formulations often comprise more than 40 compounds, such as inorganic salts,

amino acids, vitamins, growth factors, sugars, co-factors, and metals and some of

these components are soluble at different pH, the order of addition of some com-

pounds is important (see Table 5.4). In a few cases, certain components are not

stable (e.g., glutamine, only 1−2 months of shelf life, degradation with side-product

ammonium which may inhibit cell growth and virus production) and are, thus,

TABLE 5.4

Specific media components, typical concentrations, characteristics,

and functions

Name

Concentration

Function

Characteristics

A

Glucose (gluc)

10−40 mM

Substrate, growth and energy

metabolism

Conversion to lactate:

growth inhibitor & pH

decrease

Glutamine (gln)

2−8 mM

Substrate, growth and energy

metabolism; decomposes to

pyrrolidone-carboxylic acid

and ammonia with time

Conversion to ammonia:

growth inhibitor,

inhibition of virus

replication

Amino acids

0.2−2 mM

Protein synthesis, growth

Some: pH value decrease;

some: ammonia release

Keto-acids (pyruvate)

1−4 mM

Growth

Additional carbon source

Dipeptides, ala-gln

(GlutaMAX)

2−6 mM

E.g., more stable supply of

glutamine, reduced

ammonia release

Using the di-peptide ala-gln

gln monitoring to follow

substrate uptake is not

straightforward

Glutathione

0.5−1 mg/L

Protects from oxidative

stress, redox environment

control, facilitates protein

secretion

Tripeptide

Lipids (e.g., cholesterol) 0−10 mg/L

Membrane synthesis

including viral membranes

Plant or animal components

Insulin

1−20 mg/L

Promotes glucose and amino

acid uptake

Rec. or animal component

Vitamins (folic acid,

niacinamide, i-inositol,

thiamine, …)

2−7 mg/L

E.g., activates pyruvate

metabolism, precursors of

various cofactors,

antioxidant effects

Present in most of the basal

media but adjusted to cell

types

B

Hypoxanthine

1−5 mg/L

Intermediate in DNA

synthesis, energy

metabolism

Purine derivative

Thymidine

0.2−0.7 mg/L

Intermediate in DNA

synthesis

Deoxy nucleoside

(Continued)

Upstream processing for viral vaccines

97