GMP Vs. cGMP: What Is The Difference?
Many who participate in the manufacturing of medical products may already be familiar with the concept of GMP, those initially delving into the industry for the first time need a primer.
This article provides some background on GMP, which stands for “Good Manufacturing Practices,” and why it is important for new initiates to work with a GMP consulting firm to ensure that the system conforms to the current understanding of GMP, known as “cGMP,” since the standards evolve over time as technology and business processes continually evolve.
What Is GMP?
In the United States, GMP for medical products is defined in separate FDA regulations. For Pharmaceutical products, the requirements are outlined in 21 CFR 210/211, and for medical devices, the requirements are spelled out in 21 CFR 820.
These regulations are intended to ensure that a product meets defined quality standards to prevent negative consequences to public health, should the medical product be introduced into interstate commerce. Similar GMP regulations and standards apply throughout worldwide jurisdictions, but for the purposes of this article, we will focus on the U.S.
GMP Requirements
For pharmaceuticals, GMP, has distinct requirements, beginning with the need for a Quality Unit, whose responsibility is to ensure that every batch of product is controlled, reviewed, tested and released according to specified criteria and that no batch of nonconforming product is released.
Requirements covered in 210/211 include training, cleanliness, design of manufacturing equipment, laboratory work, purchasing controls, requirements for investigation of discrepancies, design of container/closures, and drug labeling requirements.
Requirement Implementation
It is up to the firm to identify processes and procedures to define exactly how all the requirements are implemented, and to implement them. For this reason, startup cGMP manufacturers need to work with an experienced consultant.
On the medical device side, the requirements become even murkier because medical devices have a huge range of designs, intended uses, indications for use, and parameters, with mechanical devices ranging from X-ray machines to pulse oximeters to in vitro blood analyzers, and therapeutic devices ranging from pacemakers to wheelchairs, to bandages.
The Quality System Regulation
For this reason, 21 CFR 820 is called, “The Quality System Regulation,” and is nonspecific as to how the product is made, and focuses on the way that an organization is managed so that it properly designs the device to be free from defects, properly trains people to operate within the boundaries of accepted practice, and has a quality management system to patrol the safety and identify and correct problems before they have an opportunity to cause harm.
So, What Is cGMP?
Inherent in GMP is cGMP, which stands for “current Good Manufacturing Practices.” As the nation fights one public health crisis to the next, an evolving understanding of what constitutes GMP evolves as well.
One telling example is the requirements for validation, which is only briefly discussed in 21 CFR 820, and not discussed at all within 21 CFR 210/211, but this is definitely a requirement.
FDA Validation Requirement
The FDA implemented a requirement for validation when it was found that injectable pharmaceutical products were causing hospital-acquired infections, due to improperly sterilized product.
From that point on, the FDA required companies to validate that the sterilization methods were effective, and from there, the FDA expects all critical operations to be validated, such as laboratory tests that substantiate SQUIPP (Safety, Quality, Identity, Potency, and Purity of product).
This carries down to the instrumentation that performs the laboratory tests, as well as to the machinery used for manufacturing the medical product, since it is understood that an operation cannot be consistently executed if the equipment and materials for its completion are not fully operational.
FDA Guidance Documents
Current GMP practices are more fully documented in FDA Guidance Documents. Do not be fooled by the verbiage that states, “Not for Implementation, Contains Non-Binding Recommendations.”
This verbiage, which implies that the document is a mere suggestion, is only saying that the FDA is defining one method by which to produce the discussed outcome. If a company is found to lack the desired outcome in its GMP process, the FDA will find the company out of compliance with current GMPs.
Does The FDA Certify Facilities Are GMP?
Another question that comes up from the uninitiated is whether the FDA certifies that a facility is GMP, and that answer is, “No.” The FDA does perform inspections and will confine its conclusions only to the inspection itself.
Inspection Classifications
The three inspection classifications, NAI (No Action Indicated – i.e. “passing” inspection) VAI (Voluntary Action Indicated – i.e., “Fail-Firm Needs to Make Corrections”) and OAI (Official Action Indicated – i.e. “Fail-FDA Enforcement Required”) are not permanent dispositions of a company, and a company that passes its inspection this year may fall out of compliance and become a bad actor three years hence.
However, options are available for companies seeking a GMP certification, it is just understood that the FDA does not issue the certification.
How To Obtain GMP Certifications
ISO offers certification for medical devices (ISO 13485) cosmetics GMP (ISO 22716) and certification for laboratories (ISO 17025). Pharmaceutical GMPs do not have a specific ISO certification, but certification under ISO 13485, 17025, or ISO 9001, can carry authority with a pharmaceutical manufacturer’s customer base. Furthermore, other certifying bodies can evaluate a pharmaceutical company’s supply chain, or other operations that can impact product quality to the end-customer (patient).
A newcomer to GMP would want to work with a consultant to select the appropriate certification, and then continue to work with a consultant to implement the processes and procedures necessary to facilitate implementation.
Meeting cGMP Requirements
Important to GMP and cGMP is a process to sustain and continually improve the system so that something that is cGMP today continues to meet cGMP in the future. Key to this is a robust internal auditing and CAPA (Corrective Action/Preventive Action) process, which feeds into Management Review, so executives apply appropriate resources toward focused improvements that fuel ongoing cGMP compliance. A robust CAPA process is the Ounce of Prevention that is worth the Pound of Cure which is applied if the FDA finds an inspectional nonconformance.
Do You Need GMP Consultants?
If a company lacks experienced auditors and CAPA experts on staff, it is important to work with a Consultant to ensure that these processes are implemented correctly to effectively close the loop whenever a nonconformity has the potential to destroy the company’s cGMP status.
If you have more question about GMP Consulting, GMP meaning, what is GMP, medical GMP, or GMP vs. cGMP, feel free to drop us a line and we will do what we can to provide the answers you need to get your cGMP operation up and running as quickly and compliantly as possible.