• Ph. Eur. Chapter 2.6.16 [“Tests for extraneous agents in viral vaccines

for human use”] was revised in the 9th edition of the European

Pharmacopoeia (9.3), which became effective on 01 January 2018. A new

paragraph requests the introduction of a risk assessment to build the testing

strategy that must be based on a full package of suitable tests with re-

ference to Chapter 5.1.7. In the paragraph regarding the testing for ex-

traneous agents in cell cultures, it is requested that the testing for

extraneous agents must be carried out based on a risk assessment for each

virus-seed lot, each virus harvest, and each production cell culture (control

cells or control eggs).

• Ph. Eur. Chapter 5.2.3: “Cell Substrates for the production of vaccines

for human use,” Version 9:0 and updated Version 9.3 in July 2017. A

greater flexibility is proposed when testing for infectious extraneous agents

between master cell bank (MCB) and working cell bank (WCB), based on

a risk assessment. Table 5.2.3.-1 is updated accordingly, and molecular

methods are now considered.

• The new Ph. Eur. Chapter 5.2.14: [“Substitution of in vivo method(s) by

in vitro method(s) for the quality control of vaccines”], Version 9.3 pub-

lished in July 2017, was created to facilitate the introduction of in vitro

methods.

•

Finally, the Ph. Eur. Chapter 5.1.7 provides general requirements con-

cerning the viral safety of medicinal products whose manufacture has in-

volved the use of materials of human or animal origin. The relevant factors

to be considered in a risk assessment are listed.

Other general regulatory requirements in terms of viral risk assessments are also

described in the following guidance:

• ICH Q5A ‘Viral Safety Evaluation of Biotechnology Products Derived

from Cell Lines of Human or Animal Origin’ [20].

• ICH Q5D ‘Derivation and Characterization of Cell Substrates Used for

Production of Biotechnological/Biological Products’ [21].

• Guidance for Industry: Characterization and Qualification of Cell

Substrates and Other Biological Materials Used in the Production of Viral

Vaccines for Infectious Disease [22].

• USP 1050 – Viral Safety Information / General information [23].

• EMA Guideline on Virus Safety Evaluation of Biotechnological

Investigational Medicinal Products [24].

• WHO Recommendations for The Evaluation of Animal Cell Cultures as

Substrates for The Manufacture of Biological Medicinal Products and for

the Characterization of Cell Banks [5].

The development of risk assessment is also requested in product-specific guidance.

For example, the European “Guideline on the use of porcine trypsin used in the

manufacture of human biological medicinal products” [25] provides general quality

specifications for porcine trypsin, especially with respect to viral safety. It is

Cell lines for vaccine production

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