Good Manufacturing Practice (GMP) regulations in 21 CFR 210-211 require drug manufacturers to prove—through contemporaneous records—that people, premises, processes, and products consistently meet quality standards. FDA investigators verify compliance via audits and issue Form 483s or Warning Letters when deficiencies are found.
Table of Contents
- Definition and regulations
- The ten core GMP principles
- Common compliance gaps
- Verification methods
- FDA enforcement trends
- Benchmark your site
- FAQ
Definition and regulations
As of this spring, FDA has resumed onsite inspections. As you prepare for your next FDA inspection, you are probably wondering what investigators consider the top GMP compliance issues.
(Keep in mind, quality should be the foundation of your GMP operations. Otherwise, it becomes “compliance for the sake of compliance” to use a term often referenced by seasoned FDA investigators. But more on this later!)
The ten core GMP principles
Common compliance gaps
Investigators hone in on the following issues:
- Lack of a “well-established” data-governance plan to ensure data integrity.
- Need to review audit trails for analytical instruments and identify the critical ones.
- Ineffective use of consultants—one consultant finds no significant issues while a second uncovers several.
- A robust quality culture that filters across all organizational levels, starting with executive involvement.
Verification methods
Internal and supplier audits
Get a step-by-step walkthrough of internal, supplier, and FDA audit workflows—complete with red-flag checklist items—in the full audit guide here
Quality agreements
Dive into clause-by-clause responsibilities, change-control triggers, and dispute-resolution language—full quality-agreement guide here
Accountability and liability
See an accountability matrix mapping GMP tasks, deviation investigations, and CAPA approvals across owners, CMOs, and suppliers—roles & safeguards guide here
Benchmark your site
Need to benchmark your GMP readiness? Redica tracks every FDA Form 483 and Warning Letter worldwide—filterable by product type, site, and citation code. Book a 15-minute walkthrough to see your risk profile in real time.
Frequently Asked Questions
What does GMP stand for?
Good Manufacturing Practice.
What is the difference between GMP and cGMP?
The “c” stands for “current,” emphasizing up-to-date practices.
Why are GMP audits important?
They verify that processes, premises, and products meet quality standards.
Who is responsible for GMP compliance in contract manufacturing?
Both the contracting company and the CMO share accountability, defined in quality agreements.
What should a GMP quality agreement include?
Detailed responsibilities, documentation requirements, change control, and audit rights.
How can companies stay inspection-ready?
Maintain a risk-based QMS, run mock audits, trend deviations, and close CAPAs promptly.
Further Reading
- FDA Regulators Address Data Integrity and Lab Audit Trails
- Quality Culture Assessments and Records Request Responses
- FDA on Cross-Contamination, Sustainable Compliance, and Contract Ops
- Is Your Quality System Up to Par for Your Next FDA Inspection?
Stay on top of GMP compliance ahead of your next FDA inspection! See the most recent FDA for-cause GMP inspections involving sites manufacturing human drugs. Contact us today to learn more!
As of this spring, FDA has resumed onsite inspections. As you prepare for your next FDA inspection, you are probably wondering what investigators consider the top GMP compliance issues.
(Keep in mind, quality should be the foundation of your GMP operations. Otherwise, it becomes “compliance for the sake of compliance” to use a term often referenced by seasoned FDA investigators. But more on this later!)
Investigators Hone in on Top Compliance Issues
Last year, Redica Systems Senior GMP Quality Expert Jerry Chapman covered the inspection-focused “Ask the Regulators” session at the 2021 PDA/FDA Joint Regulatory Conference. Common issues these investigators continue to see are:
- Lack of a “well-established” data governance plan to ensure data integrity.
- Need to review the audit trails for analytical instruments and identify the ones that are critical.
- Ineffective use of consultants. One panelist mentioned cases where a consultant failed to find any significant issues while a second one found several, signifying that the first consultant was not thorough.
- A robust quality culture that filters across all levels of an organization, starting with executive involvement.
Compliance that is Sustainable
At the 2021 ISPE Annual Meeting, FDA Commander (CDR) Tara Gooen Bizjak spoke about GMP compliance issues. She explained that companies need to adopt a “sustainable compliance ” mindset. By this, she stated that companies should not only meet minimal GMP requirements but focus on “mature systems and continually operate above that bar.”
Gooen Bizjak also identified data integrity as a concern, explaining she and her colleagues continue to “see different flavors of data integrity issues.” Additionally, she pointed to increasing reliance on contract operations. Here, quality culture is essential in ensuring that quality is carried over into the GMP operations at a contract manufacturing organization (CMO).
“Sustainable compliance” was also identified as critical to quality systems by FDA Director for the Division of International Drug Quality Carmelo Rosa in a separate PDA/FDA session. He used the example of responses to 483 observations and Warning Letters. In many cases, these responses address specific inspection findings but lack a comprehensive analysis of the quality system itself.
Rosa used the example of one frequent citation–batch failure investigations. Since investigators continue to find batch failure investigation issues during inspections, it leads investigators to conclude that the quality system is lacking.
GMP Compliance Case Studies
For specific examples of recent GMP compliance issues, FDA Office of Regulatory Affairs National Drug Expert Captain Ileana Barreto-Pettit presented four in-depth case studies from recent GMP inspections conducted by the agency.
- Inadequate change management processes
- Cleaning practices that could lead to potential cross-contamination
- Discolored HEPA filters at an aseptic manufacturing site
- Contamination potential from perforated tables
This should give you a sense of the top GMP compliance issues for 2022!
Additional Resources
FDA Regulators Address Data Integrity and Lab Audit Trails
Quality Culture Assessments and Records Request Responses
FDA on Cross-Contamination, Sustainable Compliance, and Contract Ops
Is Your Quality System Up to Par for Your Next FDA Inspection?
Stay on top of GMP compliance ahead of your next FDA inspection! See the most recent FDA for-cause GMP inspections involving sites manufacturing human drugs. Contact us today to learn more!
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