The Principles and Examples of Cost-Effective and Time Saving Qualification and Validation

Transcription

1 The Principles and Examples of Cost-Effective and Time Saving Qualification and Validation Presentation: Eva Baumgartner

2 PRESENTATION OVERVIEW LEAN QUALIFICATION Syntacoll GmbH short company presentation Principles of lean qualification used as «SYNTACOLL STYLE» Equipment Categories: benefit during qualification Other accelerating tools 13/3/2019 Page 1

3 SYNTACOLL GMBH SHORT COMPANY PRESENTATION Syntacoll GmbH Donaustrasse Saal a. d. Donau, close to Regensburg, Bavaria 13/3/2019 Page 2

4 SYNTACOLL GMBH SHORT COMPANY PRESENTATION 1927, Company founded as Ruhland GmbH: manufacture of surgical threads 1980s, Manufacture of collagen implants with and without APIs, registrated as drug products 1996, Manufacture of collagen implants with and without APIs, registrated as drug products and medical devices 2003, Development of further drug products, Gradual expansion of the facility as well gradual upscale of equipment 2016, Qualification of new QC laboratories and warehousing areas, New clean room areas and water systems Purified Water and Water for Injection Gradual qualification of all relevant equipment Upscale of processes / process validations Acceptance of building and equipment from TÜV Süd and ROB 2017, new product filed for US market, registrated as combination product 2018, PAI 13/3/2019 Page 3

5 SYNTACOLL GMBH SHORT COMPANY PRESENTATION manufacturing facility of the Innocoll group since staff members 41 classified clean room areas GMP class A-D Building B m 2 classified clean room areas Building A - 340m 2 sterilisation and aeration area, final sealing 13/3/2019 Page 4

6 SYNTACOLL GMBH SHORT COMPANY PRESENTATION Relevant equipment: mills agitator vessels pressure vessels centrifuges pumps filling machines sealing devices for blister and pouches freeze dryers water system for purified water and water for injection Relevant processes: collagen rendering from bovine and equine tendons manufacture and filling of collagen dispersions (with and without API) freeze drying of collagen dispersions packaging of lyophilized collagen dispersions sterilization of lyophilized collagen dispersions and final sealing after aeration final packaging and serialization of products 13/3/2019 Page 5

7 PRINCIPLES FOR LEAN QUALIFICATION - ASPECTS Aspects for URS: Focus on aspects which affect product quality Focus on aspects which affect fitness for intended use No wish-list Tool: Risk assessment or experimental design used to identify critical process parameters, features and functions KISS (Mind-set) Aspects for further Qualification Activities: leveraging supplier involvement / cooperation by: Use of supplier documentation but only if perfect value is given Lean documentation from the supplier Clarify the role of all parties: Avoid non relevant details Tools: Design review via Traceabilitymatrix Risk-based Test Matrix KISS (Mind-set) the quality unit, process owner, system owner, subject matter experts, supplier 13/3/2019 Page 6

8 PRINCIPLES FOR LEAN QUALIFICATION - ASPECTS FOR URS Core Aspects from common standards: Critical aspects of manufacturing systems and typically functions, features, abilities, and performance or characteristics necessary for the manufacturing process and systems to ensure consistent product quality and patient safety. Focus on aspects which affect product quality. (ASTM E2500) A systematic, efficient, and effective way of ensuring that manufacturing systems and equipment are fit for intended use, and that risk to product quality, and consequently to patient safety, are effectively managed to the extent that are affected by such systems and equipment. (ASTM E2500) It is a GMP requirement that manufacturers control the critical aspects of their particular operations through qualification and validation over the life cycle of the product and process. (EU GMP guideline Annex 15) 13/3/2019 Page 7

9 PRINCIPLES FOR LEAN QUALIFICATION - ASPECTS FOR URS Core Aspects from common standards: Critical Process Parameter (CPP): A process parameter whose variability has an impact on a critical quality attribute and therefore should be monitored or controlled to ensure the process produces the desired quality. (ICH Q8) Material Attributes that can have an effect on product CQAs (ICH Q8) Critical Quality Attribute (CQA): A physical, chemical, biological or microbiological property or characteristic that should be within an appropriate limit, range, or distribution to ensure the desired product quality. (ICH Q8) 13/3/2019 Page 8

10 PRINCIPLES FOR LEAN QUALIFICATION - TOOLS FOR URS / QUALIFICATION Core Facts from common standards: This guide describes a risk-based and science-based approach to the specification, design and verification of manufacturing systems and equipment that have the potential to affect product quality and patient safety. (ASTM E2500) A quality risk management approach should be applied throughout the lifecycle of a medicinal product. A quality risk management approach should be used for qualification and validation activities. The basis by which process parameters and quality attributes were identified as being critical or non-critical should be clearly documented, taking into account the results of any risk assessment activities. (EU GMP guideline Annex 15) 13/3/2019 Page 9

11 PRINCIPLES FOR LEAN QUALIFICATION - SYNTACOLL STYLE 13/3/2019 Page 10

12 PRINCIPLES FOR LEAN QUALIFICATION - SYNTACOLL STYLE Quality Risk Management: method 1: HACCP (Hazard Analysis on Critical Control Points) or FMEA (Failure Mode and Effect Analysis) Risk analysis together with monitoring of the identified critical control points, leads to a preventive and effective quality assurance concept. - ldentification of critical control points - Determining critical limit values for the individual critical points - Determining the monitoring and control procedures - Determining the corrective actions to be taken where necessary QRA 0 (Process development) 13/3/2019 Page 11

13 PRINCIPLES FOR LEAN QUALIFICATION - SYNTACOLL STYLE Quality Risk Management: method 2: Risk Assessment if requirement is GMP relevant / general critical aspect QRA 1 (part of URS) URS template.pdf; URS Water System.pdf URS Clean Rooms.pdf 13/3/2019 Page 12

14 PRINCIPLES FOR LEAN QUALIFICATION - DESIGN PHASE / REVIEW reference: Guide Modern Qualification 13/03/2019 Page 13

15 PRINCIPLES FOR LEAN QUALIFICATION - SYNTACOLL STYLE Design review / Traceability matrix: Comparison between URS and Functional Specification / Design Documents Design Review: Design Review template.pdf Traceability Matrix: Traceabilitymatrix Water System.pdf Quality Risk Management QRA2: RISK Assessment new clean room areas.pdf RISK-Assessment freeze dryer.pdf 13/3/2019 Page 14

16 PRINCIPLES FOR LEAN QUALIFICATION - INTERIM SUMMARY Overall Project extent: Qualification projects: 139 Process validation projects: 15 Cleaning validation projects: 12 Method Validations: 16 Qualification / Validation staff members Syntacoll: 6 ½ Qualification / Validation staff members temporary (+ consultants): 7 13/3/2019 Page 15

17 PRINCIPLES FOR LEAN QUALIFICATION - INTERIM SUMMARY Total Qualification projects: 139 New equipment / facilities / systems equipment category group C: 67 New equipment / facilities / systems equipment category group B: 15 Transferred inventory equipment (requalifications): 57 13/3/2019 Page 16

18 PRINCIPLES FOR LEAN QUALIFICATION - EQUIPMENT CATEGORIES USP <1058>: categorisation into groups A/B/C regarding the equipment complexity and the intended use: A) Simple / Standard equipment: no critical aspects; low coordination and only commissioning work) B) Standard / Configurated equipment: few critical aspects; still low coordination and few qualification intensity C) Custom equipment: specific quality critical aspects; high coordination and qualification intensity Skipping of qualification steps 13/3/2019 Page 17

19 PRINCIPLES FOR LEAN QUALIFICATION - SYNTACOLL STYLE New equipment New and complex but same as inventory Comparable, standard or configurable New and simple Change control (risk assessment, content assessment) + Questionnaire Questionnaire GMP relevance - qualification scope.pdf Test protocol for Qualification category group B.pdf 13/3/2019 Page 18

20 PRINCIPLES FOR LEAN QUALIFICATION - SYNTACOLL STYLE Transferred inventory (requalification after relocation) Change control (risk assessment, extent assessment) generic form for requalification - relocation or change of intended use.pdf More accelerating tools 13/3/2019 Page 19

21 PRINCIPLES FOR LEAN QUALIFICATION - ACCELERATING TOOLS - Use change management - Supplier involvement / documents - Use design documents for verification - Distinguish between deficiencies and deviations - Define quality involved steps - Use the flexibility of Annex 15 13/3/2019 Page 20

22 PRINCIPLES FOR LEAN QUALIFICATION - ACCELERATING TOOLS - For initiation of the equipment project smaller, non-formal risk assessments - Define change management concept linking the project change management and the supplier s internal change management (punch list) start of design freeze = start of documented change control 13/3/2019 Page 21

23 PRINCIPLES FOR LEAN QUALIFICATION - ACCELERATING TOOLS - Supplier audit: to verify documentation quality and structure to verify flexibility of document modifications - Contract / Project Quality Plan: clarification of responsibilities linking of change and / or deviation management 13/3/2019 Page 22

24 PRINCIPLES FOR LEAN QUALIFICATION - ACCELERATING TOOLS - linking of design documents and verification documents lean verification documents - use design documents as protocols e. g. room books for installation qualification 13/3/2019 Page 23

25 PRINCIPLES FOR LEAN QUALIFICATION - ACCELERATING TOOLS - deficiency: no or indirect impact on product, process or method - deviations: direct impact on product, process or method Deficiency form template.pdf 13/3/2019 Page 24

26 PRINCIPLES FOR LEAN QUALIFICATION - ACCELERATING TOOLS - lean involvement: few reviews and signatures - quality and non-quality steps / documents: define required quality approval 13/3/2019 Page 25

27 PRINCIPLES FOR LEAN QUALIFICATION - ACCELERATING TOOLS 2.5. Qualification documents may be combined together, where appropriate, e.g. installation qualification (IQ) and operational qualification (OQ) OQ normally follows IQ but depending on the complexity of the equipment, it may be performed as a combined Installation/Operation Qualification (IOQ) PQ should normally follow the successful completion of IQ and OQ. However, it may in some cases be appropriate to perform it in conjunction with OQ or Process Validation A formal release for the next stage in the qualification and validation process should be authorised by the relevant responsible personnel either as part of the validation report approval or as a separate summary document. Conditional approval to proceed to the next qualification stage can be given where certain acceptance criteria or deviations have not been fully addressed and there is a documented assessment that there is no significant impact on the next activity. (EU GMP guideline Annex 15) 13/3/2019 Page 26

28 PRINCIPLES FOR LEAN QUALIFICATION - SYNTACOLL STYLE Thank you very much for your attention QUESTIONS? 13/3/2019 Page 27