Regulatory Affairs


Our experienced team has a proven track record of success in the following FDA and EMA applications, approvals, and meetings:


FDA Applications

The Orphan Drug Act of 1983 defines a rare disease as a disorder or condition that affects less than 200,000 people in the US. This act provides incentives that allows companies to develop drugs for a disease that affects a small portion of the US population without the daunting financial obstacles associated with a reduced market size.

The complete list of benefits of an ODD includes:

  • Prescription Drug User Fee Act (PDUFA) fee waiver (a value of over $2 million)
  • Guaranteed 7 years of drug exclusivity
  • 50% tax credits for all us clinical studies
  • Eligibility for Research Grants for Orphan Drug Clinical Programs
  • FDA Meetings to assist with study/clinical trial design

The main criteria needed to apply for an Orphan Drug Designation are as follows:

  1. Reputable Data supporting the indicated disease affects a population of less than 200,000 people in the US
  2. Positive drug efficacy data (can be preclinical data) showing that the active ingredient in the proposed drug has been shown to be effective in treating the clinically relevant endpoints associated with the indicated disease.

Our regulatory personnel specialize in Orphan Drugs, and have a masterful understanding of the rare disease space. Biopharma Global is ready to chaperone you though this application process, which will net a major benefit for your company’s funding.

Federal Law requires that a drug is approved for market before it can be transported or distributed across state lines. However, since a drug sponsor will need to transport the drug across state lines to reach out-of-state clinical investigators, the FDA created the IND application to grant an exemption from that legal requirement.

There are three types of IND application:

  1. Investigator IND – submitted by the physician who both initiates and conducts the investigation, and is responsible for the administration and distribution of the drug.
  2. Emergency use IND – allows for authorization of an experimental drug by the FDA in an emergency situation where there is not enough time for the entire application submission and approval process.
  3. Treatment IND – reserved for experimental drugs already  that show promise in clinical testing for serious or immediately life-threatening conditions and is considered appropriate by the FDA to use on patients outside of the clinical trials.

To be considered, an application must cover the following:

  • Positive preclinical animal efficacy and toxicology data proving the drug is safe for use in humans.
  • Manufacturing information outlining the composition, manufacturer, stability, and quality controls used for manufacturing the drug.
  • Protocols for the proposed clinical studies to assess risks and safety for the subjects.

Our vast knowledge of the FDA and the expertise which lies within the team gives our clients a distinct advantage when filing an IND. Biopharma Global’s proprietary program for strategy review, identifying barriers, and then creating a comprehensive maintenance program makes filing an IND a seamless, efficient process.

Formal meetings with the FDA facilitate communication between the sponsors of a drug and the FDA Review Staff on regulatory requirements and development. In fact, formal FDA meetings are shown to shorten drug development time by up to 5 years. These meetings are scheduled for critical junctures in the drug development process, including:

  • Pre-Investigational New Drug (Pre-IND) Application
    • Held before the submittal of the IND, this meeting allows for very valuable planning and guidance for a drug sponsor on clinical trial design, minimizing clinical holds, IND application submittal, and fosters early interactions with the FDA. Efficient and early utilization of the FDA’s guidance allows for more efficient drug development.
  • End-of-Phase 1 (EOP1)
    • Held for drugs targeting severely debilitating and life-threatening illnesses to review and reach agreement on the design of Phase 2 controlled clinical trials.
    • Also assesses the need for pediatric studies, as well as their design.
  • End-of-Phase 2 (EOP2)
    • Determines the safety of proceeding to Phase 3 trials and the Phase 3 plan, the ability of current studies to assess pediatric safety and effectiveness, and organizes the information necessary for a marketing application.
  • Pre-New Drug Application (Pre-NDA) and Pre-Biologics License Application (Pre-BLA)
    • Allows for the clarification of requirements and the organization of information for the NDA and BLA. Early communication with the FDA will also allow for the reviewers to be familiar with the research and drug beforehand, ensuring better chances of approval.


There are three types of FDA Meetings:

  • Type A
    • Intended for the continuation of the development of a stalled drug program.
    • Dispute Resolution
    • Clinical Holds
    • Protocol Assessment and Evaluation
    • Post-Action Meetings
  • Type B
    • Pre-investigational new drug application (pre-IND) meetings
    • Certain end-of-phase 1 meetings for Subpart E or Subpart H or similar products
    • End-of-phase 2 and pre-phase 3 meetings
    • Pre-new drug application (pre-NDA) pre-biologics license application (pre-BLA) meetings
    • Risk Evaluation and Mitigation Strategies (REMS) or post-marketing requirements that occur outside the context of the review of a marketing application
    • Post-action meetings requested by the sponsor 3 months or more after an FDA regulatory action other than an approval
    • Meetings held to discuss the overall development program for products granted Breakthrough Therapy designation (BTD) status.
  • Type C
    • A written response to questions posed in pre-IND or Type C meeting requests may be requested by the sponsor
    • FDA may determine that a written response would be the most appropriate means for responding to a meeting request
    • FDA shall notify the requester of the date it intends to send the written response
    • FDA shall provide this notification within the specified time frame for responding to the meeting request


Biopharma Global provides a full spectrum of FDA Type A/B/C meeting services including preparing the meeting request and briefing packages as well as attendance and leading meetings if that is desirable. We also provide a variety of similar services for EU meetings.

The New Drug Application form has been used by every FDA-approved drug in the US since its establishment in 1938. The goal of this application is to summarize information for the FDA to determine the following:

  • Drug Safety and Efficacy
  • Drug Labeling and Package Insert
  • Quality of Drug Manufacturing

This information is derived from clinical studies, preclinical animal data, manufacturing protocols, and drug ingredients.

Our team can review your NDA documentation and application to ensure it is thoroughly ready for review by the FDA.

Fast Track Designation allows for better facilitation of drug development and an expedited review process by the FDA. The review process is also supplemented with additional meetings with the FDA, including pre-IND meetings, end-of-phase 1-2 meetings to discuss study design, reviewing the safety data required for approval, dose-response concerns, and use of biomarkers. Additional meetings can be scheduled as appropriate to discuss other issues.

Fast Track Designation also allows for a Rolling Review submittal process, allowing the sponsor of the application to submit portions of the marketing application for review by the FDA before submitting the complete application.

The two main criteria for a drug to be considered for Fast Track Designation are the following:

  1. The drug treats a serious condition.
    • The FDA considers a disease as a Serious Condition when it is associated with morbidity that has substantial impact on day-to-day functioning.
    • In addition, the drug itself must be intended to treat the serious condition. To satisfy this, the drug’s intended effect must apply to a serious condition or a serious aspect of the condition. This can be a serious manifestation or symptom.
  2. The drug fills an unmet medical need.
    • The information required to prove a drug can address an unmet medical need depends on the stage of drug development at which fast track designation is requested.
      • Early in development: evidence of activity in a nonclinical model, a mechanistic rationale, or pharmacologic data.
      • Later in development: available clinical data should demonstrate the potential to address an unmet medical need.

Biopharma Global provides assistance not only with obtaining fast track approval, but can also assist you in preparation for Pre-IND meetings, IND preparation and submission, NDA/BLA submission, as well as performing a strategic review of your current forms and data to ensure your drug is on the right path to approval.

The FDA normally takes a maximum of 10 months to act on a marketing application for a drug. When granted priority review, this timeframe shrinks to a maximum of 6 months. This designation will direct the FDA’s resources to the evaluation of applications for drugs that would be significant improvements in the safety or effectiveness of the diagnosis, treatment, or prevention of serious conditions when compared to normal applications.

There are two requirements for Priority Review:

  1. The disease must be recognized as a Serious Condition.
    • The FDA considers a disease as a Serious Condition when it is associated with morbidity that has substantial impact on day-to-day functioning.
    • In addition, the drug itself must be intended to treat the serious condition. To satisfy this, the drug’s intended effect must apply to a serious condition or a serious aspect of the condition. This can be a serious manifestation or symptom.
  2. The drug must demonstrate the potential to be a significant improvement in safety or effectiveness.
    • The FDA will determine if the proposed drug would be a significant improvement in the safety and efficacy of treatment, prevention, or diagnosis of a serious condition. A significant improvement can be demonstrated by increased effectiveness of treatment/diagnosis/prevention, elimination or reduction of adverse reaction to treatment, enhancement of patient compliance leading to improved outcomes, or evidence of safety and effectiveness in a new subpopulation.

Biopharma Global has vast experience in submitting PRV applications. Our superior epidemiological knowledge and our vast experience in working with the FDA provides our clients a proven roadmap forward and ultimately a successful application and designation.

The Priority Review Voucher (PRV) is distributed by the FDA as an incentive for the development of orphan drugs which would otherwise not be worth development due to their small markets. The voucher, once submitted, grants priority review to any one of the submitting sponsor’s drugs in development. The voucher is also transferrable to other sponsors or companies, and is also allowed to be sold. These options allow for the drug’s sponsor to decide if they would rather generate large amounts of funding for their drug development programs, or expedite the review process by turning in the voucher for priority review status.

The PRV was originally limited to a list of neglected tropical diseases, but was then extended to rare pediatric diseases and Ebola. If the approved drug qualifies, the FDA may grant the voucher for use on a future drug’s marketing application.

The FDA has awarded a total of 14 PRVs to various drug companies. To date, PRVs have been sold to other companies at a range of roughly $60-$350 million.

In certain cases, an investigational drug will take years to show any significant effects on a very slow-acting or long-lasting disease. Accelerated approval was instituted by the FDA in 1992 to allow drugs that treat serious conditions and filled an unmet medical need to be approved based on a surrogate endpoint from preclinical data to save time in the drug approval process.

A surrogate endpoint is a radiographic image, laboratory measurement, physical sign, or other measure that is used to predict a clinical benefit without itself being a measurable endpoint for clinical benefit. The FDA makes the final decision to accept a proposed surrogate endpoint, usually referring to the scientific research and evidence that supports the endpoint’s validity.

Our regulatory team is highly versed in analyzing preclinical and clinical data, and is ready to assist you in determining surrogate endpoints to present for accelerated approval. We are also able to research prevalence data of the target indication to determine unmet need, and will guide you through the overall potential of your investigational drug.

Breakthrough Therapy Designation allows for the expedited development and review of a drug that is intended to treat a serious disease, and has preclinical evidence that shows a substantial improvement over current therapy for clinically significant endpoints.

Upon designation, the FDA ensures that the sponsor receives timely interactive communications to help them design an efficient drug development program by involving experienced regulatory project managers in a cross-disciplinary review. Where appropriate, a cross-disciplinary project lead is assigned to the review team to facilitate an efficient review of the drug development program, as well as act as a scientific liaison between the review team members.

Designation also includes a rolling review to allow the sponsor to submit portions of a marketing application for review by the FDA before submitting the complete application.

The Requirements for Breakthrough Therapy Designation are as follows:

  1. The disease must be recognized as a Serious Condition.
    • The FDA considers a disease as a Serious Condition when it is associated with morbidity that has substantial impact on day-to-day functioning.
    • In addition, the drug itself must be intended to treat the serious condition. To satisfy this, the drug’s intended effect must apply to a serious condition or a serious aspect of the condition. This can be a serious manifestation or symptom.
  2. The preliminary clinical evidence must show that the investigational drug exhibits a substantial improvement on one or more of the clinically significant endpoints.
    • FDA generally considers available therapy as a therapy that is approved or licensed in the United States for the same indication being considered for the new drug, and is relevant to current U.S. standard of care (SOC) for the indication. This consideration is carried out by the FDA themselves, but FDA may consult with special Government employees or other experts as needed when making an available therapy determination.
    • The FDA expects that this data generally comes from credible Phase 1 or Phase 2 clinical trials. These studies usually also compare the investigational drug to an available therapy or placebo if no current therapy exists. An improvement is considered to be substantial depending on the drug’s magnitude of effect on a clinically significant endpoint, and the importance of the effect in relation to the overall improvement of the serious condition or aspect of the serious condition.
      • A Clinically significant endpoint is generally an endpoint that measures an effect on irreversible morbidity or mortality (IMM) or on symptoms that represent serious consequences of the disease. A sponsor should provide a justification for why the endpoint or other findings should be considered clinically significant.

Biopharma Global has a very deliberate process for constructing Breakthrough Therapy designations. It starts with a feasibility assessment which when complete informs the client on whether or not a BTD is viable. If the feasibility assessment indicates a positive path forward, then our experts create a roadmap forward taking into consideration their deep knowledge and expertise in working with the various review divisions.

RMAT Designation is reserved for drugs that are considered regenerative medicine therapies, such as cell therapy, therapeutic tissue engineering products, human cell and tissue products, or any combination product using the listed therapies. Similar to BTD, RMAT Designation grants earlier interactions with the FDA, as well as potential eligibility for priority review and accelerated approval.

Requirements for RMAT Designation include:

  1. The drug is a considered a regenerative medicine therapy.
  2. The drug is intended to treat, modify, reverse, or cure a serious or life-threatening disease or condition.
  3. Preliminary clinical data shows that the drug can address an unmet medical need.

Medical devices fall into a category of their own within the FDA, and have unique applications associated with their approval. These include:

Humanitarian Use Device – HUD

A Humanitarian Use Device is defined as a medical device that is intended to benefit patients in either treatment or diagnosis of a disease that affects or is manifested in not more than 8,000 individuals in the US annually. Similar to Orphan Designation, this program was created to encourage the development of medical devices intended for rare conditions by creating an alternative pathway to market.

Humanitarian Device Exemption – HDE

If a medical device is approved to have the Humanitarian Device Exemption, it becomes exempt from the effectiveness requirements in the HUD application. This exemption was created as a part of the Safe Medical Devices Act of 1990 due to the increasing difficulty of obtaining positive clinical efficacy data from a population size of below 8,000 Americans. However, an HDE has a prohibition put on the profits it can generate, involving a set Annual Distribution Number (AND) of devices that can be sold for profit. In addition, an HDE is only eligible to be sold for profit if the device is indented for the treatment or diagnosis of a pediatric disease or condition, a disease or condition that occurs in adults only, or a disease or condition that affects a subset size where development of the device is not feasible or highly impractical.

Premarket Approval – PMA

Mandatory Premarket Approval is performed on Class III medical devices to evaluate their safety and effectiveness in treating their intended target. Class III devices are categorized by being high risk, whereas Class I devices are low risk and don’t require as stringent regulatory control. Approval is based on safety and efficacy data on the device, and require 180 days of review time by the FDA.


EMA Applications

Similar to the FDA Orphan Drug Designation, the EMA provides incentives for developing drugs that treat rare diseases where the drug is not likely to generate enough sufficient profit to justify the cost of its own research and development. The EMA defines an Orphan Medicine as a drug intended for the diagnosis, prevention, or treatment of a life-threatening or chronically debilitating rare disease. The EMA deems a disease as rare when it affects less than five in 10,000 people in the EU.

Benefits of Orphan Designation in the EU include:

  • Reduced fees for protocol assistance meeting
  • Guaranteed 10 years of drug exclusivity
  • Centralized Marketing Authorization Procedure

Biopharma Global works closely with our clients to determine the best roadmap for a successful EMA application submission. In some cases, a Pre-Submission meeting may increase the likelihood of success but those decisions are reached collaboratively between Biopharma Global and the client. Similar to the FDA Orphan Designation the Biopharma Global team constructs the entire application. Our European entity handles all submissions for those clients who do not have their own European based entity.

The PRIME program was established to aid the development of drugs that target an unmet need. Like Fast Track, PRIME provides support for the clinical research and development of a medicine via accelerated assessment and initiating earlier dialogue with the EMA. Other benefits of PRIME also include:

  • The appointment of a rapporteur to the drug development project
    • The rapporteur can be from the Committee for Medicinal Products for Human Use (CHMP), or from the Committee on Advanced Therapies (CAT) in the case the drug is considered an advanced therapy
    • The project will be provided with continuous support and information before the submittal of the Marketing Authorization Application
  • A scheduled kick-off meeting with the rapporteur and a multidisciplinary group of experts to provide guidance on development and regulatory strategy
  • Assign a dedicated contact point
  • Provide scientific advice at certain milestones in development, while also involving other stakeholders
  • Confirm the potential for accelerated assessment before Marketing Authorization

Priority Medicines are considered as drugs that could offer a significant advantage over current therapies, or benefit patients who do not currently have any other treatment options. To be accepted, a medicine must show potential benefit to patients with unmet medical needs based on early clinical data.

The EMA will approve a drug for market after a full scientific evaluation following submission by the drug sponsor. Once a drug is approved, the marketing authorization applies to all European Union Member States, as well as Iceland, Norway, and Lichtenstein.