Quality Defect Investigation and

Reporting

Rob Smyth, Scientific Officer, QDR Team

GMP Conference

7 February 2017

Dublin

New and Updated HPRA Guidance

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 2 2017 – further changes

• experience of cases / feedback from industry

• Chapter 8 revision 2015 (e.g. 8.9, 8.15)

207/02/2017

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

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Reporting Timelines

• 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).

Difficult to precisely define or allocate, but now more specific

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Time Risk

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Specific Guidance on Defect Categories

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:

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Previously, split into two

groups

Defects Which Always

Need to be reported

Defects Which May/May

Not Need to be Reported

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Product Mix-ups & Rogues

• labelled contents and product / strength do not match

• Still considered reportable

Product Mix-ups

• 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

Rogues

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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

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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)

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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

→ not reportable defects if no confirmed falsification, but should be

notified to compliance@hpra.ie, for forwarding to other sections, where

necessary

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Illegitimate Sale or Supply

- Online or direct to Healthcare Professional

Theft

- Suspicion of intent to falsify

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Leakage / Closure / Sterility Assurance

• 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.

Common defect, wide range of types and risk levels

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Stability Issues

• Reportable as per GMPs, many don’t need to be and HPRA has reflected in revised

guidance

2015 - 19% of all defect reports, one of the highest again in 2016

• 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)

Not Reportable

1007/02/2017

Stability Issues (contd)

• 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

Reportable

Delays to be avoided – usually only while awaiting confirmation of

OOS

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MA Non-compliances

CMC Non-compliances Artwork Non-compliances

Manufacturing / Test methodSuperseded Carton

Label

Leaflet

Blister

RM / API suppliers Often due to failure to meet implementation

timelines for variations / transfers

IPCsReportable Defects, as some level of assessment

of impact of missing information is neededMinor N-Cs may not be deemed reportable, if

evidence that there has been no effect on FP

batches

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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

(not mandatory to report everything, if not possible to obtain. Delays

to reporting while gathering information to complete fields should be

avoided)

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Product Details BN(s) and Distribution Complaint / Defect Details

Manufacturer MAH Wholesaler(s)

Contact Details Proposed Action(s)

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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

1407/02/2017

Questions

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