GLP vs. GMP vs. GxP - What's the Difference?

October 19, 2020

The pharmaceutical and medical instrumentation industries are, of course, very heavily regulated. One mistake at any stage of the process, from development to distribution, can have disastrous consequences. In fact, it was a manufacturing failure that resulted in the passing of the Food, Drug, and Cosmetics Act in 1938, which defined much of how the Food and Drug Administration (FDA) operates today. Over the years, the FDA and other organizations like it around the world, such as the World Health Organization (WHO), have responded to failures of process with a variety of new regulations and criteria for compliance.

At the core of these regulations are a set of processes and guidelines known collectively as “good practices” or “GxP”. There are several iterations of good practices that govern different phases of the discovery to distribution pipeline and understanding the differences between them can be somewhat confusing. In this article, we explore the differences between the most common good practice guidelines and attempt to shed some clarity on the matter.

What are Good Practices?

Good practices in the pharmaceutical industry arose as an attempt by regulators to standardize the quality of research and manufacturing coming from different laboratories. They do not pertain to the scientific method in which research is conducted, but rather to the conditions under which it is conducted and the documentation of those conditions. Collectively, they serve as a quality assurance system that is designed to protect against failures and make them easily auditable when they do occur.

The Difference Between GMP and GxP

GMP, or Good Manufacturing Practice, is perhaps the most commonly used and recognizable of the good practice standards. GMP refers to the entire process of manufacturing from the point that a drug receives FDA approval to the point that it goes into distribution. Representing a combination of different standards that pertain to the training of personnel, process validation, records management, equipment maintenance, and more.

GxP, on the other hand, does not refer to a single set of standards or guidelines for a specific portion of the pharmaceutical pipeline. Instead, as we briefly touched on above, GxP is shorthand for all the various sets of good practice standards and guidelines and is often used in place of GMP. In the same way that all salmon are fish, but not all fish are salmon, all good practices can be referred to as GxP, but one set of good practices will not be identical to another.

GMP

At the core of GMP are principles that are fundamental to all GxP. The details of implementation differ from one set of good practices to the next, but the core concept of establishing processes and properly documenting actions taken remains consistent. The details of the regulations involved, like the FDA’s 21 CFR, are very complex. Thankfully though, there are five simple principles that make up the core of GMP:

  • People

    • Any manufacturing facility should have clearly defined roles and responsibilities and adequately trained personnel.

  • Procedures

    • All manufacturing procedures should be properly documented at each stage of the process so that deviations can be investigated fully if necessary.

  • Products

    • This refers to the proper documentation of specifications for raw materials or components, the documenting of batch records, and the establishing of correct methods for manufacturing and testing.

  • Premises and equipment

    • All premises should be properly designed to allow for effective cleaning and to prevent cross-contamination of materials. Equipment should be regularly validated and calibrated, with records of both.

  • Processes

    • Every process involved in both the manufacturing of the drug or instrumentation and in the documentation of compliance should be clearly recorded and made available to all personnel.

GxP

As mentioned above, GxP does not have a specific set of guidelines in the same way that GMP or GLP does. The difference between GxP and GMP is one refers to the broader system of quality assurance, while the other refers to the details of specific regulation and standards. However, with that being said, the five P’s listed above do broadly apply to all of the sets of good practices housed within GxP.

The Difference Between GLP and GMP

While GMP covers a very large phase of the manufacturing process, one that is particularly crucial because it generally occurs after a drug or product has received FDA approval, Good Laboratory Practice (GLP) focuses on a much more specific segment of the pharmaceutical pipeline. Specifically, GLP refers to the procedures and standards to be followed during non-clinical trials - a crucial step on the road to FDA approval.

As with most GxP, the five P’s of people, procedures, products, premises, and equipment all still apply to GLP. However, there are some key specifics within each of those that are unique to GLP and should be explored in order to understand the difference between GMP and GLP:

  • Because GLP often refers to facilities conducting animal testing, GLP-compliant facilities should have adequate space and trained personnel for the humane handling of animals.

  • Due to GLP covering research and testing rather than manufacturing, GLP requires that each individual study have a pre-approved study plan with all stages of the study, and all personnel involved, clearly documents.

  • GLP requires that a single individual with appropriate training and certifications be appointed as the head of the study.

  • The testing methods used in the study should be suitably validated.

The Difference Between GLP and GCP

Where GLP refers specifically to studies that are classified as non-clinical or pre-clinical, Good Clinical Practice (GCP) refers specifically to clinical trials. Clinical trials are any trials that involve human subjects. While all stages of the development and manufacturing process are critical, naturally the stakes are higher when human subjects become involved in a study. Clinical studies will generally be the last phase of research before FDA approval for a product meant for use in the human population.

The main focus of GCP, therefore, is ensuring the safety of study participants and making sure that a product only moves into human trials once it is absolutely necessary. This introduces the component of ethics to GCP, which is not something that affects other good practices. As with GLP, the fundamentals of GxP still apply, but there are several key differences that are specific to GCP:

  • GCP introduces human subjects, so their civil, human, and privacy rights must be upheld throughout the trial. All actions taken to ensure this must be fully documented.

  • Actions must be taken at every step of the study to minimize risk for human subjects. All of these should be included in a study plan and documented as they are performed.

  • Informed consent must be provided by each study participant. This requires the education of the participants on the nature of the study and their role in it, their rights as participants, and the documenting of both their understanding of the above and their consent to participate.

  • Non-clinical trials must be conducted first and the data must support the need for clinical trials.

  • Medical care must be provided to participants throughout by a qualified physician who is independent to the trial itself.

Summary

There are multiple stages to the pharmaceutical and medical instrumentation manufacturing and distribution process. Each one is governed by one or more sets of regulations, each of which requires adherence to a set of “good practices” to meet compliance. These practices all follow a set of core principles designed to protect the consistency and quality of both the products or studies themselves and the data and records used to prove compliance.

However, each subset of GxP, whether it be GMP, GLP, GCP, or another, has differences in the specifics of how they are implemented and what they pertain to. Understanding the core principles of GxP will go a long way as a foundation for understanding all good practices, but ultimately meeting compliance means following regulation and guidelines to the letter. The easiest way to do that is to implement compliance-ready systems that can take the guesswork out of the equation for you and protect against human error.

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