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Vaccination is the most cost-effective and efficient measure for preventing and controlling infectious diseases. Before vaccines were developed, epidemics such as plague and smallpox ravaged humanity, and even influenza claimed the lives of tens of millions. We must not let a few vaccine-related incidents make us forget the fear of being at the mercy of infectious diseases.
1 How are vaccines produced?
The production processes of vaccine manufacturers typically encompass cell culture and amplification, purification, formulation, and filling. In addition to conducting in‑house quality control, each batch must also undergo lot release by the National Institute for Food and Drug Control. Meanwhile, driven by evolving regulatory requirements, post‑marketing surveillance feedback on potential risks, and advances in new technologies, vaccine producers continue to optimize and refine their manufacturing processes—such as transitioning from flask‑based cultivation to cell factories and bioreactor systems to minimize contamination and enhance product uniformity, and eliminating unnecessary excipients to reduce the risk of exogenous allergens—while ensuring the annual supply of hundreds of millions of doses.
The 2010 revised edition of GMP, which vaccine manufacturers are required to follow during production, can be regarded as a “Sinicized” version of EU GMP, aligning with international standards. The 2010 GMP mandates that manufacturers adhere to several essential requirements:
● Vaccine manufacturers must procure raw materials from qualified suppliers.
● Factory facilities and equipment must be used only if they have passed validation.
● Continuous training and assessment of staff must be ensured.
● Production must be carried out in accordance with the manufacturing process approved by the drug regulatory authority.
● Intermediate products, raw materials, semi-finished products, and finished products must be properly tested and released at each stage and stored in accordance with the specified requirements.
●All these steps must be documented meticulously and comprehensively, ensuring that every batch of vaccine produced meets the required quality standards.
For processes such as formulation, filtration, transfer, and filling in vaccine production, the cleanroom environment must meet Class A conditions under a Class B background. What does Class A cleanliness entail? It means that no bacteria are permitted; the number of airborne particles ≥0.5 μm per cubic meter must not exceed 20. This is a very stringent standard, further supported by online environmental monitoring and alarm systems to ensure continuous surveillance.
2 Safety vs. Having Efficacy: What are the quality control indicators for vaccines?
Vaccine quality standards are broad‑based, encompassing end‑to‑end process control. Specifically, on the basis of stringent specifications for manufacturing process parameters, each production step must be equipped with designated testing points and control requirements, and the final product must meet established criteria for safety and efficacy. Taking the “Group A and Group C Meningococcal Polysaccharide Conjugate Vaccine” listed in the 2015 edition of the Chinese Pharmacopoeia as an example, the manufacturing process includes no fewer than 53 intermediate‑product tests. In addition, the finished‑product testing protocol further specifies the following 13 assay items: identification test, appearance, fill weight variation, water content, pH, osmotic molality, polysaccharide content, free polysaccharide content, potency assay, sterility test, pyrogen test, bacterial endotoxin test, and abnormal toxicity test.
For example, sterility testing, pyrogen testing, bacterial endotoxin testing, and abnormal toxicity testing are indicators closely related to product safety. Polysaccharide content, free polysaccharide content, and potency assays are indicators closely associated with vaccine efficacy. Other parameters, such as physical appearance, serve as general quality‑control criteria.
3 Low potency does not equal unsafe.
Zeng Guang, chief epidemiologist at the Chinese Center for Disease Control and Prevention, pointed out that an不合格 (non‑compliant) potency indicator may compromise the vaccine’s immune protective efficacy, but it poses no direct harm to human health. Like other pharmaceutical products, a vaccine’s efficacy and safety are its two fundamental pillars. According to the explanation, the potency indicator reflects the vaccine’s effectiveness, while sterility and other related parameters assess its safety. A non‑compliant potency indicator means that the content of the vaccine’s active antigenic components falls below the established standard range, indicating insufficient protective efficacy—distinct from safety. Such a non‑compliance does not increase safety risks.
He also stated that a decline in vaccine potency does not necessarily mean the loss of protective efficacy. Individuals exhibit variable responses to vaccine antigens; some may mount an adequate immune response even to low levels of antigenic potency. Moreover, because combination vaccines require multiple doses administered at different intervals, insufficient potency in a single dose does not equate to a complete loss of protection.
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