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Cited by 14Molecular Biology Techniques and ApplicationsViral Infectious Diseases and Gene Expression in InsectsAnalytical Methods in Pharmaceuticals

Comparative analysis of the performance of residual host cell DNA assays for viral vaccines produced in Vero cells

Open access
Vernay, Olivier, Sarcey, Eric, Detrez, Valérie, Abachin, Eric, Riou, Patrice, Mouterde, Bénédicte, Bonnevay, Thierry, Mallet, Laurent·2019·Journal of Virological Methods
DOI 10.1016/j.jviromet.2019.01.001
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Abstract

Residual host cell DNA (rcDNA) from continuous cell lines used for manufacturing of biological medicinal products has been considered as safety risk. Historically, several analytical methods have been used for rcDNA quantitation including hybridization assay, Threshold® assay and quantitative polymerase chain reaction (qPCR). Sanofi Pasteur has a wealth of experience in the development of methods quantifying rcDNA in vaccines. Here, we compared the performance of our in-house assays for quantifying rcDNA in viral vaccines produced in Vero cells. Vero alpha-satellite sequence qPCR was compared with the hybridization and Threshold® assays in terms of specificity, sensitivity and precision. The impact of viral inactivation with β-propiolactone (BPL) on rcDNA, within the vaccine production process, was also assessed. We demonstrate that the quantity of rcDNA measured is influenced by the analytical method used. Vero cell DNA-specific qPCR assay was shown to be robust with a large dynamic range and no matrix interference on a range of products. The qPCR assay demonstrated greater sensitivity and specificity versus the hybridization and Threshold® methods. Vero alpha-satellite sequence qPCR is a specific and sensitive method for the assessment of the quantity of Vero rcDNA in the highly purified vaccines.

AI snapshot

Written from the paper’s full text.

TL;DR

This paper compares Sanofi Pasteur’s Vero alpha-satellite qPCR assay with hybridization and Threshold® assays for quantifying residual host cell DNA (rcDNA) in Vero-cell viral vaccines. The qPCR method was more sensitive, specific, and precise, and BPL inactivation reduced rcDNA content and larger DNA fragments.

Key findings

  • Vero alpha-satellite qPCR had a much lower limit of quantitation than Threshold®: LOQ 0.40–0.60 pg/mL depending on vaccine, versus 230 pg/mL for Threshold® in IPV, about 400-fold lower.
  • qPCR validation across three vaccines showed linear ranges of 0.40–1084 pg/mL (RMAO-free rabies), 0.50–652 pg/mL (dengue), and 0.60–1743 pg/mL (IPV), with recoveries of 77–90%, 83–104%, and 94–128%, respectively.
  • In rabies vaccine benchmarking, qPCR measured higher rcDNA than Threshold® in 3 of 5 competitor vaccines and higher than hybridization in 4 of 5; one competitor vaccine had rcDNA fragments of 407 and 620 bp, while Sanofi Pasteur’s rabies vaccine had fragmented rcDNA of 59–240 bp, with 81% below 108 bp.
  • BPL inactivation reduced rcDNA content by an average of 30% for VERORAB® and 46% for the RMAO-free rabies vaccine, with marked reduction of fragments ≥240 bp; in VERORAB® harvests H2 and H3, fragments ≥108 bp were reduced by more than 50%.

Methods

  • Comparative analytical validation and benchmarking study using Sanofi Pasteur’s in-house assays: Vero alpha-satellite qPCR, Threshold® total DNA assay, and hybridization assay.
  • Samples included three Vero-cell viral vaccines at drug substance stage (RMAO-free rabies vaccine, dengue vaccine, IPV), VERORAB® and RMAO-free rabies vaccine before/after BPL inactivation, and five competitor rabies vaccines compared with VERORAB®.
  • qPCR validation followed ICH Q2(R1) for specificity, linearity, accuracy, precision, LOQ, and range; rcDNA size distribution was assessed by qPCR of five overlapping β-actin amplicons from 59 bp to 620 bp.

Limitations

  • Stated in the paper: the qPCR method cannot detect residual DNA shorter than the amplicon size; the smallest alpha-satellite amplicon assessed was 90 bp, though smaller fragments were not expected to pose significant safety risk.
  • Stated in the paper: size evaluation is impossible for products with very low rcDNA, e.g. less than 1 pg/mL in Drug Substance, and BPL fragment-size effects could not be determined for the RMAO-free rabies vaccine because rcDNA levels were very low.
  • Evident from the text: all authors are employees of Sanofi Pasteur and the study was funded by Sanofi Pasteur, so the comparative conclusions favoring the in-house qPCR assay may be subject to conflict-of-interest concerns; the competitor comparison was limited to five rabies vaccines.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1016/j.jviromet.2019.01.001

Cites

10 of 10 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

2 of 17 cited sources checked · 1 supported · 0 flagged · accuracy not yet measured

  • Findingnone given

    Some products contain very low levels of rcDNA (e.g., less than 1 pg/mL in the Drug Substance).

    “Some products contain very low levels of rcDNA (e.g. less than 1 pg/mL in the Drug Substance); in these cases, it is impossible to evaluate the size of the DNA fragments with the current best performing assays such as qPCR.”
    Quote in the paperSubstantial claim
  • Findingown data

    It was not possible to determine any effect of BPL on RMAO-free rabies vaccine rcDNA fragment content due to the very low level of rcDNA.

    “It was not possible to determine any effect on RMAO-free rabies vaccine rcDNA fragments content due to the very low level of rcDNA.”
    Quote in the paperNot a substantial claim
  • Findingown data

    For IPV, the lower limit of the linearity domain was about 400-fold lower for Vero alpha-satellite qPCR than for the Threshold assay.

    “The upper limit of the linearity domain were validated at a similar level between the two assays, but the lower end was much lower for qPCR (about 400-fold lower) than the Threshold ® assay.”
    Quote in the paperSubstantial claim
  • Findingown data

    For the Threshold assay at the LOQ of 230 pg/mL, the 95% CI of intermediate precision for two independent runs with one measurement is x/÷1.31.

    “The 95% CI of intermediate precision at the LOQ of 230 pg/mL for two independent runs with one measurement was equal to x/÷ 1.31.”
    Quote in the paperNot a substantial claim
  • Findingown data

    The quantity of rcDNA determined may be influenced by the analytical method used.

    “These results confirm that the quantity of rcDNA determined may be influenced by the analytical method used; in three of the five vaccines from competitors, qPCR appears to measure higher rcDNA content than the”
    Quote in the paperSubstantial claim
  • Classified as probably not a substantial claim. 15
  • May combine two claims. 20
  • The quote only partly states this claim. 1

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The main risks associated with rcDNA in viral vaccines are infectivity and oncogenicity.

    “The main risks associated with rcDNA in viral vaccines are infectivity and oncogenicity; rcDNA might be capable of transmitting viral infections if retroviral proviruses, integrated copies of DNA viruses, or extra chromosomal genomes are present (FDA, 2010;Sheng-Fowler et al., 2009), or may pose a potential risk for oncogenesis if viral or cell substrate (derived from tumors or which are tumorigen”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites FDA, 2010

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites Sheng-Fowler et al., 2009 source
    • cites Sheng-Fowler et al., 2010 source

  • Classified as probably not a substantial claim.

    Premisecitation

    Residual host cell DNA (rcDNA) from continuous cell lines used for manufacturing biological medicinal products has been considered a safety risk.

    “Residual host cell DNA (rcDNA) from continuous cell lines used for manufacturing of biological medicinal products has been considered as safety risk.”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites FDA, 2010

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites Sheng-Fowler et al., 2009 source
    • cites Sheng-Fowler et al., 2010 source

      The Introduction (page not available in our copy) says residual DNA from cells used to produce viral vaccines has been considered a potential safety risk, particularly when the cells are tumorigenic or derived from tumors. It does not extend that assessment to biological medicinal products generally or specifically identify continuous cell lines as the source of the risk. (LLM, conf=0.85)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Findingown data

    The qPCR method was accurate over the range 0.50-652 pg/mL for the dengue vaccine, with a recovery of 83-104%.

    “The method was found to be specific and linear over the range 0.50-652 pg/mL, and accurate over the same range, with a recovery of 83-104%.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In four of five rabies vaccines from competitors, qPCR measured higher rcDNA than the hybridization assay; for the fifth, results were comparable.

    “In four of the five vaccines from competitors, qPCR measured higher rcDNA than hybridization assay, for the fifth vaccine from competitors the results were comparable.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The qPCR method was specific and linear over the range 0.60-1743 pg/mL for the Inactivated Poliovirus Vaccine.

    “The method was found to be specific and linear over the range 0.60-1743 pg/mL, and accurate over the same range, with a recovery of 94-128%.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The Sanofi Pasteur rabies vaccine had fragmented rcDNA ranging 59-240 bp, with 81% of rcDNA less than 108 bp.

    “The Sanofi Pasteur rabies vaccine was found to have fragmented rcDNA ranging 59-240 bp, with 81% of rcDNA less than 108 bp.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    The LOQ was defined at 0.50 pg/mL for the dengue vaccine.

    “The LOQ was defined at 0.50 pg/mL as the lower level at which the method was precise and accurate.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The qPCR method was specific and linear over the range 0.40-1084 pg/mL for the rabies vaccine produced in a RMAO-free process.

    “The method was shown to be specific and linear over the range 0.40-1084 pg/mL, and accurate over the same range, with a recovery of 77-90%.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Vero cell DNA-specific qPCR assay was shown to be robust with a large dynamic range and no matrix interference on a range of products.

    “Vero cell DNA-specific qPCR assay was shown to be robust with a large dynamic range and no matrix interference on a range of products.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingreasoning

    The proposed qPCR targeting Vero alpha-satellite sequences is a specific and sensitive validated method for Vero DNA across several viral vaccines, with a low LOQ.

    “Our proposed qPCR, targeting Vero alpha-satellite sequences, shows that it is possible to have a specific and sensitive validated method for Vero DNA across several viral vaccines, with a low LOQ.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The qPCR method was accurate over the range 0.60-1743 pg/mL for the Inactivated Poliovirus Vaccine, with a recovery of 94-128%.

    “The method was found to be specific and linear over the range 0.60-1743 pg/mL, and accurate over the same range, with a recovery of 94-128%.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The qPCR method was specific and linear over the range 0.50-652 pg/mL for the dengue vaccine.

    “The method was found to be specific and linear over the range 0.50-652 pg/mL, and accurate over the same range, with a recovery of 83-104%.”
    Quote in the paperSubstantial claim

  • The quote only partly states this claim.

    Findingown data

    The qPCR method was precise with 95% CI of repeatability and intermediate precision for one run with one measurement equal to x/÷ 1.42 and x/÷ 1.60, respectively, for the dengue vaccine.

    “The method was precise with 95% CI of repeatability and intermediate precision for one run with one measurement equal to x/÷ 1.42 and x/÷ 1.60, respectively.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The effect of BPL inactivation on rcDNA content in VERORAB did not differ significantly by individual harvest or by batch.

    “Though some variability was observed among the individual harvests, there was no significant effect according to individual harvests or by batch.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    The LOQ was defined at 0.60 pg/mL for the Inactivated Poliovirus Vaccine.

    “The LOQ was defined at 0.60 pg/mL as the lower level at which the method was precise and accurate.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The three vaccines involved in analytical validation studies contained only small amounts of rcDNA: approximately 40 pg/mL for RMAO-free rabies vaccine, <0.50 pg/mL for dengue vaccine, and <0.60 pg/mL for IPV.

    “The three vaccines involved in the analytical validation studies (rabies vaccine produced in a RMAO-free process, dengue vaccine and IPV), contained only small amounts of rcDNA (approximately 40 pg/ mL, < 0.50 pg/mL and < 0.60 pg/mL, respectively), which is far below the limit of detection of the universal qPCR method described by Andre et al (Andre et al., 2016).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    The limit of quantitation (LOQ) was defined at 0.40 pg/mL for the rabies vaccine produced in a RMAO-free process.

    “The limit of quantitation (LOQ) was defined at 0.40 pg/mL as the lower level at which the method was precise and accurate.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The qPCR method was accurate over the range 0.40-1084 pg/mL for the rabies vaccine produced in a RMAO-free process, with a recovery of 77-90%.

    “The method was shown to be specific and linear over the range 0.40-1084 pg/mL, and accurate over the same range, with a recovery of 77-90%.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    BPL alters the structure and capability of rcDNA to be used as a template by various polymerases.

    “In addition, BPL alters the structure (Kubinski and Szybalski, 1975;Perrin and Morgeaux, 1995) and capability of rcDNA to be used as a template by various polymerases, further reducing the potential associated risk.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Kubinski and Szybalski, 1975 source
    • cites Perrin and Morgeaux, 1995 source

  • Classified as probably not a substantial claim. May combine two claims.

    Premisenone given

    Test results provide a ratio of each amplicon relative to the shortest; this ratio is proportional to the fraction of residual Vero DNA greater than 59 bp that is also greater than the size of the target amplicon.

    “Test results provide a ratio of each amplicon relative to the shortest.This ratio is proportional to the fraction of residual Vero DNA greater than 59 bp (the value of total residual DNA) that is also greater than the size of the target amplicon.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    For each series of extractions, there was a negative extraction control and a positive extraction control.

    “For each series of extractions, there was a negative extraction control (500 μL of nuclease-free water) and a positive extraction control (500 μL of a vaccine with a known amount of Vero rcDNA for the qPCR assay; 500 μL of ZC spiked with 50 pg High Calibrator DNA for the Threshold ® assay; 500 μL of a solution of Vero cell DNA at 200 pg/mL for the hybridization assay).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The IC was quantitated in parallel to Vero DNA by qPCR using a homologous standard range to determine the recovery of the spike, individually for each sample.

    “The IC was then quantitated in parallel to Vero DNA by qPCR using a homologous standard range to determine the recovery of the spike, individually for each sample.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The membrane hybridization and Threshold ® assays have traditionally been used for the quantitation of host rcDNA in biopharmaceuticals.

    “The membrane hybridization and Threshold ® assays have traditionally been used for the quantitation of host rcDNA in biopharmaceuticals.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Chinese Pharmacopoeia, Chapter 3407, 2015

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites USP, General information chapter < 1130 >, 2018

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisereasoning

    PCR-based technologies are generally considered the most practical and robust method for routine rcDNA quantitation because they are species/sequence specific, sensitive, quick to undertake and amenable to high-throughput formats.

    “Polymerase chain reaction (PCR)-based technologies have gained in popularity for the detection and quantitation of rcDNA in recent years, and are generally considered the most practical and robust method for routine rcDNA quantitation as they are species/sequence specific, sensitive, quick to undertake and amenable to high-throughput formats.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given

    qPCR can be used for DNA sizing for complementary characterization of the product where applicable.

    “In parallel, qPCR can be used for DNA sizing for complementary characterization of the product where applicable.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    For the Threshold ® assay, all samples and negative controls (ZC) are assayed with and without a 50 pg DNA spiking.

    “For the Threshold ® assay, all samples and negative controls (ZC) are assayed with and without a 50 pg DNA spiking.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisereasoning

    Targeting genes that are highly conserved among mammalian species to detect mammalian rcDNA, such as the multicopy ribosomal 18S RNA gene or Alu sequences, may be susceptible to the presence of human DNA in the environment or contamination during experimental procedure and would be difficult to control.

    “For example, targeting genes that are highly conserved among mammalian species to detect mammalian rcDNA, such as the multicopy ribosomal 18S RNA gene or Alu sequences, may be susceptible to the presence of human DNA in the environment or contamination during experimental procedure and would be difficult to control.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    The Vero alpha-satellite qPCR assay is robust in terms of performance, sensitivity, specificity, and precision, with a large dynamic range and no matrix interference.

    “The analytical validation of our Vero alpha-satellite qPCR assay performed on three different vaccines shows that the method is robust in terms of performance, sensitivity, specificity, and precision, with a large dynamic range and no matrix interference; as such it would be applicable for use on a wide range of vaccines produced on Vero cells including live vaccines and formaldehyde or BPL-inact”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    The choice of the targeted genome region has an impact on the assay results; selecting target DNA sequences that are found in multiple copies in the host genome would increase the likelihood of detection and accurate quantitation of rcDNA.

    “The choice of the targeted genome region has an impact on the assay results; selecting target DNA sequences that are found in multiple copies in the host genome would increase the likelihood of detection and accurate quantitation of rcDNA (Wang et al., 2012).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Wang et al., 2012 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    DNA extraction using the DNA Extractor ® Kit is recognized as an appropriate method for rcDNA recovery.

    “Recognized as an appropriate method for rcDNA recovery (USP, General information chapter < 1130 > , 2018), residual Vero cell DNA was extracted from 500 μL of sample using the DNA Extractor ® Kit (Wako Chemicals GmbH, Neuss, Germany) according to the manufacturer's instructions.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites USP, General information chapter < 1130 >, 2018

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    All samples were assayed with a spike of 5 × 10 4 copies of the IC before DNA extraction.

    “All samples were assayed with a spike of 5 × 10 4 copies of the IC before DNA extraction.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationreasoning

    The DNA standard purified from the Vero cell line is representative of the actual residual DNA from Vero cell substrates.

    “This system uses a DNA standard purified from the Vero cell line, and is therefore representative of the actual residual DNA from these cell substrates.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    The susceptibility of conserved mammalian gene targets to human DNA contamination would limit the method sensitivity, making it inappropriate for highly purified products with the most stringent specifications.

    “This would limit the method sensitivity, making it inappropriate for highly purified products with the most stringent specifications.”
    Quote in the paperSubstantial claim
33 of 33

  • The paper relies on this without support.

    There is no universally appropriate method for the quantitation of rcDNA of animal origin.

    “Although rcDNA assay can be undertaken at various stages throughout the manufacturing processes using appropriate methods, there is no universally appropriate method for the quantitation of rcDNA of animal origin.”

  • The paper relies on this without support.

    The Threshold ® assay is limited in the detection of fragments shorter than 800 bp and may be inhibited by high DNA concentration (> 1 ng/mL) through the consumption of reagents or generation of signals too high to accurately quantitate.

    “The Threshold ® assay is limited in the detection of fragments shorter than 800 bp, and may be inhibited by high DNA concentration (> 1 ng/mL) through the consumption of reagents or generation of signals too high to accurately quantitate.”

  • The paper relies on this without support.

    The most appropriate stage to quantify impurities, including rcDNA, is the most concentrated purified stage before formulation, i.e. the drug substance.

    “For highly purified vaccines containing very low levels of rcDNA, the most appropriate stage to quantify impurities, including rcDNA, is the most concentrated purified stage before formulation, i.e. the drug substance.”

  • The paper relies on this without support.

    The number of repeats of universal target genes may vary from one species to another.

    “Indeed, the number of repeats of the universal target genes may vary from one species to another.”

  • The paper relies on this without support.

    Generic qPCR assays may be associated with a high risk of contamination, high background measurements, and reduced sensitivity.

    “Generic qPCR assays may also be associated with a high risk of contamination increasing the difficulty in managing negative controls, as well as high background measurements, thus reducing the sensitivity of the assay.”

  • The paper relies on this without support.

    Residual DNA fragments smaller than the amplicon size (e.g., <90 bp) do not pose a significant safety risk.

    “smaller fragments are not expected to pose a significant safety risk.”
6 of 6

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Table 6 reports a size fraction above 100%

    Minor

    For harvest H3 before inactivation, the fraction at ≥108 bp is reported as 108%, although the fraction at ≥59 bp-the defined total-is 100%. The ≥108 bp fraction cannot exceed that total.

  • Table 4 has more DNA at 620 bp than at 240 bp

    Minor

    For competitor vaccine #5, the reported fraction at 620 bp is 84%, exceeding the 56% reported at 240 bp. Under the paper's definition of these fractions, DNA at least 620 bp long must also be at least 240 bp long.

2 of 2

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Related

Authors
Vernay, O., Sarcey, E., Detrez, V., Abachin, E., Riou, P., Mouterde, B., Bonnevay, T., & Mallet, L.
Affiliations
Sanofi (France) (FR)
Corresponding author
Vernay, Olivier
ORCID
Venue
Journal of Virological Methods
Publisher
Elsevier BV
Published
2019-06
Volume
268
Pages
9-16
ISSN
0166-0934 (ISSN-L)
DOI
10.1016/j.jviromet.2019.01.001
OpenAlex
W2908092951
Semantic Scholar
63070bdbe826feb67d9e0da67f27210d4e704e9c
Cited by
14
References
10
Citations by year
2026: 2 · 2025: 3 · 2024: 1 · 2023: 2 · 2022: 1 · 2021: 2 · 2020: 2 · 2019: 1
FWCI
0.43
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Virological Methods (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
  • Sanofi
  • Sanofi Pasteur
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Molecular Biology Techniques and Applications
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Viral Infectious Diseases and Gene Expression in Insects
  • Physical Sciences › Chemistry › Analytical Chemistry › Analytical Methods in Pharmaceuticals
Keywords
viral vaccines, Vero cells, hybridization assay, beta-propiolactone inactivation, analytical method comparison, method sensitivity and specificity
MeSH terms
Host Microbial Interactions, Animals, Chlorocebus aethiops, DNA, Humans, Vero Cells, Viral Vaccines, Virology, DNA Contamination

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