Good Distribution Practices Awareness training Masterclass GDP Antwerpen 5 March 2015 Claude Goldszmidt Senior IT & Equipment Compliance Consultant and Rescop Academy Trainer 1

Practical examples: case studies Case: Cold chain Case: Vaccine Index Some basic rules Practical examples: case studies Case: Cold chain Case: Vaccine Example: Cornea bank Existing tools 2 2

Quality Management System: Some basic Rules Every Distribution company must have a permanently available Responsible Person (RP) Quality Management System: Quality Manual + CAPA system + SLA Adequate number of trained personnel External audits Premises and Equipment Qualification and Validation Distribution Company is a contractor (vendor) for the Pharma company producing APIs. Quality level must be acceptable for the customer  Vendor Audit Quality Assurance department provides Quality policies and rules = SOPs Basic and simple definition of Quality: write what you want to do, do what is written and be able to prove it (traceability). Premises (storage area) and equipment (trucks, data loggers, cooling system, …) qualification. 3 3

Responsible Person (oversees Quality System) Written procedures (SOPs) Some basic Rules Responsible Person (oversees Quality System) Written procedures (SOPs) Checking sincerity of suppliers and customers Staff Training Records/traceability (tracking devices) Emergency plans Difference between Qualified Person (Pharma) and Quality Assurance Director SOPs management in a DMS. Staff training: TMS = Training Management System What is mandatory to track? Emergency plans: risk assessment + what if? 4 4

Possible effect on patient Possible consequence for the Company Practical examples: case studies Case study workflow: Problem description Root-cause Possible effect on patient Possible consequence for the Company Noticed in time 5 5

Therefore the product quality could not be assured Cold chain management and monitoring Problem Temperature data loggers did not log any data during Cold chain truck shipment Therefore the product quality could not be assured www.rescop.com www.rescop.com 6 6 6 6

SOP not followed correctly: Why? Cold chain management and monitoring Root cause The temperature loggers were not switched on because both packers expected the other one switched on the temp data loggers. SOP exists: It is not allowed to work with 2 persons on one shipment at the same time SOP not followed correctly: Why? Training management Other possible reasons? www.rescop.com www.rescop.com 7 7 7 7

Possible patient effect Cold chain management and monitoring Possible patient effect Out-of-spec temperature during transport could lead to instable medicine Instable medicine could harm patient www.rescop.com www.rescop.com 8 8 8 8

Possible Consequences for the Company Short term impact: Cold chain management and monitoring Possible Consequences for the Company Short term impact: Extra work for deviation (cost for raising deviation, launching the investigation, closing the deviation) Costs for recall (when product already with patient) When patient safety compromised the company may be (temporarily) closed by authorities Long term impact: When it happens often the company name could be damaged, resulting in being forced out-of-business www.rescop.com www.rescop.com 9 9 9 9

It was noticed before the package reached the patient Cold chain management and monitoring Noticed in time? It was noticed before the package reached the patient Product was placed in quarantine Where: in a LSP (Logistic Service Provider) www.rescop.com www.rescop.com 10 10 10 10

Official stability studies with regards to RTE exist Cold chain management and monitoring Actual patient effect Temperature logger installed within the truck: room temperature exposure (RTE) could be rolled out Official stability studies with regards to RTE exist Data from these stability studies could be used: interest of a LIMS to manage stability studies Conclusion: no direct impact! www.rescop.com www.rescop.com 11 11 11 11

Actual Consequences for the Company Financial impact: Cold chain management and monitoring Actual Consequences for the Company Financial impact: Extra work for deviation (cost for raising deviation, launching the investigation, closing the deviation)  use of a dedicated registration tool (i.e. RC-QMS) Analysis of data: difference with and without a LIMS Other shipments could be sent in time to patient No consequences for the patient: the most important! www.rescop.com www.rescop.com 12 12 12 12

Vaccine Problem Customers complained that there were observed white flocks in the delivered rabies vaccine for dogs In the leaflet is mentioned that the vaccine must contain a milky solution without flocks! www.rescop.com www.rescop.com 13 13 13 13

Product should be stored and maintained at 4-8 C Vaccine Root cause Product should be stored and maintained at 4-8 C Product was exposed to temperatures < 0 C causing the white flocks to form in the product www.rescop.com www.rescop.com 14 14 14 14

Possible patient / human safety effect Vaccine Possible patient / human safety effect The vaccine does not work and the dog is not protected for rabies disease When the dog bites a human, this might lead to infection of human www.rescop.com www.rescop.com 15 15 15 15

Possible Consequences for the Company Short term impact: Vaccine Possible Consequences for the Company Short term impact: Extra work for deviation (cost for raising deviation, launching the investigation, closing the deviation) Costs for recall (when product already with patient) When human safety compromised the company may be (temporarily) closed by authorities Long term impact: When it happens often the company name could be damaged, resulting in being forced out-of-business www.rescop.com www.rescop.com 16 16 16 16

Vaccine Noticed in time? It was noticed multiple times by customers (veterinarians) that there were white flocks in the vaccine  complaints There was sufficient temperature logging data available to support that the product was not exposed to too low temperatures at the producer or during transport by the LSP and the exposure happened at the veterinarian www.rescop.com www.rescop.com 17 17 17 17

The compromised vaccine was not delivered to the dog Actual patient effect The compromised vaccine was not delivered to the dog A new vaccine was provided by the national distributor Conclusion: no direct impact! www.rescop.com www.rescop.com 18 18 18 18

Actual Consequences for the Company Financial impact: Vaccine Actual Consequences for the Company Financial impact: Extra work for complaint handling and root cause investigation Replacement shipments were made by the local distributor No (potential) impact on human safety: the most important! www.rescop.com www.rescop.com 19 19 19 19

The Client’s challenge Cornea bank in Switzerland The Client’s challenge Historically no cornea bank in the Geneva catchment area. Patients needing a cornea transplant had to rely on cornea stocks located in other Swiss cantons, or even abroad. Cornea banks exist at Lucerne, Zurich, Berne, Lausanne and Olten. Beginning 2013, Hôpitaux Universitaires de Genève (HUG) decided to establish a cornea bank for patients in the Geneva region. The process of stocking human tissue for transplantation is highly regulated both at Swiss and international levels. Swissmedic, the Swiss regulatory agency, sets strict rules at every step of the process. 20 20

Logistic service provider answer Cornea bank in Switzerland Logistic service provider answer Through extensive interaction with many clients over the years, the LSP observed an increasing and world-wide move towards ever more stringent safety regulations in the life sciences field. The LSP wanted to get their competencies, their processes and their infrastructure validated. Hence time, effort and resources were allocated to acquire the much sought after Swissmedic certification for transporting, distributing and stocking medicinal products. 21 21

6 selection criteria Swissmedic certification. Cornea bank in Switzerland 6 selection criteria Swissmedic certification. Adhere to the Good Distribution Practices (GDP) scheme Guaranteed CRT (Controlled Room Temperature) Up-to-date know-how and consulting services. Classification Packaging Transport Real Time Shipping Visibility Cost a. Classification Based on interviews with the cornea bank’s scientific team and our deep understanding of the classification regulations as determined by UNEC / ADR, we were able to identify our client’s cornea shipments as meeting the Exceptions regulations under section 3.6.2.2.3 of the IATA Dangerous Goods Regulations (DGR) manual (page 129). Consequently, we recommended the classification as “non-infectious biological substance”. b. Packaging We were delighted to be part of the Cornea Bank’s scientific team. Based on in-depth discussions and insights gained, we were able to draw up customised specifications and then commissioned a packaging company to create a project-specific cornea packaging solution for HUG. Corneas are immersed in a biological solution which ensures their conservation. Maintaining the solution at pre-defined and constant temperate levels is essential for preserving the tissues at their optimum state. We achieve this with a Triple Layer System for packaging, and a fleet of vehicles who’re equipped to maintain the packaged substances’ temperatures at requested levels. The photo here below shows the various components: The primary receptacle: Sealed plastic flask (packed in a leak proof plastic bag). The secondary receptacle: a sealed pot. The tertiary receptacle: an aluminium-clad thermo protection box. c. Transport We own the transport chain from A-Z. Entirely in-house – and using our own modern fleet of cold-chain approved vehicles – we’re able to guarantee a controlled and seamless transport solution during which temperature is maintained at the prescribed range of +15°C à +25°C. 22 22

Cornea bank in Switzerland The end result Geneva’s Cornea Bank is one of only few in Europe who respond to the latest and strictest regulations at all levels of the supply chain. When HUG extends its collaboration to include other cornea banks, inside and outside of Switzerland, everything is already in place. As Swissmedic certified shippers, the LSP is always up-to-date with the latest regulatory information, they make sure all necessary authorisations are in place, and they deliver on time. For shipping biological substances, an ongoing and mutually trusting working relationship between the client and the supplier is absolutely essential. 23 23

Rescop can provide you with: Quality Management System: RC-QMS Existing tools Rescop can provide you with: Quality Management System: RC-QMS Document Management System for SOPs: RC-DMS Training Management System: RC-Training Exception Handling and CAPA: RC-CAPA Automation Compliance Management Suite: RC-ACMS System Management and Electronic Logbook: RC-Logbook Validation, Qualification and Commissioning: RC-SDLC Electronic Laboratory NoteBook: RC-ELN Laboratory Information Management System: RC-LIMS 24 24

Laboratory Information Compliance & Quality Management Software Products LIMS Laboratory Information Management System www.rescop.com www.rescop.com 25 25 25

ANY QUESTION ? Thank You Challenges of the Industry: Up-to-date overview, Maintain compliance, Keep it efficient 26 26