E55.04 - General Biopharmaceutical Standards

SIGNIFICANCE AND USE
4.1 Single-use systems (SUSs) used for biopharmaceutical manufacturing must maintain sterility and product quality of the fluid inside. Such articles or systems should therefore be validated as providing an effective barrier against microbial ingress. The microbial barrier properties of a SUS may be demonstrated using deterministic physical tests that have been correlated to microbial integrity. Two test methods (aerosol exposure and immersion exposure) are described that can be used to demonstrate microbial integrity of a SUS or determine the MALL, the maximum defect size that does not allow microbial ingress, into a SUS.  
4.2 It is important to note that the results of microbial ingress tests are heavily dependent on the conditions under which the test is performed and are not suitable for routine checking of a SUS due to the test’s destructive nature.  
4.2.1 Any size defect may be forced to fail under sufficiently aggressive conditions (including a large enough sample size, high differential pressure, or high hydrostatic pressure, for example) that would not ordinarily reflect normal use conditions. Thus, it is necessary to clearly define the relevant conditions for a test through a risk assessment of both the actual SUS claims and its final use (Practice E3244). Once that is established, the size of defect that can be detected under those conditions can be determined, if required, using defined defects.  
4.2.2 “Relevant conditions” refers to worse-case actual use conditions but does not mean that a SUS must be tested under theoretically absolute (extreme) “worst-case” conditions.  
4.2.3 Testing may be performed on individual components or entire systems. Considerations for defining “relevant conditions” and testing design should be based on a risk assessment for the SUS intended use and should include:
4.2.3.1 A channel created by a defect or breach through the film thickness or through a seam or connection which must be filled with liquid to allow mic...
SCOPE
1.1 The microbial test method outlined in this document applies to microbial ingress risk assessment of a single-use system (SUS) or its individual components that require integrity testing either by the assembly supplier or the end user of the assembly based on a potential risk of a breach to the product or manufacturing process.  
1.2 The aim of microbial ingress testing of sterile SUSs used in biopharmaceutical manufacturing is two-fold:  
1.2.1 Firstly, it is used to evaluate the ability of a SUS fluid path to remain sterile after a SUS has been challenged by microbial exposure. Microbial exposure is achieved either by directly placing a SUS into a container of microbial challenge solution, or by delivering an aerosolized microbial challenge onto a SUS that is placed inside a test chamber designed to generate and deliver the aerosol. The choice of the test challenge organism should be justified based on a risk assessment of the SUS and conditions of use.  
1.2.2 Additionally, microbial ingress testing can be used to determine the maximum allowable leakage limit (MALL) that does not allow microbial ingress under specific test conditions. The defect size that can be detected by specific physical integrity testing methods can be correlated to this MALL in order to claim microbial integrity. Test articles bearing calibrated defects over a range of dimensions, including up to a defect size expected to consistently allow microbial ingress as a positive control (defect-based positive control), may be tested to determine the MALL.  
1.3 Both purposes for microbial ingress testing as described in 1.2.1 and 1.2.2 can either be conducted by liquid immersion or aerosol exposure. For the purpose described in 1.2.2, the type of exposure should be determined according to the SUS’s use-case conditions and a risk assessment.  
1.4 The method used to create a breach, hole or defect in single-use film or in a SUS test article, as ...

SIGNIFICANCE AND USE
4.1 This practice provides:  
4.1.1 A holistic approach to evaluate risks associated with an integrity breach in a SUS, considering its life cycle from development to disposal.  
4.1.2 An overview of physical and microbial test methods that could be applicable to SUS testing, for qualification and validation purposes, as well as for routine testing.  
4.1.3 Information on the main challenges faced when testing SUSs for integrity.  
4.2 This practice can be used by SUS suppliers and SUS end users to define an integrity assurance strategy for SUSs, with the relevant tests when appropriate.
SCOPE
1.1 This practice uses quality risk management (QRM) and life-cycle approach to establish integrity assurance of single-use systems (SUSs), such as but not limited to bag assemblies and liquid transfer sets for processing, storage, and shipping of (bio)pharmaceutical products. It gives recommendations to identify failure modes and risks associated with such systems and their use-cases and how to identify the relevant leak(s) of concern. Integrity assurance in this context is limited to the barrier properties of the SUS, linked to microbial integrity and bioburden control (product quality) and liquid product loss (operator and environmental contamination). The required level of integrity assurance will depend on how critical the application is and can be interpreted in different ways. Other package barrier properties different from that, such as but not limited to gas barrier properties for gas headspace preservation, are not considered.  
1.2 The test method overview provides descriptions that focus on the standard test setup and the identification of challenges in combination with SUSs. Details, including specific test setups, test parameter, and result interpretation, are not discussed.  
1.3 This practice is not intended to apply to the use of single-use technology for primary containers, combination products (products composed of any combination of a drug, device, or biological product), or devices. Appropriate procedures related to these products are discussed in documents covering the integrity assurance for primary containers (1)2 or medical products (2, 3).  
1.4 Techniques and procedures for complaint management and root cause analysis related to integrity failures are also not discussed.  
1.5 The values stated in SI units are to be regarded as standard. No other units of measurement are included in this standard.  
1.6 This standard 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, health, and environmental practices and determine the applicability of regulatory limitations prior to use.  
1.7 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.

SIGNIFICANCE AND USE
4.1 This guide is intended for use by individuals maintaining and handling hazardous biological material in liquid nitrogen freezers.  
4.2 This guide does not cover all aspects of every situation that may be encountered in maintaining hazardous biological material in liquid nitrogen; each situation must therefore be assessed individually using these guidelines.  
4.3 This guide is not intended for use with systems other than liquid nitrogen storage.  
4.4 This guide does not cover practices for preservation by freezing which are covered in Practice E1342.
SCOPE
1.1 This guide covers recommended procedures for maintaining and handling hazardous biological materials at liquid nitrogen temperatures.  
1.2 This guide covers the safety precautions recommended when handling material stored in liquid nitrogen.  
1.3 This guide does not cover the maintenance and handling of hazardous biological materials maintained at cryogenic temperatures in systems other than liquid nitrogen.  
1.4 The values stated in SI units are to be regarded as standard. No other units of measurement are included in this standard.  
1.5 This standard 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.

SIGNIFICANCE AND USE
4.1 The proper design of low-temperature storage facilities ensures that sensitive biological materials are maintained under conditions providing maximum storage stability.  
4.2 Properly designed and operated low-temperature storage facilities ensure that the handling of sensitive biological materials at low temperatures does not compromise stability (see Guide E1565).  
4.3 Properly designed low-temperature storage facilities ensure that adequate safeguards are provided to prevent untoward events from compromising the stability of sensitive biological materials.
SCOPE
1.1 This guide covers recommended procedures for developing and maintaining low-temperature storage facilities for freezers with mechanical refrigeration.  
1.2 This guide covers recommended procedures for developing and maintaining low-temperature storage facilities for freezers cooled with liquid nitrogen.  
1.3 This guide does not cover practices for preservation by freezing which are covered in Practice E1342.  
1.4 The values stated in SI units are to be regarded as standard. No other units of measurement are included in this standard.  
1.5 This standard does not purport to address all of the safety problems, 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.

SIGNIFICANCE AND USE
4.1 The proper handling of material stored at low temperatures ensures that the stability of sensitive biological materials is not comprised.  
4.2 Properly designed inventory control systems ensure the maximum use of freezer space, that all material can be located easily, and that any item is retrieved easily without compromising the stability of other items in the freezer.  
4.3 Properly designed safety and security procedures ensure that material stored at low temperatures is not comprised during storage, and that if material is lost due to freezer failure or operational problems, replacement material is available (see Guide E1566).
SCOPE
1.1 This guide covers recommended procedures for handling material stored at low temperatures in mechanical freezers and liquid nitrogen freezers.  
1.2 This guide covers recommendations for implementing procedures for ensuring adequate inventory control.  
1.3 This guide covers recommendations for implementing procedures for safeguarding material stored at low temperatures.  
1.4 This guide does not cover the development or maintenance of equipment and facilities for low-temperature storage which are covered in Guide E1564.  
1.5 This guide does not cover practices for preservation by freezing which are covered in Practice E1342.  
1.6 The values stated in SI units are to be regarded as standard. No other units of measurement are included in this standard.  
1.7 This standard 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.

SCOPE
1.1 This practice assures 5 log10 inactivation of non-defective C-type retroviruses, which are endogenous to murine hybridoma and CHO cells and are potentially present in the production stream of biopharmaceutical processes that use rodent derived cell culture.  
1.2 The process parameters specified in this practice consistently assure 5 log10 inactivation of murine retrovirus by adjusting the pH of a process solution after initial affinity capture chromatography purification.  
1.3 This practice is applicable to mAb, IgG fusion, or other recombinant proteins produced from rodent cell lines (for example, CHO or murine hybridoma), which do not target retroviral proteins. Additionally, the low pH step is performed on a cell-free intermediate, post initial capture using protein A chromatography.  
1.4 The 5 log10 inactivation of murine retrovirus claimed by using this practice will be utilized in conjunction with other clearance unit operations (for example, chromatography and virus retentive filtration) to assure sufficient total process clearance of murine retroviruses, which will be supportive of early phase regulatory filings.  
1.5 The values stated in SI units are to be regarded as standard. No other units of measurement are included in this standard.

SIGNIFICANCE AND USE
This guide applies to the determination of the safety of non-metallic materials used in contact with biotechnology product containing solutions. Process materials leach low level of residues into water, cell culture media, buffers, and other product containing solutions. This document offers guidance on determining the safety of these materials (process materials) for use. The goal is to prevent toxic extractables from entering process streams and ultimately contaminating the final product in unacceptable levels.
The purpose of this guide is to describe tests to qualify materials with respect to any extractable substances so as to prevent unintentional introduction of a potential source of objectionable substances. An extractable material is objectionable if it is toxic, interacts with product constituents, interferes with required assays, or otherwise affects the process stream so as to adversely affect critical quality parameters, for example, purity, safety, efficacy, identity, strength of the final product or its successful production. All organizations producing pharmaceutical products should consider the points in this guide when qualifying process materials for use in their production processes.
This guide outlines the application of the process material tests primarily in ASTM or USP. Typical process materials include high molecular weight polymers and solids such as hoses, filters, filter housings, containers, valve diaphragms, gaskets, o-rings, chromatography resins, and chromatographic columns.
The battery of tests described in this guide is intended to cover a wide variety of potential attributes of materials and to characterize possible extractables.
The material specification will vary depending on the impact on the final product and the point in the process that the product solution contacts the material. Tighter specifications should be considered for extractables for final product purification process materials than for fermentation media pr...
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.

SIGNIFICANCE AND USE
This guide is intended for use by individuals maintaining and handling hazardous biological material in liquid nitrogen freezers.
This guide does not cover all aspects of every situation that may be encountered in maintaining hazardous biological material in liquid nitrogen; each situation must therefore be assessed individually using these guidelines.
This guide is not intended for use with systems other than liquid nitrogen storage.
This guide does not cover practices for preservation by freezing which are covered in Practice E 1342.
SCOPE
1.1 This guide covers recommended procedures for maintaining and handling hazardous biological materials at liquid nitrogen temperatures.
1.2 This guide covers the safety precautions recommended when handling material stored in liquid nitrogen.
1.3 This guide does not cover the maintenance and handling of hazardous biological materials maintained at cryogenic temperatures in systems other than liquid nitrogen.
1.4 The values stated in SI units are to be regarded as the standard.
This standard 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.

SIGNIFICANCE AND USE
The proper design of low-temperature storage facilities ensures that sensitive biological materials are maintained under conditions providing maximum storage stability.
Properly designed and operated low-temperature storage facilities ensure that the handling of sensitive biological materials at low temperatures does not compromise stability (see Guide E 1565).
Properly designed low-temperature storage facilities ensure that adequate safeguards are provided to prevent untoward events from compromising the stability of sensitive biological materials.
SCOPE
1.1 This guide covers recommended procedures for developing and maintaining low-temperature storage facilities for freezers with mechanical refrigeration.
1.2 This guide covers recommended procedures for developing and maintaining low-temperature storage facilities for freezers cooled with liquid nitrogen.
1.3 This guide does not cover practices for preservation by freezing which are covered in Practice E 1342.
1.4 The values stated in SI units are to be regarded as standard.
This standard does not purport to address all of the safety problems, 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.

SIGNIFICANCE AND USE
The proper handling of material stored at low temperatures ensures that the stability of sensitive biological materials is not comprised.  
Properly designed inventory control systems ensure the maximum use of freezer space, that all material can be located easily, and that any item is retrieved easily without compromising the stability of other items in the freezer.
Properly designed safety and security procedures ensure that material stored at low temperatures is not comprised during storage, and that if material is lost due to freezer failure or operational problems, replacement material is available (see Guide E 1566).
SCOPE
1.1 This guide covers recommended procedures for handling material stored at low temperatures in mechanical freezers and liquid nitrogen freezers.
1.2 This guide covers recommendations for implementing procedures for ensuring adequate inventory control.
1.3 This guide covers recommendations for implementing procedures for safeguarding material stored at low temperatures.
1.4 This guide does not cover the development or maintenance of equipment and facilities for low-temperature storage which are covered in Guide E 1564.
1.5 This guide does not cover practices for preservation by freezing which are covered in Practice E 1342.
1.6 The values stated in SI units are to be regarded as the standard.
This standard 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.

SIGNIFICANCE AND USE
4.1 This guide applies to the determination of the safety of non-metallic materials used in contact with biotechnology product containing solutions. Process materials leach low level of residues into water, cell culture media, buffers, and other product containing solutions. This document offers guidance on determining the safety of these materials (process materials) for use. The goal is to prevent toxic extractables from entering process streams and ultimately contaminating the final product in unacceptable levels.  
4.2 The purpose of this guide is to describe tests to qualify materials with respect to any extractable substances so as to prevent unintentional introduction of a potential source of objectionable substances. An extractable material is objectionable if it is toxic, interacts with product constituents, interferes with required assays, or otherwise affects the process stream so as to adversely affect critical quality parameters, for example, purity, safety, efficacy, identity, strength of the final product or its successful production. All organizations producing pharmaceutical products should consider the points in this guide when qualifying process materials for use in their production processes.  
4.3 This guide outlines the application of the process material tests primarily in ASTM or USP. Typical process materials include high molecular weight polymers and solids such as hoses, filters, filter housings, containers, valve diaphragms, gaskets, o-rings, chromatography resins, and chromatographic columns.  
4.4 The battery of tests described in this guide is intended to cover a wide variety of potential attributes of materials and to characterize possible extractables.  
4.5 The material specification will vary depending on the impact on the final product and the point in the process that the product solution contacts the material. Tighter specifications should be considered for extractables for final product purification process materials than f...
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 standard. No other units of measurement are included in this 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 standard 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.
WITHDRAWN RATIONALE
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 manufacturi...

ABSTRACT
This practice covers the procedures used for detection of mycoplasma contamination of cell cultures by growth on agarose medium. This practice does not cover identification of mycoplasma and indirect methods for detection of mycoplasma. This practice will not detect cultivar strains of Mycoplasma hyorhinis nor intended for use in detection of mycoplasma contamination in sera, culture media, vaccines, or other systems. The practice involves DM-1 solid medium preparation, quality control, and mycoplasma isolation.
SCOPE
1.1 This practice covers the procedures used for detection of mycoplasma contamination by direct microbiological culture.
1.2 This practice does not cover indirect methods for detection of mycoplasma such as DNA staining, biochemical detection, or genetic probes.
1.3 This practice does not cover methods for identification of mycoplasma organisms.
1.4 This practice will not detect cultivar strains (1) of Mycoplasma hyorhinis.
1.5 This practice is not intended for use in detection of mycoplasma contamination in sera, culture media, vaccines, or other systems.
This standard 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.
WITHDRAWN RATIONALE
This practice covers the procedures used for detection of mycoplasma contamination by direct microbiological culture.
Formerly under the jurisdiction of Committee E55 on Manufacture of Pharmaceutical Products, this practice was withdrawn in August 2014. This standard was withdrawn without replacement due to its limited use by the industry.

SIGNIFICANCE AND USE
Mycoplasma hyorhinis, cultivar α strains (1)3 do not grow on any of the standard media used for mycoplasma cultivation. These strains, which are found as contaminants in cell cultures, are detected by indirect methods.
A specialized medium has been described but it is not yet in wide use (2).
This practice should be used in conjunction with Practice E 1531.
All cell cultures to be examined for mycoplasma should undergo a minimum of two passages in antibiototic-free tissue culture medium before testing.
SCOPE
1.1 This practice covers the use of cell cultures and DNA-binding flurorochrome techniques to detect mycoplasma contamination of cell cultures.
1.2 This practice does not cover axenic cultivation or identification of mycoplasmas.
This standard 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.
WITHDRAWN RATIONALE
This practice covers the use of cell cultures and DNA-binding flurorochrome techniques to detect mycoplasma contamination of cell cultures.
Formerly under the jurisdiction of Committee E55 on Manufacture of Pharmaceutical Products, this practice was withdrawn in August 2014. This standard was withdrawn without replacement due to its limited use by the industry.

SIGNIFICANCE AND USE
This guide is intended for use in a biotechnology laboratory when the need arises to identify a preparation containing M13 bacteriophage or DNA.
SCOPE
1.1 This guide covers the identification of bacteriophage M13 used in biotechnology.
1.2 There are many variants of M13 that have been developed specifically for cloning technology. These variants have foreign DNA inserted into the M13 genome, causing the M13 to differ in size and genotype.
1.3 If the M13 is to be used to construct a recombinant molecule, then the criteria described in Section 6 should be used to characterize the newly made DNA.
WITHDRAWN RATIONALE
This guide covers the identification of bacteriophage M13 used in biotechnology.
Formerly under the jurisdiction of Committee E55 on Manufacture of Pharmaceutical Products, this guide was withdrawn in August 2014. This standard was withdrawn without replacement due to its limited use by the industry.

SIGNIFICANCE AND USE
The prime purpose of this test method is to provide data expressed as either electrophoretic mobility or zeta potential distribution of protein particles.
Both sellers and purchasers of protein particles will find this test method useful to determine either mobility or zeta potential distributions for protein specifications, manufacturing control, and development and research.
SCOPE
1.1 This test method describes a procedure for determining the electrophoretic mobility of proteins of molecular weight greater than 10 000 Daltons.
1.2 This test method uses automatic Electrophoretic Light Scattering (ELS) principles to determine the electrophoretic mobility.
1.3 The instrument simultaneously measures the Doppler shifts of scattered light at four different angles to determine the electrophoretic mobility distribution of protein particles. The mobility is expressed as m-cm/V-s (micron-centimeter/volt-second).
This standard 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.
WITHDRAWN RATIONALE
This test method describes a procedure for determining the electrophoretic mobility of proteins of molecular weight greater than 10 000 Daltons.
Formerly under the jurisdiction of Committee E55 on Manufacture of Pharmaceutical Products, this guide was withdrawn in August 2014. This standard was withdrawn without replacement due to its limited use by the industry.

SIGNIFICANCE AND USE
Mycoplasma contamination of cell cultures is a common problem that can affect the growth, metabolism, and function of cultured animal cells. The ability to detect mycoplasma in cell cultures provides an opportunity to ensure that cells are free of contamination, and to replace those that are not. For additional information, see Practices E 1531, E 1532, and E 1536. Strict adherence to established, well-tested procedures is necessary. This practice was developed by Task Group E48.01.02 to assist in developing and maintaining an established regimen for mycoplasma detection by indirect 4′-6-Diamidino-2-Phenylindole (DAPI) fluorochrome staining.
This practice is intended for use in examining cultured animal cells for the presence of mycoplasma contamination.
This practice is not intended for use in the detection of mycoplasma contamination in serum, culture media, or systems other than cultures of animal cells.
All cell cultures to be examined for mycoplasma should undergo a minimum of two passages in antibiotic-free tissue culture medium before testing.
SCOPE
1.1 This practice covers procedures used for the detection of mycoplasma contamination by indirect DNA staining.
1.2 This practice does not cover direct methods for the detection of mycoplasma or other indirect methods such as enzymatical detection or DNA probes.
1.3 This practice does not cover methods for the identification of mycoplasma organisms.
1.4 The values stated in SI units are to be regarded as the standard. The values given in parentheses are for information only.
This standard 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.
WITHDRAWN RATIONALE
This practice covers procedures used for the detection of mycoplasma contamination by indirect DNA staining.
Formerly under the jurisdiction of Committee E55 on Manufacture of Pharmaceutical Products, this practice was withdrawn in August 2014. This standard was withdrawn without replacement due to its limited use by the industry.

SIGNIFICANCE AND USE
This guide is intended for use in a biotechnology laboratory whenever the necessity arises for identifying a biological preparation believed to contain primarily HSV or its DNA. The characterization criteria used for the identification shall be performed by an individual trained in molecular virology.
This guide is not meant to be used in a clinical laboratory for the identification of HSV isolated from patient specimens.
SCOPE
1.1 This guide covers laboratory characterization procedures sufficient to identify purified specimens of HSV types 1 and 2 (HSV-1 and HSV-2) or HSV-1 DNA and HSV-2 DNA used in biotechnology. For cases in which identification of HSV DNA specimens is required, the characterization criteria of and of this guide are sufficient.
1.2 This guide does not cover the identification of HSV in HSV-infected host cells. To apply this guide to such a case, it would first be necessary to isolate the virus from such samples using standard techniques of HSV purification. This guide does not cover characterization of segments of HSV DNA or of vectors containing HSV DNA segments.
1.3 This guide does not cover the specific methodology used in the identification characterization. It does not address the question of degree of purity required for herpes virus preparations: this would vary depending on the particular biotechnology use of the virus.
1.4 Warning-Laboratory work involving herpes simplex viruses can be hazardous to personnel. Biosafety 2 level facilities are recommended (). Safety guidelines shall be adhered to according to NCCLS M29-T2 and other recommendations ().
This standard 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.
WITHDRAWN RATIONALE
This guide covers laboratory characterization procedures sufficient to identify purified specimens of HSV types 1 and 2 (HSV-1 and HSV-2) or HSV-1 DNA and HSV-2 DNA used in biotechnology.
Formerly under the jurisdiction of Committee E55 on Manufacture of Pharmaceutical Products, this guide was withdrawn in August 2014. This standard was withdrawn without replacement due to its limited use by the industry.

SIGNIFICANCE AND USE
This guide is intended for use in any laboratory utilizing PCR or RT-PCR to amplify and detect a specific nucleic acid sequence.
The criteria used for evaluation of the amplification reactions should be administered by an individual trained in the use of molecular biological techniques associated with PCR.
SCOPE
1.1 This guide covers guidelines, recommendations, basic considerations, criteria, and principles to be employed when developing, utilizing, or assessing PCR procedures and specific protocols for the amplification and detection of nucleic acid sequences. This guide is not intended to be a standard procedure with a list of requirements for PCR detection of nucleic acids. This guide is intended to provide information that will assist the user in obtaining quality and reliable data.
1.2 Nucleic acid targets for PCR include DNA, as well as RNA ; RNA sequences are suitable targets for PCR following reverse transcription of the RNA to complementary DNA (cDNA). This type of amplification technique is known as reverse transcription-PCR (RT-PCR).
1.3 This guide has been developed for use in any molecular biology/biotechnology laboratory. This includes, but is not limited to, laboratories that specialize in the diagnosis of human, animal, plant, or bacterial diseases.
1.4 This guide conveys the general procedural terminology of PCR technology used for the detection of nucleic acids.
1.5 This guide is general; it does not cover the additional guidance that would be needed for specific applications, for example, for the PCR detection of nucleic acid sequences of specific microorganisms.
1.6 This guide does not cover details of the various methods that can be utilized to identify PCR-amplified DNA sequences.
1.7 This guide does not cover specific variations of the basic PCR or RT-PCR technology (for example, quantitative PCR, real-time PCR, multiplex PCR, and in situ PCR), and it does not cover details of instrument calibration.
1.8 Warning-Laboratory work involving certain clinical specimens and microorganisms can be hazardous to personnel. Warning-Biosafety level 2 (or higher) facilities are recommended for biohazard work (). Safety guidelines should be adhered to in accordance with CLSI M29-A2 and other recommendations  ().
WITHDRAWN RATIONALE
This guide covers guidelines, recommendations, basic considerations, criteria, and principles to be employed when developing, utilizing, or assessing PCR procedures and specific protocols for the amplification and detection of nucleic acid sequences.
Formerly under the jurisdiction of Committee E55 on Manufacture of Pharmaceutical Products, this guide was withdrawn in August 2014. This standard was withdrawn without replacement due to its limited use by the industry.

SIGNIFICANCE AND USE
Mycoplasmas of bovine origin are prevalent contaminants of cell cultures. Contamination can be detected by the large volume method.3 ,4  
Heat inactivated serum need not be tested for mycoplasmas. Heating serum to 56°C for 30 min will kill mycoplasmas.
Mycoplasmas may be present in any particular lot of serum but may not be detected because of inadequate sample size; thus, negative test results do not provide absolute assurance that the test serum is free of mycoplasmas.
SCOPE
1.1 This practice covers the procedures used for detection of mycoplasma contamination in serum by direct microbiological culture.
1.2 This practice does not cover procedures used for detection of mycoplasma in cell cultures.
1.3 This practice does not cover indirect methods for detection of mycoplasma contamination.
1.4 This practice does not cover methods for identification of mycoplasma cultures.
This standard 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.
WITHDRAWN RATIONALE
This practice covers the procedures used for detection of mycoplasma contamination in serum by direct microbiological culture.
Formerly under the jurisdiction of Committee E55 on Manufacture of Pharmaceutical Products, this practice was withdrawn in August 2014. This standard was withdrawn without replacement due to its limited use by the industry.

SIGNIFICANCE AND USE
This guide suggests analytical methods generally applied within the pharmaceutical industry to identify and quantitate the level of impurities and contaminants present in the preparation of a biological drug product. These methods are not intended to be all-inclusive. The methods used by an individual manufacturer must be specific to the product and process of production.
SCOPE
1.1 This guide covers the concepts of purity, impurity, and contamination in biological drug products.
1.2 This guide suggests methods for determination of impurities and contaminants in such products.
1.3 This guide is arranged as follows:
1.4 This standard 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.
WITHDRAWN RATIONALE
This guide covers the concepts of purity, impurity, and contamination in biological drug products.
Formerly under the jurisdiction of Committee E55 on Manufacture of Pharmaceutical Products, this guide was withdrawn in August 2014. This standard was withdrawn without replacement due to its limited use by the industry.

SIGNIFICANCE AND USE
This guide is intended for use in any laboratory utilizing PCR or RT-PCR to amplify and detect nucleic acid sequences of mycobacteria from a biological preparation and to identify the species of origin.
The criteria used for the identification and evaluation of the amplification reactions should be administered by an individual trained in the use of molecular biological and microbiological techniques associated with PCR and MTB.
SCOPE
1.1 This guide covers basic considerations, criteria, principles and recommendations that should be helpful when developing, utilizing, or assessing PCR-specific protocols for the amplification and detection or identification of mycobacterial nucleic acids. This guide is not a specific protocol for the detection of specific mycobacteria. It is intended to provide information that will assist the user in obtaining high quality and reliable data. The guide is closely related to and should be used concurrently with the general PCR Guide E 1873.
1.2 This guide has been developed for use in any molecular biology or biotechnology laboratory. It may be useful for the detection of mycobacteria in clinical, diagnostic laboratories.
1.3 This guide does not cover details of the various methods such as gel electrophoresis that can be utilized to help identify PCR-amplified mycobacterial nucleic acid sequences, and it does not cover details of instrument calibration.
1.4 This guide does not cover specific variations of the basic PCR or RT-PCR technology (for example, quantitative PCR, multiplex PCR and in situ PCR), and it does not cover details of instrument calibration.
1.5 Warning-Laboratory work involving certain clinical specimens and microorganisms can be hazardous to personnel. Precaution: Biosafety Level 2 facilities are recommended for potentially hazardous work, and Biosafety Level 3 facilities are required for propagating and manipulating Mycobacteria tuberculosis cultures (). Safety guidelines should be adhered to according to NCCLS M29-T2, I17-P and other recommendations ().
WITHDRAWN RATIONALE
This guide covers basic considerations, criteria, principles and recommendations that should be helpful when developing, utilizing, or assessing PCR-specific protocols for the amplification and detection or identification of mycobacterial nucleic acids.
Formerly under the jurisdiction of Committee E55 on Manufacture of Pharmaceutical Products, this guide was withdrawn in August 2014. This standard was withdrawn without replacement due to its limited use by the industry.

ABSTRACT
This guide covers laboratory characterization procedures for identifying bacteriophage lambda or its DNA and assumes that the reader has basic knowledge in virology and molecular biology. Bacteriohage lambda is a temperate bacteriophage with an icosahedral hear and a single, non-contractile tail ending in a single tail fiber. The lambda genome consists of a single molecule of linear double-stranded DNA and has cohesive ends. The naturally preferred hosts is Escherichia coli K12. Hundreds of lambda variants derived from wild type lambda can be used in biotechnology and differ in genome size and genotype. These are used primarily as DNA vectors for cloning DNA fragments. Judging uncontaminated, pure lambda should be done through restriction enzyme analysis DNA characterization and the presence and identification of lambda DNA is accomplished by polymerase chain reaction. The primers used for detection of bacteriophage lambda should be chosen based on the reason for detection.
SCOPE
1.1 This guide covers the procedures for identifying bacteriophage lambda used in biotechnology.
1.2 There are hundreds of lambda variants that can be used for biotechnology. These lambda variants are derived from wild type lambda and differ in genome size and genotype.
1.3 If the bacteriophage lambda is to be used to construct a recombinant molecule, then the same criteria as prescribed in Section 5 should be used to characterize the newly made DNA.
WITHDRAWN RATIONALE
This guide covers the procedures for identifying bacteriophage lambda used in biotechnology.
Formerly under the jurisdiction of Committee E55 on Manufacture of Pharmaceutical Products, this guide was withdrawn in August 2014. This standard was withdrawn without replacement due to its limited use by the industry.

SIGNIFICANCE AND USE
Isoaspartic acid residues are generated during incubation of proteins under a wide variety of conditions in aqueous solution. Such residues are generated most commonly through the deamidation of aspargine residues although some reports of isoaspartic acid formation through the rearrangement of aspartic acid residues have been published.
The presence of such residues can indicate that the protein containing such residues has suffered damage that may affect the biological activity of the protein. The precise correlation between the level of isoaspartic acid content and the biological activity of the protein needs to be determined on a case by case basis.
The test measures the level of isoaspartic acid content in a protein sample. This level will often be correlated with the degree to which the protein has suffered deamidation at asparagine residues. In addition, isoaspartic acid residues can arise on occasion through the rearrangement of aspartic acid residues. For these reasons, the level of isoaspartic acid residues in proteins can be used as a general indication that the protein sample has suffered some level of damage and should not be interpreted to indicate the precise level of damage to any one region within a protein without further testing.
SCOPE
1.1 This test method covers the determination of isoaspartic acid residues in a protein or peptide sample. This test method is applicable for the determination of isoaspartic acid residues in a sample in the range of 2.5-50 μmol/L. Higher concentrations can be determined following dilution. The reported lower range is based on single-operator precision.
1.2 The values stated in SI units are to be regarded as the standard.
1.3 This standard 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.
WITHDRAWN RATIONALE
This test method covers the determination of isoaspartic acid residues in a protein or peptide sample.
Formerly under the jurisdiction of Committee E55 on Manufacture of Pharmaceutical Products, this test method was withdrawn in July 2012 in accordance with section 10.5.3.1 of the Regulations Governing ASTM Technical Committees, which requires that standards shall be updated by the end of the eighth year since the last approval date.