Panel discussion

Global trends in the field of GMP – topical initiatives, tendencies,

best practices

EDQM part: trend on GMP deficiencies found during API

inspections

Dr. Florence Benoit-GuyodEuropean Directorate for the Quality of Medicines (EDQM)

Overall figures relating to EDQM API inspections in 2018

82 sites covered by EDQM,Among them 36 sites by EDQM risk based inspections4 non-compliances, all with critical findings relating to poor Quality Management System From 2009-2018 Mean rate of 18% of Inspected sites found non-compliant: The high proportion of non-compliant sites is seen as a result of the ability of EDQM to identify sites with higher risk of non-compliance and to focus on them.

Quality related matters: • Quality

management,• Personnel, • Documentation,• Validation,• Change control,• Complaints & recalls, • Contract

manufacturers

Quality Unit overview and Quality Risk Management

• APQR: not all batches reflected, trends not detected and investigated• Deviation: Underreported, Deviations not investigated in depth, No proper

CAPA, Several minor or repeated deviations not treated as major• Personnel: insufficient GMP training of upper management • Change control: underreported/opened after initiation, Not properly done• Validation of processes not done (blending, micronization, solvent

recovery)• Poor cleaning validation• Complaints: insufficient investigation

Documentation practices

• Rewriting documents• Not recording operation at the time of performance• Insufficient control of electronic documents• Unavailability of documents (e.g. batch records)• Falsification in order to demonstrate acceptable, expected or presentable

results, values or dates:• Rewriting to cover OOS, deviations, incorrect or unapproved procedures• Falsified layouts/premises: Hiding unacceptable parts of the facility, covering doors• Pretesting in unofficial laboratory to select acceptable batches for official testing• Deleting OOS results and replacing by correct ones

Buildings and equipment

• Improper design, cleaning schedule and maintenance schedule (risks of contamination and/or cross-contamination)

• Computerised systems: insufficient URS, Validation, Access levels • Controls to prevent data manipulation• IT staff: insufficient or without knowledge of GMP requirements• Lack of proper maintenance/monitoring of the potable water

Laboratory controls

• Lack or insufficient review of audit trail• Unreliable analytical results/data integrity concerns• Fraudulent practices: manipulation, pretesting, deleting OOS results• Poor OOS investigation/root-cause determination, “easy” invalidation• Unreliable microbiological results• Insufficient qualification and maintenance of equipment• Chemical reference standards: lack of the Ph. Eur. CRS, insufficient

establishment of secondary standards

Materials management

• Risk of loss of traceability• Insufficient key starting material vendor approval/management• Lack of understanding the different concept/GMP requirements when

qualifying suppliers (i.e. CMOs) of intermediates or solvent/reagent recovery

• Improper storage• Insufficient control of Sub-contracted activities: instrument calibration,

computerised systems validation, recovery of solvent/reagent

Thank you for

your attention…