ASTM E2097-00(2014)

NOTICE: This standard has either been superseded and replaced by a new version or withdrawn.
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Designation: E2097 − 00 (Reapproved 2014)
Standard Guide for
Determining the Impact of Extractables from Non-Metallic
Materials on the Safety of Biotechnology Products
This standard is issued under the fixed designation E2097; 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 F619 Practice for Extraction of Medical Plastics
1.1 This guide covers procedures and test methods for
3. Terminology
process component qualification by the end user.The goal is to
assess the safety impact of extractables from non-metallic
3.1 See the Dictionary of Engineering Science and Technol-
process components used in contact with bioprocessing solu-
ogy. Review with Subcommittee E48.91 on Terminology. See
tions. This encompasses the impact of extractables on the
Section A7 on Terminology and Part E on Terminology in
safety of the final product as it passes through the various
ASTM Standards in Form and Style for ASTM Standards for
stagesofthemanufacturingprocess.Thisguideisnotdesigned
details.
for evaluation of metallic materials, final product container/
3.2 Definitions:
closures or those components intentionally added to the prod-
3.2.1 biopharmaceutical—any drug product produced from
uct or production streams during the manufacturing process.
living organisms.
Testing of solids and extracts is specified in other ASTM
standards. Materials must be qualified by specific use. 3.2.2 biotechnology solution—a solution containing or pro-
ducing products from living microbial, animal or plant cells or
1.2 The values stated in SI units are to be regarded as
by the enzymes from those cells.
standard. No other units of measurement are included in this
standard.
3.2.3 biotechnology product—a discrete chemical entity
producedbygrowingsinglecellorganismswithuniquegenetic
1.3 There is no companion guide available.
information.
1.4 Safety/Fire Hazards: Extractions with organic solvents
3.2.4 elution cytotoxicity—see USP.
will be infrequent under this guide, but, when used must be
treated as potential fire/explosion hazards.
3.2.5 emission spectrographic analysis (ESA)— an analyti-
cal technique for determining metals in a sample vaporized in
1.5 This standard does not purport to address all of the
a plasma arc.
safety concerns, if any, associated with its use. It is the
responsibility of the user of this standard to establish appro-
3.2.6 extractables—residues from solid process components
priate safety and health practices and determine the applica-
not intentionally part of the product process stream.
bility of regulatory limitations prior to use.
3.2.7 fermentation—the biochemical reaction process where
microorganisms in a nutrient medium convert a feedstock to a
2. Referenced Documents
product.
2.1 ASTM Standards:
3.2.8 inductively coupled plasma (ICP)—an analytical tech-
D4951 Test Method for Determination ofAdditive Elements
nique designed to quantitate chemical elements.
in Lubricating Oils by Inductively Coupled Plasma
Atomic Emission Spectrometry
3.2.9 materials of construction—high molecular weight or
solid materials, used in biopharmaceutical process equipment
which contact process solutions and can potentially release
This guide is under the jurisdiction of ASTM Committee E55 on Manufacture
extractable residues.
ofPharmaceuticalandBiopharmaceuticalProductsandisthedirectresponsibilityof
Subcommittee E55.04 on General Biopharmaceutical Standards.
3.2.10 non-volatile residue (NVR)—non-volatile material
Current edition approved Dec. 1, 2014. Published January 2015. Originally
remaining after evaporating a solvent into which the residue
approved in 2000. Last previous edition approved in 2006 as E2097 – 00 (2006).
has been extracted (see USP).
DOI: 10.1520/E2097-00R14.
For referenced ASTM standards, visit the ASTM website, www.astm.org, or
3.2.11 oxidizable substances (OS)—chemical compounds
contact ASTM Customer Service at service@astm.org. For Annual Book of ASTM
which may be oxidized by potassium permanganate under
Standards volume information, refer to the standard’s Document Summary page on
the ASTM website. specified conditions (see USP).
Copyright © ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959. United States
E2097 − 00 (2014)
3.2.12 product contact material—a material which physi- 6. Procedure
cally contacts a solution containing the chemical entity desig-
6.1 During research and development to define the manu-
nated the product.
facturing process for a desired biotechnology product, select
3.2.13 process materials—high molecular weight or solid
functional product contact materials predicted to be suitable
materials which contact process solutions potentially releasing
based on manufacturer specifications. Choose materials which
extractable residues.
have specifications defined by pharmaceutical compendia to
3.2.14 purification—the process by which the desired prod- the extent possible. The goal is to find and use materials that
will permit an acceptable level of extractables into the process
uct is separated from the production process solution.
solution. Materials should be approved by specific process use.
3.2.15 residue on ignition (ROI)—the residue remaining
Awritten protocol should be prepared outlining the tests to be
after ashing a material at high temperature.
done on each process material qualified. Qualified materials
3.2.16 total organic carbon (TOC)—an analytical technique
must be well defined and documented to assure equivalent
for measuring the carbon associated with organic molecules in
replacements may be obtained.Vendor audits are necessary for
a solution.
all suppliers of product contact material with significant
extractables.
4. Significance and Use
6.2 When a high quality, functional material is identified,
4.1 This guide applies to the determination of the safety of
subject it to the following procedure as part of the validation of
non-metallic materials used in contact with biotechnology
the process.
product containing solutions. Process materials leach low level
of residues into water, cell culture media, buffers, and other
6.3 Choose the production function from Table 1. Use
product containing solutions. This document offers guidance
already validated ASTM or USP test methods wherever pos-
ondeterminingthesafetyofthesematerials(processmaterials)
sible. If the product is to be licensed in a country with other
for use. The goal is to prevent toxic extractables from entering
compendial requirements, those will have to be considered as
process streams and ultimately contaminating the final product
well. If test methods are the same but limits are different, use
in unacceptable levels.
the more stringent limits.
4.2 The purpose of this guide is to describe tests to qualify
NOTE 1—The cumulative effect of the ongoing removal of extractables
materials with respect to any extractable substances so as to
can potentially affect the performance of plastics in certain applications.
prevent unintentional introduction of a potential source of
6.4 Perform the tests designated in Table 1. Where extrac-
objectionable substances.An extractable material is objection-
tions are done, follow Practice F619 – 79 (1991). Increase the
able if it is toxic, interacts with product constituents, interferes
time, temperature and concentration of the extraction several
with required assays, or otherwise affects the process stream so
foldbeyondproductionconditionstobuildinsafetyfactorsand
as to adversely affect critical quality parameters, for example,
insure worst case. Also it may be appropriate to exacerbate
purity, safety, efficacy, identity, strength of the final product or
other factors affecting the extraction capability of the solvent
its successful production.All organizations producing pharma-
such as organic concentration and pH. Demonstration of
ceutical products should consider the points in this guide when
depletion of extractable material can be shown by repeated
qualifying process materials for use in their production pro-
extraction and testing for non-volatile residue or oxidizable
cesses.
substances.
4.3 This guide outlines the application of the process
6.5 Characterize the product contact process material by
material tests primarily in ASTM or USP. Typical process
through the film, pyrolysis, attenuated total reflectance or
materials include high molecular weight polymers and solids
solution infrared methods. The infrared scan will become the
such as hoses, filters, filter housings, containers, valve
reference for subsequent lots of the material unless a manu-
diaphragms,gaskets,o-rings,chromatographyresins,andchro-
facturer or other valid scan is available.
matographic columns.
4.4 The battery of tests described in this guide is intended to 6.6 Evaluate the product contact process material for heavy
cover a wide variety of potential attributes of materials and to
metals using Residue on Ignition followed by Emission Spec-
characterize possible extractables.
trographic or Inductively Coupled Plasma methodologies. In
this case the amount of Residue on Ignition is not important
4.5 The material specification will vary depending on the
except as it allows you to calculate the concentration of metals
impact on the final product and the point in the process that the
in the solid. If unacceptable levels of heavy metals are found,
product solution contacts the material. Tighter specifications
appropriate extracts should be tested by Atomic Absorption
should be considered for extractables for final product purifi-
Spectroscopy to determine if the metals are extractable into the
cation process materials than for fermentation media process
relevant process solution.
materials.
6.7 Distilled Water Extract—Follow Practice F619 –79
5. Reagents
(1991), Sections 6 through 12. When choosing a set of
5.1 The quality of reagents used for the procedures indi- extractionconditions,chooseatemperaturesimilartotheworst
cated in this guide are specified in the test standards referenced case use conditions. Extend the extraction time as appropriate
(for example, ASTM and USP). to create safety factors.
E2097 − 00 (2014)
TABLE 1 Recommended Tests on Non-Soluble, Non-Metallic Process Components Used in Biotechnology Manufacturing
Test Test Method Fermentation Purification Final Product
Solid Component
Characterize by IR Thin film or ATRIR A B C
Metals by ESA or ICP Ash, and analyze residue A B C
Dried Extract
Characterize by IR KB
...