What is cGMP in the biopharmaceutical industry

Current good manufacturing practice (cGMP) is a set of quality systems that helps maintain product quality during manufacturing in the biopharmaceutical and other industries regulated by the U.S. Food & Drug Administration (FDA).

cGMP provides a structure the biopharmaceutical industry uses to consistently manufacture products according to quality standards required for their intended purpose. Standards in cGMP specify minimum requirements for methods, facilities and controls used in manufacturing, processing and packing biopharmaceutical products to ensure they are safe to use.

Biopharmaceutical companies can use cGMP throughout the production process, including developing quality management systems, obtaining appropriate raw materials, establishing robust operating procedures, detecting and investigating deviations in product quality and maintaining reliable testing laboratories. In practice, cGMP can help prevent contamination, mix-ups, deviations, failures and errors.

The fundamentals of cGMP

cGMP was developed to allow biopharmaceutical companies to implement process and quality controls based on scientifically sound design, processing methods and testing procedures. The regulations allow companies to use advanced technology and innovation to achieve higher quality through continual improvement.

That’s why the “c” in cGMP stands for current. Biopharmaceutical companies should use up-to-date technology and systems to comply with the regulations. The technology and systems that worked years ago may no longer be good enough according to today’s standards. Many biopharmaceutical companies use advanced quality systems and risk management approaches that exceed the minimum requirements required by cGMP.

Key principles of cGMP

Several fundamental principles are the basis of cGMP in the biopharmaceutical industry. They include:

• Quality control and assurance to help ensure products consistently meet quality standards. This includes rigorous testing, documentation and meeting specifications
• Facility and equipment maintenance helps prevent contamination, ensures cleanliness and promotes safe production
• Validating processes, systems and equipment demonstrates their effectiveness and reliability
• Qualification ensures that equipment is suitable for its intended use
• Employee training that includes hygiene and safety protocols helps minimize risks
• Documentation and record-keeping throughout manufacturing and testing help ensure traceability and accountability
• Maintaining the quality and integrity of raw materials used in production is an integral part of cGMP. Raw materials must meet specifications and should be properly stored and handled
• Monitoring critical processes to maintain consistency and prevent deviations helps build consistency and minimize variability
• Rigorously testing finished products to verify their potency, purity and safety helps ensure they are ready for distribution
• Controlled systems help manage changes to processes, equipment or procedures so any deviations can be identified and corrected
• Regular inspections can help ensure compliance with FDA regulations and identify areas for improvement

cGMP in bioprocessing

GMP provides a framework for safe, efficient, high-quality bioprocessing techniques for several applications. One such application is stem cell bioprocessing for clinical applications. Stem cells, including mesenchymal stem cells (MSCs) and pluripotent stem cells (PSCs), can be used for several purposes, including drug discovery, disease modeling, and tissue engineering. Adhering to cGMP guidelines makes it possible for bioprocess engineering to produce large quantities of functional and safe stem cells for research and therapeutic uses.

Similarly, following cGMP guidelines makes it possible to meet quality standards for recovering and purifying bioproducts in biologics production. This helps manufacturers ensure that proteins, antibodies, vaccines, and other biologics meet quality standards for clinical use.

Continuous bioprocessing manufacturing is becoming more commonly used in biopharmaceutical production because it helps increase flexibility, reduce costs and improve product quality. Manufacturers can achieve efficient and consistent biologics production when continuous bioprocessing is done per cGMP guidelines.

Because cGMP mandates robust methods of monitoring and controlling bioprocesses, adequate record-keeping is essential to track process parameters and ensure consistency. Under cGMP, standard operating procedures (SOPs) that help guide the entire process must be written and approved.

Analytical techniques for cGMP compliance

Complying with cGMP is an ongoing commitment that requires continuous monitoring and staying informed about changing regulations and technological advancements. Here are some of the most important techniques to monitor cGMP compliance:

• Method validation. Rigorous testing, validation and verification are essential to validate methods. That includes monitoring and tracking parameters such as accuracy, precision, specificity, linearity and robustness. Techniques such as high-performance liquid chromatography (HPLC), mass spectrometry (MS) and enzyme-linked immunosorbent assay (ELISA) are commonly used for method validation. ICH Q2(R2) is a commonly used method for validating tests for analytical procedures
• Quality control (QC) testing. QC testing helps ensure that raw materials, intermediates, and final products meet specifications. Gel electrophoresis, spectrophotometry, potency assays, and other analytical techniques can be used for QC testing
• Stability studies. Biopharmaceutical products must be tested to monitor stability and assess their shelf life and degradation patterns. Techniques such as forced degradation studies, accelerated stability testing, and real-time stability studies can be used
• Process monitoring. Critical process parameters must be monitored during biopharmaceutical production. Techniques such as liquid chromatography-mass spectrometry (LC-MS), capillary electrophoresis (CE), and biological assays can help track product quality during manufacturing
• Cleaning validation . It is essential to ensure any equipment used in bioprocessing is sufficiently clean to prevent cross-contamination. Among the techniques used to measure cleanliness are total organic carbon (TOC) analysis, HPLC, and FTIR for residue analysis. For more information on cleaning validation guidelines, refer to Guide: Cleaning Validation Lifecycle - Applications, Methods, & Controls | ISPE | International Society for Pharmaceutical Engineering
• Documentation and data integrity. Compliance with cGMP requires proper documentation of analytical data. Electronic laboratory notebooks (ELNs) and audit trails help maintain data integrity and meet documentation requirements
• Risk assessment and management. Techniques such as failure mode and effects analysis (FMEA) and criticality assessments can help identify and mitigate risks associated with analytical processes

Common challenges of cGMP

While cGMP is well-established in the biopharmaceuticals industry, it continues to present challenges as it evolves and changes. Among the challenges are balancing supply and demand, maintaining sustainability, allocating resources effectively and staying compliant with evolving regulations. Here is a closer look at some of those challenges:

Supply and demand

Outsourcing biopharmaceutical development and manufacturing has been increasing for several years. Many small and virtual biotechnology companies now rely entirely on outsourcing for development and production activities.

The COVID-19 pandemic escalated demand for certain drugs at an unprecedented rate. Regular booster vaccinations further increased this need for manufacturing support. Supply chain disruptions, worker isolations and prioritizing materials such as glass vials for vaccine production led to delays and shortages in the consumables needed for biopharma manufacturing.

Biopharmaceutical manufacturers can help prepare for supply chain challenges by accurately predicting needs and supply, maintaining higher inventory levels and qualifying alternate suppliers.

Sustainable sourcing

Companies in all industries are under increasing pressure for sustainable sourcing, and the biopharmaceutical industry is no different. In response to those demands, companies focus on climate change and other environmental issues, social aspects, such as human rights and ethics, and potential economic impacts.

Among the things biopharma manufacturers can do to meet sustainability challenges while staying compliant with cGMP are:

• Sustainable sourcing, including:

o Collaborating with suppliers to ensure sustainable sourcing of raw materials.

o Evaluating supply chains for their environmental impact.

o Prioritizing eco-friendly materials by choosing materials with a lower environmental footprint or using recyclable or biodegradable packaging materials.

• Increase energy efficiency and green practices by:

o Optimizing processes, including energy-efficient manufacturing processes. Use advanced technology to reduce energy consumption.

o Use renewable energy sources. Explore renewable energy options for powering facilities, such as solar or wind.

• Minimize waste generation by reusing, recycling or repurposing materials. Implement waste management practices that align with sustainability goals.

Other solutions for sustainable sources include assessing the lifecycle of products , designing products with sustainability in mind and collaborating with others in the industry.

Resource constraints

Some biopharmaceutical companies, particularly smaller companies, face resource constraints on financial investment, skilled personnel and time needed to comply with cGMP and other regulatory affairs.

Stringent quality control and assurance

Meeting cGMP standards demands rigorous quality control and assurance processes. It can be challenging for smaller companies to dedicate the resources needed to monitor and ensure consistent product quality throughout manufacturing.

Data integrity and security

Biopharmaceutical manufacturers handle large amounts of data about product development, production and quality control. That’s why maintaining data integrity and security at all times is critical. Companies must do everything possible to protect data accuracy and prevent unauthorized access or cyber-attacks.

Global management

Operating in global markets requires managing regulations across different regions and countries. Biopharma companies must be able to navigate different requirements and standards while also maintaining cGMP compliance.

Rapid technological advancements

The biopharmaceutical industry continually adopts new research, manufacturing, analytics and quality control technology. Companies must be able to integrate new technology and techniques into their operations while they continue to adhere to cGMP standards.

The future of cGMP

Digital technology will drive transformative changes in the biopharmaceutical industry. Digitalization, personalized medicine, collaboration and other technological advancements will shape the future of drug development and manufacturing.

Here are some future trends to expect in cGMP for the biopharma industry:

• Digital transformation and analytics will significantly help biopharma companies improve research and manufacturing operations. Digital twins — real-time virtual versions of physical processes — allow companies to balance supply and demand, optimize production planning and improve scheduling. Automation, line sensing and augmented reality will help human operators achieve productivity gains. Finally, advanced analytics models will let companies predict and mitigate risks, help ensure cGMP compliance and maximize product quality.
• Personalized medicine will likely drive new cGMP regulations to address the unique challenges of producing smaller, more targeted batches of drugs tailored to specific patients.
• More biopharma companies will integrate their research and production facilities in collaborative spaces and hybrid models to foster innovation and efficiency. That shift will include environments and operations covered by cGMP.
• Technology in clinical research. The biopharma industry is finding new ways to apply technology in clinical research. Areas to watch include expanding trials to cover diverse populations, improving drug safety and enhancing clinical research methodologies.
• Global collaboration and innovation. Some of the most important biopharmaceutical developments in recent years have come from countries other than the United States. Global collaborations play an increasing role in shaping the industry’s future.

Learn More

Learn more about the critical role cGMP chemicals and single-use technologies can play in cell & gene therapy manufacturing. Find out how Avantor can help biopharmaceutical researchers and manufacturers comply with cGMP regulations here.