Successful Audits in API Manufacturing Begin and End with Ongoing Quality Processes

The Steps To Ensure Smooth Sailing with FDA Inspections and Internal Audits

by | Aug 31, 2021 | API Manufacturing, Audits, Blog, CDMO, FDA

API manufacturers maintaining compliance to current Good Manufacturing Practices (cGMP) understand the critical role audits play.  They help them stay on track, uncovering areas where there could be problems and helping them ensure that the pharmaceutical ingredients they produce are manufactured under stringent protocols, using advanced equipment in order to increase their chances for becoming safe and effective drugs for consumers.  While there are several different types of audits, or inspections, that are conducted: from sponsor audits and supplier audits, to internal and FDA audits, we’ll focus on the last two, which may be the most common types.

FDA Audits

The Food and Drug Administration (FDA) conducts inspections and assessments of regulated facilities to determine their compliance with applicable laws and regulations. It typically conducts four different types: Pre-approval, post-approval, surveillance and For-Cause inspections, which occur because of a specific issue that has come to the attention of the FDA.

Whether conducted on a routine basis, or as the final assessment prior to drug approval, the FDA inspection usually is hosted by the API manufacturer’s  Quality Assurance (QA) team.

Sometimes, requirements of an FDA inspection can be unexpected (designed to keep you on your toes), but there are typically some general processes and steps that are standard practice with all FDA inspections.

Review of the application.  A Contract Development & Manufacturing Organization (CDMO) or another API manufacturer that wants to commercialize a drug product submits an application and the FDA evaluates it and schedules an inspection, often providing no advance warning.

Thorough inspection of critical areas. FDA inspectors, or “investigators,” usually are  chemistry experts, microbiology experts, facility experts and formulation experts. They look for quality in four key areas: facilities & equipment, materials, production, packaging & labeling and laboratory controls. They’re looking to see that a manufacturer is operating in accordance with GMP guidelines.

Issuance of Form 482. When the inspection happens, the investigators will give you a Form 482 (notice of inspection), then, during the course of the inspection, if there are any significant issues or non-compliances observed, they will be documented on Form 483. This form will identify the issue that the CDMO needs to address and gives it an opportunity to appeal it.

Today, while FDA inspections are more rigorous, and can take up to a few weeks, as opposed to 2-4 days, the FDA often will not require frequent inspections prior to approvals, if there is a good history of passed inspections.

When the FDA investigators come knocking on the door, it’s good to be well prepared. Front office staff should be well-versed in the necessary protocols and practices. They should request proper identification and follow standard operating procedures (SOPs) for visitors entering the plant, and show them to the senior official within the company. Since many types of documentation may be required, the CDMO should be able to easily produce documented customer complaints, training records and preventative maintenance programs.

Internal Audits

Companies should be always on the ready for an FDA inspection, and one of the ways they can accomplish this is with an internal audit, which provides a check-up of sorts of SOPs, critical systems and best practices. They provide an additional layer of checks and balances that can go a long way to nipping problems in the bud. By starting out with a solid audit plan, appointing key people to the task and quickly acting upon issues identified, CDMOs can ensure they pass with flying colors when audited by the FDA or sponsors. 


An internal audit should address routine facility and personnel behaviors, and in-depth critical system reviews, such as: preventative maintenance, customer complaints, deviation investigations, and comprehensive process surveys.

Internal audits can identify areas for improvement that can proactively be addressed to help ensure a successful regulatory inspection. These audits can be performed by company personnel, but are often more productive when they involve an independent consultant who can see things from a different perspective and offer new ideas.

Best Practices to Ensure Audit Success

Whether conducting an internal audit or hosting an FDA audit, there are key best practices that can be employed to ensure you’re ready to pass with flying colors. 

Offer sustained training. The key to success is well-trained staff. Regular and consistent training of the activities regularly performed by each department should take place. It’s often a good idea to have a routine gap assessment, which measures each person’s level of current training against a predetermined standard or matrix of responsibilities. Training sessions also can encourage employees to offer suggestions for improvements to the systems they use and support.

Establish KPIs. Regular analysis of data from quality systems is critical to finding and correcting hidden or subtle systemic weakness. For this to be effective, a CDMO should identify quantifiable metrics or key performance indicators (KPI) for the critical systems and processes.

Define and update SOPs. While SOPs help to make sure that tried and true processes are in place throughout development and manufacturing, they should be revisited from time to time to remain current with changing situations, new regulations and cGMP.

Appoint an internal auditor.  There should be one person whose central role is to manage audits and that typically is the Quality Assurance manager. He/she should set the direction and take the lead in audits, reporting findings and results to senior management.

There’s no question that both internal and FDA audits take time and resources to be prepared and to nail them. But once an audit is complete, CDMOs should not stop there. Any issues that are uncovered should be addressed immediately with preventative and corrective actions. Whether this means conducting new training sessions, changing SOPs or upgrading equipment, a sound audit provides the opportunity for continuous improvement.

For more insights check out: APIs: The Superheroes of Drug Development; The Role of ICH and How To Meet Quality Guidelines; or Avoiding FDA Drug Rescissions.