The Importance of Supplier Qualification of the Full Distribution Life-cycle in Pharmaceuticals

Transcription

1 The Importance of Supplier Qualification of the Full Distribution Life-cycle in Pharmaceuticals William Dale Carter IPEC Americas Chair-Elect & GMP Committee Chair ExcipientFest April 25,

2 Challenges in Today s Excipient Supply Chain Diversity in locations and sourcing strategies has created a maze of supply routes for ingredients Increased awareness of supply chain vulnerability Closure of a manufacturing facility Raw material/feedstock issues Terrorism/fraud Increased interest in alternate sources of excipients New developments in regulation, compliance, testing and innovation have forced the pharmaceutical industry to pay more attention to excipients

3 2007 Action Plan for Import Safety USA - Report to the President Interagency Working Group on Import Safety November 2007

4 Excipient Supply Chain Drug Product consumed by patient Excipients used in making the drug product Received, inspected and released Delivered to Drug Product Manufacturer Excipient Transportation and Distribution Export Import Storage - Repackaging Excipient initial storage and packaging Manufacturing of bulk excipient Sourcing of raw materials to make excipient

5 Goal is to Manage Risk Risk to Both Drug Maker & to Patient Quality of excipient causes failure of drug batch during Manufacturing Availability of drug Product Quality of excipient causes failure of drug in use or results in hazardous product 21 CFR (a)(9) 21 CFR 330.1(e) 5

6 How do you identify and control RISK in the excipient supply chain? For the RISK Not going to see the full picture from a certificate of analysis a questionnaire a label stating USP inspection on receipt lab analysis audit of the manufacturer/distributor purchasing contract Supplier Qualification is the foundation for controlling and managing risk in the supply chain.

7 The journey from the manufacturing site

8 Who is in the supply chain? The owner s of the product along the way are responsible for the product and act according to their own advantage which may be different than the end users requirements. Shipping companies, tanking terminals, cross-dock sites, warehouses, and repackaging operations all work under the contract of the owner of the product. In the absence of specific directives the handler will apply their common practices.

9 Supplier Qualification is a discovery process between the user and maker of the excipient. Knowing the true risk is the first step in preventing programs that look good on paper but offer only a false sense of security. You can not manage risk you do not see.

10 Qualification provides information for Supply Chain Controls Excipient Pedigree Do you know where your ingredients are produced? Do you know how they were distributed? What evidence do you have which demonstrates this? More than One Up and One Down in supply chain is needed! What is your weakest link..?

11 Using an excipient without knowing the manufacturing location and its path to your front door is like using a toothbrush you find laying in a public restroom.

12 More than just sourcing location You can leap from a building any where in the world and the results will be the same. Qualification of suppliers that use good manufacturing & distribution practices make excipients safe, not manufacturing locations!

13 Know your supply chain Starting point of an excipient qualification program IPEC Excipient Qualification Guide Ask your supplier and follow the chain to the manufacturer IPEC-Americas Standardized Excipient Information Protocol Excipient Pedigree White Paper Know the history and reputation of each party Understand the practices followed at each step IPEC-PQG GMP Guide for Pharmaceutical Excipients IPEC Good Distribution Practices Guide IPEC-Americas Significant Change Guide IPEC-Americas Certificate of Analysis Guide IPEC Stability Guide Match risk and controls IPEC Standardized Quality Agreement Template

14 Excipient Qualification is like a marriage Need to know that maker and user - Are compatible Can satisfy Will be supportive Will be reliable Will understand Will contribute Will communicate

15 Not like a marriage Your supplier will have many partners Many excipient suppliers have their primary business in food, cosmetic, or industrial markets Products targeted at Food, Beverage, Industrial, and Cosmetic Small fraction of Main Production Volumes for excipient Varying degrees of dedicated R&D related to excipient uses Specifications-driven by main market (usually not Pharma) Global Market and Manufacturing Base Some excipient manufacturers only ship bulk or full truck load thus making repacking or shipping by a distributor necessary Qualification must achieve mutual agreement

16 Before and after Before ISO9001:2000 Q10 After The squeezing of the supply chain in the late 1980s and the 1990s Quality Management Principles ISO/TC176/SC2 1997/05/29

17 Quality Management Principles Customer-Focused Organization Leadership Involvement of People Process Approach Systems Approach to Management Continual Improvement Factual approach to decision making Mutually Beneficial supplier relationships

18 IPEC Excipient Qualification Guide The Guide is a consensus document between IPEC-Americas and IPEC Europe. It is a Guide, not a regulation but an aid to help users and makers find reach understanding and agreement The Guide represents sound advice for the introduction and assessment of new excipients or new sources of existing excipients. It is not necessary to follow the Guide to the letter, or the precise order of steps. Three phases of qualification The Excipient Supplier s Process The User s Process The Negotiation Process

19 Phase 1: Excipient Supplier s Process Section 2: General Guidance Differentiation of Excipient Manufacture Preliminary Marketing Decision Regulatory Assessment Safety New Compendial requirements Excipient master files Harmonization Manufacture and Packaging

20 Phase 1: Excipient Supplier s Process Section 3: Excipient Development and Specification Process Excipient Consistency and Control Performance Indicators Production Specifications and Master Batch Record Marketing Materials Customer Feedback Post Launch Confidentiality

21 Phase 2: The User s Process Section 4: Assessment, Selection and Specification Process Project initiation New Formulation Development Selecting the Excipients Selecting the Supplier Regulatory Assessment Refining the Excipient list Formulation Design, Development and Optimization Alternate Excipient Sourcing

22 Phase 3: The Negotiation Process Section 5: Negotiating the Supply Review of User Requirements Quality Agreement Modification of Requirements Potential solutions Lot selection Manufacture to order Other approaches In-house processing Reformulation Custom manufacture

23 Flow Diagrams The flow diagrams are intended to augment the explanation given in the body of the Guide. Three interlinked flow diagrams Phase 1: The Excipient Manufacture s Process Phase 2: The Excipient User s Process Phase 3: The Negotiations The flow charts each cover more than one page: (Phase 1: 2 pages, Phase 2: 3 pages, Phase 3: 3 pages)

24 How do you know your excipients were made following GMPs distributed following GDP? Receipt testing? Not practical to test for everything Sampling is still just a sample Testing tells you about this lot not the next Ask the supplier? Good start but who are you asking? Are the answers the whole story? Ask the Government? Good start but absence of information is not conformation that all is well Audit the supplier? 24

25 Why do we audit? Primary Goal Document what is right Collect objective evidence to show the quality system is functioning as designed and the desired outcome is being achieved Show the system is suitable, adequate, and effective Secondary outcome Identify opportunities To reduce risk and improve supply To identify areas that do not add value To identify process that do not meet their target Provide management information to make fact based decisions regarding the quality system

26 Help bring your suppliers up You came all this way to get evidence to support in support of qualification Why not support the supplier Language differences exist between the chemical and pharma industries You came all this way to get some information don t let the words get in the way of finding out what s going on IPEC Guides help with translation

27 Conclusions Qualification is necessary across the entire supply chain from manufacture to end user The IPEC Excipient Qualification Guide is the document that links together all other IPEC Guides. The guide helps users and makers build mutually beneficial relationships The guide cannot cover all possible scenarios. Users of the guide should decide for themselves what is relevant to their needs. Good qualification process makes for a happy marriage IPEC Guides help

28 Resources IPEC Download IPEC Guidance documents Available for free (do need to register)

29 THANK YOU! Special thanks to: Janeen Skutnik Pfizer / IPEC-Americas Irwin Silverstein IPEA Dave Schoneker Colorcon/IPEC-Americas Chris Moreton FinnBritt Consulting dale.carter@huber.com William Dale Carter Director of Global Quality JM Huber, Engineered Materials Silica 1000 Parkwood Circle Suite 1000 Atlanta, GA Phone