: The Fast Track designation offers more regular interactions with the FDA, which helps to quickly resolve issues and streamline the drug development process.

Did You Know? Even after Fast Track approval, the FDA monitors drugs through post-marketing surveillance. If new risks arise, the FDA can withdraw the drug from the market—several fast-tracked drugs have faced this outcome!

2. Accelerated Approval

Drug trials can take several years to confirm clinical effectiveness, but the Accelerated Approval pathway speeds this up by:

1. Allowing the use of surrogate endpoints, like tumor shrinkage or disease progression, instead of traditional survival rates.

2. Enabling trial designs with fewer patients to measure these surrogate markers.

This approach is particularly useful for cancers like prostate or breast cancer, where survival studies can take 5 to 10 years and require long-term follow-up with many patients.

Eligibility

✅Treats a serious condition

✅No existing treatment available OR significant improvement over current therapies

✅Relies on surrogate endpoints

Did you know? Cancer drugs with Accelerated Approval reach the market almost 4 years faster, thanks to surrogate markers. However, insurers face challenges in pricing and coverage without long-term clinical data.

3. Priority Review

Before any drug is approved in the U.S., it must undergo a thorough FDA review. However, in 1992, the FDA set goals to streamline this process by introducing a two-tiered system:

• Standard Review: this typically takes 10 months.

• Priority Review: this process takes 6 months

The FDA determines if a drug qualifies for Priority Review—no application from the company is required for this designation.

Eligibility

✅Treats a serious condition

✅Significant improvement over current therapies

Key Incentive

• Reduces the FDA’s review time from 10 months to 6 months

Did you know? The FDA’s Priority Review Voucher is like a golden ticket for drug companies developing treatment for rare pediatric diseases. It not only speeds up the review process but if a company doesn’t need it, they can sell the voucher to another company, for over $100 million!

4. Breakthrough Designation

The Breakthrough Therapy program was designed to speed up the development and approval of drugs showing significant early benefits for serious or life-threatening diseases. Unlike other FDA programs, Breakthrough Therapy emerged due to advancements such as gene therapies and precision medicine, which allow drug effectiveness to be assessed much earlier in development.

Congress recognized that for these cutting-edge treatments, large randomized controlled trials (RCTs) might be unnecessary—or even unethical—if early data shows strong potential. This designation allows drugs to use nontraditional trial methods and advanced data analysis techniques, such as real-world evidence (RWE), observational studies, biomarkers, and surrogate endpoints.

Eligibility

✅Treats a serious condition

✅Significant improvement over current therapies

Key Incentives

1. Rolling FDA Review: Companies can submit sections of their application as they’re completed, allowing the FDA to begin reviewing sooner.

2. Skipping Phase 3: Drugs showing early effectiveness, like in Phase 2 trials, can be approved without completing full Phase 3 trials, provided post-approval studies are conducted.

3. Frequent FDA Communication: Companies benefit from more regular, in-depth guidance from the FDA, which helps resolve issues faster and accelerates approval.

4. Adaptive Trial Design: Flexible trial designs allow for adjustments during the study, speeding up development and shortening timelines.

5. Cross-Disciplinary Project Lead: A senior FDA official oversees the drug’s progress, ensuring smooth coordination across clinical, manufacturing, and regulatory teams to streamline development.

How Designations are Linked?

When a drug qualifies for Breakthrough Therapy designation, it automatically becomes eligible for Fast Track as well, since Fast Track designation meets the eligibility requirement for Breakthrough Therapy designation.

Additionally, drugs with Fast Track designation can potentially qualify for Accelerated Approval and Priority Review, if they meet the respective requirements:

• Accelerated Approval: Allows approval based on early data using surrogate endpoints, speeding up access to treatments for serious conditions.

• Priority Review: Reduces the FDA review time from 10 months to 6 months for drugs offering significant improvements over existing therapies.

Key Takeaways

• Fast Track: Facilitates development and speeds review of drugs for serious conditions with unmet needs

• Accelerated Approval: Approves drugs for serious conditions based on surrogate endpoints instead of clinical endpoints

• Priority Review: Shortens FDA review time to 6 months for drugs offering major treatment improvements

• Breakthrough Therapy: Expedites drugs showing significant improvement over available treatments

FAQs

References

1. FDA (2019). Fast Track, Breakthrough Therapy, Accelerated Approval, Priority Revie. [online] U.S. Food and Drug Administration. Available at: https://www.fda.gov/patients/learn-about-drug-and-device-approvals/fast-track-breakthrough-therapy-accelerated-approval-priority-review.

2. FDA (2018). Fast Track. [online] U.S. Food and Drug Administration. Available at: https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/fast-track.

3. FDA (2018). Breakthrough Therapy. [online] U.S. Food and Drug Administration. Available at: https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/breakthrough-therapy.

4. FDA (2018). Priority Review. [online] U.S. Food and Drug Administration. Available at: https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/priority-review.

5. FDA (2018). Accelerated Approval. [online] U.S. Food and Drug Administration. Available at: https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/accelerated-approval.

6. FDA (2021). Biologics License Applications (BLA) Process (CBER). [online] U.S. Food and Drug Administration. Available at: https://www.fda.gov/vaccines-blood-biologics/development-approval-process-cber/biologics-license-applications-bla-process-cber.

7. FDA (2022). New Drug Application (NDA). [online] U.S. Food and Drug Administration. Available at: https://www.fda.gov/drugs/types-applications/new-drug-application-nda.

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Glossary

NDA (New Drug Application): A type of submission to the FDA requesting approval to market a new drug in the U.S., including safety and effectiveness data from animal studies and clinical trials.

BLA (Biologics License Application): A type of submission to the FDA which is required for biological products, such as vaccines or proteins. It focuses on the biological product's safety, purity, and potency

clinical effectiveness: This refers to how well a treatment works in real-world settings, measuring its ability to improve patient health outcomes.

surrogate endpoint: an indicator or sign used in place of another to tell if a treatment works. Surrogate endpoints include a shrinking tumor or lower biomarker levels.

trial design: This is the plan outlining how a clinical trial will be conducted, including its structure, methods, and analysis.

markers: Biological indicators such as certain proteins that are used to assess the presence of a disease

gene therapy: This is a treatment that involves altering or replacing faulty genes to treat or prevent diseases, often by introducing healthy copies of a gene into a patient's cells.

precision medicine: This approach tailors medical treatment to the individual characteristics of each patient, considering factors like genetics, environment, and lifestyle to improve outcomes.