Electronic Batch Recording

1. Electronic Batch Recording Kevin Walls Senior Solutions Consultant

2. The Canadian Market • Canada has the 4th largest concentration of pharmaceutical and biotech companies in North America with over • 100 bio tech firms; • 112 manufacturing facilities; • 21 research institutions; • large number of headquarter locations. • Account concentration is primarily in Ontario and Quebec. • Toronto, Mississauga, Kingston,Ottawa, London, and Guelph, Montreal, Laval, Quebec City Get Pacific NW Data

3. Agenda • What is EBR ? • Making the Business case • Operational and Financial Benefits • Strategies • Best Practices-Implementation • How Electronic Batch Records aid in Regulatory Compliance • What Comprises a World Class EBR Solution • Conclusion

4. "We Are Producing Two Things: Paper And Drugs" Look familiar ?!

5. Research Clinical Trials Small Batch Full Production

6. What is EBR ?

7. What is EBR ? • Electronic Batch Recording • Operator Instructions • Data Collection • Electronic Batch Record • Final electronic record of the Batch • Compilation in a single electronic record of all • Information • Data • Documents

8. Electronic Batch Record • Electronic Batch Record • Collection of Information required for reporting to • QA • Contract Customers • FDA • Provides for • Complete history of Batch • Identification of Material and Quality data of materials • Operator interactions • Electronic Signatures • Systems Data • LIMS • Automation • Historian • QA Reports • Quality due-diligence Information

9. What an Electronic Batch Record is Not • Your Old forms, reports scanned into a system i.e. “Paper Under Glass” • An Electronic Document Management Systems (EDMS) • Generally manages the creation of SOP’s, forms, memo’s, procedures • Electronic Records Management Systems (ERMS). • Contains scanned or other electronic forms of documents

10. It’s Simple ! • Implement an EBR System!!!! • Pull together… • Product definition (master data management) • BOM • Work instructions • Production execution (electronic batch sheets) • Weigh and dispense operation reports • Primary Manufacturing • Formulation • Filling • Compression • Etc. • Secondary Manufacturing • Sub assembly • Finished goods • Production information (Automation batch records) • Capture processing formation directly • Automation layer information • Select Data Historian Data

11. Lessons Learned • Build a Business Case first • Analyze the Business Process • Utilize previous work in • Standards • Vendor Systems • Implement in successful phases • What makes sense for You • Change management – People

12. Develop High Level Project Plan • Early phases • Education • Solve problems • Go for “low hanging fruit” • Later phases • Advance future strategy • Improve enterprise workflow (integrate) • Implement additional components of the strategy • Information access “gold mining” • Process improvements • Analyze optimum production batches • Deviation analysis • Tool for improved decision making

13. Critical Issues • Failure to observe and understand current processes that will be covered by EBR • Missing, erroneous, inadequate operator Instructions • Incorrect sequencing of steps that will impact enforcement of sequence • Lack of knowledge of source of the data • Missing, erroneous, inadequate equipment information

14. Critical Issues • Lack of processing specifications that become alarms • Current MBR is not aligned with process validation • Understanding process to handle documents not part of MBR • Willingness to modify the current SOP’s with new EBR system • 80% of SOP’s should be handled by the EBR not in an SOP • Requirements on tracking items and samples • Decisions on interfaces and other systems

15. Legal • The law does allow for records to “be retained either as original records or as true copies such as photocopies, microfilm, microfiche, or other accurate reproductions of the original records. • To adopt such a system the standard operating procedures (SOPs) must have a consistent approach to scanning documents and the SOPs must specify who is to perform the scanning. Despite the allowance for maintaining copies within the CFR, many pharmaceutical companies are hesitant to implement this type of solution because the electronic version of the document is not the original and they are reluctant to make decisions that are not based on original documentation.

16. Canada Law • The Natural Health Products Regulations contain requirements for manufacturing, packaging, labeling, storing, importing, distributing and selling natural health products. It is the sale of natural health products for the purposes of manufacturing, packaging, labeling etc. that is captured by these Regulations, not the sale of natural health products by retailers. • These Regulations are intended to ensure that all Canadians have ready access to natural health products that are safe, effective and of high quality, while respecting freedom of choice and philosophical and cultural diversity. • The Natural Health Products Regulations • Administered by the Natural Health Products Directorate (NHPD), Health Products and Food Branch, Health Canada. • Published in the Canada Gazette, Part II on June 18, 2003. • The NHP Regulations will come into force on January 1, 2004, with a transition period ranging: • Two years (for site licensing) to • Six years (for product licensing, for products already issued a Drug Identification Number).

17. Natural Health Products Regulations • Module 10: Records • Among manufacturers, packagers, labelers, importers and distributors of natural health products, who shall maintain: • A. The master production document • B. The list of ingredients contained in each lot or batch • C. Records of any assessment conducted • D. A copy of the specifications • E. Records containing sufficient information to enable the recall of every lot or batch of the natural health product that has been made available for sale

18. US Law Code of Federal Regulations, Title 21, Food and Drugs http://www.access.gpo.gov/cgi-bin/cfrassemble.cgi Part 11 Electronic records; electronic signatures 200 General • Labeling GMP 210 Current good manufacturing practice in manufacturing, processing, packing, or holding of drugs; general 211 Current good manufacturing practice for finished pharmaceuticals 226 Current good manufacturing practice for Type A medicated articles

19. Making the Business Case

20. Factors for Consideration Validation Maintenance Training Acceptance Integration test Integration HW installation Pre-acceptance System test SW module test SW design / implementation Basic design User requirements specification Maintenance / support Developing system Specify • Quick successes • Enroll • Show a return to your organization • Manage scope • Watch for scope creep • Map all decisions to the future strategy • Cost associated with each solution • Licenses • Services • Validation • Develop metrics for measuring success • 1st time approval rate on batch records • Cycle time reduction • Reduction of batch related exceptions

21. Current “As-Is” Situation • Interview key individuals • Identify their pain • Solicit ideas • Assess existing support systems • Look for redundancy • Identify functional gaps • Analyze current business operation • Study current workflow/processes • Review audit reports • Internal • External (e.g. FDA) • Review deviation logs/reports • Analyze a cross section of executed batch records • Identify “real cycle time” • Calculate impact of a MES solution • Labor intensive process! • Requires a knowledgeable individual

22. Supply Chain • Visibility to plant floor • Electronic “white” board • Real time information • Lower Cost of operations • Cycle time reduction • Increase inventory turns • Reduce WIP • Improved customer delivery performance • Competitive tool

23. Design Future State Strategy (To-Be Model) • Summarize findings • Identify real “pain” to the organization • Myth-busting or paradigm shift • Develop a vision of the future • Review best practices • Describe the interaction of people and technology • Describe how strategy will solve existing problems • Outline a plan to attain that vision • Identify strategies to support organizational goals • Develop Benefits • Identify additional benefits to the organization • Provide metrics to measure success ($$) • 2 Batches saved = $$$$$$$$$

24. Operational and FinancialBenefits

25. Average Improvements with EBR • Reduced lead time 22 – 32% • Reduced cycle time 35 – 45% • Reduced data entry time 36 – 75% • Reduced WIP inventory 17 – 32% • Reduced defect rates 15 – 72% Payback periods range from 3 to 25 months MESA Survey (Averages)

26. Benefits • The advantages of an EBR system can be grouped into two categories: operational efficiency and compliance improvements. • Reduced cycle times – reductions in the physical passing of records between departments will lead to an overall reduction in the time needed to produce and ship product. • Inventory Reductions – reduction in “WIP” and held un-released inventory • Improved accuracy and consistency of batch record – the structure provided by the electronic batch records will decrease errors, which in turn will decrease the time spent by quality assurance in the review of these records.

27. Benefits • Reduced costs of compliance – automation of quality assurance functions and reporting features in the software will decrease the effort required to research product deviations. • Increased productivity – electronic exchange of batch records decreases the amount of time spent collecting the various components of the batch record from different departments. • Cost avoidance – batch records must be retained for at least one year after the expiration of product. Use of electronic batch records can eliminate the need to allocate resources to the storage and retrieval of archived batch records. • Increased speed of product changes and product introductions– use of electronic batch records in the development process will lead to greater efficiencies in a New Drug Application.

28. Benefits • Error reduction in documentation • Enforce data entry and sequencing • Provide immediate user feedback to adverse results • Eliminate calculation errors • Efficiency improvements • Eliminate redundant verifications • Materials checks • Weight verifications • Product Checks • Documentation requirements • Begin PAT indicatives • Time reduction in review cycle • Review by exception • Eliminate this step • Improve the demonstration of compliance! TRUE ROI!

29. Strategies

30. Shareholder Value

31. Strategic to the MES • MES with an EBR component. • Many manufacturers have an MES; however, it lacks the ability to capture all necessary data and summarize it in a format that is useful as a batch record • The real value to be gained by the MES is that it can be integrated with much of the equipment and systems used in the production process. This has two key advantages over data collection systems • The integrated MES will allow • Data to be captured in electronic form without the need to retain certain printouts • Significantly reduces the amount of human interaction that must occur in recording batch record information

32. Best Practices- Implementation

33. 4 Phase Approach • Phase 1 - Pre-Assessment Review ( MAP ) – • Definition of opportunity, Readiness and Scope • Time Required: 2-3 days • Phase 2 - Proof of Concepts (Select Recipe’s) • Initial Re-design • Documentation Guidelines • Pilot Testing, Change Control and Implementation • Time Required: 8-13 weeks • Phase 3 - Redesign & Harmonization • Re-design and harmonize remaining documents • Pilot Testing, Change Control and Implementation • Time Required: 13-16 weeks • Phase 4 - Additional opportunities • Add Manufacturing Execution System (MES) modules • Interface to business systems

34. 4 Phase Approach Benefits • See results following a thorough assessment and challenge of the current documentation • Simplification and elimination of all unnecessary, superfluous and redundant content that was not required for process control or cGMP reasons.

35. Document Reductions • Documents • Pages 30 - 50% reduction in pages • Entries 30 - 60% reduction in entries • Creation 25 - 40% reduction in document creation / revision time • Number 10 - 25% reduction in number of documents

36. Review Time Reductions • Review • Errors 50 - 80% reduction in documentation / procedural errors • Review 40 - 70% reduction in review cycle time

37. Cycle Time Reductions • Cycle Time • Release 30 - 60% reduction in product release • Manufacturing 15 - 20% reduction in manufacturing • Investigations 20 - 30% reduction in investigation time • New Recipe 10 – 45% reduction in Prep Time • Training 20 - 30% reduction in training time

38. World Class Solution • Meets all 21 CFR 11 Requirements • passwords, access, audit trails and Archiving • Creates new documents • in 10 to 20 percent of the time it normally takes • Makes simultaneous changes to multiple documents quickly and easily • Document Library • Documents are built using a library of work instructions (building blocks) that contains variable parameter fields for process or product specific information • Ensures documentation content • consistency through the use of building blocks and process templates • Archives all master documents

39. Phase 1 Head Text Weighing protocol Isolated dispensing system SCADA Equipment data Head Text Equipment Manual documentation and signature Head Text Operators Alarm lists and sensor curves Head Text Environment (e.g. sterile rooms) BATCH PROTOCOL Analyze and Re-engineer the Paper Batch Record

40. Phase 2 MASTER BATCH DOCUMENT Dispense Weighing protocol Integrated dispensing system SCADA Equipment data Equipment Manual documentation and signatures Head Text Operators Historian Alarming lists and sensor curves Environment (e.g. sterile rooms) BATCH PROTOCOL Uniform Style & Partial Automatic Data Acquisition

41. Phase 3 Complete Electronic Data Acquisition MASTER BATCH DOCUMENT DISPENSE Weighing protocol Integrated dispensing system SCADa LIMS Equipment data Equipment EBR Online-documentation and electronic signatures Operators Alarming lists and sensor curves Historian Environment (e.g. sterile rooms) BATCH PROTOCOL ?

42. Phase 4 • Phase 4 - Additional opportunities • Add Manufacturing Execution System (MES) modules • Dispensing • Finite scheduling • Key performance monitoring • Training qualification • Interface to business systems • Enterprise resource planning system (e.g., SAP, etc.) • Documentation (e.g., Documentum etc) • Laboratory management • Learning management

43. How Electronic Batch Records Aid in Regulatory Compliance

44. Even More Lessons Learned Master Data ERP data exchange via LAN, WAN, INTRANET Dynamic download of planned order Functions Finite scheduling at the electronic planning board Automated accounting of consumptions Production- control / data management,Reconciliation of resources Electronic order processing at the line monitoring system Order data Batch requirements Material data Trigger for material deliveries according to the pull principle Material Resources Don’t try to automate a disorganized paper system ! Validated Database

45. Good Models to Understand ERP Other Product definition Production capability Production schedule Production performance MES Detailed production scheduling Production tracking Production resource management Production dispatching Production Performance analysis Product definition management Production data collection Production execution Factory/Plant Automation Level 2 Control (Batch, Discrete, Continuous) Source: ISA SP95 Committee (modified)

46. Vertically Integrated Solutions PMX Time to Market, Financial Performance, Quality Web Marketplace Seamless Connectivity Primary Commercial Production Secondary Commercial Production Enterprise Systems ERP Manufacturing Execution Automation Platforms Intermediate Automation Components Bulk Plant Floor

47. What Comprises a World Class EBR Solution

48. What makes a Good Solution ? • Browser Based • Forward and Backward Visibility • Full Data Integration • ERP • Weigh and Dispense • LIMS • eDMS • Machine Devices • Process Control • Data Historian • MSDS • Material Certifications • SOP’s

49. Batch Recording Features EBR is the mechanism to enforce Good Manufacturing Practices and the ability to record the execution of GMP • Web based procedures • View and select orders • Execute electronic procedures • See forward and backward • Full security • Access SOPs and other supporting documents • Import Outside image and Documents • Electronic batch record review

50. Basic Instructions to Operator Graphics and Instructions Graphics and Instructions 21CFR part11 E-Signature And Comment SOP Jump to SOP or HTML or PDF Link in E-Document System Commit but stay on procedure