Good Manufacturing Practice — universally referred to as GMP — is the regulatory framework that governs how pharmaceutical and biotechnology products are produced, tested, and released for use. In the case of modern biotech facilities, which are required to operate in compliance with Good manufacturing practice, compliance is not merely a requirement. It forms the basis of operation upon which the safety, uniformity, and compliance with regulations of their products depend. Knowing what GMP requires of a biotech plant, and how these requirements have changed as the science has improved, is crucial to anyone working within or developing a manufacturing facility in this industry.
What GMP In fact Needs
Fundamentally, GMP and Cryogenic Storage is focused on just one aspect: that of ensuring that every single product batch produced is systematically and consistently produced and controlled to the level of quality that a product of that specific product type will perform the intended function when utilized in the intended application that the product is designed to carry out. That seemingly simple statement gives rise to a massive body of specifications to support facility design, equipment validation, personnel training, documentation, process validation, quality control, and change management.
The regulatory authorities that issue and regulate GMP standards, which are mostly the United States Food and Drug Administration, the European Medicines Agency, and the Therapeutic Goods Administration in Australia, provide elaborated guidance documents, which translate the general principles of GMP into specific expectations to be made to manufacturers. Although these documents are based on the same framework, there are significant differences in the manner in which each of the agencies establishes and enforces certain requirements, which is of great importance when facilities are operating in one or more different markets.
Design and Environmental Controls of the facility
A biotech plant and in-process testing that is designed to meet all the needs of GMP design is grounded on the need to prevent contamination, cross-contamination, and mix-up of products. A physical structure of the facility must support a logical and controlled movement of materials, people, and waste, a principle that is known as unidirectional flow, which will minimise the risk of contamination at each stage of the manufacturing process.
One of the technically challenging areas of the construction of biotech facilities is cleanroom design. Various manufacturing processes need various levels of environmental control, which is expressed through the standards of ISO classification, which sets the maximum allowable concentration of airborne particles in the manufacturing process at different sizes. The operations that are the toughest to the environment, such as filling sterile products, are put there under the most rigorous environmental control conditions, ISO 5 classification at the point of fill, and those operations that are not the most intense are put there under the most relaxed but yet rigorously controlled environmental conditions.
GMP facilities are not just mere heating and cooling systems installed in the HVAC systems of these facilities. They are critical systems in which differentials in pressure between zones are maintained to ensure that no airborne contamination moves between less clean and cleaner zones, to ensure that temperatures and humidity are controlled to maintain product integrity, and to ensure the necessary air change rates to maintain cleanroom classification. These systems are qualified and watched over, and can be the subject of regular maintenance and re-qualification.
Equipment Qualification and Process Validation
Any equipment installed in a GMP biotech plant has to be formally qualified prior to being put into use in the production process. The qualification process, which extends to the installation qualification, the operational qualification, and the performance qualification, documents that the equipment has been correctly installed, correctly operated within the limits of its design capability, and that it behaves consistently under the circumstances of an actual use environment.
The complementary activity that establishes that the manufacturing process itself, as opposed to the equipment used in the process, is marked by a constant production of a product that is within the pre-determined specifications. Process validation is especially stringent with biologics and biopharmaceuticals (where the product of interest is the process), and where it is not true of small molecule drugs that everything proceeds fine at the conditions of commercial manufacture.
Withdrawal: The Workhorse of the GMP Compliance
One of the most basic principles of GMP is that everything must be documented, not part of a bureaucratic process, but as an engine whereby the consistency is controlled and demonstrated. It is well known that the GMP principle can be summed up as follows: whatever was not written did not happen.
All of these constitute a portion of the documentation system that a GMP manufacturing facility must have. Regulatory inspectors directly evaluate the quality of this documentation, and it is one of the areas in which the facilities most often receive observations taken during the inspection.
The advent of electronic systems to assist with GMP documentation has become commonplace in the present-day biotech facility, but it is not without its regulatory implications regarding data integrity, the principle that data needs to be attributable, legible, contemporaneous, original, and accurate. In recent years, regulatory agencies have placed significantly greater emphasis on data integrity than they have previously, and facilities must be able to demonstrate that their electronic systems fulfil these requirements to an extremely high degree.
Personnel: Training/Qualification
The ultimate human resource factor of GMP is people, and training and the qualification of all personnel working in a GMP facility are major control requirements. All personnel should be trained in the GMP principles applicable in his/her role, and the training must be documented, evaluated on how effective it is, and it should be kept up to date as procedures and requirements change.
In the technical jobs (process scientists, quality control analysts, validation engineers) role-specific training programmes incorporate GMP awareness into the technical knowledge needed to do the job. In senior positions, it is at least as important to have an understanding of the regulatory environment and the implications of GMP failure as it is to be competent.
Quality Systems and Continuous Improvement
A GMP facility does not merely pass compliance and hold on to it in the future. It has a quality management system that constantly monitors performance, identifies non-conformance with expected performance, applies corrective and preventive measures, and periodically examines the general levels of adherence to expected performance.
A quality system is the mechanism by which the GMP facilities are handled in a more controlled and documented manner, in such a way as to maintain the safety of the products throughout.
Conclusion
The standards of Good Manufacturing Practice of the present-day biotech facility represent one of the most exigent regulatory ordinances in any industry that exists in the first place. In the case of facilities that do not undermine good science with their standards, the standards are not considered as limiting good science. They are the institutions in which good science is made safe, consistent, and reliable medicine.
Xellera Therapeutics focuses on strong testing and clean processes. You can do the same by staying aware and careful at all times. Sign up for more information.
Comments