Insufficient water system design: warning letter in Mexico

Recommendation

17-19 September 2024

Granulation & Tableting - Live Online Training
GMP Compliance and Technology for the Manufacture of Oral Solid Dosage Forms

Due to severe GMP violations, the US FDA has issued a warning letter after inspecting a Mexican pharmaceutical manufacturer. Major deficiencies have been found in the pharmaceutical water system as well as in microbial laboratory testing. The topical product range includes products for skin disinfection and skin preparation for surgery.

The FDA criticises the insufficient microbial testing of manufactured products. Those had not been tested for microbial contamination or sterility, where appropriate. FDA now expects a compilation of all batches distributed to the USA, microbial testing of the related retain samples and, if necessary, actions required based on the test result. The FDA further expects the preparation of a product specification regarding microbial quality parameters and the validation of appropriate tests.

Another point in the warning letter is dedicated to the manufacturer's water system. The FDA believes the system to be unfit to produce pharmaceutical water in accordance with the USP requirements for purified water. Specifically, the letter lists flaws in the system's design as well as deficiencies in its control, monitoring and maintenance. Another major inspection finding is that half the laboratory data from the last year has been lost according to an employee's statement. The FDA expects the implementation and validation of a suitable water system, as well as the development of an effective system that will ensure the correct functionality. This includes a maintenance and routine monitoring program. The FDA also expects a risk assessment to the extent to which the missing laboratory data poses a risk for the products manufactured during that time.

An even more critical deficiency is to be found in the section about the quality assurance unit. The statement that the QA unit is unable to fulfil its responsibilities can be counted as a gross systemic error.

Due to the severity of the defects found, the FDA recommends the company commissions a cGMP consultant in order to support them in correcting those defects.

For more information please see the complete FDA warning letter to the Mexican pharmaceutical manufacturer.