Evaluation of the Efficacy of the Vaccine Production Process in Removing Residual Host Cell DNA from the Vero Cell Rabies Vaccine

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

After passage and adaptation to Vero cells, the CTN strain was transformed into a fixed strain with suitable safety and immunogenicity.

“After passage and adaptation to Vero cells, it was transformed into a fixed strain with suitable safety and immunogenicity [18].”

• cites [18] Zhou, 2022, A simulated, randomized study on the safety and immunogenicity of three consecutive commercial-scale batches of the CTN-1V strain human rabies vaccine to verify the inter-batch consistency, Hum. Vaccines Immunother. sourcePartly supported

  The Introduction (page unavailable) identifies CTN-1 V as the vaccine’s production strain and describes its good immunogenicity. The Abstract (page unavailable) reports reliable safety and stable immunogenicity for the Vero-cell vaccine. Neither passage says that passage and adaptation to Vero cells transformed the CTN strain into a fixed strain. (LLM, conf=0.82)

  Experimental — accuracy not yet measured

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

Shaddeau et al. used tandem ion-exchange and size-exclusion chromatography to separate vaccine components from host cell proteins and other components in cell media to detect vaccine titres.

“Shaddeau et al. used tandem ion-exchange and size-exclusion chromatography to separate vaccine components from host cell proteins and other components in cell media to detect vaccine titres [27].”

• cites [27] Shaddeau, 2019, Development of a New Tandem Ion Exchange and Size Exclusion Chromatography Method To Monitor Vaccine Particle Titer in Cell Culture Media, Anal. Chem. sourceSupported

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

Ion-exchange chromatography is a promising purification method that purifies vaccine process products using physical methods without adding exogenous products.

“Previous research has confirmed that ion-exchange chromatography is a promising purification method. It purifies vaccine process products using physical methods without adding exogenous products.”

• cites [26] Yang, Z., Xu, X., Silva, C.A.T., Farnos, O., Venereo-Sanchez, A., Toussaint, C., Dash, S., González-Domínguez, I., Bernier, A., and Henry, O. (2022). Membrane Chromatography-Based Downstream Processing for Cell-Culture Produced Influenza Vaccines. Vaccines, 10. sourcePartly supported

  The Results (§3.3.2) call ion-exchange membrane chromatography a promising method for purifying influenza strains. But the Methods (§2.2.2) say the material was supplemented with MgCl2 and Zwittergent 3-14 before loading, so the claim that purification occurs without adding exogenous products is not supported. (LLM, conf=0.92)

  Experimental — accuracy not yet measured
• cites [27] Shaddeau, 2019, Development of a New Tandem Ion Exchange and Size Exclusion Chromatography Method To Monitor Vaccine Particle Titer in Cell Culture Media, Anal. Chem. sourcePartly supported

  The Abstract (page not provided) describes ion-exchange chromatography combined with size-exclusion chromatography separating vaccine particles from cell-culture components. But the method is for analytical titer measurement without prior purification, not a vaccine-product purification process. The Materials and Methods describe buffers and salt used in the assay; the paper does not establish the claim that purification occurs without adding exogenous products. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

May combine two claims.

Gel chromatography is a common purification method in human rabies vaccine production, but it has limited efficiency in DNA removal.

“Currently, gel chromatography is a common purification method in human rabies vaccine production, but it has limited efficiency in DNA removal [25].”

• cites [25] Trabelsi, 2019, Purification of rabies virus produced in Vero cells grown in serum free medium, Vaccine sourcePartly supported

  The Discussion (page unavailable) cites examples of Sepharose gel chromatography and gel filtration used to purify rabies virus, supporting their use in vaccine production. It does not establish that gel chromatography is common or that it has limited efficiency in removing DNA; its DNA-removal results concern other purification methods. (LLM, conf=0.82)

  Experimental — accuracy not yet measured

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

Vero cells are widely used in the production of viral vaccines due to their suitability for large-scale culture and sensitivity to various virus strains.

“Vero cells are widely used in the production of viral vaccines due to their suitability for large-scale culture and sensitivity to various virus strains [15,16].”

• cites [15] Liu, 2020, Epidemiology of Rabies and Current US Vaccine Guidelines, Rhode Isl. Med. J.Not checked — no full text of the source
• cites [16] Rourou, 2019, Adaptation of Vero cells to suspension growth for rabies virus production in different serum free media, Vaccine sourcePartly supported

  The Introduction says low-passage Vero cells are widely used for human vaccine manufacturing because they are permissive to different viruses. But the Discussion describes scale-up limitations of conventional adherent Vero cultures; suspension adaptation is presented as a way to overcome them. The source therefore does not support unqualified suitability for large-scale culture as a reason Vero cells are widely used. (LLM, conf=0.85)

  Experimental — accuracy not yet measured

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

Longitudinal clinical data revealed that the CTN-1 vaccine is safe and effective, making it suitable for rabies prevention and control in China.

“longitudinal clinical data revealed that the vaccine is safe and effective, making it suitable for rabies prevention and control in China [18,21,22,23].”

• cites [18] Zhou, 2022, A simulated, randomized study on the safety and immunogenicity of three consecutive commercial-scale batches of the CTN-1V strain human rabies vaccine to verify the inter-batch consistency, Hum. Vaccines Immunother. sourcePartly supported

  The Discussion (page not provided) reports reliable safety and sustained antibody responses up to 12 months for the CTN-1V vaccine. The study measured immunogenicity, not prevention of rabies, and does not establish that the vaccine is suitable for rabies prevention and control across China. (LLM, conf=0.84)

  Experimental — accuracy not yet measured
• cites [21] Wang, 2024, Study on immune persistence of the CTN-1V strain rabies vaccine in humans, J. Virus Erad. sourcePartly supported

  The Abstract (page not provided) reports good safety, immunogenicity, and antibody persistence for the CTN-1V vaccine in a longitudinal clinical trial in China. The study did not measure prevention of rabies, so its findings do not establish clinical effectiveness or the broader conclusion that the vaccine is suitable for rabies prevention and control in China. (LLM, conf=0.84)

  Experimental — accuracy not yet measured
• cites [22] Huang, 2023, Safety and immunogenicity of freeze-dried rabies vaccine (Vero-cells) for human use in healthy people aged 9–65 years, Zhonghua Yu Fang Yi Xue Za Zhi [Chin. J. Prev. Med.] sourceNot checked — no full text of the source
• cites [23] Wu, X., Li, J., Zhou, L., Chen, J., Jin, Z., Meng, Q., Chai, J., Gao, H., Wang, Y., and Zhao, D. (2023). A Randomized, Double-Blind, Controlled Phase III Clinical Trial to Evaluate the Immunogenicity and Safety of a Lyophilized Human Rabies Vaccine (Vero Cells) in Healthy Participants Aged 10–60 Years Following Essen and Zagreb Vaccination Procedures. Vaccines, 11. sourcePartly supported

  The Investigational Vaccine section identifies the vaccine as containing the CTN-1V strain. The Conclusions (page unavailable) report that it was safe and had good immunogenicity, calling it a valuable alternative for rabies prevention. The study measured immunogenicity and safety in healthy participants, however, not clinical effectiveness in preventing rabies; that stronger part of the claim is not established. (LLM, conf=0.84)

  Experimental — accuracy not yet measured

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

qPCR has generally been considered one of the most practical methods for routine HCD content determination because of its sequence specificity, sensitivity, and rapid and high-throughput nature.

“In recent years, qPCR has generally been considered one of the most practical methods for routine HCD content determination because of its sequence specificity, sensitivity, and rapid and high-throughput nature [35,36].”

• cites [35] Varnamkhasti, 2021, Design and development of a simple method for the detection and quantification of residual host cell DNA in recombinant rotavirus vaccine, Mol. Cell. Probes sourceSupported
• cites [36] Zheng, W., Jiang, L., Lei, Q., Yang, J., Gao, X., Wang, W., Zhang, Y., Kong, T., Chen, Q., and Li, G. (2019). Development and Validation of Quantitative Real-Time PCR for the Detection of Residual CHO Host Cell DNA and Optimization of Sample Pretreatment Method in Biopharmaceutical Products. Biol. Proced. Online, 21. sourcePartly supported

  The Background (page unavailable) calls qPCR the most practical method for residual DNA quantitation, citing sensitivity and time-saving features. The Results > Specificity section (page unavailable) shows that the assay amplified CHO DNA but not the other genomes tested. The paper does not identify high throughput as a reason for qPCR’s practicality. (LLM, conf=0.85)

  Experimental — accuracy not yet measured

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

Li et al. used the CTN-1 strain to develop vaccines against various representative rabies virus strains from clades I-VII in China.

“Li et al. used the CTN-1 strain to develop vaccines against various representative rabies virus strains from clades I-VII in China [20]”

• cites [20] Li, 2024, Safety and efficacy assessment of an mRNA rabies vaccine in dogs, rodents, and cynomolgus macaques, npj Vaccines sourceSupported

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

Yang et al. used anion-exchange chromatography to purify influenza virus.

“Yang et al. used anion-exchange chromatography to purify influenza virus [26]”

• cites [26] Yang, Z., Xu, X., Silva, C.A.T., Farnos, O., Venereo-Sanchez, A., Toussaint, C., Dash, S., González-Domínguez, I., Bernier, A., and Henry, O. (2022). Membrane Chromatography-Based Downstream Processing for Cell-Culture Produced Influenza Vaccines. Vaccines, 10. sourceSupported

May combine two claims.

Both the virus harvesting solution and the virus ultrafiltration concentrate solution contained large amounts of residual HCD fragments.

“Both the virus harvesting solution and the virus ultrafiltration concentrate solution contained large amounts of residual HCD fragments, with the fragment distribution dominated by fragments larger than 1 kb.”

• AssumptionRests on an assumption: CGE can be used to detect the size distribution of residual HCD fragments in vaccines.

May combine two claims.

In this study, before virus inactivation, the virus harvest solution was first subjected to ultrafiltration and concentration to remove large particle impurities, followed by ion-exchange chromatography, which achieved a stable HCD removal rate of up to 99.99%.

“In this study, before virus inactivation, the virus harvest solution was first subjected to ultrafiltration and concentration to remove large particle impurities, followed by ion-exchange chromatography, which achieved a stable HCD removal rate of up to 99.99%”

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

Because the CGE method involves sequential injection of a single needle capillary, the retention time of the HCD characteristic peak of each sample fluctuates slightly.

“because this method involves the sequential injection of a single needle capillary, the retention time of the HCD characteristic peak of each sample fluctuates slightly.”

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

FDA requires testing of DNA fragment size distribution in rabies vaccine.

“and also requires the testing of DNA fragment size distribution [11].”

• cites [11] FDA (2010). Guidance for Industry Characterization and Qualification of Cell Substrates and Other Biological Materials Used in the Production of Viral Vaccines for Infectious Disease Indications, FDA.Not checked yet

  Not checked in the free run.

May combine two claims.

The production process achieved effective recovery of viral antigens and efficient removal of residual HCD.

“The production process described in this study achieved effective recovery of viral antigens and efficient removal of residual HCD”

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

WHO considers residual HCD a process impurity that lowers product safety and should be removed as much as possible.

“the World Health Organization (WHO) considers residual HCD a process impurity that lowers product safety and should be removed as much as possible [8].”

• cites [8] Grachev, 1998, WHO requirements for the use of animal cells as in vitro substrates for the production of biologicals (requirements for biological substances No. 50), Biologicals sourceNot checked — no full text of the source

May combine two claims.

The process enabled continuous and stable production of vaccine products that meet WHO recommendations and the relevant requirements of the current edition of the Chinese Pharmacopeia.

“the process was stable and controllable, enabling the continuous and stable production of vaccine products that meet WHO recommendations and the relevant requirements of the current edition of the Chinese Pharmacopeia.”

May combine two claims.

The bulk human rabies vaccine produced by this process had excellent safety and efficacy.

“The results of the process stability studies on multiple commercial batches showed that the bulk human rabies vaccine produced by this process had excellent safety and efficacy and that the production process was stable and thus suitable for large-scale batch production.”

Classified as probably not a substantial claim.

Removal and/or inactivation can be used to reduce the content of residual HCD in the virus passaging, cell culture, production, and purification processes.

“During the production process, methods such as removal and/or inactivation can be used to reduce the content of residual HCD in the virus passaging, cell culture, production, and purification processes [9].”

• cites [9] Holm, P., Allesø, M., Bryder, M.C., and Holm, R. (2017). Q8 (R2) Pharmaceutical Development. ICH Quality Guidelines: An Implementation Guide, John Wiley & Sons. sourceNot checked — no full text of the source

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

FDA requires testing of residual DNA in rabies vaccine at the finished product stage using appropriate methods, with a limit of <10 ng/dose.

“Additionally, the FDA requires the testing of residual DNA in rabies vaccine at the finished product stage using appropriate methods, with a limit of <10 ng/dose”

• cites [11] FDA (2010). Guidance for Industry Characterization and Qualification of Cell Substrates and Other Biological Materials Used in the Production of Viral Vaccines for Infectious Disease Indications, FDA.Not checked yet

  Not checked in the free run.

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

CGE is an effective method for high-precision and high-sensitivity analysis of HCD fragment size distribution.

“CGE is an effective method for high-precision and high-sensitivity analysis of HCD fragment size distribution [31].”

• cites [31] Shen, 2013, Size analysis of residual host cell DNA in cell culture-produced vaccines by capillary gel electrophoresis, Biologicals sourceNot checked — no full text of the source

May combine two claims.

The AGMr(HindIII)-1 fragment is the unique sequence of the Vero cell genome, and the fragment distribution of this sequence and its derivatives is broad-spectrum representative of Vero cells and can be used for quantitative analysis of HCD.

“This fragment is the unique sequence of the Vero cell genome, and the fragment distribution of this sequence and its derivatives is broad-spectrum representative of Vero cells and can be used for the quantitative analysis of HCD [38,39].”

• cites [38] Li, 2008, The probe selection in Vero cells DNA residue detection by spot hybridization, Chin. J. Pharm. Anal.Not checked yet

  Not checked in the free run.

• cites [39] Cao, 2013, Development of a Vero cell DNA reference standard for residual DNA measurement in China, Hum. Vaccines Immunother. sourceNot checked — no full text of the source

May combine two claims.

There is a highly repetitive satellite sequence, AGMr(HindIII)-1, in Vero cells, with a monomer length of 172 bp, accounting for approximately 15% of the total genome.

“There is a highly repetitive satellite sequence, AGMr(HindIII)-1, in Vero cells, with a monomer length of 172 bp, accounting for approximately 15% of the total genome.”

• cites [37] Singer, 1979, Arrangement of a highly repeated DNA sequence in the genome and chromatin of the African green monkey, J. Biol. Chem. sourceNot checked — no full text of the source

May combine two claims.

The CGE method has high sensitivity and the ability to objectively and accurately reflect the nucleic acid profile of complex samples.

“Therefore, this method has the characteristics of high sensitivity and the ability to objectively and accurately reflect the nucleic acid profile of complex samples”

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

In accordance with the current edition of the Chinese Pharmacopeia, a standard curve is drawn using Vero cell genomic standards with OD260/OD280 values, and a quantitative analysis is performed on the 154 bp sequence of AGMr(HindIII)-1 in the HCD of the test product, with the quality standard being no higher than 3 ng/dose.

“A standard curve is drawn using Vero cell genomic standards with OD260/OD280 values, and a quantitative analysis is performed on the 154 bp sequence of AGMr(HindIII)-1 in the HCD of the test product, with the quality standard being no higher than 3 ng/dose.”

• cites Chinese PharmacopeiaNot matched

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

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

The residual HCD components in vaccine products are complex and lack identification methods, making the purification method for effective and stable removal of HCD a key challenge in vaccine production research.

“the residual HCD components in vaccine products are complex and lack identification methods, making the purification method for the effective and stable removal of HCD still a key challenge in vaccine production research [24].”

• cites [24] Zhao, 2019, DNA Residue Control in Human Rabies Vaccine (Vero Cells), Chin. J. Biol.Not checked yet

  Not checked in the free run.

May combine two claims.

Based on the FDA's recommendation that residual HCD should not be greater than 200 bp, the quantitative amplification of the 154 bp target fragment produces amplification products of the monomeric AGMr(HindIII)-1 sequence with no less than 154 bp and a long tandem repeat sequence, providing scientific validity to its safety evaluation.

“Based on the FDA’s recommendation that the residual HCD should not be greater than 200 bp, the quantitative amplification of the 154 bp target fragment produces amplification products of the monomeric AGMr(HindIII)-1 sequence with no less than 154 bp and a long tandem repeat sequence, providing scientific validity to its safety evaluation.”

May combine two claims.

The production process described in this study can achieve the effective recovery of viral antigens and the efficient removal of residual HCD.

“The production process described in this study can achieve the effective recovery of viral antigens and the efficient removal of residual HCD”

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

qPCR is widely used in the detection of nucleic acids due to its high specificity, high sensitivity, and wide linear range.

“Due to its high specificity, high sensitivity, and wide linear range, this method is widely used in the detection of nucleic acids [13].”

• cites [13] Peper, 2014, Direct real-time quantitative PCR for measurement of host-cell residual DNA in therapeutic proteins, J. Pharm. Biomed. Anal. sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S2 (checkable).

The distribution of residual HCD fragments in the product should be examined to improve vaccine safety evaluation.

“and that the distribution of residual HCD fragments in the product should be examined to improve vaccine safety evaluation.”

• cites [14] Yang, 2013, Establishing acceptable limits of residual DNA, PDA J. Pharm. Sci. Technol. sourceNot checked — no full text of the source

May combine two claims.

Since the qPCR detection method cannot detect sequences smaller than 154 bp or non-AGMr(HindIII)-1 Vero cell genome sequences, the CGE method serves as a necessary supplement for directly observing HCD sequences.

“Moreover, since this detection method cannot detect sequences smaller than 154 bp or non-AGMr(HindIII)-1Vero cell genome sequences, the CGE method serves as a necessary supplement for directly observing HCD sequences.”

• AssumptionRests on an assumption: The qPCR detection method cannot detect sequences smaller than 154 bp or non-AGMr(HindIII)-1 Vero cell genome sequences.

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

Shen et al. introduced and validated the CGE-LIF method for analyzing the size distribution of HCD in influenza viruses cultured in MDCK cells and confirmed that the detection limit of the method for nucleic acids can be lower than 1 ng/mL.

“Shen et al. introduced and validated the CGE-LIF method for analyzing the size distribution of HCD in influenza viruses cultured in MDCK cells and confirmed that the detection limit of the method for nucleic acids can be lower than 1 ng/mL [31].”

• cites [31] Shen, 2013, Size analysis of residual host cell DNA in cell culture-produced vaccines by capillary gel electrophoresis, Biologicals sourceNot checked — no full text of the source

May combine two claims. The quote only partly states this claim.

After gel chromatography purification, there is no possibility of adding or removing external HCD, meaning that the gel chromatography solution can effectively represent the residual HCD level in the final vaccine product.

“the gel chromatography solution can effectively represent the residual HCD level in the final vaccine product”

May combine two claims.

The AGMr(HindIII)-1 sequence mainly appears in the form of long tandem repeats and is interspersed with unrelated sequences; the former has a maximum observed number of 29 long tandem repeats, and the latter accounts for approximately 37% of the total genome.

“This sequence mainly appears in the form of long tandem repeats and is interspersed with unrelated sequences. The former has a maximum observed number of 29 long tandem repeats; the latter accounts for approximately 37% of the total genome [37].”

• cites [37] Singer, 1979, Arrangement of a highly repeated DNA sequence in the genome and chromatin of the African green monkey, J. Biol. Chem. sourceNot checked — no full text of the source

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

The CGE technique has been used for the isolation of nucleic acids of different lengths or different conformations in complex samples, such as analysis of plasmid supercoiled conformations, mRNA vaccine nucleic acid integrity and PolyA tail distribution, and human genome sequencing.

“The CGE technique has also been used for the isolation of nucleic acids of different lengths or different conformations in complex samples, such as the analysis of the purity of plasmid supercoiled conformations as well as the analysis of the nucleic acid integrity and PolyA tail distribution of mRNA vaccines, and it has also assisted in completing the human genome sequencing project [34].”

• cites [34] Wei, B., Goyon, A., and Zhang, K. (2022). Analysis of therapeutic nucleic acids by capillary electrophoresis. J. Pharm. Biomed. Anal., 219. sourceNot checked — no full text of the source

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

The CTN strain is the only virus strain isolated in China that is approved by the WHO for vaccine production and has independent intellectual property rights.

“It is the only virus strain isolated in China that is approved by the WHO for vaccine production and has independent intellectual property rights [19].”

• cites [19] WHO (2005). Expert Committee on Biological Standardization, World Health Organization. 56th Report.Not checked yet

  Not checked in the free run.

May combine two claims.

The nuclease process increases production costs and carries safety uncertainties.

“In addition, this process increases production costs [29,30] and carries safety uncertainties.”

• cites [29] Li, 2014, Removing residual DNA from Vero-cell culture-derived human rabies vaccine by using nuclease, Biologicals sourceNot checked — no full text of the source
• cites [30] Lothert, 2020, A scalable downstream process for the purification of the cell culture-derived Orf virus for human or veterinary applications, J. Biotechnol. sourceNot checked — no full text of the source

Classified as probably not a substantial claim.

WHO recommends that the limit of HCD residues in human rabies vaccines prepared from Vero cells be no more than 200 bp.

“For human rabies vaccines prepared from Vero cells, the WHO’s recommendation is that the limit of HCD residues be no more than 200 bp [14]”

• cites [14] Yang, 2013, Establishing acceptable limits of residual DNA, PDA J. Pharm. Sci. Technol. sourceNot checked — no full text of the source

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

After binding to double-stranded DNA, SYBR Gold asymmetric cyanine dye has a high quantum yield and can enhance fluorescence intensity by more than 1000 times.

“After binding to double-stranded DNA, this dye has a high quantum yield and can enhance the fluorescence intensity by more than 1000 times [32].”

• cites [32] Kaloyanova, 2011, Synthesis and fluorescence characteristics of novel asymmetric cyanine dyes for DNA detection, J. Photochem. Photobiol. A Chem. sourceNot checked — no full text of the source

May combine two claims.

The production process described in this study is stable and controllable, allowing the continuous and stable production of high-quality vaccines with excellent safety and efficacy.

“and the process is stable and controllable, allowing the continuous and stable production of high-quality vaccines with excellent safety and efficacy.”

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

There have been reports on the analysis of particle size distribution of residual HCD fragments in lentiviral products from different processes.

“There have been reports on the analysis of particle size distribution of residual HCD fragments in lentiviral products from different processes [33].”

• cites [33] Wang, 2023, Size distribution analysis of residual host cell DNA fragments in lentivirus by CGE-LIF, Electrophoresis sourceNot checked — no full text of the source

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

The vaccine strains approved in China for production of Vero cell rabies vaccines include aG, CTN-1V, PV, and PM strains.

“Currently, the vaccine strains approved in China for use in the production of Vero cell rabies vaccines include the aG, CTN-1V, PV, and PM strains [17].”

• cites [17] Shi, 2022, Progress in Vero cell research and applications in rabies vaccines for human use, Chin. J. ZoonosesNot checked yet

  Not checked in the free run.

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

In the current edition of the Chinese Pharmacopeia, qPCR is used for the detection of residual HCD in bulk human rabies vaccine.

“In the current edition of the Chinese Pharmacopeia, this method is used for the detection of residual HCD in bulk human rabies vaccine.”

• cites [12] Chinese Pharmacopoeia Commission (2020). Pharmacopoeia of the People’s Republic of China, Chinese Pharmacopoeia Commission.Not checked yet

  Not checked in the free run.

May combine two claims.

The vaccine production process is stable and suitable for large-scale batch production.

“demonstrating that the process is stable and suitable for large-scale batch production.”