Study on the production of measles antibody used for vaccine quality control

Background: With the help of Japan, the Center for Research and Production of vaccines and biologicals, Hanoi has received a WHO standard measles vaccine production technology, including techniques in the examination of vaccine quality. Therefore, it is needed to be initiative on production of measles antibody. Objective: Study on production of measles antibody in rabbits and selecting the appropriate antibody for production of high titre antibody, which meets the standard of vaccine quality control in Vietnam. Subject and methods: Using the measles antigen from Edmonston and AIK-C strains, which were provided by the Kitasato Institute, to produce measles antibody. Making immunoreaction in rabbits and determination of neutralization antibody titre. Results and Conclusion: Measles antigen of Edmonston Vero 7/P2 strain used in the production of measles antibody in rabbit created the highest antibody titre in comparison with AIK-C strain from vero cell and FL cell supplied by the Kitasato Institute of Japan. Antibody titre of Edmonston Vero 7/P2 strain reached up to 1/8192 and met the sera standard required for measles vaccine quality control, it is similar to the measles sera to be produced from the Kitasato Institute.

Study on the stable of gene sequence of seed lot system G1P8 KH0118 during production rotavirus vaccine

Background: Rotavirus strain (KH0118) is used as the primary material to produce original rotavirus vaccine strains with the symbol of G1P8 MS. According to the World Health Organization\u2019s standard, the strain is needed to evaluate the stability of gene throughout analysis of gene and amino acid sequence during vaccine production. Objective: To determine the sequence of genes 4 (VP4), 6 (VP6), 9 (VP7) and 10 (NSP4) with base pair correlative 855:866:1345:745 of seed lot system and vaccine of G1P8 strain and to evaluate the stability of seed lot system during vaccine production. Subject and methods: ARN was divided from the original strain of rotavirus vaccine G1P8 MS, rotavirus vaccine productive strain (G1P8 WS) and rotavirus vaccine (G1P8 VX). Then using primer pairs to determine gene sequence VP4, VP6, VP7, NSP4 and comparing gene and amino acid sequence of the seed lot system. Results and Conclusion: The study demonstrated that, there was no difference for the nucleotide and amino acid sequence from the original strain during production of rotavirus vaccine G1P8 KH0118.

The difference for quantity of nucleotide and amino acid between human rotavirus strain \u2013 Vietnam candidate for rotavirus vaccine production and international standard wild strains

Background: Rotavirus induced diseases is most commonly seen in children between 6 and 36 months old. In developing countries, rotavirus is also a common cause of gastrointestinal inflammation in below 2 years old children. Study on production of vaccine strains is a target that the World Health Organization is providing. Objective: To determine the quantity of different nucleotide and amino acids of genes 4, 6, 9, 10 of the Vietnam seed lot system and vaccine G1P8, G1P4 and G4P6. Subject and methods: By sequence method determine the quantity of different nucleotide and amino acids of gene 4 (VP4), gene 6 (VP6), gene 9 (VP7) and gene 10 (NSP4) of the Vietnam seed lot system and vaccine G1P8 (KH0118), G1P4 (2001019210) and G4P6 (2001019203) in comparison with international standard wild strains such as Ku, DS1, ST3, Hochi, TB-chen. Results and Conclusion: Each strain had a different nucleotide and amino acid sequence and it was characterized by each country. However, these strains had the same general chemical components including nucleic acid and protein. Nucleic acid was a double fiber ARN with 11 genes, and 18 thousand base pairs. 3 proteins with specific antigens were VP4, VP6 and VP7. 57 nucleotide of gene 4 (VP4) of the seed lot system G1P8 were different with Ku (AB22772) strain but there were only 17 different amino acids. For gene 7 (VP7), 70 nucleotide were different between G1P8 strain and Ku (AB222784) strain but there were 15 different amino acids. For gene 6 (VP6), although 141 nucleotide were different between G1P8 strain and Ku (AB222784) strain but there were only 9 different amino acids. For gene 10 (NSP4), 62 nucleotide were different between G1P8 strain and Ku strain (AB222772), making 12 different amino acids.

Epidemiology of rotavirus diarrhea in the National Pediatric Hospital

Background: Rotavirus type A is the most common cause of acute gastrointestinal inflammatory in children under 5 years old, especially in age groups 6 and 36 months. Some rotavirus strains are common; seen recently in Vietnam are G1, G2, G3, G4 and G9, P4, P6 and P8. Objective: Surveillance of epidemiological characteristics of rotavirus induced diarrhea in the National Pediatric Hospital from September, 2007 to March, 2008. Subject and methods: Collection of 322 stool specimens of pediatric patients with acute diarrhea (including 213 specimens from male, 109 specimens from female), who were treated in the National Pediatric Hospital. All of these specimens were determined for causes of rotavirus with the enzyme immunoassay (EIA). Results and Conclusion: Among these 322 stool specimens, there were 195 rotavirus positive specimens, accounted for 60.56%. The rate of monthly distribution of rotavirus diarrhea from September, 2007 to March, 2008 were 76%, 56%, 62%, 61%, 64%, 56% and 44%, respectively. Number of rotavirus positive cases in male and female was 56 (26.29%) and 79 (72.48%), respectively. The rate of rotavirus positive children compared to total number of specimens with the age 0-3 months, 3-6 months, 6-12 months, 12-24 months, 24-36 months and over 36 months was 7.69%, 15.9%, 41.54%, 32.82%, 1.54% and 0.51%, respectively. The results of type identification indicated that phenotypes of 37 among 40 specimens were identified (92.5%) in which there were 5 specimens of G1P8 (12.5%), 20 specimens of G3P8 (50%), 1 specimen of G9P8 (2.5%), 2 specimens of G1Pmixed (5%), 9 specimens of G3Pmixed (22.5%), 1 specimen of G unidentified-type P8 (2.5%) and 2 specimens of G3 P unidentified-type (5%).

Stable study of gene sequence of seed lot system G1P4 (2001019210) during production of rotavirus vaccine

Background: Presently, toxicity decreased oral live rotavirus is a candidate for vaccine for the prevention of rotavirus induced diarrhea. According to the World Health Organization, the seed lot system is robustly checked, in which determining the stable of gene sequence. Objective: To determine the sequence of genes 4: 6: 9: 10 with base pair correlative 855: 824: 1314: 734 of seed lot system G1P4 (2001019210) during production of rotavirus vaccine. Subject and methods: Gene 4 (VP4), gene 6 (VP6), gene 9 (VP7) and gene 10 (NSP4) of seed lot system G1P4 were determined for gene sequencing and then comparing the nucleotide sequence as well as deduced amino acids from original strain with the produced strain and vaccine virus. Results and Conclusion: There was no different for nucleotide and deduced amino acid sequence from the original strain during the production of rotavirus vaccine of G1P4 MS (2001019210) to producing strains of G1P4 WS and vaccine strains of G1P4 VX.

Epidemiology of ROTA virus diarrhea in Ho Chi Minh city from 12/2006-11/2007

Background: Acute gastroenterophathy usually caused by the Rota virus for children under 5 years old. Objectives: To present various types of data on epidemiology of ROTA virus diarrhea in Ho Chi Minh city from 12/2006-11/2007. Material and method: The data were collected from 500 stool specimens of diarrhea diagnosed chilren hosptalised at Thuy Dien Pediatric hospital 1, Ho Chi Minh city from December/2006 to November /2007. Results:There were 322 rotavirus-positive specimens, representing 64.4%. The proportions of monthly distribution of cases with diarrhea due to rotavirus were 90.1%, 54.39%, 85.37%, 74.51%, 72.92%, 41.67%, 26.67%, 58.33%, 79.31%, 52.63%, 69.05% and 57.78%, respectively. The numbers of rotavirus-positive cases in male and female were 216 (65.26%) and 106 (62.72%), respectively. The proportions of Rota virus positive children compared to total number of diarrheal cases with age 0-3, 3-6, 6-12, 12-24, 24-36 and over 36 months were 2.80%, 7.76%, 40.06%, 40.68%, 5.28% and 3.42%, respectively.\r\n', u'The results of typing identification indicated that the phenotypes of 98 among 100 specimens were identified (98%) in which there were sixty-one specimens of G1P8 (61%), one specimen of G2P8 (1%), fourteen specimens of G3P8 (14%), four of specimens of G4P8 (4%), eighteen specimens of GmixedP8 (18%). There were only two specimens of GnontypeableP8 (2%). Conclusion: Further studies should be carried out to clear this issue.\r\n', u'

Study on the stability of gene sequences of seed lot system G4P6 (2001019203) during production of rotavirus vaccine

Background: Currently, the World Health Organization is encouraging developing countries to establish a seed lot system of rotavirus vaccine for production of this vaccine. Objectives: To determine gene sequences of rotavirus strain that was used for vaccine production and to evaluate its stability. Materials and method: Master seed (G4P6MS), Working seed (G4P6WS) and vaccine strain (G4P6VX) of Rotavirus were used for analysis at the US Center for Disease Control and Prevention (CDC). Results: 855 base pairs of gene 4 (VP4); 1195 base pairs of gene 6 (VP6); 824 base pair of gene 9 (VP7) and 715 base pairs of gene 10 (NSP4) from seed lot system and vaccines of G4P6 strain were determined. The results demonstrated this seed lot system is completely stable during vaccine production. There is no difference for nucleotide and amino acid sequence in this seed lot system. Conclusion: G4P6 strain (2001019203) is completely stable during vaccine production.

IgG immune response of Macaca mulatta monkeys after immunization with human rotavirus strains that were used for vaccine production

Background: Rotavirus acute diarrhea is a common disease in children aged 6 to 24 months, accounting for 50-70% of hospitalizations in Vietnam. Vaccines recommended by the WHO are quite expensive, so vaccination for this disease isn\u2019t widely used in Vietnam. Objectives: To evaluate the immune responses of 3 human rotavirus strains in Macaca mulatta monkeys. Subjects and method: 32 healthy monkeys aged 6-12 monthswere divided into 4 groups that received orally the G1P8 strains (Master seed- MS and Working seed- WS), G1P4 strains (MS and WS), G4P6 strains (MS and WS),and placebo. All monkeys were evaluated on general status, gastrointestinal symptoms and blood samples taken for immune analysis. Results: By ELISA technique, the Master Seed (MS) and Working Seed (WS) of Rotavirus, including G1P8 (KHI008), G1P4 (2001019210) and G4P6 (2001019203) strains showed high titer of IgG antibody in monkey at least four-fold after 3 doses of immunization. Conclusion: These 3 rotavirus strains produced by the Center for Research and Production of Vaccines and Biologicals could be candidates for vaccine production.

Sequencing VP4, VP7, NSP1, NSP4 genes of human rotavirus strain G1P8

Background: Rotavirus is the main cause of acute viral gastroenteritis in children under 5 years old. The virus leads to over 600000 children deaths a year in the world, 80% of which occur in the developing countries. In Viet Nam, 50%-70% the children\u2019s hospitalizations for acute diarrhea were resulted from rotavirus infection. Objective: To sequence nucleotides and amino acids of VP4, VP7, NSP1, and NSP4 genes of 5 passages of human rotavirus strain G1P8. Materials and method: A study was conducted in rotavirus sample of 5 passages of human rotavirus strain G1P8: B17A3; B17.3; B17.3 pp32vero15; B17.3 pp36TKP2; B17.3 pp43.7vero in Centre for Disease Control and Prevention, Atlanta, United State. Methods: using NucliSen Kit for detection of ARN; RT-PCR; sequencing genes by ABI 3100 machine. Results and Conclusion: Sequencing nucleotides and amino acids of VP4, VP7, NSP1, and NSP4 genes of 5 passages of human rotavirus strain G1P8 showed that: the number of nucleotide mutations ofVP4, VP7, NSP4 genes occurring among the passages were 3 (at nucleotit 175, 419, 790), 1 (at nucleotit 644), 3 (at nucleotit 134, 254, 482), respectively. All these mutations resulted in changes in amino acid composition. No mutation was found in NSP1 gene.

Study of sequencing of VP4, VP7, NSP1, NSP4 genes of human rotavirus strain G4P6 (2001019203)

Background: Rotavirus is the main cause of acute viral gastroenteritis in children under 5 years old. In Viet Nam, about 50-70% hospitalized children with acute diarrhea caused by rotavirus. This indicated the importance of vaccination against diarrhea in Vietnam and researching on creating safe diarrhea vaccine for infants was a imperative. To achieve a good result of the research, it\u2019s necessary to understand the genetic characteristics of rotavirus.Objectives: To determine sequencing of VP4, VP7, NSP1, NSP4 genes of human rotavirus strain G4P6. Subjects and method: The research was performed on rotavirus samples (203pp16TK; 203pp27TK; 203pp30vero; 203pp37vero; 203pp38vero lot11; 203pp38TK lot12) by using ARN separation and RT-PCR methods. Results and Conclusion: We presented the results of sequencing of VP4, VP7, NSP1, NSP4 genes in some passages of human rotavirus strain G4P6 including their deduced amino acid sequence. The nucleotide mutants of VP7, NSP4 genes of passages are 2, 1 respectively. All the mutants result in amino acid changes. There was no mutation on VP4, NSP1 genes. The result confirmed that all passages of human rotavirus strain G4P6 had no contamination. They had similar degree respectively 89-93%, 85-97%, 81-93%, 92-95% with strains in the world.

Determine the quality of vero cells using for rota vaccine development

Background: Vero cell (ATCC) is from kidney of Blue Monkey in Africa. Because of its strong points such as non tumor form, non exotic virus infection, this cell strain is commonly used for vaccin development in the world. Objective: To determine the quality of vero cell supplying by Japan Polio-myelitis Research Center and WHO vero cell supplying by the Company for Vaccine and Biological Production No.1 in use for develop rota vaccine. Subjects and method:A study was conducted in 2 kinds of vero cell (one ATCC 134 generation supplying by Japan Polio-myelitis Research Center and another WHO ATTC 137 generation supplying by the Company for Vaccine and Biological Production No.1) using standard methods. Results and Conclusion: Both these ATCCs had no exotic agents in generation from 134 to 137. The vero working cell bank for vaccine development has been established by the POLYVAC by using standard methods, in accordance with the WHO regulations. The vero working cells established by POLYVAC had the same quality as that of Vabiotech cell bank. Rota virus strains multiplied well on WHO ATTC 137 generation and ATCC 134 generation supplying by Japan Polio-myelitis Research Center.

Safety and potency of rotavirus master seed G1P4 (2001019210)

Background: Rota vaccine is used to prevent diarrhea in children under 5 years old. Two vaccines are being used in developed countries: Rotarix (GSK) and RotaTeq (Merk). Rotarix vaccine was produced from master seed G1P8 and RotaTeq vaccine was from the coordination of human rotavirus strains G1, G2, G3, G4 and cow rotavirus strain.Thanks to the helps of WHO, Ministry of Health and Ministry of Science and Technology, Center for research and production of vaccines and biologicals \ufffd?Ha Noi made study of creating rotavirus master seed G1P4 for Rota vaccine production in Vietnam. Objectives: To evaluate the safety and potency of rotavirus master seed G1P4 in the laboratory and experimental animals. Subjects and method: Rotavirus master seed G1P4 (2001019210) lot 1 (MS-P5) and lot 2 (MS-P5) produced in 2005, preserved at -800C were determined potency by Immunofluorescence (IF) method and tested for safety on rabits and rats. Results:2 lots of Rotavirus master seed G1P4 that had been produced in Center for research and production of vaccines and biologicals \ufffd?Ha Noi had high titre and safety in the laboratory and experimental animals. Conclusion: The result was the basis of Rota vaccine production in Vietnam.

Determining the potency of measles vaccine using plaque method

Background: Measles vaccine was the only vaccine in the expanded vaccination program still must be imported. Center for research and production of vaccines and biologicals \ufffd?Ha Noi was conducting the first stages of measles vaccine manufacturing technology transfer from the Kitasato Institute in Japan. The Center received semi-finished vaccine to set up finished vaccine production process as well as the testing process. Potency test and its consistency is very essential in quality control. Objectives: In order to identify standard potency assessment methods and potency of 13 lots of finished measles vaccine produced in Viet Nam from imported semi-finished products. Subjects and method: 13 lots of the finished vaccine were determined potency by plaque method based on 13 samples of semi-finished vaccine and the standard sample M16-6 had potency from 4.2 to 4.6 lg PFU/0.5 ml provided by the Kitasato Institute. Results: The result of 13 lots show that the reduction of potency during freeze-drying is within the range (0-0.76 lg); and 4 last consecutive lots are met WHO criteria on heat stability. Conclusion: This shows that the measles vaccine freeze-drying process in Vietnam was officially set up to use for the measles vaccine production in 2007.

Propagation of AIK- Measles virus in chicken embryo cell culture derived from Valo SPF egg (Germany)

Background: \r\n', u'Chicken embryo cell was the most effective fibroblast cell line for producing the attenuated measles vaccines. Many countries as Japan, in Kitasato, an attenuated virus derived from the Edmonston virulent strain adapted in chick embryo cells, it was call AIK- C strain, and used for measles vaccine production. In Vietnam, the POLYVAC have applied the Kitasato institute\u2019s technology into measles vaccines production. The Valo SPF egg (Lohmann-Germany) was used in the chick embryo culture \r\n', u'Objectives: \r\n', u'To study the inoculation, and clone of the human AIK-C strain in the chick embryo in order to achieve a high yield of virus for measles vaccine production \r\n', u'Subjects and method:\r\n', u'Suitablecells (AIK- C Strain, an attenuated virus derived from the Edmonston virulent strain, chicken embryo cell cultured from SPF egg Valo Germany) are selected. Then methods as inoculating and culturinglive viruses on the chicken embryo cell are applied.\r\n', u'Results:\r\n', u'After 9 days for infection, viruses which were observed via microscope, propagated and in infectious clone by the measles virus.\r\n', u'Conclusion: \r\n', u'Many tests for propagation of AIK measles virus in chicken embryo cell cuture derived from Valo SPF egg (Germany) showed that chicken embryo cell culture from Valo SPF egg (Germany) is appropriated fro AIK- C measles vaccine production in Vietnam.\r\n', u'

Titre and safety of rotavirus master seed G1P8 (KH0118)

Background: Rotavirus vaccines used to prevent acute diarrhea among children under 5 years old. In Vietnam, with the assistance of the World Health Organization (WHO), Centers for disease control and prevention (CDC), Atlanta, United States, Ministry of Health and Ministry of science and technology researched to create rotavirus master seed G1P8 which would use to produce Rota virus in Vietnam. Objectives: to evaluate titre and safety of rotavirus master seed G1P8 in vitro and in experimental animals. Subjectives and Method: experimental studies in vitro and experimental animals. Rotavirus master seed G1P8 (KH0118) series 1 (MS-P5) and series 2 (MS-P5) produced in 2005, preserved 80oC, were determined by immunofluorescence method (with unit of FFU/ml). The strains were tested in experimental animal\u2019s safety like the safe requirements of World Health Organization on live-attenuated vaccine (OPV). Results: no detection for exotic virus strains in virus suspension by PCR and titres of rotavirus master seed were similar and were more than 107 FFU / ml. 10 intervened rabbits were healthy life during follow up period, 8/10 these rabbits increased weight after follow up period, only two rabbits reduced weight but increase of mean weight of all 10 rabbits was 106%. 5 intervened guinea-pig increased mean weight (158%) and healthy during follow-up period. 4 experimental white mice increased mean weight (195%), higher than control groups. It was safety in experimenting on baby mice. Conclusions: two lots of rotavirus master seed G1P8 produced in POLYVAC had high titre and safety both in vitro and in experimental animals.

The safety and immune response of rotavirus master seeds in monkeys

Background: Group A Rotavirus is the main cause of diarrhea in human especially in children under 5 years old. Rotavirus master seeds were established from group A Rotavirus (mainly 3 strains: G1P8, G1P4 and G4P6) causing acute diarrhea for children in Vietnam. The master seeds must meet the potency and safety in the laboratory as well as animal experiments under the guidance of WHO. Objectives: To determine the safety and immune response of rotavirus master seeds in monkeys to confirm their safety and effect in preclinical stage. Subjects and method: Baby Macacca mulatta monkeys had average weight of 1.5 kg (provided by monkey ranch in Reu island in Quang Ninh province) were tested and determined neutral antibody by immunofluorescence technique. Results: The rotavirus master seeds: G1P8 (KH0118); G1P4 (2001019210) and G4P6 (2001019203) had good safety and immune response with high neutral antibody after 3 dose vaccination in baby Macacca mulatta monkeys. Conclusion: The rotavirus master seeds would be a base for diarrhea vaccine production in Viet Nam under the guidance of the World Health Organization.

Evaluation of the quality of trivalent poliomyelitis vaccine produced in 2007

Background: Trivalent poliomyelitis vaccine was produced from strains which had been supported by Japan. One of the standards of vaccine quality required by WHO is potency and thermostability. Follow that potency at 370C and within 48 hours is not less effective than potency at -200C exceedingly 0,5 lgCCID50. Objectives: To assess the potency of Trivalent poliomyelitis vaccine and the thermostability of mokey vaccine preserved at 370C within 48 hours. Subjects and method: 12 lots of trivalent poliomyelitis vaccine (included 3 types) produced in January 2007 were evaluated by microneutralization technique. Results: Potency of 12 type I lots were all 106,0 CCID50/0,1ml and the disparity of potency at two temperatures were all < 0,5 lgCCID50/0,1ml. Potency of 12 type II lots were all 105,0 CCID50/0,1ml and the disparity of potency at two temperatures were all < 0,5 lgCCID50/0,1ml. Potency of 12 type III lots were all 105,5 CCID50/0,1ml and the disparity of potency at two temperatures were all < 0,5 lgCCID50/0,1ml. Conclusion: 12 final poliovaccine lots produced in Center for research and production of vaccines and biologicals \ufffd?Ha Noi in 2007 met WHO requirements for potency and thermostability.

Determination of adventitous agent in monkeys and monkey kidney cells culture using for OPV production in 2006

Background: In 2006, Center for research and production of vaccines and biologicals \ufffd?Ha Noi produced 10 million doses of poliomyelitis vaccine met quality standard which given by World Health Organization (WHO). The monkeys for vaccine production were selected and monkey kidney cells were tested arcording to the WHO requirements (the strong moykeys with no adventitous agents). Objectives: To assess the rates of mokeys (at the Reu island in Quang Ninh province) with no adventitous agent infection and the cells using to produce type 1 poliomyelitis vaccine in 2006. Subjects and method: The study was performed by using microneutralization technique on 39 Macaca mulatta mokeys with weights were 1.5 to 2.5 kg. Results: 11 out of 39 monkeys (28,21%) are negative to SIV, SV40, poliomyelitis viruses, foamy virus as well as tuberculin test. 100% lots of primary monkey kidney cells culture produced in 2006 are free from adventitous agents arcording to the WHO requirements. Conclusion: Center for research and production of vaccines and biologicals - Ha Noi implemented strictly under the WHO guidelines on selection of monkeys and monkey kidney cells for OPV production from Sabin strains.

Assessment on Quality of single polio vaccine type 1 produced on primary monkey cells

Background: \r\n', u'October 2000, Vietnam was acknowledged as the country to successfully eradicate the polio by WHO.This success was partly due to the oral polio vaccine (OPV) produced on the primary money cells by the Centre of Research, Production of vaccines and biologicals, Ha Noi. In 2006, the Centre developed the single polio vaccine type 1 from primary monkey cells.\r\n', u'Objectives: \r\n', u'To evaluate the safety and antibody titre .\r\n', u'Subjects and method: \r\n', u'6 lots of single polio vaccine type 1 (ISO- 90, Antibodies of Polio type 1,2,3; the standard sample F113 from Japanese research on Polio Institute\ufffd?\r\n', u'Using the tests (T- maker, D maker, PFU, CCID50) to check the safety of single polio vaccine type 1. \r\n', u'Results:\r\n', u'After 14 days, 6/6 lots of viruses were observed via the microscope that they stayed in well developed, and of no serious adverse affects.There was no appearance of degenerated cells. \r\n', u'Conclusion:\r\n', u'6/6 lots of single polio vaccine type 1 produced on Macca mulltta monkey kidney cells with the first time passage at POLYVAC in 2006 are safe and high antibody titre.\r\n', u'

Evaluation of the documentation for OPV production in the year of 2006

Background: Good Manufacturing Practice (GMP) is a important part of quality assurance (QA). Implementation of GMP request to establish the documentation system and should be reviewed as well as evaluated strictly. Documentation is important because it helps the competent person make decisions whether to finish the product or not and it is used as a base for inspection. In the year of 2006, 100% OPV production line in Center for research and production of vaccines and biologicals (POLYVAC) had established the document system. Objectives: To evaluate of the documentation for OPV production in the year of 2006 in POLYVAC. Subjects and method: Documentation for OPV production in 2006 were evaluated by standard operating procedure (SOP) (recommended by WHO). The standards included blank space; erase; code and unit of measurement; revision; no signage and others. Results and Conclusion: Documentation is different between departments. Onlymonkey ranch in Reu island applied 100% SOP. 776 errors were found. Among them blank space (32.2%), erase (27%), code and unit of measurement (21%), revision (5%), no signage (12%) and others (3.6%). The results were the basis of promoting implementation of GMP in vaccine manufacturing in POLYVAC.