Regulatory programs: Expediting product development for special populations and unmet medical needs

Some drugs or medical devices are developed to help treat rare and life-threatening conditions with unmet medical needs, and some are developed for use by a special population (for example, a pediatric population). Different regulatory agencies have designated programs that offer incentives to companies that develop these products to help them go to market. These regulatory programs can include features such as a faster review process, scientific advice, conditional approval, marketing protection, or reduced or waived submission fees.1


Orphan drugs

Products intended to treat rare diseases or conditions (affecting fewer than 200,000 persons in the US, or not more than 5 in 10,000 persons in the EU) may be categorized as orphan
drugs.1-3 The criteria for this designation vary slightly in the US and the EU (Table 1). Orphan-drug provision is not available in Canada.4

Table 1: Orphan-drug designation criteria: US and EU

A rare disease or condition is any disease or condition which:

  • Affects less than 200,000 persons in the United States
  • Affects more than 200,000 persons in the US and for which there is no reasonable expectation that the cost of development and making available in the US a drug for such a disease or condition will be recovered from sales of such a drug in the US
A medicinal product shall be designated as an orphan medicinal product if the sponsor can establish that:

  • It is intended for the diagnosis, prevention or treatment of a life-threatening or chronically debilitating condition
    • that affects not more than 5 in 10,000 persons in the community when the application is made


    • that without incentives is unlikely to generate sufficient return to justify the necessary investment


    • No satisfactory method for the diagnosis, prevention or treatment of the condition has been authorized in the EU; or, if such a method does exist, the new medicinal product will be of significant benefit to those affected by the condition.

To have a product designated as an orphan drug, the company developing it must submit an Application for Orphan Medicinal Product Designation to the EU Committee for Orphan Medicinal Products (COMP) and/or a request for orphan drug designation to the US Office of Orphan Products Development (OOPD).
Incentives are offered for orphan-drug products in the following areas:

  • Market exclusivity (seven years in the US and 10 years in the EU)
  • Financial assistance (up to a 50% tax credit in the US against expenses incurred during clinical trials, or grant aid in the US and the EU to support orphan-drug research)
  • Scientific assistance (assistance in developing clinical trial protocols)
  • Reduced application fees (exemption from US prescription drug user fees for NDAi review, or reduced MAAii and application fees for variation submissionsiii in Europe).

Pediatric applications

In Canada, an additional six-month extension to the eight-year data protection period will be applied if a company includes in their new drug submission, or in its supplement (filed within the first five years of the eight-year data protection period), the results of clinical trials designed and conducted to increase knowledge regarding pediatric use of a drug which would lead to a health benefit for children.5

In the US, unless a waiver is granted, a company must assess the safety and efficacy of a drug for use by pediatric patients in a marketing application. An application with pediatric indications is granted six months of extra market exclusivity.

In the EU, companies who undertake an agreed-upon pediatric investigation plan for new or existing drugs may gain an additional market-protection period that ranges from six months to two years, if the product is considered an orphan drug. Financial aid is also available for conducting research and development of pediatric drugs.7

Expedited review

Drugs that are intended to treat or diagnose serious, life-threatening or severely debilitating diseases or conditions may qualify for a faster review process in Canada, the US and the EU (Table 2).1,8-10

Table 2: Expedited review programs in Canada, the US and the EU: Summary Jurisdiction Programs and their highlights


Programs and their highlights


Priority review A shortened regulatory review target of 180 days instead of 300 days
Conditional approval (NOC/c) The company must agree to carry out additional clinical trials to verify the clinical benefit(s) of the drug. In addition, the conditional approval includes:

  • A requirement to undertake increased monitoring of the drug and reporting to Health Canada
  • A requirement to provide educational material, including the nature of the conditions of use, to healthcare practitioners and patients
  • Restrictions on advertising and labelling

Such conditions will be removed once the company submits satisfactory evidence of the drug’s clinical effectiveness and all the agreed-upon conditions have been met


Fast track designation Frequent interactions with the U.S. Food & Drug Administration (FDA) and the possibility of a “rolling submission” (that is, the FDA will review the completed sections of an NDA [for example, quality, non-clinical] rather than waiting until every section of the application is completed―usually the clinical section is the last component)
Accelerated approval(21 CFR 314 Subpart H) An approval based on a surrogate end point with the Phase IV confirmation clinical trial to be conducted post-marketing
Priority review A review period of six months instead of 10 months


Accelerated assessment A review of an application can be conducted within 150 days instead of 210 days


Medical devices


In Canada, a priority review is granted to a class III or class IV medical-device licence application in cases where:

  • the medical device is intended for the diagnosis or treatment of a serious, life-threatening or severely debilitating disease or condition


  • substantial clinical evidence exists supporting the device

A written request for a priority review must be submitted at least 21 calendar days prior to the filing of the licence application. The targets for screening and review for class III and IV of the original application are 15 days and 60 days, respectively. For any required screening and review of additional information, the targets are 15 days and 30 days, respectively. Applications granted priority review status will be assigned an interim performance target of 45 days from time of receipt, including both screening and review time.11


In the US, an application for a humanitarian device exemption (HDE) may be submitted if a device is intended to benefit patients by diagnosing or treating a disease or condition that affects fewer than 4,000 individuals annually. An HDE is similar to a PMAiv but is exempt from the effectiveness requirements. It must, however, contain sufficient information to show that:

  • the device does not pose an unreasonable or significant risk of illness or injury


  • the probable health benefit outweighs the risk of injury or illness from its use, considering the existing available medical devices or alternative treatment


  • no comparable device exists to diagnose or treat the disease or condition

An approved HDE authorizes the marketing of a “Humanitarian Use Device” (HUD). However, the authorization is limited and an HUD may only be used in facilities that have a local institutional review board (IRB) to supervise the clinical testing of devices with an IRB approval for such use. It must bear a label stating that “although the device is authorized by Federal Law, the effectiveness of the device for the specific indication has not been demonstrated.”12

iNDA = New Drug Application
iiMAA = Marketing Authorization Application
iiiPost-marketing changes are submitted to EMA as “variation” submissions (Type Ia, Type Ib and Type II)
ivPMA = Premarket approval application


The information presented in these articles is intended to outline the general processes, principles and concepts of the healthcare product development lifecycle. Since regulatory requirements are ever-changing, it is current only as of the date of publication and not intended to provide detailed instructions for product development. Every healthcare product is unique and therefore so is its associated product development lifecycle. Specific advice should be sought from a qualified healthcare or other appropriate professional.
Published: October 17, 2012