You have a new biotherapeutic in development that has shown promise in pre-clinical studies against a life-threatening disease. Affected patients and their providers are anxiously awaiting a new treatment option. How do you get your drug into the clinic quickly?

Navigating regulatory requirements can be overwhelming. Below, we map out basic information to help you approach regulatory policies and offer helpful strategies to facilitate efficient regulatory review and drug approval.

Leverage modern science and the digital age in drug development

Scientific advancements, a better understanding of biology, and digital tools are accelerating some of the early efforts in drug development versus 30 years ago. Leading up to regulatory filing, modern advancements such as novel cellular imaging techniques, 3D cell culture, big data analytics, predictive modeling, and a vast amount of historical study results help make certain aspects of drug development much more efficient. But the regulatory approval process remains, in many ways, thorough and demanding, for good reason – to protect patients.

So, where to begin when first approaching regulations and drug approval? Regulatory priorities will shift as investigational drug products move through the approval process, but the core expectations remain the same from phase to phase. You need to demonstrate a strong understanding of your science and your patients and present a purposeful plan to analyze drug performance through clinical studies.

Get to know your investigational drug product, from start to finish

Pharmacology and toxicology data from in vitro and animal studies are essential to submit an investigational new drug (IND) application. The IND application represents a pivotal milestone as the data included is reviewed by regulators to determine if there is sufficient justification for a Phase 1, or a first-in-human (FIH), trial. These small studies with few healthy volunteers confirm drug candidate safety for further investigation.

Regulatory bodies expect pre-clinical experiments conducted for the IND to be compelling, complete, and in compliance with good laboratory practice (GLP) regulations. An experimental drug’s chemistry, manufacture, and control (CMC) section assures reviewers that developers have accurately identified a drug candidate using defined quality, purity, and strength metrics. In defining a product’s CMC, you might discover the need to adapt existing processes, raw material sources, and protocols to meet quality standards of safety and efficacy needed for FIH studies. While lower quality optimization might be acceptable for early studies, a higher quality threshold is maintained for clinical investigations.

More specific pharmacological characterization will also be required, including the drug’s mechanism of action and the body’s anticipated drug processing. These metrics are mapped through toxicity and pharmacokinetic studies of drug candidate absorption, distribution, metabolism, and excretion (ADME). ADME studies help identify potential drug interactions, pharmacogenomic considerations, and safety endpoints to include in study design.

While IND applications need to include basic product characterization data for Phase 1 protocol clearance, the information included in the IND builds continuously over time. The document will follow you through the regulatory approval process, expanding to include data from all studies done from phase to phase and in parallel.

The steady development of information included in the IND is critical, as regulators use this data to determine a drug’s eligibility to advance through the approval process. For example, you might not finalize formulation, route of administration, indication, and dosing specifics until several options are tested in exploratory Phase 2 studies with affected patients. Once these key metrics are defined, the data supporting final formulation, dosing, target population, and indication is added to the IND. With each round of regulatory reporting, regulators review new information and, if deemed suitable, clear the candidate drug for larger studies, such as confirmatory Phase 3 trials.

Work smarter, and harder, to achieve regulatory compliance

The drug approval process can be arduous to ensure only safe, efficacious therapies enter the clinic. Regulations are not designed to be prohibitive but are in place to protect patients in need of treatments. Regulators expect you to approach the workflow with efficiency, adapt, and learn based on new information that comes along the way.

Efficient troubleshooting, creative problem solving, and the ability to customize studies and experimental plans based on your unique and specific drug, target population, and disease metrics are all expected in the process.

The pursuit of thoughtful experiments that validate your drug’s performance is favored over the completion of duplicative or extra tasks that could be deemed unnecessary. Take a mindful approach to study design to demonstrate a strong understanding and command of regulatory requirements and expectations. Exclude areas that are not relevant or necessary for your therapy, backed by scientific logic and evidence. In short, be prepared to do the minimum work required to reach your next milestone.

To prevent unnecessary delays, it is best to work on multiple parts of your drug candidate’s 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 should be developed in parallel while early trials are underway, to save time. This approach will accelerate the production of larger quantities for later phase trials and commercialization.

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 months (1). Studies of Trikafta showed improvement in multiple CF endpoints, and its approval offered a treatment possibility for a whole new subset of CF patients who previously had limited options in managing their lifelong disease.

The FDA has developed the following designations to accelerate drugs that treat serious diseases to market as quickly as possible (2, 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 Union (4) 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 have potentially curative modality and are primed for future growth (5).

Incorporate gap analyses and a quality by design approach

In drug development, “quality by design” promotes proactive and systematic planning with the intention of reducing patient risk. This strategy is strongly encouraged by regulatory agencies and counters the trial-and-error or “quality by experimentation” methodology that can result in backtracking, inefficiencies, and avoidable risk. With quality by design, goals and objectives are defined and critical quality attributes are specified and mapped. A risk analysis is performed, and mitigation activities put in place. The overarching aims include a greater understanding of product and processes so risk and variability are reduced. This strategy also helps to identify and address deficiencies preemptively, expediting regulatory approvals.

Conducting a thorough gap analysis early on can identify use cases from comparable studies or approvals, find shortcuts or shortcomings, and address potential limitations prior to regulatory review (6). Start a gap analysis by performing an unbiased evaluation of background information available for both your drug and similar products. The results of this exercise can be used to gauge a proposed drug’s similarity to existing treatments and construct and modify your process, as well as offer insights into key aspects of your candidate’s journey to market.

When performing a predicate search, relevance in time, active ingredient, and indication should all be considered. It is important to rely on the precedent information of similar drug candidates that have been approved recently but no more than ten years prior, as regulations and requirements have likely changed. Your drug candidate might also be entirely novel, with no similar treatment having gone through the regulatory compliance process. In either case, it is important to extensively review available scientific literature and develop an evidence-based proposal for regulatory review, looking for potential areas to streamline and add efficiency.

Throughout the regulatory process and after approval, gap analyses can continue to be used to check products and processes against standards, identify and mitigate risks, and ensure adequate use of resources. For example, as organizations move candidate drugs through the pipeline, there will likely be an increase in staffing needs for regulatory affairs to maintain regulatory compliance. A gap analysis can point to where and when those resources should be adjusted.

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 and touchpoints with regulators early and throughout the approval process to map out scientific data and review studies 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 regulatory agencies. The experience and expertise gained from these collaborations are invaluable in navigating the ever-changing regulatory oversight 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?

Managing the array of regulatory policies and compliance requirements in drug development and approval can easily become overwhelming. 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.

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.