Common pharma compliance concerns cited by FDA warning letters

A review of the last decade of FDA warning letters finds quality control operations, manufacturing process validation, and data record and integrity are the key points of scrutiny.

Cartoon of hands opening an envelope and the letter inside having a big exclamation mark (indicating a warning)

A study of the causes of warning letters issued by the US Food and Drug Administration (FDA)’s Center for Drug Evaluation and Research (CDER) and Center for Devices and Radiological Health (CDRH) between 2010 and 2020 revealed that poor current good manufacturing practice (cGMP) compliance and misbranding were the most common citations.

Of the cGMP letters, three major types of violations – deficiencies in process validation, documentation practices (data integrity) and quality control – accounted for 26 percent, 21 percent and 15 percent of warning letters respectively.

Warning letters issued by FDA can be an important source of data to study and analyse violations that occur in pharmaceutical manufacturing. Such studies can also help companies prepare for their upcoming inspections by enabling them to identify and rectify any issues.

FDA warning letters are issued to a manufacturer when violations are observed during an inspection; however, they are only issued if a company’s response to deficiencies listed in a form 483 are unsatisfactory. Upon receiving a warning letter, the company is expected to take appropriate measures to rectify the listed issues.

In a study published in the Journal of Pharmaceutical Innovation, researchers revealed not only the major causes of warning letters, but also key areas FDA investigators may focus on during inspections of pharmaceutical manufacturers.

The authors identified and analysed a total of 3777 warning letters from CDER and CDRH. Overall, validation, documentation and quality control were the major cGMP violations.

However, the researchers noted that a larger number of warning letters were issued to pharmaceutical manufacturers (ie, by CDER) than to medical device manufacturers (by CDRH) between 2015 and 2020. The major reasons for this were poor cGMP compliance and misbranding.

According to the authors, FDA operates a six-system inspection model, where the quality system is the core with five manufacturing systems – production, facilities and equipment, laboratory control system, materials system, and packaging and labelling systems – linked to it.

The researchers concluded that in order to have a successful inspections, pharma companies should focus on establishing effective quality management systems that govern the entire manufacturing process, quality control, employee training and documentation practices, as well as keeping up to date with guidance documents to ensure they are aware of the expectations of the regulatory agency. They also suggest that companies develop an internal compliance check list and prepare themselves to make corrective actions as and when required.

One response to “Common pharma compliance concerns cited by FDA warning letters”

  1. Manny Karos says:

    While quality system is at the core of the six step FDA inspection model, the CGMP and quality systems regulations as a whole should the over arching concern of the FDA six step inspection model.

    The purpose of a model is to simplify something that is complex. Medical drug and medical device CGMP and quality system regulations are surely complex. As any FDA investigator or any quality control specialist at a drug or device manufacturing facility.

    Suggest FDA issues more good guidance practices to simplify the process especially for small businesses that manufacture medical devices and even larger companies that manufacture medical drugs.

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