What are the regulatory requirements for pediatric medicines?

Regulations in the US and EU both require and incentivize (via pediatric exclusivity) development of pediatric medicines. These regulations are designed to ensure that every new drug will be evaluated for use in pediatric patients and studied in this population when appropriate.

A key requirement is the submission of detailed plans that outline the studies to be conducted as part of the pharmaceutical and clinical development program:

  • EMA – Paediatric Investigation Plan (PIP)
  • FDA – Pediatric Study Plan (PSP)

The regulatory agencies require that companies demonstrate the “palatability” of drug products in pediatric patient populations as part of the pharmaceutical and clinical development program (unless a PIP or PSP waiver is granted).

So what is a palatable drug product?

Many Active Pharmaceutical Ingredients (API) are extremely bitter or have other aversive sensory attributes such as a malodor, trigeminal irritation, or a gritty texture that can adversely affect doing compliance.

There are many definitions of “palatable” – dictionaries, expert opinions and regulatory perspectives. However, the shortcoming of all of them is that they are subjective.

Senopsys has advanced a definition of “palatable” that is based on the scientific principles of perception:

“Palatable drug products are those in which the aversive sensory attributes
are below the recognition threshold”

 

A key feature of Senopsys’ definition of palatable is that it has a measurable endpoint.

A Tradition of Excellence in Pediatric Drug Formulation Development

Senopsys has conducted over 160 studies supporting the development of taste-masked pediatric drugs since our founding in 2006.

Developing palatable pediatric drug formulations can be a daunting undertaking filled with many clinical, regulatory, and technical challenges.

Our clients rely on our experience and expertise to guide development of palatable, taste-masked pediatric drug formulations throughout the clinical and commercial development process.

Taste Assessment (Following Successful First-in-Human Studies)

  • Identify the aversive sensory attributes of the drug active or prototype pediatric formulations – bitterness, malodor, irritation
  • Quantify the taste masking challenge using trained human taste panels
  • Establish recognition (palatability) threshold concentrations for the aversive attributes

Drug Product Design

  • Develop Pediatric Investigation Plan (PIP) / Pediatric Study Plan (PSP) strategy:
    • Age-appropriate dosage form(s)
    • Requirements for taste masking, including need for an API modification technology (e.g., particle coating or adsorption)
    • Dosing vehicle selection (e.g. appropriate foods and beverages)
  • Define Critical Quality Attributes for taste, aroma, mouthfeel and texture

Pediatric Formulation Development

  • Develop palatable pediatric drug formulations that enable dose titration, applying Quality by Design (QBD) principles:
    • Liquids – solutions, suspensions
    • Solids – tablets (chewable, dispersible, orally disintegrating, mini-tabs), powders (sprinkles, sachets)
  • Identify pediatric-appropriate dosing vehicles to simultaneously optimize for:
    • Taste masking
    • Ease-of-preparation and administration
    • Ease-of-swallowing
    • In-use stability
  • Measure taste effects of solubility enhancement technologies:
    • API form – salts vs free base
    • Excipients – surfactants, lipids, emulsifiers
    • Particle size reduction
    • Hot melt extrusion
    • Spray dry dispersion

Taste Masking Technology Guidance

  • Determine maximum free (soluble) API concentration required for palatability
  • Measure effectiveness of taste masking technology – particle coating/encapsulation, adsorption, complexation, hot melt extrusion
  • Verify taste masking performance of pediatric drug formulations in dosing vehicles (e.g., bitter breakthrough)

Senopsys is a unique specialty pharma service provider, conducting both taste assessment of APIs and taste masking of drug products using GCP-compliant human taste panels, following internationally recognized analysis methods.

Explore the Art and Science of Taste Masking

We invite you to explore the art and science of taste masking by viewing a recent case study or downloading our white paper.

Palatability Should Never Be The Reason A Medicine Fails

Trusted by 15 of the top 25 global pharma companies, Senopsys brings sensory science and formulation expertise to the most challenging taste masking problems.

Reach out to schedule a technical discussion with our experts.

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