Understanding Current Good Manufacturing Practices (cGMP) in the pharmaceutical industry can, at first, seem like trying to pick up a handful of water. It's a broad concept that is hard to hold together.
The FDA currently offers 34 distinct final guidance documents for cGMP in the pharmaceutical industry, which include requirements for process validation, data integrity, quality metrics, and countless other topics.
The FDA's definition of cGMP is accurate. The information included in a final guidance document, which typically ranges from 10-30 pages long, is comprehensive but that doesn't mean it's clear. Reading cGMP guidelines provided by the regulatory agency can leave you with a lot of questions.
If you're wondering why "current" good manufacturing practices and why "quality by design" matters, you're not alone. In this post, we'll cover the official definition for these essential guidelines in terms you can understand with insights from pharma industry experts. Read on for some extra color and context on the definition of what cGMP is, why it's important, and how to achieve compliance in your organization.
What is cGMP in the Pharmaceutical Industry?
Current good manufacturing practices are defined by the FDA as systems to assure proper design, monitoring, and control over manufacturing processes and facilities in pharma and other FDA-regulated industries. These systems are designed to help organizations assure drug products are the correct identity, strength, purity, and quality.
cGMP systems include a series of controls for quality focused operations, including:
- Management Systems
- Quality Raw Materials
- Operating Procedures
- Detecting Deviations
- Investigating Deviations
- Reliable Testing
If cGMP are followed, organizations can avoid many of the most common causes of quality failure which threaten patient safety, such as drug contamination, deviations, or mix-ups. The FDA is very clear that cGMP is designed for flexibility to provide a universal framework for the entire pharmaceutical industry. Also, the guidelines aren't a checklist; they're a set of "minimum requirements" for total quality management.
The latest cGMP was published in 2016, the Q7 Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients. This 58-page document provided some excellent updates to prior cGMP for the industry, but it also sparked more questions than it answered in the eyes of many pharmaceutical organizations. The FDA followed up with a Q&A in 2018 to clarify some of the most common questions about the latest guidance. Some of these questions are addressed here, with insights from pharma industry subject matter experts.
Why "Current" GMP?
Why is “good manufacturing practice” preceded by “current”? Does the first letter of this acronym matter?
The "c" stands for "current," reminding manufacturers that they must employ technologies and systems which are up-to-date to comply with the regulation. Systems and equipment used to prevent contamination, mixups, and errors, which may have been first-rate 20 years ago may be less than adequate by current standards.
Maud Breitbarth, Quality Audit Manager, Norgine:
Maybe you already faced an inspection, resulting in observations due to aging facilities, processes, or procedures. There are also a couple of other influencers to aging facilities. First, governmental legislation can change. Second, industry advancements and developments can also alter what is considered state-of-the-art. This evolution takes place faster than your facilities do. You've probably already experienced that the ‘c' in the cGMP status needs to be brought back into your facility, processes, or procedures and it appears to be a big hurdle to overcome.
The FDA publishes systems for "current good manufacturing practice" to emphasize the need for flexibility in total quality management. Organizations can't afford to adopt a rigid, guidelines-focused approach to total quality management (TQM), or they'll struggle to adapt when the next set of cGMP is released, or any other issue occurs which requires organizational change.
Quality management isn't a checklist, it's a moving target, and organizations must continually adapt their practices to integrate emerging knowledge, real-time data, and other sources of insight.
No Single Set of Standards
Since these best practices keep changing from time to time and the latest developments overshadow the existent ones; the FDA expects manufacturers to stay abreast of the latest regulations it passes, called cGMP, meaning "current" Good Manufacturing Practice.
GMPs and cGMPs are not a single, rigid and monolithic set of standards or rules that everyone is expected to implement in their manufacturing systems. The regulatory agencies prescribe a broad set of general principles, from which a manufacturer from particular industries has to perform at a minimum level of quality requirements, the ones appropriate to it.
It's not possible to write a universal prescription for quality in the pharmaceutical industry, especially when the industry is in an active state of change. The standards which work for a mature enterprise with an extensive portfolio of market-approved drugs aren't the right standards for a small, pharma startup with a globally distributed workforce. Organizations need to understand the cGMP and how they align with other systems for total quality management to discover an approach which eliminates risk and scales.
Related Reading: Quality vs. Compliance: These 5 Questions Will Determine Your Focus
Design Over Inspection
Anthony P. Banaszewski, Technical Director, Sonneborn, LLC:
The premise of cGMP is that the quality system is based on the principles of Quality by Design instead of Quality by Inspection.
If you’ve been in the pharmaceutical industry for a decade or more, you will recognize that “design over inspection” is a relatively new principle within the cGMP. The FDA added the principle of “Quality by Design” (QbD) in 2011, following the success of a multi-year QbD pilot program and the success of the ICH Q8, Q9, and Q10 guidelines. But what does it mean?
Quality by Design means building control into your processes, instead of relying on inspection to capture deviations or risks.
Organizations need to implement a comprehensive system for quality management or eQMS software which integrates data with operations to build quality into design and manufacturing. The QMS system should facilitate continuous risk assessment and allow leaders to update controls in real-time instead of relying on inspection, testing, or complaints to identify issues. Quality by design can save costs, facilitate organizational agility, and improve outcomes.
Benefits Outweigh the Risks
John David, Senior Quality Assurance Specialist, Kite Pharma:
The bottom line is, when the FDA enforces cGMP, they're ensuring that drugs are safe for consumers and their health benefits outweigh their risks.
From the FDA’s standpoint, very few pharmaceuticals have no risk to patient safety. Risks can occur in many forms, including:
- Harmful interactions between drugs, foods, or supplements
- Risks that a drug will not provide the expected outcome
- The chance of adverse side effects
The FDA approaches drug safety as a benefit-risk equation by continuously working on compiling and understanding data on drug efficacy and risks. These insights are collected from sources such as clinical trial data, clinical patient data, billing information, and emerging academic research. If the risks to the target population begin to outweigh benefits, the FDA may take actions, including recommending the pharma manufacturer adopt a formal strategy for Risk Management and Mitigation (REMs).
A Reliable Safeguard
Gary E Ritchie, Consultant / Director, InfraTrac, Inc:
Compared to the potential financial and safety-related consequences of noncompliance, properly implemented cGMP should not be seen as a regulatory burden, but a reliable safeguard against potentially disastrous outcomes—a point made clear in 2012 when improper compounding at the New England Compounding Pharmacy sparked an outbreak of fungal meningitis which resulted in 64 deaths, 751 injuries, and 25 counts of second-degree murder.
Tragedies such as the compounding error in New England highlight the real purpose of the FDA's cGMP. The system isn't designed to provide a rigid framework for pharma companies. Perceiving cGMP as a set of hoops to jump through is a mistake. Failure to comply can have real and devastating consequences.
Every organization should understand how the cGMP apply to their operations and how the FDA will assess this compliance. Instead of focusing on merely meeting the requirements, organizations should focus on adopting management systems which comply with FDA requirements and enhance patient safety.
Establishing Strong Systems
To follow cGMP includes creating strong quality management systems, using good quality raw materials, implementing robust operating procedures, meticulously screening and investigating product quality deviations, and maintaining reliable testing laboratories.
Put simply, to follow cGMP a company must have: Facilities that are kept in good condition; Equipment that is carefully maintained and calibrated; Employees who are qualified and fully trained and; Operating procedures that are reliable and reproducible.
In recent years, the idea of “establishing strong systems” has evolved far beyond its original scope. This cGMP principle was initially designed to require pharma manufacturers to handle their own materials testing. Today, “strong systems” includes effective partnerships with your upstream suppliers for raw materials and components.
Testing raw materials at your quality control laboratory when you receive them is no longer enough, especially if you're dealing with critical materials. Today, pharma companies need to audit their suppliers and establish effective working relationships actively. The subject of third-party risk is currently subject to a great deal of attention and discussion in the pharma industry, and it's critically important.
If bad materials are hitting your dock, your organization lacks robust systems. It's too late to implement controls upstream. As a pharma manufacturer, "strong systems" means developing a working understanding of your supplier's controls and quality management system. It also requires a great partnership and trust.
Is Your Pharma Company Quality-Driven?
The cGMP is not a management system. Instead, they're a set of principles compiled by the FDA which act as a minimum standard for operations in the pharmaceutical industry. Following the cGMP to the letter of the law can help your organization comply with FDA requirements, but it's not the most effective approach to operations.
The FDA's guidance acknowledges the role and limitations of the cGMP and encourages organizations to adopt healthy and flexible systems for total quality management to exceed these requirements. By understanding the definition and purpose of the cGMP, you can make the shift from focusing your energy and resources on compliance to become a quality-driven organization.
When it comes to cGMP, is your organization lagging, meeting the requirements, or setting the bar? To learn how you stack up against pharma industry best practices for quality and your risk of adverse findings, take a short, insightful and self-guided survey.