Seeking drug approval involves a rigorous process, for good reason — to protect patients. But when those same patients’ only hope lies in your research, how can you get a therapy to the clinic quickly and safely?

Navigating regulatory requirements can be an overwhelming and time-consuming part of the translational journey. From the submission of an investigational new drug (IND) application, regulators will want to see a purposeful plan to assess drug safety, quality, and efficacy over time. Below, we outline some basic information and helpful strategies to facilitate efficient drug review.

Prepare your drug and data for human trials

When submitting an IND, pharmacology data from in vitro and animal studies play a key role in showing preliminary safety and efficacy. Regulatory reviewers expect these preclinical experiments to be compelling, complete, and in compliance with good laboratory practices (GLP) to justify a Phase 1, or a first-in-human (FIH), trial.

While lower quality products can suffice for early research, a higher quality threshold is needed for human studies. As you move toward clinical trials, be prepared to adapt existing processes, raw material sources, and protocols to meet this threshold. Regulators will look for comprehensive chemistry, manufacture, and control (CMC) data to ensure a drug can be produced with a known quality, purity, and strength.

To establish a study protocol, you will need additional pharmacological characterization, including how the drug works and is processed in the body. This information is gathered through toxicity and pharmacokinetic studies and helps to identify potential interactions, contraindications, and safety endpoints for a robust trial.

Learn as you go through each study phase

The IND document will follow you through the regulatory approval process, expanding to include data from all studies done from phase to phase and in parallel. With each round of regulatory reporting, regulators review new information to determine if a candidate can be cleared for larger studies.

For example, you might not finalize formulation, route of administration, indication, and dosing specifics until several options are tested in Phase 2 studies with affected patients. Once these key metrics are defined, supporting data will be added to the IND and used to determine if confirmatory Phase 3 trials are appropriate.

Work smarter, and harder, to achieve regulatory compliance

The drug approval process can be arduous to ensure only safe, effective therapies enter the clinic — but it is not meant to be prohibitive. Regulators expect you to approach the workflow pragmatically and to adapt as you go. Efficient troubleshooting, creative problem solving, and the ability to customize studies based on your unique therapy, specific target population, and disease metrics will all be critical elements to regulatory success.

To start, take a mindful approach to study design to demonstrate a strong understanding of regulatory requirements. Avoid doing anything extra work that isn’t relevant to your therapy. In short, be prepared to do the minimum work required to reach your next milestone.

It is also best to work on multiple parts of your development process simultaneously. For example, small amounts of drug product are needed in early phase studies with few participants, but manufacturing processes for larger scale production can be developed in parallel while early trials are underway. This approach will accelerate the production of larger quantities of therapy for later phase trials and commercialization.

Seek an accelerated approval, if eligible

When a drug is expected to meet an unmet medical need and is critical to serve a patient population, regulatory bodies can consider a revised study schedule or expedited review. In October 2019, the FDA approved the cystic fibrosis (CF) drug Trikafta™ by Vertex in about three months1 after studies of showed improvement in multiple CF endpoints. Its approval offered a treatment possibility for a whole new subset of CF patients who previously had limited options to manage their disease.

The FDA has developed the following designations to accelerate drugs that treat serious diseases to market as quickly as possible2,3:

  • Priority Review
  • Breakthrough Therapy
  • Accelerated Approval
  • Fast Track
  • Regenerative Medicine Advanced Therapy (RMAT)

For rare diseases, the FDA also has the Orphan Drug designation that provides additional financial support and incentives to develop therapies for diseases that affect fewer people. Orphan drugs can also be considered for the expedited approval programs listed above. The FDA can, for example, grant a drug candidate both Orphan Drug and Fast Track designations.

Similar processes exist at the European Union4 so developers can develop much needed products in several countries simultaneously. The FDA and European Commission have also recognized the importance of an efficient approval process for cellular and gene therapies, as these treatments are potentially curative and are primed for future growth.5 

Incorporate quality by design and gap analyses

Instead of a trial-and-error approach to drug development, quality by design (QbD) is strongly encouraged by regulatory agencies. QbD includes defining goals and objectives, mapping critical quality attributes, and performing a risk analysis to put mitigation activities in place. Ultimately, these exercises can increase understanding of your product and processes, help identify and address deficiencies, reduce risk and variability, and expedite regulatory approvals.

Conducting a thorough gap analysis early on can also help identify shortcuts or shortcomings and address potential limitations prior to regulatory review.<6 Start a gap analysis by performing an unbiased review of background information available for both your drug and similar products. The results of this exercise can help you determine how similar your therapy is to existing treatments and use other candidate journeys as a way to better understand and plan for your own.

Collaborate with regulatory bodies and experienced consultants for success

Regulatory bodies offer resources to help investigational drug candidates stay on course. Don’t be afraid to have regular meetings with regulators early and throughout the approval process to map out what’s needed to reach key milestones. Developing a collaborative relationship with regulators helps prevent setbacks, ensures alignment, and gives your application the best chance for success.

As you develop your process, you might also seek partnerships with consultants who have a known history of working closely with regulators. The experience and expertise gained from such collaborations are invaluable in navigating the ever-changing regulatory landscape. These robust partnerships help you anticipate regulatory requirements, incorporate regulatory policies, and modify your processes and technology accordingly.

Remember, the drug approval journey ends with hope

For every ground-breaking drug that gets approved, there are people who never had the chance to take it. What if the medication had been investigated more efficiently? How many more lives could have been saved or improved?

When you feel overwhelmed managing complex regulatory policies and compliance requirements, try to remember why the checks and balances are in place and why you do what you do — patients. Act smartly, work efficiently, lean on history, evolve as necessary, and keep pushing forward. Every step closer to market approval means one step closer to changing lives, providing hope, and offering someone the much-needed chance they might not have today.

Visit our translational research solutions page for more information on navigating the path to patients, including a wide selection of regulatory courses. You can also download the Business of Biotech podcast series to hear from guests who turned biotherapy ideas into clinical realities.


  1. Saltzman J, McDonald D. Vertex wins fast approval for cystic fibrosis drug. Boston Globe. Updated October 21, 2019. Accessed February 4, 2020.
  2. Fast Track, Breakthrough Therapy, Accelerated Approval, Priority Review. US Food and Drug Administration. Updated February 23, 2018. Accessed February 4, 2020.
  3. 21st Century Cures Act. US Food and Drug Administration. Updated January 31, 2020. Accessed February 26, 2020
  4. European Commission Approves Spark Therapeutics’ LUXTURNA® (voretigene neparvovec), a One-time Gene Therapy for Inherited Retinal Disease Caused by Confirmed Biallelic RPE65 Mutations. Spark Therapeutics. Updated November 23, 2018. Accessed February 4, 2020.
  5. Global Gene Therapy Market Forecast to Hit $363 Million by 2022. MarketWatch. Updated March 8, 2019. Accessed February 4, 2020.
  6. Kumar M, Bugin K. Forecasting for Success: The Power of Regulatory Gap Analysis. Updated March 8, 2019. Accessed February 4, 2020.