Good Manufacturing Practices for Biologics
Good Manufacturing Practices, or GMP, is a set of guidelines and procedures for the production of pharmaceuticals, biologics and medical products. These standards not only ensure that these products are safe for consumers, but also help to maintain the integrity and quality of the final product.
The quality and safety of biologics are of utmost importance, as these products have the potential to impact human health in a number of ways. Biologics are frequently sourced from other living things, and act with human metabolism to enhance an existing biological process. For example, vaccines enhance immune response, and hormones are administered to patients with endocrine insufficiency. Therefore, it is essential that manufacturers adhere to strict Good Manufacturing Practices in order to ensure product quality and safety, since failure to create a safe product has the potential to cause great harm. GMPs prevent or minimize errors or defects during the manufacturing process, minimize contamination, and maintain the integrity and stability of biologic products.
The goal of GMP is to produce high-quality medical products that are safe for human use, including people who may be very ill, with numerous medical problems. To achieve GMP, manufacturers must follow a strict set of procedures and guidelines, designed to ensure product safety. Such procedures include ensuring the cleanliness of all production facilities, maintaining accurate and up-to-date records of all ingredients and products, and regularly testing finished products for quality control purposes.
This article will discuss GMP for Biologics, how it is different from GMP for other products and things you should consider when designing a GMP program for a biologics product.
Biologics products, because of their dissimilarities from other medical products, have different GMP requirements from other medical products. Biologics include drugs such as vaccines and therapeutic proteins, and also include devices that ensure the safety of the blood supply, such as the tests required for blood banks. Biologic products are typically more complex than traditional pharmaceuticals, due to the fact that they originate from living organisms. The source material, originating from a living thing introduces variability due to genetics, environment, diseases, and impurities inherent to naturally-occurring biochemistry in the living thing. For example, a recombinant insulin product may undergo a series of manufacturing steps, including fermentation to grow the cells generating the insulin, followed by a series of purification steps to obtain the desired product. A product derived from human blood carries significant risk of bloodborne pathogens.
Clearly biologic products have numerous risks resulting from their inherent nature. Given this complexity and risk several additional GMP requirements must be met to achieve GMP compliance. For example, manufacturing facilities used to produce biologics must be designed and constructed specifically for this purpose. In addition, all personnel working in these facilities must undergo rigorous training and certification procedures, and personnel are not permitted to work in other areas outside the vaccine production facility within the same working day. Other additional requirements, in the United States, are codified in 21 CFR 600, “Biological Products: General.”
Key areas of Concern for Biologic GMPs
1) Facilities and equipment: All manufacturing facilities and equipment must be designed, constructed, and maintained in a way that minimizes the risk of contamination. In addition, all production areas must be kept clean and free of debris. Many facilities need barriers or dedication to prevent cross-contamination with other processes. Some equipment for biologics manufacturing may be highly-specialized, and will require special testing to ensure its use is suitable for making biologic product.
2) Personnel: All personnel working in manufacturing facilities must be properly trained and qualified. They must also follow all procedures and protocols to minimize the risk of contamination, including clothing requirements and health monitoring to prevent disease crossover into the product.
3) Materials: All materials used in the manufacturing process must be of high quality and free of contaminants, with validated sterilization cycles, segregation from materials used for non-biologics, and testing for containers/closures. Specialized gowning and segregation procedures ensure that materials retain their purity through manufacturing, holding, and distribution.
4) Quality Control: There must be a strict quality control program in place to ensure that all products meet the required standards, including microbial control, standards for animal care, holding retain samples 6 months past expiration, temperature control during shipment. Furthermore, the FDA requires reporting of deviations, as well as complaints and adverse events related to manufacturing of blood component or source plasma. All biological product deviations, even if not related to blood component manufacturing are required to be investigated, regardless of whether they require reporting. Such a report is called a BPDR (Biological Product Deviation Report).
Quality Controls
Needless to say, Quality Control testing for biologic products is extensive, from raw material receipt through the end product. Laboratory testing is just part of a comprehensive quality control program. Much of the QC work involves assuring that the designed quality controls continue to work, verifying that controls in the design of the biologic facility continue to perform as designed. Post-production, stability testing is also required.
Quality Control also includes validation of facilities and equipment as well as laboratory testing. Equipment sterilization requirements are specified in the standard, and sterility via equipment handling procedures to assure continued sterility. Quality control extends to areas where biologic material is harvested from animals, with specified requirement for assuring cleanliness, including fly screens, assurance of animal health, and preventing incursion of spore-forming microorganisms. Tests may include screening for specified animal diseases, and reporting certain diseases to the FDA if an outbreak is detected. Monkeys used in vaccine production require necropsy to prevent disease crossover to humans.
Laboratory testing, requires validation in much the same way that validation is required for non-biologic medical devices and pharmaceuticals, but the specific laboratory tests required will differ. Several types of test methods are used for testing biologic products , including in-vitro assays, immunoassays, and chromatography. Each of these methods has its own advantages and disadvantages, and the choice of testing method will depend on a number of factors including the type of product being produced, the scale of production, and regulatory requirements. Regardless of the testing method used, it is essential to ensure that all testing is carried out in a way that minimizes the risk of contamination, the equipment used in testing is qualified, and the test methods are validated to provide a true, reliable result.
Stay up to date on GMP Guidelines
GMP guidelines are continuously evolving. In the industry, this is called, cGMP, with the little “c” standing for “current.” As such, it is important for manufacturers to stay up-to-date with the current GMP requirements. Failure to do so can result in subpar products and potential safety risks for consumers, or products failing to meet the expected medical state-of-the-art.
While GMP guidelines may seem daunting, they are essential for ensuring the safety and quality of biologic products. By following these guidelines, manufacturers can be confident that their products will meet the highest standards of quality and safety.
Why you should work with a Biologics GMP Expert?
If you are looking to develop or manufacture biologic products, it is essential to work with a biologics GMP expert. These experts have extensive knowledge and experience in all aspects of GMP for biologics, including regulatory requirements, testing methods, production processes, and more. Their expertise can help ensure that your products meet the highest standards of quality and safety.