Tissue engineering - Orthopaedic Biomaterials in Research and Practice - page 237

identify any side effects. This initial phase can take several months to
complete and usually includes a small number of healthy volunteers (20
to 100). Once the product has demonstrated its initial safety in a small
group of patients, the product is then given to a larger group of patients
to test safety AND effectiveness in Phase II trials. This second phase
may last from several months to 2 years and involves up to several
hundred patients. Most Phase II studies are randomized trials where
one group of patients receives the experimental product, while a sec-
ond “control” group receives a standard treatment or placebo. During
Phase III, the treatment is given to large groups of people to confirm
its effectiveness, monitor side effects, compare it to commonly used
treatments, and collect further information that may guide the use of
the product. This large-scale phase, which can include several hun-
dred to several thousand patients, can last several years. If all Phase
III requirements are met, the product can be considered for market
approval by the FDA. A fourth phase of clinical trial is also performed
later to gather information on the product's effect in various popula-
tions and any side effects associated with long-term use. This is also
known as “post-market” surveillance trials. In the case that there are
unintended or unforeseen events that are observed during the post-
market phase, the device may be taken off the market or subjected to
some restrictions to its use.
Basic characteristics of the tissue-engineered components are also
required, as is expected with any other classes of products. For example,
for cell-device combination products, characterization of the cells and
scaffold is necessary. The source of the cells (auto-, allo-, or xenograft),
along with their sterility, purity, viability, cell number, stability, and
potency/biologic activity, is specified. This also includes the identity of
the cells, that is, morphologic evaluation, unique biochemical markers,
phenol-type specific cell surface antigens, and gene and protein expres-
sion analysis. The characterization of the scaffold includes evaluation of

Phase I: Initial evaluation of safety, dosage, side
effects (~20-100 people)

Phase II: Expansion to more people, randomized trial
comparing against standard treatment of placebo (up to
a few hundred people)

Phase III: Confirm treatment effectiveness, monitor side
effects, compare it to commonly used treatments (up to a
few thousand people)

Phase IV: Post-market surveillance trial, gather information
on the product's effect in various populations and any side
effects associated with long-term use

FIGUre 9.2 Clinical trial phases.