ASTM E2888-12(2019)

This international standard was developed in accordance with internationally recognized principles on standardization established in the Decision on Principles for the
Development of International Standards, Guides and Recommendations issued by the World Trade Organization Technical Barriers to Trade (TBT) Committee.
Designation: E2888 − 12 (Reapproved 2019)
Standard Practice for
Process for Inactivation of Rodent Retrovirus by pH
This standard is issued under the fixed designation E2888; the number immediately following the designation indicates the year of
original adoption or, in the case of revision, the year of last revision. A number in parentheses indicates the year of last reapproval. A
superscript epsilon (´) indicates an editorial change since the last revision or reapproval.
1. Scope quence (usually a human receptor-like protein or protein
fragment) fused to the carboxyl-terminal of the Fc-domain of a
1.1 This practice assures 5 log10 inactivation of non-
human IgG antibody.
defective C-type retroviruses, which are endogenous to murine
2.1.1.1 Discussion—Dimerization occurs by way of the Fc
hybridoma and CHO cells and are potentially present in the
domain.
production stream of biopharmaceutical processes that use
rodent derived cell culture.
2.1.2 immunoglobulin G (IgG), n—an antibody molecule
composed of four peptide chains — two γ heavy chains and
1.2 The process parameters specified in this practice con-
sistently assure 5 log10 inactivation of murine retrovirus by two light chains.
adjusting the pH of a process solution after initial affinity
2.1.2.1 Discussion—Each IgG has two antigen binding
capture chromatography purification.
sites. IgG constitutes 75 % of serum immunoglobulins in
humans. IgG molecules are synthesized and secreted by plasma
1.3 This practice is applicable to mAb, IgG fusion, or other
B cells. There are four IgG subclasses (IgG1, 2, 3, and 4) in
recombinant proteins produced from rodent cell lines (for
humans, named in order of their abundance in serum (IgG1
example, CHO or murine hybridoma), which do not target
being the most abundant). Only human IgG1, IgG2, and IgG4
retroviral proteins. Additionally, the low pH step is performed
show significant affinity to protein A.
on a cell-free intermediate, post initial capture using protein A
chromatography.
2.1.3 log10 reduction value (LRV), n—typically used to
describe the degree of reduction of a population, in this case
1.4 The 5 log10 inactivation of murine retrovirus claimed
rodent retrovirus, by the treatment process.
by using this practice will be utilized in conjunction with other
clearance unit operations (for example, chromatography and
-1
2.1.3.1 Discussion—Each log reduction (10 ) represents a
virus retentive filtration) to assure sufficient total process
90 % reduction in the population. So a process shown to
clearance of murine retroviruses, which will be supportive of
-6
achieve a 6-log reduction (10 ) will reduce a population from
early phase regulatory filings.
a million (10 ) to 1.
1.5 The values stated in SI units are to be regarded as
2.1.4 monoclonal antibody (mAb), n—monospecific anti-
standard. No other units of measurement are included in this
bodies which have affinity for the same antigen and are made
standard.
from a master cell bank, cloned from a parent cell.
1.6 This international standard was developed in accor-
2.1.5 murine leukemia virus (MuLV), n—retroviruses named
dance with internationally recognized principles on standard-
for their ability to cause cancer in murine (mouse) hosts.
ization established in the Decision on Principles for the
2.1.5.1 Discussion—MuLV is a member of the genus Gam-
Development of International Standards, Guides and Recom-
maretrovirus. MuLV is an enveloped spherical RNA virus
mendations issued by the World Trade Organization Technical
which has a diameter of 80–110 nm and has low chemical
Barriers to Trade (TBT) Committee.
resistance. MuLV is used as a model for non-defective C-type
2. Terminology endogenous retrovirus or retrovirus like particles produced by
murine hybridoma and CHO cell lines. MuLV is used to assess
2.1 Definitions of Terms Specific to This Standard:
rodent retrovirus clearance of protein purification processes
2.1.1 IgG fusion protein, n—a dimeric protein comprised of
that use rodent cells for production.
two monomers, each monomer consisting of a peptide se-
2.1.6 recombinant protein, n—produced from the expres-
sion of recombinant DNA within living cells.
This practice is under the jurisdiction of ASTM Committee E55 on Manufac-
ture of Pharmaceutical and Biopharmaceutical Products and is the direct responsi-
2.1.6.1 Discussion—Recombinant DNA is genetically engi-
bility of Subcommittee E55.12 on Process Applications.
neered by inserting foreign DNA into the DNA of an appro-
Current edition approved Feb. 1, 2019. Published March 2019. Originally
priate host so that the foreign DNA is replicated along with the
approved in 2012. Last previous edition approved in 2012 as E2888 – 12. DOI:
10.1520/E2888-12R19. host DNA.
Copyright © ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959. United States
E2888 − 12 (2019)
2.1.7 retrovirus, n—an RNA virus that is propagated in a depends on reactant concentration (that is, H+ ion concentra-
host cell using the reverse transcriptase enzyme to produce tion as measured by pH), time of reaction and temperature of
DNA from its RNA genome. reaction. Implementing the parameters that give robust and
2.1.7.1 Discussion—DNA is then incorporated into the effective rodent retrovirus inactivation established by this
host’s genome by an integrase enzyme. The virus is thereafter pratice, in conjunction with other clearance unit operations (for
replicated as part of the host cell’s DNA. Retroviruses are example, chromatogr
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