522
23.8.1.1 Pre-Clinical Studies
Preclinical study is conducted before exposing the ingredient to human subject. It
consists of in vitro study and in vivo study which conducted on laboratory animal.
In USA the Committee on the Evaluation of the Addition of Ingredients New to
Infant Formula recommends pre-animal tests if the ingredients to be added to infant
formulas are not well known and if there is no adequate literature about them to
determine their safety. Therefore, the complete chemical structure and functional
groups and the purity and stability of the ingredients present in the matrix should be
determined using well-established method such as high performance liquid chromatography (HPLC), liquid chromatography-mass spectrometry (LC-MS), and thin
layer chromatography (TLC) (Lönnerdal 2012).
Toxicity studies should be conducted in animals to ensure the safety of the product in the formula. Rodent models (rats, mice) are mostly used for toxicity studies.
But difference in metabolism and development limit their result. The rat has short
reproductive cycle (21 days gestation) which allows for rapid cycle studies and
assessment of generational effects. However, rat consume low fat diets (5% while
human 45–55%) of their calories as fat. Piglet models are also used due to comparable in size to neonatal humans and metabolize fatty acids like humans. Piglets can
be used for assessment of high-fat infant formulas. Generally investigators should
choose healthy animals, animals that have never been exposed to any experimental
procedure, male and female animals, and animals that are capable of completing the
entire study (National Academy of Sciences 2004).
23.8.1.2 Clinical Trial
Clinical trial is conducted on human subject for different reasons. The first reason is
extrapolation from animal studies are limited by difference of animal and human
structure, development and physiology. Extrapolation from tissue isolate is also
limited due to inability of such model to assess the function which needs coordination of different organ system (i.e. digestion and absorption of nutrient). Preclinical
trial gives clue on the safety, absorption and the dose (amount of nutrient) that
should be added to the formula. Therefore, to ensure the safety and efficacy of the
medical food and infant formula clinical trials are mandatory (Frestedt 2017).
FDA describes the concept of ‘healthy growth’ including all aspects of physical
growth and normal maturational development, including maturation of organ systems and achievement of normal functional development of motor, neurocognitive,
and immune systems. These all growth and maturational developmental processes
affects an ability of infant’s to achieve his/her biological potential, and all can be
affected by the infant nutritional status. Clinical trial include these end points in
consideration and answers the following questions (National Academy of
Sciences 2004).
Absorption, metabolism, distribution, and excretion, half-life of the food or food
additive in the human body. It also used to assess interactions between the food or
A. G. Mtewa et al.
23.8.1.1 Pre-Clinical Studies
Preclinical study is conducted before exposing the ingredient to human subject. It
consists of in vitro study and in vivo study which conducted on laboratory animal.
In USA the Committee on the Evaluation of the Addition of Ingredients New to
Infant Formula recommends pre-animal tests if the ingredients to be added to infant
formulas are not well known and if there is no adequate literature about them to
determine their safety. Therefore, the complete chemical structure and functional
groups and the purity and stability of the ingredients present in the matrix should be
determined using well-established method such as high performance liquid chromatography (HPLC), liquid chromatography-mass spectrometry (LC-MS), and thin
layer chromatography (TLC) (Lönnerdal 2012).
Toxicity studies should be conducted in animals to ensure the safety of the product in the formula. Rodent models (rats, mice) are mostly used for toxicity studies.
But difference in metabolism and development limit their result. The rat has short
reproductive cycle (21 days gestation) which allows for rapid cycle studies and
assessment of generational effects. However, rat consume low fat diets (5% while
human 45–55%) of their calories as fat. Piglet models are also used due to comparable in size to neonatal humans and metabolize fatty acids like humans. Piglets can
be used for assessment of high-fat infant formulas. Generally investigators should
choose healthy animals, animals that have never been exposed to any experimental
procedure, male and female animals, and animals that are capable of completing the
entire study (National Academy of Sciences 2004).
23.8.1.2 Clinical Trial
Clinical trial is conducted on human subject for different reasons. The first reason is
extrapolation from animal studies are limited by difference of animal and human
structure, development and physiology. Extrapolation from tissue isolate is also
limited due to inability of such model to assess the function which needs coordination of different organ system (i.e. digestion and absorption of nutrient). Preclinical
trial gives clue on the safety, absorption and the dose (amount of nutrient) that
should be added to the formula. Therefore, to ensure the safety and efficacy of the
medical food and infant formula clinical trials are mandatory (Frestedt 2017).
FDA describes the concept of ‘healthy growth’ including all aspects of physical
growth and normal maturational development, including maturation of organ systems and achievement of normal functional development of motor, neurocognitive,
and immune systems. These all growth and maturational developmental processes
affects an ability of infant’s to achieve his/her biological potential, and all can be
affected by the infant nutritional status. Clinical trial include these end points in
consideration and answers the following questions (National Academy of
Sciences 2004).
Absorption, metabolism, distribution, and excretion, half-life of the food or food
additive in the human body. It also used to assess interactions between the food or
A. G. Mtewa et al.