EMA non-compliance report on Brazilian manufacturer of sterile medicinal products

Recommendation

18/19 June 2024
Copenhagen, Denmark

Environmental Monitoring
Compliant and Reasonable

Non-compliance reports are published in the EudraGMDP database of the European Medicines Agency (EMA) by European supervisory authorities. They refer to inspections inside as well as outside of the European Union. The non-compliance reports are independently submitted into the database by National Competent Authorities via a standardised form. For the company concerned, a non-compliance report has severe consequences until the violations are rectified. Amongst other things, a suspension of the marketing authorisation as well as recalls of the products in question could be mandated.

On April, 24th 2017, the EMA published a non-compliance report on the Brazilian company Nova DFL Industrie E Commercio SA in Rio de Janeiro, which was inspected by the French supervisory agency "French National Agency for Medicines and Health Products Safety". During a pre-approval inspection, they observed 7 critical and 7 major deficiencies, a more detailed description of which can be found in the non-compliance report:

Critical deficiencies:

• Insufficient pharmaceutical quality system: the insufficient handling of deviations, insufficient handling of product quality reviews and lacking consideration of risk management in the quality manual had been criticised
• It took more than six months for action to be taken after a critical deviation was discovered
• Inadequate aseptic behaviour of operators; hands were occasionally held together; arms were crossed / arms were touching the body at several occasions / rapid movements of the clean room operators / gloves weren't disinfected before entering hands into grade A / the whole upper body moved into grade A / no dedicated storage of the tool for grabbing cartridges / an operator used tongs which had fallen on the floor
• In visual inspection, the criticality of defects was not considered; no acceptance quality limits were defined for each defect; there was no maximum reject rate for batch release; cartridges weren't turned upside down nor observed against a white background
• There was a high environmental contamination risk in production
• Not every API drum was sampled
• Falsified data was found in the QC lab. All API drums were deemed compliant even though not all drums had actually been sampled

Major deficiencies:

• The insufficient number of qualified and experienced personnel was criticised
• Data integrity was not guaranteed
• There were divergences between manufacturing yields and the amount of used materials
• Inadequate supplier qualification
• Weaknesses in handling the validation master plan; there was no performance qualification
• The handing of raw material sampling was insufficient
• The complaints management wasn't always performed by the QA

As a consequence from this inspection, the refusal of the national marketing authorisation by the national authorities is suggested. Furthermore, national authorities should evaluate the criticality of other products manufactured at this site.

Source: EudraGMDP database of the EMA