On average, it takes 10-15 years — and costs between $43.4 million and $4.2 billion — to develop a new drug from initial target discovery to full market approval. Even with that investment, 90% of drugs will ultimately fail and 10% of those failures are a result of poor strategic planning.

Many pharmaceutical startups either consider regulatory authorities too late or don’t understand how to engage with regulators at each stage of the development cycle. Considering that only 12% of drugs entering clinical trials are ultimately approved for introduction by the FDA, it’s critical to engage with regulators early and often.

By using a phase-appropriate approach, pharma startups can better engage with regulators at each stage of the drug development cycle to support a faster, more cost-effective route to seamless approval and commercialization.

Understanding Regulatory Authorities

Too often, pharma startups view regulators— like the Food and Drug Administration (FDA) — as police, expecting regulators to tell them what to do throughout the development cycle. However, this isn’t the role of regulators. Instead, startups should present a plan with a detailed package supporting their strategy. Then, regulators can review and offer feedback.

Overview of major global regulatory bodies

Depending on where you are located and where you plan to market your drug product, you will need to adhere to regulations from a variety of national and regional authorities, including:

• Food and Drug Administration (FDA): The FDA is responsible for protecting public health by ensuring the safety of food, drugs, medical devices, and other products in the United States (U.S.). The FDA review process is broken into four stages: preclinical research, clinical research, FDA review, and post-market safety monitoring.
• European Medicine Agency (EMA): The EMA is a decentralized agency of the European Union (EU) that is responsible for ensuring the safety, efficacy, and quality of medicines in the EU and the European Economic Area (EEA). The Committee for Medicinal Products for Human Use (CHMP) is responsible for scientifically evaluating applications for new human medicines and providing an opinion on whether to grant a marketing authorization for them across the EU under the centralized procedure.

• Medicine and Healthcare Products Regulatory Agency (MHRA): The MHRA is the United Kingdom’s (UK) independent regulator for medicines, medical devices, and blood components used for transfusions. Post-Brexit, one of the agency’s priorities is to accelerate routes to market by echoing some existing EU regulatory practices, such as accelerated (AA) and conditional marketing authorization (CMA), and has launched some abbreviated procedures by relying on decisions granted at the EU level.

Other key regulatory agencies include Health Canada, Japan’s PMDA (Pharmaceuticals and Medical Devices Agency), and Australia’s TGA (Therapeutic Goods Administration).

Key regulations and guidelines for pharmaceutical development

In addition to specific regulatory bodies, pharma startups should consider the following key regulations and guidelines:

• Good Laboratory Practice (GLP): Ensures the integrity and reliability of non-clinical laboratory testing, which supports the safety and efficacy of pharmaceuticals before human trials begin. GLP governs the planning, execution, and reporting of laboratory studies, emphasizing rigorous documentation, well-defined procedures, and quality assurance.

• Good Clinical Practice (GCP): Sets ethical and scientific standards for the design, conduct, and reporting of clinical trials involving human subjects. GCP ensures that trials are conducted in a way that prioritizes the rights, safety, and well-being of participants while ensuring the reliability and integrity of clinical data.

• Good Manufacturing Practice (GMP): Ensures the quality and safety of pharmaceutical products by governing all aspects of production, from sourcing materials to final packaging. GMP guidelines set rigorous standards for facilities, equipment, personnel, and processes to minimize the risks of contamination, mix-ups, and errors.

• International Council for Harmonisation (ICH) Guidelines: Works to harmonize the technical and scientific standards in pharmaceutical development across major regulatory regions. Its guidelines cover key areas like drug safety, quality, and efficacy, helping streamline regulatory submissions for pharmaceutical companies operating globally.

• Regulations for Biologics and Advanced Therapies: The FDA, EMA, and MHRA are adapting their guidelines to address emerging therapies, focusing on safety, efficacy, and long-term monitoring. Regulatory pathways often include accelerated approval options, given the high potential of these therapies for treating serious conditions, but require rigorous preclinical and clinical data due to their innovative nature.

Navigating regulations and guidelines, which can vary from region to region, can be tricky. It’s important to know your target market so you can build in regional standards and compliance from the outset. For example, the FDA’s 505(b)(2) pathway has different data requirements, including pharmacokinetics and safety profiles, compared to the EMA’s centralized approval process. Therefore, if you are seeking approval in both the U.S. and the E.U., you will need to factor both standards into your plan.

A Phase-Appropriate Regulatory Roadmap for Pharma Startups

Pharma startups often view regulators as end-of-development gatekeepers. However, for the best chance of success, startups should engage regulators as collaborators throughout the development process. Of course, time and budget constraints often make frequent regulatory engagement difficult. A strategic, phase-appropriate approach can streamline approvals and avoid costly delays.

Early-Stage Considerations

The Importance of Early Engagement: While startups may hesitate to engage early due to costs, early regulatory conversations provide vital guidance on scientific and technical expectations. Preemptive discussions reduce the need for costly rework or additional studies that could arise if changes are made too late.

Process Adaptations: Addressing regulatory concerns (e.g., manufacturing processes) before starting preclinical studies helps prevent costly and time-consuming re-validation. For example, adjusting a manufacturing process before preclinical studies results in smaller datasets to support changes versus waiting until later, which could require extensive new clinical data.

Developing a Data-Supported Plan: Ensure that preclinical research follows Good Laboratory Practice (GLP) guidelines to generate reliable data for regulatory submissions. Identify potential gaps or risks early on and propose mitigation strategies in your regulatory plan. Make sure you factor in the Investigational New Drug (IND) application process before human clinical trials.

Incorporating Regulatory Strategy into Business Plans: Build a regulatory engagement plan into your business model to align clinical and financial goals. Delaying regulatory involvement can negatively impact timelines and funding. An “early and often” approach can help you gain insights on similar cases, preventing missteps and ensuring the agency is familiar with your proposed development path.

Clinical Trials and Good Clinical Practice (GCP)

Phases of Clinical Trials and Regulatory Requirements: There are different regulatory requirements to consider at each phase of clinical trials:

• Phase 1: Focus on safety, tolerability, and dosage determination. Regulatory oversight ensures trial design and protocols are safe for participants.

• Phase 2: Expanded safety trials with efficacy studies on up to several hundred people. Engagement with the regulator provides critical feedback on data collection and trial designs.

• Phase 3: Large-scale studies (up to 3,000 participants) to confirm efficacy and monitor adverse effects. More intensive regulatory involvement as the data becomes crucial for final approval.

Ensuring Compliance with GCP: It’s important to adhere to GCP guidelines throughout trials to ensure ethical standards, patient safety, and high-quality data. Regulatory audits during trials help maintain compliance and address safety concerns early on.

Data Collection and Patient Safety Reporting: Robust data management systems ensure accurate and complete data collection, which is crucial for regulatory approval. Establish clear procedures for reporting adverse events and ensuring patient safety.

Regulatory Pathways for Approval

Navigating the NDA and BLA Processes: The type of drug or therapeutic you are developing will determine the application process you must follow to secure approval.

• New Drug Application (NDA): Required for small-molecule drugs to demonstrate safety and efficacy.

• Biologics License Application (BLA): Required for biologic products like proteins, vaccines, cell, and gene therapies.

Accelerated Approval Pathways: Explore faster approval options tailored to startups, such as:

• Orphan Drug Designation: For drugs treating rare diseases, with incentives like market exclusivity and tax credits.

• Fast Track Designation: Provides early and frequent communications with the FDA to accelerate drug review.
• Breakthrough Therapy Designation: For drugs showing substantial improvement over existing treatments in early trials.

Regulatory Submissions: Proper documentation, data quality assurance, and compliance checks are key to successful regulatory submissions. Make sure you are familiar with submission requirements, including the Common Technical Document (CTD) format to streamline global submissions.

Post-Approval Compliance

Good Manufacturing Practices (GMP) for Production Scale-Up: After regulatory approval, scaling up manufacturing operations while maintaining quality and compliance with GMP standards is critical. Focus on process validation, batch consistency, and quality control during production scale-up.

Pharmacovigilance and Post-Market Safety Monitoring: Post-approval monitoring (pharmacovigilance) is required to track adverse events and ensure ongoing safety. Startups must establish systems for adverse event reporting and periodic safety updates.

Continuous Regulatory Updates and Long-Term Compliance: Maintain ongoing communication with regulatory agencies to stay compliant with evolving regulations. Ensure proper documentation and audit trails to support long-term product integrity and market access.

Common Pitfalls and How to Avoid Them

Planning for and streamlining regulatory engagement throughout every stage of the drug development cycle is imperative for startups. Without regulator approval, you can’t bring your product to market. Without regulator engagement, you run the risk of wasting time and money reworking trials and data to secure follow-up review.

In addition to following the phase-appropriate roadmap above, avoid these common pitfalls that can prevent startups from securing regulator approval.

• Inadequate regulatory planning and underestimating timelines:
  Startups often underestimate the complexity and time involved in regulatory approvals. This can lead to unrealistic project timelines, which may impact funding, partnerships, and market entry. Each stage of development requires thorough preparation and review by regulatory authorities. Inadequate planning can result in back-and-forth revisions, lengthy delays, or, worse, outright rejection of submissions.

• Failure to maintain clear documentation and data integrity:
  Regulators rely on thorough and accurate documentation to assess safety, efficacy, and quality. Incomplete or poorly organized records can raise red flags, lead to delays in approval, or require expensive rework. Startups must maintain the integrity of clinical and preclinical data. Errors, omissions, or lack of traceability in data can lead to failed audits and require additional studies.

• Skipping early consultations with regulatory experts:
  Prioritize early consultations with regulatory authorities and experienced consultants. These engagements can provide clarity on regulatory expectations and reduce the risk of missteps, allowing startups to align their development strategy with the requirements of their target market.

Navigate Regulatory Complexity with Pharmatech

Navigating the regulatory landscape is a complex and time-consuming process that can make or break the success of a new drug. With the average drug development timeline stretching up to 15 years and costs soaring into billions, startups need a well-planned regulatory strategy to avoid unnecessary delays and costly reworks. By adopting a phase-appropriate approach and engaging with regulatory authorities early and often, startups can streamline their path to approval, improve the likelihood of success, and bring innovative therapies to market faster.

At Pharmatech, we offer years of experience engaging with regulators, including the FDA. We can help you craft the right narrative for approval and adequately respond to agency feedback. With our expertise, we can help you avoid common regulatory pitfalls and ensure a smoother, faster path to approval. Don’t risk delays or failure due to regulatory missteps—partner with us to take the guesswork out of the process.

Ready to accelerate your path to regulatory success? Contact us today for a consultation, and let’s discuss how we can help you bring your breakthrough treatments to market,