FDA criticises the Use of pharmaceutical Facilities for industrial Products

Recently, several Warning Letters have been published by the US FDA criticising the use of non-dedicated equipment for pharmaceutical and non-pharmaceutical products. A recent Warning Letter makes this very clear once again.

The FDA criticises the production of over-the-counter (OTC) drugs on the same equipment used to manufacture industrial products such as detergents. The FDA also criticises the lack of cleaning validation studies, including with regard to disinfection.

In response to the company's reply to conduct cleaning validation studies, the FDA replied that this was not sufficient. The authority expects:

• Details of corrective actions, such as cleaning validation plans 
• A retrospective assessment of the products that are on the market and still within the shelf life with regard to potential cross-contamination with other medicinal products and/or industrial products. This should include a risk assessment for all medicinal products previously manufactured on the shared facilities. 
• A comprehensive, retrospective assessment of the cleaning efficiency with regard to the risk of cross-contamination. This includes the identity of residues and other equipment that may not have been cleaned correctly. The assessment should identify any shortcomings in cleaning processes and practices. This should be done for each part of the production equipment that was used to manufacture more than one product. 
• Plans for addressing product quality and patient safety risks for all products still in distribution, including potential recalls or withdrawals 
• Confirmation that the manufacture of medicinal products will be discontinued in facilities not intended for this purpose 
• If the manufacture of medicinal and non-medicinal products is maintained, a plan showing how the segregation of dedicated facilities for the manufacture of medicinal and non-medicinal products will be maintained. 
• Confirmation that appropriate controls are in place to prevent cross-contamination 
• A corrective and preventive action plan (CAPA) that identifies appropriate corrective actions for the cleaning and disinfection processes and practices and a timeline showing when the actions will be completed 
• Detailed summary of weaknesses in the cleaning and disinfection process as part of the equipment cleaning and disinfection life cycle 
• Description of improvements in the cleaning and disinfection programme, including monitoring measures regarding cleaning and disinfection for all products and equipment 
• Measures in the change management system as new manufacturing equipment or a new product is introduced 
• Updated work instructions to ensure that an appropriate programme for verification and validation of cleaning processes is implemented for products, processes and new products.  

The FDA is also calling for improvements to the cleaning validation programme with a particular emphasis on worst-case scenarios for drug manufacturing. This includes the identification and evaluation of worst-case scenarios:

• Medicinal products with higher toxicities 
• Medicinal products with higher active ingredient contents 
• Medicinal products with low solubility in the cleaning agent 
• Medicinal products with properties that make them difficult to purify 
• Swab sampling points at locations that are most difficult to purify 
• Standing time before cleaning

Conclusion: The FDA does not permit the manufacture of non-drug products on equipment that is also used to manufacture medicinal products. All products on the market that have been manufactured in this way must be retrospectively assessed for cross-contamination. A cleaning validation programme must be introduced prospectively.

You can find the entire Warning Letter on the FDA website.