European GMP Inspector discovers Cleaning and Process Validation Deficiencies

It's a well-known fact that the US FDA publishes GMP deficiencies in their Warning Letters. For some years now, there has also been a European portal (see: "85 Company listed with GMP-Non Compliance Statements in the New EMA Database"), where non-compliance results are published.

In August 2017, a Bavarian supervisory agency has issued such a statement of non-compliance with GMP to an Indian manufacturer of medicinal products. We reported on this before: "EU Inspection Complaints due to inadequate Handling of OOS Results". The company produces and packages solid dosage forms.

Which deficiencies were found?

One of the critical deficiencies named was that essential elements of the Pharmaceutical Quality System were not effective. To give an example, the report spoke of hundreds of cases in which OOS-results had been invalidated without scientific and traceable root-cause analysis because of human errors. It was further considered a critical deficiency that the deviation and OOS management (including related protocol and review systems) was designed in a way so that discrepancies were systematically not documented. The cleaning of rooms and equipment in direct product contact were not or not successfully performed - even though the manufacturing and packing records claimed they were. In conclusion, the agency states that the integrity of the manufacturing and packing records cannot be guaranteed; therefore, an adequate batch release is not possible. Furthermore, due to the insufficient records, market-complaints cannot be investigated, either.

In addition, five major deficiencies with corresponding sub-items are named (sub-items are only listed in parts):

• Deviation management and QP batch certification (e.g. unacceptable high threshold for the investigation of discrepancies, no assessment of the possible impact of equipment break downs on the product quality in the manufacturing and packing records, etc.);
• Inadequate design, condition and maintenance of rooms and equipment (e.g. unsuitable doors and surfaces in the manufacturing rooms, etc.);
• Insufficient cleaning of the rooms and equipment (dirty rooms and equipment, insufficient integrity of cleaning documentation);
• Process validation (no suitable root-cause analysis into failed process validation, release of manufacturing documentation in spite of failed process validation, etc.);
• OOS investigation (no GMP-compliant handling of OOS results, etc.)

Conclusion: the grave GMP deficiencies mentioned above lead to recalls and a withdrawal of the GMP certificate. Products may not be exported to the EU until a successful re-inspection has taken place.

The complete report is available in the EU GMDP database.