Important improvements with the Barycela vaccine - The key to WHO-PQ

The World Health Organization's (WHO Prequalification - WHO-PQ) certification is considered a "golden passport", affirming the quality, safety and effectiveness of the vaccine, while opening the door to access the global market, especially the procurement programs of the United Nations, UNICEF and many international organizations.

The vaccine is a special biological product, requiring the highest level of sterility production conditions. WHO's requirements for good manufacturing practices (GMP) are constantly updated, notably the technical document on the production of sterilized pharmaceuticals (WHO.TRS 1044. Appendix 2) issued in 2022 [1]. These regulations pose a significant challenge for vaccine manufacturers:

- Factories and equipment: must meet the requirements of closed, highly automated production, especially in the stage of pasteurization.

- The production process needs to minimize manual operations, strengthen control of pollution risks.

- Personnel must be highly qualified, have in-depth training, and limit the number of direct participants.

- The raw material source must meet international standards and be synchronously standardized.

Vietnam has many advantages to access WHO-PQ certification. Vietnam's National Drug Administration (NRA) has been recognized by WHO, affirming that the drug management system operates stably and effectively [2].

Along with that, Vietnam has now mastered the technology of producing many potential vaccines in the WHO priority pre-assessment list, such as measles vaccine, measles- rubella combination vaccine, diarrhea vaccine issued by the rota virus, BCG vaccine and hepatitis B [3] vaccine.

These Vietnamese vaccines all have international quality requirements similar to GC Biopharma's Barycela chicken vaccine, a vaccine that immediately achieved WHO-PQ pre-assessment certification after applying improvements in the production process to improve product quality.

GC Biopharma (Korea) has successfully developed and licensed the raw chickpea vaccine, reducing the toxicity of the MAV/06 strain - the first generation vaccine since 1993. The vaccine is available in many countries around the world under the commercial name Varicella and has been licensed in Vietnam since 2008.

Varicella vaccine has proven its safety and effectiveness in preventing chickenpox over many years of use. Faced with increasingly strict requirements of WHO as well as high standards of vaccine importing countries, aiming to achieve WHO-PQ pre-assessment quality certification as the destination of the improved chickenpox vaccine - the 2nd generation vaccine - Barycela. GC Biopharma has implemented a comprehensive and continuous improvement program - from the factory, equipment to the production process and input materials.

Important improvements with the 2nd generation chickenpox vaccine - Barycela - The key to WHO-PQ achievement is:

- Automation and single-use technology: The entire line of refining, piping, freezing, completely automatically and completely closed; applying single-use technology (SUT) using devices in direct contact with products that are only used once during the stages of cell culture, infection, viral proliferation and harvest. This helps reduce human contact, limit the risk of cross-infection and completely eliminate the use of antibiotics in the production process, towards optimal safety for the product, reducing the risk of allergies in people vaccinated.

- Improve product stability: Adding Urea during the blending process helps maintain more stable viral price signals when temperature fluctuations in production, transportation and storage. The minimum price at the end of the storage period is ≥ 3,800 PFU, significantly higher than ≥ 1,400 PFU of the first generation vaccine.

- Change the production cell line: switch from LuMA cell line to MRC-5 cell line - a bilistic cell line recognized by WHO, widely used and suitable for large-scale production, stable in genetics.

Thanks to these improvements, the second generation of chickenpox vaccine from the MAV/06 strain, with the trade name Barycela, has been officially granted a pre-assessment certificate (WHO-PQ) by WHO since 2023. By 2025, the vaccine will be licensed for circulation and use in Vietnam and many other countries such as Pakistan, Turkey, Egypt, Libya, Brazil, etc.

Lessons from Korea affirm that WHO-PQ is not a short-term destination but a long journey, requiring a strategic vision, proper investment and continuous improvement. Standardizing raw materials, upgrading factories, modernizing equipment and building a comprehensive quality management system are key factors.

Not only to "achieve WHO standards", when these improvements are applied, it will help improve the quality of Vietnamese vaccines, reduce production risks, increase international competitiveness and expand export opportunities. More importantly, it is a necessary step for Vietnam's vaccine to affirm its position on the global vaccine industry map.

Reference documents:

1. WHO, WHO good manufacturing practices for sterile pharmaceutical products, Annex 2, WHO Technical Report Series 1044, 2022, https://www.who.int/publications/m/item/trs1044-annex2, access date 14/12/2025

2. WHO, List of National Regulatory Authorities (NRAs) operating at maturity level 3 (ML3) and maturity level 4 (ML4), https://www.who.int/publications/m/item/list-of-nras-operating-at-ml3-and-ml4, access date 14/12/2025

3. WHO, Vaccines Prequalification Priority List 2024 - 2026, https://extranet.who.int/prequal/vaccines/vacines-eligible-who-prequalification, access date 14/12/2025