ABB自控-01_Life Science Sales for ABB 2014 Channel Partner Conference Rev 1.

1、Life Science Sales Zenith Technologies 姓名，职位，过程自动化控制技术业务部，姓名，职位，过程自动化控制技术业务部，2014年年2月月26日日 Zenith Technologies Privately Owned Company Head Office: Cork, Ireland Founded: 1998 Employment: 400 14 Offices on 3 Continents Dedicated to Life Sciences markets , largest life science vertical integrator Ven

2、dor Independent Exclusively aligned with ABB in China Electronic Signatures and Validation. If Record Keeping is Electronic in Nature, then organization must follow these rules for Electronic Records; Electronic Signatures and Validation. Regulatory and Guidance Overview Regulatory Environment In al

3、l countries manufacture, storage and distribution of food and pharmaceuticals are regulated by law to protect the consumer. This originates from accidents in medicine production which caused serious illness or injury, most notably relating to the drug Thalidomide “Thalidomide had passed safety tests

4、 performed on animals, primarily because the proper tests particularly those involving pregnant animals had not been done. A court trial revealed that some tests were either conducted inadequately, or the results were faked. There is also some evidence that the tests were carried out on a particular

5、 isomer of the drug” Regulatory and Guidance Overview Role of the Regulatory Authorities Provide Best Practice directives as part of the law Carry out audits of manufacturers to make sure they are complying with directives Its all about Documentation If it moves, train it If it doesn t move, calibra

6、te it If its not written down, it didn t happen Regulatory and Guidance Overview USA the FDA In the USA, GMPs are written into law and are policed by the Food and Drug Administration through the Code of Federal Regulations. 21 Code of Federal Regulations Part 210 Current Good Manufacturing Practice

7、in Manufacturing, packing or holding of drugs; General Part 211 Current Good Manufacturing Practice for finished pharmaceuticals Regulatory and Guidance Overview EC Commission In Europe, the guidelines are provided through the EC directives. Commission Directive 2003/94/EC, of 8 October 2003, laying

8、 down the principles and guidelines of good manufacturing Replacement of Commission Directive 91/356/EC of 13 June 1991 Commission Directive 91/412/EEC of 23 July 1991 laying down the principles and Guidelines of good manufacturing practice for veterinary medicinal products. Regulatory and Guidance

9、Overview Other Local Regulatory Bodies MHRA in UK IMB in Ireland HSA in Singapore TGA in Australia Regulatory and Guidance Overview China CFDA in China Adopted regulations and standards very similar to those in the EU Regulatory and Guidance Overview The ICH The International Conference on Harmonisa

10、tion of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) Unique in bringing together the regulatory authorities and pharmaceutical industry of Europe, Japan and the US* to discuss scientific and technical aspects of drug registration. * the China ICH Group held a Study

11、Workshop in Beijing 25- 26 Oct 2012 Regulatory and Guidance Overview ICH Guidelines ICH Guidelines provide a harmonised approach to compliance. Regulatory and Guidance Overview ISPE “.ISPE is the worlds largest not-for-profit association dedicated to educating and advancing pharmaceutical manufactur

12、ing professionals and their industry. Founded in 1980 with less than 200 Members, today ISPE serves 23,000 members in 80 countries.” Parent organisation and admin to GAMP, JETT, SIGS Produces White Papers, “Baseline Guides”, GAMP Guides Runs training and seminars related to validation and regulatory

13、 issues Hugely influential, close links to FDA and other Regulatory agencies Regulatory and Guidance Overview 21CFR Part 11 - Background Before Aug 20 1997 Pharmaceutical manufacturers could not legally use electronic records even though electronic methods of document production and storage had alre

14、ady been in use for many years. The reason for this was that the existing FDA regulations clearly stipulated that for traceability reasons the hand-written signatures of 2 persons were required to validate cGMP-sensitive documents and records. The Pharmaceutical industry asked to be allowed to use e

15、lectronic records and signatures in place of paper records, to reduce the paperwork burden. Regulatory and Guidance Overview 21CFR Part 11 - Background The FDA deliberated for some years before agreeing and publishing a new chapter called 21 CFR Part 11*. The new Regulation went much further however

16、 than simply facilitating a paper-free world, 21 CFR Part 11 states that the use of electronic records is purely voluntary. But this is only for users who are currently using a completely manual/paper system. (This means almost nobody!) All companies who have any computer system whatever producing,

17、using or storing GMP-critical electronic records are now under the scope of new the regulation. The original goal was to achieve completely paperless submissions by 2002! Regulatory and Guidance Overview 21 CFR Part 11 Fundamentals E-sig/record regulations give the acceptance criteria for considerin

18、g electronic records and electronic signatures handwritten signatures executed to electronic records handwritten signatures executed on paper record EQUIVALENT Methodology Typical V model to Project execution Any deviations tracked in Incident Management System and implemented through Change Control

19、 System Methodology Typical Supplier / User interaction Supplier Audit (Performed by User) Engineering Feasibility Study Proposal (PQEP) Functional Specification (Trace to URS) Detail Design Spec. (Trace to FDS) System Acceptance Test Specs IQ/OQ System Acceptance Testing and Results Training , Main

20、tenance and Support Docs RFP Proposal PO PO Issue Approval Issue Approval Issue Approval Discussion of each major stage/deliverable Validation Plan Computer System Validation Plan typically generated for an automation project Responsibility for generating the plan differs depending on the project Mu

21、st be aligned with the Site Validation Master Plan (VMP) Corporate standards/policies GAMP - template for VMP/VP Validation Master Plan System Specific Validation Plan Discussion of each major stage/deliverable Validation Plan - Purpose VP should define (for the project scope): Definition of the sys

22、tem impact GAMP categorization What validation lifecycle activities are required How will they be performed, and whos responsible Whats the output of the activities What are the requirements for acceptance How will the validation status be maintained for the lifetime of the system Training requireme

23、nts Validation Master Plan System Specific Validation Plan Discussion of each major stage/deliverable Risk Assessment - GAMP-5 Risk based approach Why risk based approach Focus on the Quality Aspect of implementation Consider what will impact the product AND discount what will not This approach will

24、; Reduce the cost of validation Eliminate unnecessary qualification time Focus on what Matters Discussion of each major stage/deliverable URS - Purpose Define clearly and precisely, what the user needs the system to do Should express requirements, not solutions Requirements should be testable Unders

25、tandable by both user and supplier This is the user “need” list not the wish list! Communication user/supplier understanding Can have multiple URS docs for one system User Requirements Spec (Living Document) Discussion of each major stage/deliverable URS - Common Pitfalls Unintentionally Vague Requi

26、rements project not scoped properly Intentionally Vague Requirements Rush to get URS approved Dont want to update URS when changes are made Get more from the vendor open to interpretation! Requirements not concrete not testable User Requirements Spec (Living Document) Discussion of each major stage/

27、deliverable URS What was asked for User Requirements Spec (Living Document) Discussion of each major stage/deliverable URS What was given User Requirements Spec (Living Document) Discussion of each major stage/deliverable Traceability Matrix Purpose Ensure that all requirements specified in the URS

28、are addressed and delivered in the tested system, i.e. Requirement specified in the URS Requirement traced through to the approved design Requirement verified as being met during the test phase Discussion of each major stage/deliverable Traceability Matrix Purpose Very useful tool ensures nothing ge

29、ts forgotten Many ways to approach the matrix ref GAMP Matrix format very user friendly Start the RTM once URS is complete Critical is providing evidence of validation URS Reference URS DescriptionFS Reference DS Reference Test Reference Section reference List requirement text here Section reference

30、 Section reference Section reference Discussion of each major stage/deliverable Functional Specification Purpose FS is the vendor response to URS FS defines clearly and precisely what the vendor will supply in the system, i.e. Defines solutions to the requirements in URS Defines what the system will

31、 do Defines what functions/facilities will be present Supplier can do list FS outlines design objectives, i.e. input to DS Communication user/supplier understanding Can have multiple FS docs for one system Functional Specification (Trace to URS) Discussion of each major stage/deliverable Functional

32、Specification Approach Many ways to approach the FS ref GAMP All requirements identified in the URS must be traceable to the FS The functions in the FS can mirror the functional requirements in the URS if they are the same Any divergence between FS and URS should be noted in the FS and changes refle

33、cted in the URS (next rev?) FS needs to be explicit must be testable Functional Specification (Trace to URS) Discussion of each major stage/deliverable Design Specification Purpose DS defines how the system will provide the functionality outlined in the FS Allows the user to assess and approve the p

34、roposed design before build The detailed specifications used to build the system Can have multiple DS docs for a system (software, hardware etc) Detail Design Spec. (Trace to FDS) Discussion of each major stage/deliverable Design Specification Approach Many ways to approach the DS ref GAMP All funct

35、ionality identified in the FS must be traceable to the DS Any divergence between FS and DS should be noted in the DS and changes reflected in the FS (next rev?) DS needs to be explicit must be testable Detail Design Spec. (Trace to FDS) Discussion of each major stage/deliverable Modular Design/Devel

36、opment Large system modular software development makes sense Design/build/test in small manageable chunks Integrate the tested chunks and test the integrated system Bottom up approach makes sense Every module (chunk) - own design specification Software Module Design Specification (SMDS) DS would als

37、o be generated as well as SMDS S88 compliant solution such as 800XA allow this approach Detail Design Spec. (Trace to FDS) Discussion of each major stage/deliverable Modular Design/Development Detail Design Spec. (Trace to FDS) Unit Procedure 1 Procedure 1 Phase 2 Equipment Module 2 Control Module N

38、o. 5 Control Module No. 6 Control Module No. 7 Control Module No. 8 Unit Operation 2 Phase 1 Equipment Module 1 Control Module No. 1 Control Module No. 2 Control Module No. 3 Control Module No. 4 Unit Operation 1 Unit Procedure 2 Structural representation as per Unit Procedure 1 Discussion of each m

39、ajor stage/deliverable Test Specifications Lots of different types of acceptance test specifications: Software Module Test Specifications Software Factory Acceptance Test Specifications Hardware Factory Acceptance Test Specifications Site Acceptance Test Specifications Different types of qualificati

40、on test specifications: IQ OQ PQ System Acceptance Test Specs IQ/OQ Discussion of each major stage/deliverable Acceptance Test Specifications Purpose The purpose of the test specification is to specify tests which (when executed successfully) will verify correct implementation of the approved design

41、 Approach Acceptance test specification must be fully traceable to approved DS All functionality/system information (in the DS) must be fully tested in the acceptance test specification (leveraging supplier testing GAMP5) The following should be outlined for each test: Test objective Test method Tes

42、t acceptance criteria System Acceptance Testing and Results Discussion of each major stage/deliverable Qualification Verifies Verifies Verifies Discussion of each major stage/deliverable Qualification - Purpose IQ - verification that system is installed correctly as per specifications OQ - verifies

43、the functionality of the system throughout its operating range as defined in the specifications PQ verifies that the system works correctly and consistently as defined in the URS Zeniths Approach QMS Zenith Technology is an ISO certified organization. Zenith (China) follows guidelines as defined in

44、our Global QMS (Quality Management System) these are based on the GAMP and ISO guidelines. The QMS in continually audited and updated to be inline with latest required In Zenith Technologies Quality inspection and Quality control is monitored for every project by and Independent Quality department.

45、95% of Control systems supplied by Zenith Technologies are for cGMP projects with 21 CFR Part 11 compliance requirements. It is the way we work every day Life Science Sales What is important? + TechnologyMethodologyPeople = Customer Need Achieving a validated System People The Key to Life Science Sa

46、les People are the key to delivering what the customer needs. Knowledge is vital in understanding customer requirements Validation Process Qualification The pain points a customer faces in the context of the above It is not simply about quickly delivering the software Notice Software / Hardware is o

47、ften not a key concern Knowledge API Manufacturing The manufacture of Active Pharmaceutical Ingredients Synthesis of complex molecules using chemical reactions Use of solvents Purification and separation of finished product (usually powder) Powder including active ingredient is used to produce Table

48、ts or other finished pharmaceutical in a finishing facility. Knowledge Typical Chemical Synthesis API Process Train Chemical Reaction Phase Separation Crystallisation Distillation Solvent Addition Solvent Addition Water Solids Addition Filtration Drying Solids Addition API Solids Addition Powder Dis

49、charge Reactors Filter Dryer Liquid Processing Solids Discharge Knowledge Biological Manufacturing The manufacture of Biological agents / Vaccines Biological medicines are typically derived from living organisms Made by genetically engineering living cells Plant divided into Upstream / Downstream /

50、Utilities Sterility of facility is important design concern Batch manufacturing can range from days to weeks per batch Knowledge Biologicals - Upstream Media Preparation Buffer Preparation Fermentation Scheduling of batches important for Media and Buffer availability for Fermentation area Temperatur

51、e, pH, Dissolved O2 and Agitation control critical areas in processing Transfer Line CIP and SIP can be complex depending on the plant flexibility Stability and repeatability are key areas in producing approved product. Knowledge Biologicals - Downstream Vendor equipment skids , Ultrafiltration / Di

52、afilitration skids Chromatography skids, Depth Filter Skids, Virus filter etc. Skid Controlled with data capture to DCS Maintain communications standard for all equipment skids to reduce cost and effort integrating to DCS Fully integrate control of vendor skids on DCS Work closely with skid vendor t

53、o put DCS controls on the vendors skid Flexible peak detect algorithms for multi-product facilities. Cleaning/Steaming and storing of vendor skids integrated Knowledge Biologicals Clean Utilities Water For Injection (WFI), Purified Water (PW), Pure Steam (PS) Critical to the operation of the plant Clean utilities generation on PLCs with interface to DCS for reporting and trending Distribution loops for water systems critical as any interruptions in supply can mean process down time Critical alarms used to allow users to request and rece