Blog #5 Michelle Keyvani

Name of Guidance:
Guidance for Industry: E11 Clinical Investigation of Medicinal Products in the Pediatric Population

Status of Guidance:
Final Guidance

Guidance Release Date:
This Guidance was released December 2000

Link to Guidance: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM073143.pdf

Target Audience:
Medicine in the pediatric population is limited. This guidance is intended to encourage timely pediatric medicinal products internationally.

Laws and Regulations:
Other ICH documents with relevant information affecting pediatric studies include:
E2: Clinical Safety Data Management
E3: Structure and Content of Clinical Study Reports
E4: Dose-Response Information to Support Drug Registration
E5: Ethnic Factors in the Acceptability of Foreign Clinical Data
E6: Good Clinical Practice: Consolidated Guideline
E8: General Considerations for Clinical Trials
E9: Statistical Principles for Clinical Trials
E10: Choice of Control Group in Clinical Trials
M3: Nonclinical Safety Studies for the Conduct of Human Clinical Trials for Pharmaceuticals
Q1: Stability Testing
Q2: Validation of Analytical Procedures
Q3: Impurity Testing

Summary:
The guidance provides an outline of critical issues in pediatric drug development and approaches to the safe, efficient, and ethical study of medicinal products in the pediatric population.

Issues When Initiating a Pediatric Medicinal Product Development Program - The decision to proceed with a pediatric development program for a medicinal product, and the nature of that program, involve consideration of many factors, including:
· The prevalence of the condition to be treated in the pediatric population
· The seriousness of the condition to be treated
· The availability and suitability of alternative treatments for the condition in the pediatric population, including the efficacy and the adverse event profile (including any unique pediatric safety issues) of those treatments
· Whether the medicinal product is novel or one of a class of compounds with known properties
· Whether there are unique pediatric indications for the medicinal product
· The need for the development of pediatric-specific endpoints
· The age ranges of pediatric patients likely to be treated with the medicinal product
· Unique pediatric (developmental) safety concerns with the medicinal product, including any nonclinical safety issues
· Potential need for pediatric formulation development

Of these factors, the most important is the presence of a serious or life-threatening disease for which the medicinal product represents a potentially important advance in therapy.

Pediatric Formulations -
For oral administration, different types of formulations, flavors, and colors may be more acceptable in one region than another. Several formulations, such as liquids, suspensions, and chewable tablets, may be needed or desirable for pediatric patients of different ages. Different drug concentrations in these various formulations may also be needed. Consideration should also be given to the development of alternative delivery systems.

For injectable formulations, appropriate drug concentrations should be developed to allow accurate and safe administration of the dose. For medicinal products supplied as single use vials, consideration should be given to dose-appropriate single-dose packaging.

Timing of Studies -
During clinical development, the timing of pediatric studies will depend on the medicinal product, the type of disease being treated, safety considerations, and the efficacy and safety of alternative treatments.

Types of Studies -
Pharmacokinetics, Efficacy, Safety and Postmarketing Information

Age Classification of Pediatric Patients - The following is one possible categorization. There is, however, considerable overlap in developmental (e.g., physical, cognitive, and psychosocial) issues across the age categories: · Preterm newborn infants
· Term newborn infants (0 to 27 days)
· Infants and toddlers (28 days to 23 months)
· Children (2 to 11 years)
· Adolescents (12 to 16-18 years (dependent on region))

Ethical Issues in Pediatric Studies -
The pediatric population represents a vulnerable subgroup. Therefore, special measures are needed to protect the rights of pediatric study participants and to shield them from undue risk.

Institutional Review Board/Independent Ethics Committee (IRB/IEC) is critical to the protection of study participants.

Recruitment of study participants should be free of inappropriate inducements.

Consent and Assent: Full informed consent should be obtained from the parent(s) or legal guardian.

Minimizing Risk: Every effort should be made to anticipate and reduce known hazards.

Minimizing Distress: Practical considerations to ensure that participants’ experiences in clinical studies are positive and to minimize discomfort and distress include the following:
· Personnel knowledgeable and skilled in dealing with the pediatric population and its age-appropriate needs, including skill in performing pediatric procedures
· A physical setting with furniture, play equipment, activities, and food appropriate for age
· The conduct of studies in a familiar environment such as the hospital or clinic where participants normally receive their care
· Approaches to minimize discomfort of procedures, such as (1) topical anesthesia to place IV catheters, (2) indwelling catheters rather than repeated venipunctures for blood sampling, and (3) collection of some protocol-specified blood samples when routine clinical samples are obtained.

Rationale:
The number of medicinal products currently labeled for pediatric use is limited. The reason why this guidance is so important is because it is intended to encourage and facilitate timely pediatric medicinal product development internationally. The guidance provides an outline of critical issues in pediatric drug development and approaches to the safe, efficient, and ethical study of medicinal products in the pediatric population.

Resulting Recommendations:
Pediatric patients should be given medicines that have been appropriately evaluated for their use in those populations. Safe and effective pharmacotherapy in pediatric patients requires the timely development of information on the proper use of medicinal products in pediatric patients of various ages and, often, the development of pediatric formulations of those products. Advances in formulation chemistry and in pediatric study design will help facilitate the development of medicinal products for pediatric use.

Drug development programs should usually include the pediatric patient population when a product is being developed for a disease or condition in adults and it is anticipated the product will be used in the pediatric population. Obtaining knowledge of the effects of medicinal products in pediatric patients is an important goal. However, this should be one without compromising the well-being of pediatric patients participating in clinical studies. This responsibility is shared by companies, regulatory authorities, health professionals, and society as a whole.

Impact:
Being able to provide safe and effective medicines for the pediatric population.