Thursday, March 28, 2024
December 11, 2023
To ensure that products are safe to use, vaccine manufacturing has to comply with cGMP standards. The many rules appointed by the Food and Drug Administration are regularly updated and regulated to react to the newest developments in biotech and biopharma. In vaccine manufacturing, cGMP standards regulate the manufacturing process, facilities and equipment as well as testing and documentation.
Details on cGMPs and the challenges for manufacturers to stay compliant in vaccine production are discussed in the following.
To ensure the safety of pharmaceuticals for patients, health authorities define certain standards for drug manufacturers on drug development and manufacturing. In the U.S., these regulations are enforced by the Food and Drug Administration (FDA).
They are referred to as current good manufacturing practices, or cGMP for short, and are set to ensure “identity, strength, quality, and purity of drug products”1. It is not so much a question of following these guidelines or not, they can be seen as the baseline of requirements for safe-to-use drug products.
Details on GMPs can be found on the FDA’s website, entailing the handling of quality management, the quality of raw materials, operating procedures and maintaining of testing laboratories. The main aim of these regulations is to prevent product contamination, deviations and errors during drug handling to ensure a safe product. The word “current” is a hint to the fact that the FDA updates them regularly, because standards can change due to new technologies and developments that become available.
Important cGMP guidelines for companies2:
While cGMPs are applicable globally, each country has their own regulatory health authority which enforces rules and regulations on the production of pharmaceuticals. Among them are, for instance, the European Medicine Evaluation Agency (EMEA), the State Food and Drug Administration (SFDA) in China, HEALTH CANADA or the Central Drug Standard Control Organization (CDSCO) in India.
While there are slight differences between country specific regulations, they all orientate themselves on the regulations announced by the World Health Organization, which released a first draft for good manufacturing practices in 1968.3 For example, in contrast to the U.S. version, the EU guideline does not indicate the time limit for the equipment storage after cleaning.4 The difference to current good manufacturing practices is that they focus more on continuous improvement and try to incorporate the latest technologies.3 4
When it comes to scale-up in vaccine manufacturing, achieving cGMP compliance presents unique challenges for manufacturers and facilities. Launching a new vaccine is always an urgent mission to save as many lives as possible.
The development of vaccines includes numerous guidelines for clinical trials, case studies and constant quality controls that have to be followed before the vaccine can be approved. In events of a health crisis like the recent COVID-19 pandemic, it is important to act fast. Hence, regulatory procedures were tightened by many health authorities to release vaccines faster during the state of emergency.
In standard procedures, scaling up vaccine manufacturing is a rather slow process because it affects a lot of different stages in vaccine manufacturing. In order to master them, the most advanced equipment has to be at hand, which is often a costly investment. The lack of scalability and flexibility can be problematic, especially challenging for smaller businesses when it comes to cGMP compliant upscaling of vaccines.
Ensuring consistent scenarios from small to large volumes, such as scaling from 50mL to 10L bags, is crucial. Single Use Support addresses this challenge with standardized and scalable processes, ensuring uniformity across different volume scales.
Current good manufacturing practices exist to protect patients from ineffective or contaminated drug products. Especially in vaccines, where guaranteed efficiency is of essence to win the fight against the spreading and mutating of diseases, they have to be followed meticulously to gain approval by regulatory authorities. In the following, we will show how cGMP requirements regulate the different process steps in vaccine manufacturing.
Vaccines rely on the use of raw materials like yeast extract or natural and recombinant enzymes. These materials are often at risk of contamination because they can be derived from animal hosts and might have been exposed to microbes or viruses. cGMPs call for regular testing and standardized formulas in regard to the proportions of raw materials in vaccines.5
To maintain cGMPs compliance, manufacturers are wise to have up-to-date equipment for each step of vaccine manufacturing. These steps include filling, mixing, dispensing and freezing of vaccines. Because vaccines are very sensitive to temperature changes, cold chain handling in vaccine manufacturing must be carried out without interruption or fluctuation.
At the same time, buildings and production equipment and facilities have to be maintained and kept meticulously clean to prevent the risk of contamination. In addition, the standard operating procedures (SOPs) must be documented and followed without deviation to ensure staff safety and product quality.6
Constant quality control is an important factor in vaccine manufacturing to ensure that batches have the same quality and are safe for patients to use. They are validated by sampling, starting specifications, and a number of tests which are all documented with determined methods.
Testing is not only limited to the finished vaccine itself, but also necessary for starters, in-process fluids and packaging materials.7 Additionally, it's noteworthy that sampling for quality controls can also be integrated into the dispensing process step using single-use bags.7
When it comes to packaging and labeling vaccines, cGMPs regulate the standards for displaying ingredients and the order they have to be listed on the packaging. Vaccines rely on aseptic packaging to prevent any contamination in vials and other containers. Further, sizes for administered doses have to be standardized and equally measured so that they can be administered safely.8 Moreover, single-use bags can also be labeled in the course of aliquoting for batch allocation and subsequent track & trace, ensuring a comprehensive and compliant approach.8
Complying with cGMP documentation requirements can be challenging for manufacturers. Manufacturing and batch records must be maintained to evaluate production performance and product quality.
According to cGMP regulations, these records have to be stored for a certain period of time. That is why a lot of manufacturers switch to automated systems that help to streamline the process of documenting.9
Ensuring cGMP compliance is non-negotiable and necessary to ensure safety, but it can also put a lot of pressure on vaccine manufacturing companies and their staff. Novel methods in vaccine manufacturing have been developed to help companies focus their efforts and energy where it is needed while maintaining cGMP compliance through automation.
Fully automated platforms by Single Use Support help standardize multiple process steps in fluid and cold chain management.
RoSS.FILL is a filling and dispensing mechanism that minimizes the risk of human error and contamination by providing an aseptically closed system for aliquotation and filtration. Meanwhile, data is automatically documented and electronically saved, which removes the need for manual documentation methods.
RoSS.pFTU is an automated freezing and thawing platform that gives manufacturers the freedom of flexibility. The plate-based single-use technology is the perfect solution for a scalable and controlled freezing process that is compatible with single-use bags and bottles from other manufacturers. Highest drug quality is maintained through controlled rate freezing and thawing via plate freezer. These and other solutions by Single Use Support enable homogenization, filling, freezing, storage and shipping in a cGMP compliant manner, streamlining the process and saving cost and time for vaccine manufacturers.