pqdx product dossier deficiencies: challenges and ... · requirements for dossier compilation and...

PQDx product dossiers | 24 September 2013 1 |

PQDx product dossier deficiencies: challenges and

opportunities

Irena Prat Technical Officer, PQDx


PQDx product dossier

Content:

PQDX experience – common challenges and reasons

Timelines: why does it take do long?

Improvements and further opportunities


PQDx process


Background

Based on best international practice (ISO, EN, GHTF, CLSI): ISO 13485:2003, ISO/TR 10013:2001, ISO 18113 - Part 1-5, ISO/TR 18112: 2006, ISO15198:2004, ISO 17511:2003, ISO 14971:2007, EN 13641:2002, EN 13612:2002, EN 13612:2002, EN 13640:2002-06, GHTF/SG1/N41R9:2005, GHTF/SG1/N43:2005, GHTF/SG2/N54R8:2006, HTF/SG2/N57R8:2006, CLSI EP25-A.

Follows the content of the GHTF STED

Requirements for dossier compilation and assessment were agreed with experts from SRAs (FDA, EU, Health Canada, NRL).

Looks into critical aspects for WHO Member States often not dealt with by SRAs (stability, IFU, RA, etc.).


Why do we assess dossiers?

Key information on product and manufacturer used in conjunction with inspections and evaluation

Product identification

Risk analysis: all aspects related to the user and environment considered?

IFU: adequate for users in RLS?

Data in support of Mx claims: performance, QMS, labelling etc.

Training and support network

Does the Mx have data to support claims?


PQDx experience

73 Mx in PQ

52 Mx dossier

101 D requested

97 D submitted

91 D screened

53 D assessed

9 being D assessed


Challenges faced

Significant number of poor submissions

Long timelines at screening phase

DLT staff time implications

impact on inspections and evaluation scheduling

Content and presentation of the dossier: the type and extent of deficiencies has a direct impact on time to PQ

N° of amendments lowest 1 highest 5 average 2.25


Timelines

Time to PQ depends on the Mx ability to meet PQ requirements in each of the 3 components

Time from first dossier submission to dossier ready for full assessment:

Time taken (working days)

Shortest Longest Average

22 575 124

0 20 40 60 80

1

2

3

1

2

Mx

DLT


Dossier screening: most common deficiencies (1)

Poor layout and organization (numbering, references)

Sections missing

Out of scope data included

Regulatory version information: reference to product codes, exact differences between versions, version submitted

Overview of Mx and flowchart

Documented procedures used for the purchasing and verification of ingredients/products/services sourced from key suppliers


Dossier screening: most common deficiencies (2)

Incomplete formulation and composition info

Analytical and clinical studies: full study protocol, method of data analysis and complete study conclusion, product identification

Labels and IFU for all configurations, product identification

Training and support network not described

Uncertified copies of regulatory and QMS certificates

QMS documents missing


Dossier assessment: most common deficiencies

Unclear product identification (regulatory version, change control, site of manufacture).

Poor study design for product validation and verification.

Unclear if studies involved the product version submitted for PQ.

Poorly documented QMS procedures (purchasing, QC).

Stability testing not suited for countries of use

Labelling: content and translation

Important differences between experienced and less experienced

manufacturers.


Reasons for challenges Lack of experience and (sometimes)

expertise from Mx with less experience

in stringent regulations

First implementation of the STED.

Manufacturers with CABs support not always in line with international best practice.


Implemented improvements

Most common weaknesses identified

Enhanced interaction between the 3 PQDx components (assessors participate in inspections – follow-up on assessment findings).

Fast-track procedure in place to avoid duplication with SRAs.

Pool of assessors expanded.

Collaboration with NRAs strengthened.

Mx with several submissions have improved requirements understanding and Q of submissions


Opportunities

Capacity building for Mx and NRAs: help Mx with less experience understand requirements

Further guidance on dossier requirements; focus on most common deficiencies

Further shape the fast-tracking system based on lessons learnt

Involvement of pilot countries NRAs representatives in the assessment work to ensure synergies with capacity building.

Expanding collaboration with IMDRF NRAs (Health Canada ANVISA) and AHWP members (manufacturing sites).


Working towards...

Capacity building for Mx

An updated version of the instructions for compilation of a product dossier for the manufacturer

More guidance on critical dossier sections based on internationally accepted documents (CLSI).

Sample CD4 dossier


Conclusions

Several challenges faced by Mx and WHO

Lessons learnt by Mx and WHO

Opportunities for further improving guidance, capacity building


Thank you for your attention

Questions?

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