FDA Inspections: What Do They Look For?

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It was a Monday morning around 8.30 am, I received a call from our Quality Assurance (QA) and Regulatory (RA) department saying we have an FDA Auditor/inspector just arrived at the front desk! I said oh… OK was it scheduled or it’s a surprise visit? They told me that the audit is a PAI that our customer has requested, according to the FDA inspector. I informed the same to my team in Analytical services and rushed to the WAR room (one of the biggest meeting rooms in our facility) where our TOP management along with the QA/RA, production, pilot plant, etc. department heads was present.

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A small introductory session happen soon after everyone gathered in the room, the auditor explained us the intent of her visit and requested a total cooperation from all of us who are the stake holders of our departments and will be actively participating during the audit. She also mentioned to be very transparent and not falsify any statements. The auditor requested a tour to the entire plant to gauge the preparation of the audit she was going to perform. The audit began and at the end of the day it ended with three FDA form 483 observations. In this article I am going to share about FDA audits and what should be expected during the audit based upon my personal experiences.
According to the Food, Drug and Cosmetic Act, “Any Registered domestic or overseas drug establishments shall be inspected by the FDA at least once every two years.” Under some conditions the inspections may be even more frequent, such as when a drug is being manufactured for the first time, if there have been previous problems validating a similar process, if production of a product or a new process is substantially different from past operations, or when a process is particularly complex. The FDA has put out the word that it is ramping up enforcement efforts, so why not be prepared and audit ready everyday!!
There is always a question in everyone’s mind that “Will the inspector just show up at the back door and sneak in for a quick look, or is it a more formal process?” You may or may not receive notice; inspectors have been known to show up unannounced and there is no requirement that they provide you with a notice. But they are not allowed to sneak in the back door for a quick look around the factory.
When the inspectors does show up, whether announced or not, they must present the FDA form 482. If this form is not presented at the beginning one must ask for it. The inspector should also show an official FDA identification for review. The form 482 clearly states what an inspector may inspect and what information is off their limits. The inspector may enter, observe, collect samples, interview employees and review any kind of records associated with the production of the regulated products. He / She will/shall not demand any access to the personal data (except for training records), any kind of financial statements of the company or any confidential research/ IP related documents.
In general the FDA inspector is at a site of inspection is to make sure that the plant/site is actively following cGMP/GMP guidelines and always be in compliance, the staff that is working in various departments is competent enough to understand the requisites of the job they are doing under the GMP guidelines. Above all everything is documented and all the documents will be presented to the inspector at the time of audit. Typically the FDA assess and audits any available process validation protocols, activities, data and information , whether or not completed and reported if there are any deficiencies according to the Investigations Operations Manual (IOM). The IOM is a FDA document which provides the primary guidance on FDA inspection policies and procedures for field investigators and inspectors.
The FDA inspection is typically seen in seven subsystems in the quality management systems practices. These seven systems are often termed as types of activities that occur during the day to day operations in any Pharmaceutical manufacturing plant/site.

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Following are the typical items that an inspector will look for during the time of audit in the Quality Management subsystem (QMS):
  • Quality Policy established by the organization
  • Management representative (MR) appointed within the QMS
  • Organization conducts management reviews on regular basis
  • Internal Audits conducted and procedures established
  • Quality plan
  • Chemical hygiene plan
  • Quality Systems procedures established
  • Facilities Design procedures and plan
  • Design inputs or requirements for devices identified
  • Design outputs or specifications for device identified
  • Design verifications/validations conducted
  • Software validation
  • Risk analysis carried out
  • Designs reviewed and transferred successfully to manufacturing
  • CAPA procedures established
  • Analytical methods implemented and or validated prior to use
  • Training
  • Statistical evaluation of the data
  • Annual product/processes performance reviews
  • Data trending
  • Investigations of root cause failures
  • Deviations both planned and unplanned with reports
  • Non-confirming product controls
  • EHS control charts
  • Customer complaints and reports
  • Product recalls and rejection reports
  • Instrumentation and equipment calibration, maintenance records
  • Manufacturing processes validation reports
  • Various software used – validation records & reports
  • Any additional information pertinent to the product audited
At the end of the audit a closeout meeting will be held the inspector/auditor/investigator will meet with the management to discuss the inspection findings. They will provide active feedback on the audit and will discuss the deficiencies. If there are no regulatory deficiencies, that will be the end of the inspection. The organization will get a written letter from the FDA documenting the inspection some time later. If the Inspector has identified regulatory deficiencies the organization will be presented with the FDA form 483 list of observations. There will be also several observations for improvements which will not fit in the major or minor categories. The auditor will also provide with a time table or estimated completion date for future corrections. They will explain the procedure on where and how to send the responses to their observations.
There are several steps that occur after the responses sent at the FDA office end. The investigator will write an “Establishment Inspection Report” (EIR) to the compliance office based upon their findings. Further actions will be then taken by the office such as Warning letters, consent decree, detention etc. FDA will send out the letters accordingly and plan of action is well described in the letters to act. IF there are lots of major violations by the manufacturer their products are automatically put on detention and prevented from circulations in the market.
Once the letters are received by the organization their regulatory department has to act quickly and submit the documented evidence to FDA about corrections made to the deficiencies seen during the inspection. The FDA will then again inspect the facility in question to confirm the corrections are adequate before lifting the detentions and or removal of warnings.
The FDA inspections are often seen as an intrusion and inconvenience to the normal business activities. Some of us think it as a chance to explain your practices and get the real feedback on systems and process improvements. The FDA inspector will always like the later. The inspections are disliked due to human nature that does not permit someone else to criticize on our day to day practices. However this criticism is a good thing that will definitely help and boot the reputation of the organization by standing behind the quality of their products that will be used for safety of the mankind. Good luck and all the best with your inspections!!!

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Written by:
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Prasad Panzade, Ph.D.
Director Analytical R&D , Product Development Solid dosage
Waterloo, Iowa Area

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