Good Manufacturing Practices: When Do They Apply?

When developing a new drug, clinical project teams often struggle to know when current good manufacturing practices (cGMP) regulations apply. In this article, we will discuss the U.S. Food and Drug Administration’s (FDA) expectations for applying cGMP to investigational drugs.

FDA Regulations and Guidance

GMP is a system for ensuring drug products are safe, consistently produced, and controlled according to quality standards. It’s designed to minimize the risks involved in any pharmaceutical production that cannot be eliminated through testing the final product. The FDA cGMP regulations for drugs are published in 21 CFR 210/211. Generally, U.S. law exempts drugs used for Phase I studies from compliance with 21 CFR 210/211; however, it does not exempt:

• An investigational drug for use in a Phase I study once it is available for use in a Phase II or Phase III study
• A drug lawfully marketed as a monograph drug or by an FDA-approved market application

There is additional FDA guidance for Phase I clinical trials using cGMP for investigational drugs. According to 21 CFR 210.2(c), the cGMP regulations formally apply for drugs used in Phase II/III studies.

cGMP Implementation

There are many benefits to implementing cGMP as early as possible in drug development. Beyond protecting participant safety, cGMP provides a foundation for a sound quality management system (QMS). Adopting a QMS early allows processes to gradually integrate, which benefits research staff.

Additionally, early adoption ensures tighter controls, builds organization-wide quality, and minimizes noncompliance risks. For organizations moving toward commercialization, this helps assure a successful pre-approval inspection.

However, cGMP requirements can be difficult to understand. In an effort to clarify, FDA adopted the International Council for Harmonization (ICH) of Technical Requirements for Pharmaceuticals for Human Use:

• Q8 Pharmaceutical Development
• Q9 Quality Risk Management
• Q10 Pharmaceutical Quality System

These guidelines assist sponsors when developing a QMS. For sponsors who are also manufacturers, their QMS should address all the cGMP’s requirements. Other sponsors may want to outsource their investigational drug manufacturing. In doing so, their contracted vendors must prove their QMS is complete with appropriate facilities, systems, and fit-for-purpose processes.

In this scenario, the sponsor’s QMS should:

• Address management commitment to quality
• Include a quality policy
• Have defined processes for:
  • Resource management, including employee role based and GMP training
  • Internal communication
  • Management review
  • Document, data, and records management
  • Vendor lifecycle management
  • Product lifecycle management

Complying with cGMP throughout the drug development process helps ensure quality investigational products. This also helps protect clinical trial participant safety and reduces variability due to poor quality. Even with outsourced manufacturing processing, sponsors are still responsible for meeting cGMP requirements.

Note: This article was originally published July 15, 2020, and has been updated to include new and clarifying information.

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