PQDx product dossier deficiencies: challenges and opportunities

Transcription

1 PQDx product dossier deficiencies: challenges and opportunities Irena Prat Technical Officer, PQDx 1

2 PQDx product dossier Content: PQDX experience common challenges and reasons Timelines: why does it take do long? Improvements and further opportunities 2

3 PQDx process 3

4 Background Based on best international practice (ISO, EN, GHTF, CLSI): ISO 13485:2003, ISO/TR 10013:2001, ISO 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: , 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.). 4

5 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? 5

6 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 6

7 Challenges faced Significant number of poor submissions Long timelines at screening phase DLT staff time implications N of amendments lowest 1 highest 5 average 2.25 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 7

8 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 DLT 2 1 Mx

9 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 9

10 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 10

11 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. 11

12 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. 12

13 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 13

14 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). 14

15 Capacity building for Mx Working towards... 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 15

16 Conclusions Several challenges faced by Mx and WHO Lessons learnt by Mx and WHO Opportunities for further improving guidance, capacity building 16

17 Thank you for your attention Questions? 17