Pharmaceutical Inspections and Compliance
Current Good Manufacturing Practice (CGMP) Inspections and Compliance
Inspections Help Ensure Drug Safety and Quality
FDA works to ensure the medications that are available to hospitals, health systems and patients are safe, effective and of high quality. For application products, typically prescription drugs, FDA’s approval process is the first step. FDA’s drug application approval includes assessing the manufacturing process and the facility, including information the agency gained through inspections or alternative tools, to ensure the proposed manufacturing process can be performed in compliance with applicable standards and produce high-quality drugs.
In addition, FDA oversees the safety and quality of medications that are not marketed under an approved application, including over-the-counter monograph and compounded drugs.
More on how FDA Evaluates and Ensures Compliance:
All Drugs Manufactured for the U.S. Market Must Meet FDA's Rigorous Standards
FDA's Data Dashboard provides detailed information about FDA’s inspection, compliance, recall and import actions from 2009 to present.
FDA monitors drugs on the market to help assure they meet FDA requirements for safety and quality regardless of whether they are an application drug. All drugs manufactured for the U.S. market, whether manufactured domestically or abroad, must meet the same rigorous standards.
It is the industry’s responsibility to comply with the law regarding drug safety and quality. Key requirements for drug manufacturing quality include relevant provisions of the FD&C Act and FDA’s current good manufacturing practice (CGMP) regulations.
FDA's CGMP Requirements Keep Consumers and Patients Safe
CGMP requirements were purposefully engineered with multilayered processes, controls and quality oversight that are designed to produce high quality drugs and to detect and quickly mitigate potential issues before harm to patients or consumers occurs. When properly implemented, the requirements help ensure drugs are safe, effective and meet regulatory standards.
One way FDA works to ensure drug manufacturers comply with CGMP requirements is through inspections. The information below explains the actions FDA takes to accomplish this goal through CGMP inspections that evaluate drug manufacturers’ compliance with CGMP requirements and the actions that can be taken if those manufacturers fail to meet regulatory standards.
View the webinar on understanding FDA inspections and data for more information.
How FDA Evaluates and Ensures Compliance
For postmarket inspections, each year FDA prioritizes its surveillance inspections using a risk-based model. The frequency at which a facility is prioritized for inspection is based on multiple risk factors (although being selected for an inspection does not necessarily signal a quality issue). Additionally, FDA can inspect facilities on a for-cause basis if information warrants it.
Most manufacturers comply with CGMP requirements. In fact, more than 90% of inspections found facilities to have acceptable CGMP compliance.
When FDA investigators observe issues during an inspection, they use Form FDA 483 to document their observations related to CGMP compliance at the conclusion of the inspection. A Form FDA 483 does not constitute a final agency determination of whether any condition violates CGMP. A company generally has 15 business days to provide FDA with a voluntary response to the Form FDA 483.
FDA reviews the following information once an inspection is completed:
- Form FDA 483, if issued
- the establishment inspection report developed by the investigator(s)
- evidence collected during the inspection or via other agency activity
- the company’s response to the Form FDA 483 (if provided to FDA), including plans for corrective actions
- other information as appropriate
During the compliance review, the agency also considers:
- requirements outlined in FDA regulations
- technical standards
- scientific consultations from across the agency and literature
- profile of the manufacturing facility and the drug(s) they produce
- risk of the quality deviations based on the potential for patient or consumer harm
FDA classifies inspections based on a company’s state of compliance as acceptable or unacceptable with respect to CGMP requirements:
- No action indicated (NAI) classification indicates a facility is in an acceptable state of compliance. The facility, usually, was not issued a Form FDA 483 at the conclusion of the inspection.
- Voluntary action indicated (VAI) classification indicates the inspection found objectionable conditions or practices but the agency has determined the facility can voluntarily correct its deficiencies and will not recommend any action. Usually, the facility was issued a Form FDA 483 at the conclusion of the inspection.
- Official action indicated (OAI) classification indicates a facility is in an unacceptable state of compliance.
FDA strives to complete its CGMP classification of human drug facility inspections within 90 days of the end of the inspection. The agency sends the facility a letter with the classification (examples: NAI, VAI and OAI letters) and generally posts the classification to the data dashboard.
The facility-specific data dashboard contains information on surveillance and for-cause inspections for drugs, biologics and other medical products dating back to 2009, as well as data on a facility’s inspection history, including warning letters.
Additionally, for facilities with an OAI-classified CGMP inspections, FDA may withhold:
- approval of any pending drug applications that list the facility
- export certificates for drugs intended for distribution outside of the U.S.
- CGMP declarations for drugs intended for distribution outside of the U.S.
Government purchasing contracts may also be adversely impacted by an OAI classified inspection.
Generally, FDA will only change an OAI inspection classification after a company implements comprehensive corrective and preventive actions that are verified through an onsite follow-up FDA inspection.
FDA uses a robust set of tools to promote prompt voluntary compliance with CGMP requirements and to protect patients and consumers from poor quality drugs. This gives the facility an opportunity to take voluntary corrective actions and work towards sustainable compliance. Examples include:
- issuing a warning letter to a facility to notify a firm of federal law violations, and recommend a facility allocate appropriate resources to fully correct the violations and prevent their recurrence
- issuing an untitled letter for CGMP-related issues, which are not necessarily posted to FDA.gov
- having a regulatory meeting between company leadership and FDA when the agency wants to conduct a detailed technical discussion with the company
- recommending or requesting a drug recall
- placing a company on import alert to help stop their drugs from entering the U.S. market. FDA uses import alert 66-40 and others for CGMP-related concerns
FDA takes a risk-based approach to its regulatory activities taking into account medical need, risk of shortage and ability to assure drug quality.
The agency may take additional action brought in federal court by the Department of Justice on behalf of FDA if a facility fails to address CGMP violations, such as:
- injunctions, including consent decrees, which can shut down a facility until it complies with CGMP requirements
- seizures of violative drugs in the domestic supply chain from a company or warehouse
- criminal prosecution
Additionally, when we become aware of drugs that may present a safety hazard or other health risk to consumers, we may issue public statements, such as a press release or an alert, to notify health care practitioners and the public regarding such drugs as part of our public health mission.
More Information
ORA Frequently Requested or Proactively Posted Compliance Records: Search publicly available Form FDA 483 inspection findings and other correspondence to FDA-regulated companies located within the U.S.
CDER Frequently Requested or Proactively Posted Compliance Records: Search for publicly available Form FDA 483 inspection findings, untitled letters and other correspondence to FDA-regulated companies located within or outside of the U.S.