When a company is issued an FDA 482 Notice of Inspection and FDA 483 Warning Letter, it must prepare and be ready for the long adventure it will have to take with the FDA. Receiving an FDA 482 means an Auditor is granted authorization from the FDA to inspect your facilities, equipment, manufacturing line, and Quality Management System (QMS). The Auditor may verify that your SOPs reflect current compliance standards and satisfy regulatory requirements, and ensure you are abiding by the SOPs you have put in place. By inspecting many aspects of development, manufacturing, and quality operations, they are ensuring that the framework and execution of the business is meeting the predicate rules issued in the respective Code of Federal Regulations (CFR).
Once the inspection is concluded, and if the inspector found any violation of regulatory requirements that may lead to a compromise of product quality, patient safety, or data integrity, an inspection report along with an FDA Form 483 or Observations of the inspection may be issued. In the event of no findings or deviations during the audit, only an inspection report is given without any FDA Form 483. If there is a serious concern regarding practices or compliance, a warning letter may be issued along with the FDA Form 483. A warning letter may also be issued if there is no response or action taken to remediate the initial findings. The warning letter is an escalation and serves as a call to urgency for the recipient. Recipients must respond within two weeks with a written acknowledgement of the report and a Corrective and Preventive Action Plan (CAPA). However, one should know that there are steps you can take to make this journey with the FDA as frictionless as possible!
The process of a Lifesciences Manufacturer undergoing FDA Inspections is analogous to explorers preparing for a risky expedition into vast uncharted lands. When an FDA audit starts, the business doesn't know exactly what documents and processes will be reviewed. They know where they need to go, but don’t know exactly how they are getting there. There are many different requirements and regulations that the organization may be evaluated against; just as on an expedition, you are not sure exactly which skills will be tested. Of course, every great adventure would benefit from having a guide or leader that has scouted out different routes, and can make sure everyone has everything they need, and can answer questions as well as make critical decisions throughout the trip. The Quality Assurance (QA) team should lead the way with organizing all documentation, making sure processes meet expectations and regulations, and ensuring that all SOPs are being adhered to and observed.
As the explorers make their way through their adventure, they rely on maps, compasses and other navigational tools to stay on course and not get lost. They’ll also need the best gear and equipment to survive the trip in one piece. Similarly, your Quality Assurance team should be well-acquainted with the various regulations that are applicable to your company and Manufacturing floor. The team should ensure that manufacturing processes and documentation are adhering to SOPs and all applicable regulatory expectations. The IT/QA team can help by implementing various software tools (QMS, ALM) that automate the traceability process within their documentation.
Climbing steep mountains, crossing through treacherous landscapes, and braving frigid conditions, the adventurers make their way towards their destination. They've long prepared for this challenging journey with mock expeditions and rigorous training and exercise. Similarly, your Quality team should conduct mock internal audits to simulate a real FDA inspection. This way, the entire company is prepared and ready for when the real thing happens. Routine training should be a regular practice so that everyone is kept up to date with current procedures and the best manufacturing practices. Seeking out regulatory experts for guidance can help a company be better prepared for audits and inspections.
The Team of explorers finally make it to their destination. Reflecting on their journey, they realize and assess the various mistakes made. Maybe one member was ill-equipped and brought the wrong type of boots, or an alternative route was discovered that could have made the trip easier. They document their mistakes and come up with a detailed plan on how to implement the lessons learned to make their next trip safer and easier. Likewise, after the FDA completes their inspection of your company, any issues they may have found would need to be addressed in a quality event such as a Corrective and Preventive Action Plan (CAPA).
The CAPA(s) should start by providing an overview of the inspection, with details like the company name, date of inspection, and other background information. In addition, the CAPA(s) should include key details of all the observations, deviations, and issues found. An in-depth analysis of the root cause of these issues should be documented. Pinpointing the reason behind the deviations will help to provide a clear explanation and solution for the problem. All Teams responsible for the deviations should also be noted. Having procedures with clear roles and responsibilities helps to ensure that no task is left unaccounted for. Finaly, a detailed plan for how to remediate the issue and prevent it in the future should be laid out, with steps and timelines for estimated completion. The CAPA should also describe how the company will monitor and document the issue during the fixing stage. Include any testing and inspection strategies used to verify that the issues and deviations are truly resolved.
Having a clean inspection record with the FDA is very important for Lifesciences Manufacturers. This helps to build a positive reputation for the company and trust with potential and existing customers and partners. Preparing for audits ahead of time is one of the most important strategic moves any business can make. But remember, when embarking on adventures of risk and discovery, it's important to utilize the expertise and knowledge of someone who's done it all before.
Here at Compliance Group, we’re committed to helping you alongside your journey with the FDA by preparing tailored plans, training, and solutions so that you can make it to the finish line. Are you ready to take the first step on your journey? Contact us at info@complianceg.com.
