ASTM E2097-00
(Guide)Standard Guide for Determining the Impact of Extractables from Non-Metallic Materials on the Safety of Biotechnology Products
Standard Guide for Determining the Impact of Extractables from Non-Metallic Materials on the Safety of Biotechnology Products
SCOPE
1.1 This guide covers procedures and test methods for process component qualification by the end user. The goal is to assess the safety impact of extractables from non-metallic process components used in contact with bioprocessing solutions. This encompasses the impact of extractables on the safety of the final product as it passes through the various stages of the manufacturing process. This guide is not designed for evaluation of metallic materials, final product container/closures or those components intentionally added to the product or production streams during the manufacturing process. Testing of solids and extracts is specified in other ASTM standards. Materials must be qualified by specific use.
1.2 The values stated in SI units are to be regarded as the standard.
1.3 There is no companion guide available.
1.4 Safety/Fire hazards: Extractions with organic solvents will be infrequent under this Guide, but, when used must be treated as potential fire/explosion hazards.
1.5 This guide does not purport to address all of the safety concerns, if any, associated with its use. It is the responsibility of the user of this standard to establish appropriate safety and health practices and determine the applicability of regulatory limitations prior to use.
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Designation:E2097–00
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 E 2097; 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 (e) indicates an editorial change since the last revision or reapproval.
1. Scope D 4951 Determination of Additive Elements in Lubricating
Oils by Inductively Coupled Plasma Atomic Emission
1.1 This guide covers procedures and test methods for
Spectrometry
process component qualification by the end user.The goal is to
F 619 Standard Practice for Extraction of Medical Plastics
assess the safety impact of extractables from non-metallic
F 749 EvaluatingMaterialExtractsbyIntracutaneousInjec-
process components used in contact with bioprocessing solu-
tion in the Rabbit
tions. This encompasses the impact of extractables on the
F 750 EvaluatingMaterialExtractsbySystemicInjectionin
safety of the final product as it passes through the various
the Mouse
stagesofthemanufacturingprocess.Thisguideisnotdesigned
F 813 Direct Contact Cell Culture Evaluation of Materials
for evaluation of metallic materials, final product container/
for Medical Devices
closures or those components intentionally added to the prod-
F 895 Agar Diffusion Cell Culture Screening for Cytotox-
uct or production streams during the manufacturing process.
icity
Testing of solids and extracts is specified in other ASTM
standards. Materials must be qualified by specific use.
3. Terminology
1.2 The values stated in SI units are to be regarded as the
3.1 See the Compilation of ASTM Standard Definitions.
standard.
Review with the Terminology Committee, E48. SeeA7.2.1 for
1.3 There is no companion guide available.
details of set up and Part E, Terminology inASTM Standards.
1.4 Safety/Fire hazards: Extractions with organic solvents
3.2 Definitions:
will be infrequent under this Guide, but, when used must be
3.2.1 biopharmaceutical—any drug product produced from
treated as potential fire/explosion hazards.
living organisms.
1.5 This guide does not purport to address all of the safety
3.2.2 biotechnology solution—a solution containing or pro-
concerns, if any, associated with its use. It is the responsibility
ducing products from living microbial, animal or plant cells or
of the user of this standard to establish appropriate safety and
by the enzymes from those cells.
health practices and determine the applicability of regulatory
3.2.3 biotechnology product—a discrete chemical entity
limitations prior to use.
producedbygrowingsinglecellorganismswithuniquegenetic
2. Referenced Documents information.
3.2.4 elution cytotoxicity—see USP.
2.1 ASTM Standards:
3.2.5 emission spectrographic analysis (ESA)— an analyti-
D 1203 Volatile Loss from Plastics UsingActivated Carbon
cal technique for determining metals in a sample vaporized in
Methods
a plasma arc.
D 4754 Two-Sided Liquid Extraction of Plastic Materials
3.2.6 extractables—residues from solid process compo-
Using FDA Migration Cell
nents not intentionally part of the product process stream.
D 4874 Leaching Solid Material in a Column Apparatus
3.2.7 fermentation—the biochemical reaction process
where microorganisms in a nutrient medium convert a feed-
stock to a product.
ThisguideisunderthejurisdictionofASTMCommitteeE48onBiotechnology
3.2.8 inductively coupled plasma (ICP)—an analytical tech-
andisthedirectresponsibilityofSubcommitteeE48.03onUnitProcessesandTheir
nique designed to quantitate chemical elements.
Control.
Current Edition approved June 10, 2000. Published October 2000.
3.2.9 materials of construction—high molecular weight or
For referenced ASTM standards, visit the ASTM website, www.astm.org, or
solid materials, used in biopharmaceutical process equipment
contact ASTM Customer Service at service@astm.org. For Annual Book of ASTM
which contact process solutions and can potentially release
Standards volume information, refer to the standard’s Document Summary page on
the ASTM website. extractable residues.
Copyright © ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959, United States.
E2097–00
3.2.10 non-volatile residue (NVR)—non-volatile material 5. Reagents
remaining after evaporating a solvent into which the residue
5.1 The quality of reagents used for the procedures indi-
has been extracted (See USP).
cated in this guide are specified in the test standards referenced
3.2.11 oxidizable substances (OS)—chemical compounds
(for example, ASTM and USP).
which may be oxidized by potassium permanganate under
6. Procedure
specified conditions (See USP).
3.2.12 product contact material—a material which physi- 6.1 During research and development to define the manu-
facturing process for a desired biotechnology product, select
cally contacts a solution containing the chemical entity desig-
nated the product. functional product contact materials predicted to be suitable
based on manufacturer specifications. Choose materials which
3.2.13 process materials—high molecular weight or solid
have specifications defined by pharmaceutical compendia to
materials which contact process solutions potentially releasing
the extent possible. The goal is to find and use materials that
extractable residues.
will permit an acceptable level of extractables into the process
3.2.14 purification—the process by which the desired prod-
solution. Materials should be approved by specific process use.
uct is separated from the production process solution.
Awritten protocol should be prepared outlining the tests to be
3.2.15 residue on ignition (ROI)—the residue remaining
done on each process material qualified. Qualified materials
after ashing a material at high temperature.
must be well defined and documented to assure equivalent
3.2.16 total organic carbon (TOC)—ananalytical technique
replacements may be obtained.Vendor audits are necessary for
for measuring the carbon associated with organic molecules in
all suppliers of product contact material with significant
a solution.
extractables.
Whenahighquality,functionalmaterialisidentified,subject
4. Significance and Use
it to the following procedure as part of the validation of the
process.
4.1 This guide applies to the determination of the safety of
non-metallic materials used in contact with biotechnology 6.2 Choose the production function from Table 1. Use
already validated ASTM or USP test methods wherever pos-
product containing solutions. Process materials leach low level
of residues into water, cell culture media, buffers, and other sible. If the product is to be licensed in a country with other
compendial requirements, those will have to be considered as
product containing solutions. This document offers guidance
ondeterminingthesafetyofthesematerials(processmaterials) well. If test methods are the same but limits are different, use
the more stringent limits.
for use. The goal is to prevent toxic extractables from entering
process streams and ultimately contaminating the final product
NOTE 1—The cumulative effect of the ongoing removal of extractables
in unacceptable levels.
can potentially affect the performance of plastics in certain applications.
The purpose of this guide is to describe tests to qualify
6.3 Perform the tests designated in Table 1. Where extrac-
materials with respect to any extractable substances so as to
tions are done, follow Practice F 619-79 (1991) . Increase the
prevent unintentional introduction of a potential source of
time, temperature and concentration of the extraction several
objectionable substances.An extractable material is objection-
foldbeyondproductionconditionstobuildinsafetyfactorsand
able if it is toxic, interacts with product constituents, interferes
insure worst case. Also it may be appropriate to exacerbate
with required assays, or otherwise affects the process stream so
other factors affecting the extraction capability of the solvent
as to adversely affect critical quality parameters, for example,
such as organic concentration and pH. Demonstration of
purity, safety, efficacy, identity, strength of the final product or
depletion of extractable material can be shown by repeated
its successful production.All organizations producing pharma-
extraction and testing for non-volatile residue or oxidizable
ceutical products should consider the points in this guide when
substances.
qualifying process materials for use in their production pro-
6.4 Characterize the product contact process material by
cesses.
through the film, pyrolysis, attenuated total reflectance or
4.2 This guide outlines the application of the process
solution infrared methods. The infrared scan will become the
material tests primarily in ASTM or USP. Typical process
reference for subsequent lots of the material unless a manu-
materials include high molecular weight polymers and solids
facturer or other valid scan is available.
such as hoses, filters, filter housings, containers, valve dia-
6.5 Evaluate the product contact process material for heavy
phragms, gaskets, o-rings, chromatography resins, and chro-
metals using Residue on Ignition followed by Emission Spec-
matographic columns.
trographic or Inductively Coupled Plasma methodologies. In
4.3 Thebatteryoftestsdescribedinthisguideisintendedto
this case the amount of Residue on Ignition is not important
cover a wide variety of potential attributes of materials and to
except as it allows you to calculate the concentration of metals
characterize possible extractables.
in the solid. If unacceptable levels of heavy metals are found,
4.4 The material specification will vary depending on the appropriate extracts should be tested by Atomic Absorption
impact on the final product and the point in the process that the Spectroscopy to determine if the metals are extractable into the
product solution contacts the material. Tighter specifications relevant process solution.
should be considered for extractables for final product purifi- 6.6 Distilled Water Extract— follow Practice F 619-79
cation process materials than for fermentation media process (Reapproved 1991), Sections 6 through 12. When choosing a
materials. setofextractionconditions,chooseatemperaturesimilartothe
E2097–00
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
...
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