Cleaning and Maintenance in the Focus of the FDA

During an FDA inspection at an active pharmaceutical ingredient manufacturer, the FDA identified shortcomings in the cleaning and maintenance of the equipment. What exactly did the FDA take issue with?

The FDA criticised the inadequate cleaning of the equipment, citing the risk of contamination or the transfer of material to the intermediate and final products (active ingredient).

During the inspection, FDA inspectors found unidentified residues and rust on product-contact surfaces, as well as unidentified liquids inside, various non-dedicated process units. All units were labelled as cleaned and ready for use. In addition, the inspectors found discoloured and scratched containers.

As corrective measures, the company stated that it would clean the equipment and update its cleaning and maintenance procedures. However, this was not sufficient for the FDA. It is demanding a proactive cleaning and maintenance system. Furthermore, the FDA requires an assessment of the found residues and liquids. 

Specifically, the FDA requires a CAPA plan to be implemented for overseeing equipment and facilities management.
The plan should cover the following:

• how defects in equipment or facilities are to be identified as soon as possible
• how repairs and preventive maintenance schedules are to be carried out and managed
  regular management reviews
• describe how necessary technological adjustments are to be made
• Furthermore, it should address the risk of contaminated products entering the market and identify shortcomings in cleaning procedures and equipment used for manufacturing multiple products.

Based on the above retrospective valuation, a CAPA plan should be drawn up. This should include corrective actions for cleaning processes and practices, as well as timelines for their implementation. This includes a detailed summary of the weaknesses throughout the entire cleaning lifecycle, including the ongoing verification of cleaning activities.

Another notable shortcoming was the storage of raw materials and finished products, which were left exposed to the environment outside the building. The inspectors also noted that a freshly prepared solution contained brown flakes.

Conclusion: Cleaning and maintenance remain a key focus for the FDA.

You can find the full warning letter on the FDA website.