Quality Defect Investigation and Reporting

Transcription

1 Quality Defect Investigation and Reporting New and Updated HPRA Guidance Rob Smyth, Scientific Officer, QDR Team GMP Conference 7 February 2017 Dublin

2 HPRA (IMB) Reporting Guidance Note 2010 Publication, one further revision in 2012 Non-reporting of certain defect cases allowed criteria laid down to meet examples of defect types, reportable/not Revision further changes experience of cases / feedback from industry Chapter 8 revision 2015 (e.g. 8.9, 8.15) 2

3 Overview of Changes New / Significant Changes Further guidance on reporting timelines Specific guidance on certain defect categories Quality Defect Reporting Template Unchanged / Minor Changes Only Scope Defect Classification Information Gathering Risk Assessment 3

4 Reporting Timelines Time Risk Difficult to precisely define or allocate, but now more specific High risk (critical / major, market action potential) immediate (no more than a few days) reporting Consider immediate precautionary quarantine action Lower risk (where reportable) within 1-2 weeks. Always avoid unnecessary delays if genuine reasons for delays, HPRA can be consulted (may still not need reporting). 4

5 Specific Guidance on Defect Categories Previously, split into two groups Defects Which Always Need to be reported Defects Which May/May Not Need to be Reported Have moved away from this, so reporting is referenced separately within each section / category Also more guidance on how to investigate Some categories relatively unchanged Some with significant differences: 5

6 Product Mix-ups & Rogues Product Mix-ups labelled contents and product / strength do not match Still considered reportable Rogues One / small number of units contained within larger quantity of different product / strength Investigation Identification of rogue, manufacturing review, returns Reporting not introduced during manufacturing / wholesaling process = not reportable if information obtained quickly 6

7 Contamination / N-C with Appearance Specs Contamination confirmed = reportable. If suspected may be applicable to different section Non-compliance with appearance specs - now incorporated into non-compliance with specs section Examples Consider Obtain / Review Precipitation Crystallisation Sedimentation Clumping Viscosity Colour Change Expected Observation? External Cause (storage / transport)? Occurred during Use? Samples Photos Retain Samples Complaint History Isolated / not representative may not be reportable (but risk can mean tight timelines for high risk products) 7

8 Falsified Medicines Confirmed Falsified = Always reportable (confirmed by falsified packaging / BN / product / supply chain) - Obtaining of samples and photos of importance Potential falsified various sources Illegitimate Sale or Supply - Online or direct to Healthcare Professional Theft - Suspicion of intent to falsify not reportable defects if no confirmed falsification, but should be notified to compliance@hpra.ie, for forwarding to other sections, where necessary 8

9 Leakage / Closure / Sterility Assurance Common defect, wide range of types and risk levels cracks, pinhole leaks - lack of sterility assurance, higher risk leak of harmful product, higher risk gross leaks / evident, lower risk & non-reportable, if not widespread. Important to trend complaints. 9

10 Stability Issues % of all defect reports, one of the highest again in 2016 Reportable as per GMPs, many don t need to be and HPRA has reflected in revised guidance Not Reportable 40/75 OOSs Do not report if 30 C or 25 C are in-spec 30 C OOSs, if marketed in 25 C zones only and 25/60 in-spec OOS batch not representative of Irish product (not marketed, foreign batches affected only) or of Irish-manufactured product Lab errors, once confirmed quickly (still investigate lab error) 10

11 Stability Issues (contd) Reportable OOS batch on IE market / represents product. Includes expired batches (regression analysis) Subsequent OOSs to be investigated and reported Irish manufactured product, where OOS represents product on another market Test method issues if method is direct cause, report (method amendment may be a CAPA) OOTs reportable, if potential for OOS. Perform data extrapolation Delays to be avoided usually only while awaiting confirmation of OOS 11

12 MA Non-compliances CMC Non-compliances Artwork Non-compliances Manufacturing / Test method Superseded Carton Label Leaflet Blister RM / API suppliers Often due to failure to meet implementation timelines for variations / transfers IPCs Minor N-Cs may not be deemed reportable, if evidence that there has been no effect on FP batches Reportable Defects, as some level of assessment of impact of missing information is needed 12

13 New HPRA Defect Reporting Template Appendix to upcoming Guidance Note revision Aim to minimise delays caused by rounds of initial correspondence Information which should be obtained prior to reporting a quality defect Product Details BN(s) and Distribution Complaint / Defect Details Manufacturer MAH Wholesaler(s) Contact Details Proposed Action(s) (not mandatory to report everything, if not possible to obtain. Delays to reporting while gathering information to complete fields should be avoided) 13

14 Remember Relevant Irish / European Legislation to still be followed Consider other HPRA Guidance (recalls, EMPs) No impact upon reporting requirements of other NCAs EMA (coordinator of CAP defect cases) EEA / MRA / PIC/S Third Countries HPRA Website / Newsletter, for publication of guidance 14

15 Questions 15