Quality Defect Investigation and

Reporting
New and Updated HPRA Guidance
Rob Smyth, Scientific Officer, QDR Team

GMP Conference

7 February 2017
Dublin
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)

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Overview of Changes
New / Significant
Changes
• Further guidance on
reporting timelines
• Specific guidance on
certain defect categories
• Quality Defect Reporting
Template
07/02/2017
Unchanged / Minor
Changes Only
• Scope
• Defect Classification
• Information Gathering
• Risk Assessment
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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).

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Specific Guidance on Defect Categories
Defects Which Always
Need to be reported
Previously, split into two
groups
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:

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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

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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

Examples Consider Obtain / Review

Precipitation Expected Observation? Samples
Crystallisation External Cause (storage / transport)? Photos
Sedimentation Occurred during Use? Retain Samples
Clumping Complaint History
Viscosity
Colour Change
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
Illegitimate Sale or Supply Theft
- Online or direct to Healthcare Professional - 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
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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.

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Stability Issues

2015 - 19% 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)

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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

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MA Non-compliances
CMC Non-compliances Artwork Non-compliances

Superseded Carton
Manufacturing / Test method
Label
Leaflet
Blister

RM / API suppliers Often due to failure to meet implementation

timelines for variations / transfers

IPCs
Reportable Defects, as some level of assessment
Minor N-Cs may not be deemed reportable, if of impact of missing information is needed
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
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)
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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

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Questions

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