How to implement the electronic manuafacturing guides in pharma industry.

1. www.mesa.org2010 European Conference Unlocking Your Operations Potential
November 9-10, Düsseldorf, Germany
Improving operations
performance through eGuides
in regulated industry
David Badia
Principal consultant & CEO

2. 2
The following Strategic Initiatives of
MESA International are associated with
this presentation:
Lean Manufacturing
Quality & Regulatory Compliance
Real-Time Enterprise

3. 3
1. Traditional manufacturing operative in question
2. Common Manufacturing Guide context
3. Implementation of a Manufacturing eGuide
4. Resources to use & how to make MeG real.
5. Almirall’s way to operations excellence
6. Continuous improvement …
7. Questions & answers.
Improving operations
performance through eGuides

4. 4
Processes and Operations in the pharmaceutical plants:
– Specialized preparation of materials: weight and dispense
• Order and recipe management systems.
– Complex production processes: formulation
• advanced instrumentation, control and analytical technology.
• batch control systems.
– High integrated conditioning and packaging lines
• Supervisory, inspection and statistical quality control systems
Capacity & reliability specialization & automation
Traditional Manufacturing
operative in question

5. 5
Processes and Operations in the pharmaceutical plants:
– Production modules: granulation, mixing, drying, compression,
coating, ...
– Conditioning and packaging modules: filling, blistering, cartoning,
packing, …
– Manual activities: cleaning, sample collection, in-process quality
control, format changes, equipment setup, visual inspections, …
flexibility & productivity  manual supervision using paper !!
Traditional Manufacturing
operative in question

6. 6
Typical documentation which remains on paper:
– Product related: recipes, bills of material and material safety data.
– Job related: standard operation procedures, work order.
– Asset related: operating instructions and “set-up” specifications.
… but also:
– Reports for production release and certification.
– In-process control forms.
– Sample collection forms for analytical quality control.
– Logbooks of other daily activities.
– Operation yield control records.
– Annotations of exceptions, deviations and failures.
Traditional Manufacturing
operative in question

7. 7
1. Traditional manufacturing operative in question
2. Common manufacturing guide context
3. Implementation of a Manufacturing eGuide
4. Resources to use & how to make MeG real.
5. Almirall’s way to operations excellence
6. Continuous improvement …
7. Questions & answers.
Improving operations
performance through eGuides

8. 8
•Production and conditioning of
pharmaceutical solid dose products:
•Production:
•Granulator module,
•Blender module,
•Tableting machine,
•Coating machine.
•Conditioning:
•Blister line,
•Cartoner machine and
•Case packer.
Manufacturing operations guide applied to:
Common Manufacturing Guide
context

9. 9
Order
Scheduling
Recipe
Management
QC
Sampling
operation
Weight &
Dispense
operation
Solid
dosing
operation
Liquid
formulation
operation
Solid
formulation
operation
Quality
Assurance
Production
Supervision
Lot preparation at
production plant level

10. 10
Weighed RM
in a BIN
Empty
containers
Weighed RM
in a box
Intermediate
prod. containers
W&D
Report
Box
roadmap
BIN
roadmap
Module
SOP
Module
Logbook
Manufact.
Guide
Machine
Specs.
In-Process
Control
Selección de evacuación posterior de Palet M.P. en SAS
Comprobar Condiciones
de Manipulación
Inicio Pesada
Etiquetado y Tarado de
envase
Tarado del BIN
Recepción BIN
Lectura de Bultos y
Pesada de Materia Prima
Recepción y Validación de
la Paleta
Aceptación de la Pesada
Introducción de Materia
Prima pesada en el BIN
Evacuación de la paleta y comprobación peso SAS
Llenado de paleta
vacía con bultos pesados
Limpieza de componente
BIN (1ª Pesada)
Resto pesadas BIN
Armario o
Pesada pico
BIN
Pesada en BINPesada en Envase
Báscula 2, Pesada no aceptada
BIN y Pesada en Envase
A partir de la segunda pesada de
la misma paleta
Primera pesada,
cambio de
paleta o
reanudación
Quedan
pesadas
por
realizar
Según procedimiento
Identificación de Bulto
Pesado
Synoptic
graphs
Material
Safety Data
Scale
SOP
Production
Report
Samples to
laboratoryQA
Analysis
Lot preparation at production
module level

11. 11
Documents used or generated in the production module:
1. Weight and dispense order report,
2. Material in box container roadmap,
3. Material in BIN container roadmap,
4. Module room cleaning Standard Operating Procedure (SOP),
5. Module tasks logbook,
6. Guide of operations of manufacturing workorder in the module,
7. Set-up, configuration and cleaning SOP for equipment and
tools.
8. Synoptic graphs of equipment and accessories.
9. Material safety data specifications,
10. Test of samples for in-process control SOP,
11. Scale standardization and operation instructions,
12. Sample collection for analysis in QA laboratory and for
mandatory storage of lot samples.
Information at production
module level

12. 12
1. Traditional manufacturing operative in question
2. Common manufacturing guide context
3. Implementation of a Manufacturing eGuide
4. Resources to use & how to make MeG real.
5. Almirall’s way to operations excellence
6. Continuous improvement …
7. Questions & answers.
Improving operations
performance through eGuides

13. 13
The “electronic” guide of Manufacturing
operations is based on moving from the
shape of the “traditional” manufacturing
guide of a product or recipe on paper,
to an interactive information technology
system with the conversion of contents and
documents in digital data and files,
interrelated in a plant operations model.
+
MeG
Implementation of a
Manufacturing eGuide

14. 14
+ Added value:
• Verification of manual data entry for reliability,
• Centralized access to documents related to MeG,
• Secure access to functions and assets,
• Lifecycle management of eGuides with version
control from edition to approval,
• Electronic signature to certify critical operations,
• Historical data log records protected,
• Audit trail of data changes in regulatory records,
• Advanced reporting of genealogy and traceability.
MeG
Implementation of a
Manufacturing eGuide

15. 15
1. Traditional manufacturing operative in question
2. Common manufacturing guide context
3. Implementation of a Manufacturing eGuide
4. Resources to use & how to make MeG real.
5. Almirall’s way to operations excellence
6. Continuous improvement …
7. Questions & answers.
Improving operations
performance through eGuides

16. 16
1. Definition and approval of a eGuide.
2. Plan and assign a Guide to a work
order for a product or recipe.
3. Execute the operations of work
order.
4. Track and analyze the activity and
results.
Audit the manufacturing process.
The fundamental process of the manufacturing guides is:
1
2
3
4
Resources to use & how to
make MeG real.

17. 17
• Step by step definition of operator actions inside
the eGuide.
• Modeling of production processes and routes of
the plant.
• Specific instructions for any process,
product/recipe and manufacturing route.
• Assignment of standard steps and actions to
define each operation behavior:
• Instructions and check-lists,
• Operator confirmation of execution,
• Operators single or multiple electronic signatures,
• Manual data entry,
• Process attributes or parameters registration.
eGuide & Recipe
Management
Definition and approval of a
eGuide

18. 18
Plant operations modelling in
the MeG, examples

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• Work Order creation for product or recipe
assigning an approved eGuide.
• Work Order release assigning a route of a
specific line or process.
• Tracking the status of current orders and
operations.
• Order management to change priorities,
suspend, release, sequence, close or cancel.
WORK ORDER
SCHEDULING
Plan and assign a Guide to a
work order

20. 20
• Operations execution and steps data entry.
• Record lot of items/materials consummed and
produced in the operation based on bill of material.
• Record of process events and exceptions.
• In-Process Control data entry for process
statistical analysis and product quality control.
• Display required SOP documents. Access to
additional files in folders during execution.
• Critical operations certification including
electronic signature.
PRODUCTION &
CONDITIONING
OPERATOR
Execute the operations of
work order.

21. 21
Supervisor
Conditioning process
Operation 100
Blistering
Operation 200
Cartoning
Operation 300
Packing
Operator
Work Order WO - 1
Operation 100
Blistering
ready
Operation 200
Cartoning
pending
Operation 300
Packing
pending
WO-1
Blistering
running
Blistering
completed
Cartoning
ready
Cartoning
running
Cartoning
completed
Packing
ready
Plant operations modelling in
the MeG, an example

22. 22
eGuide operator interfase,
examples

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• Support during execution of manufacturing
orders.
• Manufacturing order tracking.
• Review of Production data and results.
• Verification and acceptance of incidences.
• eGuide final report approval.
• Order release to next process.
PRODUCTION
SUPERVISION
Track and analyze the activity
and results

24. 24
1. Traditional manufacturing operative in question
2. Common manufacturing guide context
3. Implementation of a Manufacturing eGuide
4. Resources to use & how to make MeG real?
5. Almirall’s way to operations excellence
6. Continuous improvement …
7. Questions & answers.
Improving operations
performance through eGuides

25. 25
Almirall’s mission
To provide society with
innovative medicines
that help to improve
people’s health and
quality of life.

26. 26
Almirall’s centres
Headquarters:
R&D Centers:
Chemical plants:
Pharmaceutical
plants:
Affiliates:
• Barcelona
• Sant Feliu de Llobregat
• Bad Homburg (Germany)
• Reinbek (Germany)
• Chemical Synthesis Unit in
Sant Just Desvern
• Active Ingredient Scaling-up Unit in
Sant Andreu de la Barca
• Sant Andreu de la Barca
• Sant Celoni
• Sant Andreu de la Barca
• Sant Just Desvern
• Reinbek (Germany)
• Austria, Belgium, France, Germany,
Italy, Mexico, Poland, Portugal, Spain,
Switzerland and the United Kingdom-
Ireland.

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Almirall’s figures
• 239 pharmaceutical
specialties (*)
• 543 presentations (*)
• 57 countries
• 89.3 million units of
finished product
• 3.5 million units in bulk
(**) Third parties included

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Scope of implementation in
Sant Andreu plant
• 3 QC/Sampling cabins
• 5 Weigh&Dispense cabins
• 3 Liquid formulation modules
• 3 Solid formulation modules
• 6 Doses production modules

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Recipe Edition and
Management
• Weigh, formulation and
dispensing recipe edition.
• Paperless manufacturing guide
implementation.
• General Unit Procedure.
• Bill of Equipment (BOE).
• Use of action list with steps
– Instructions with check-in lists.
– Signatures (initial, single, double)
– eDocuments: Standard operation
procedures (SOP), material safety
data sheets (MSDS), process
synoptic graphs and other specs.
• Recipe review and approval cycle.

30. 30
Manufacturing Orders
Scheduling
• Orders are released from the ERP
based on plant capacity.
• Automatic generation of mfgt.
orders in the POMS MES system.
• Batch generation for weight, liquid
formulation, solid formulation and
solid dosing operations.
• Assignment of related process
unit.
• Exception monitoring.
• Procedure traceability.

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Solids Formulation Operation
• 2 formulation lines: dryer line and
mixer line.
• Combined or separated operation.
• Manufacturing eGuide by actions
• Check-in process unit and assets.
• Registration of raw material and
WIP containers.
• Minor raw materials preparation in
auxiliary tank.
• Cleaning control of cabin &
assets.
• Automated BIN movement control.
• Formulation batch report.

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Solids Dosing Operation
• 6 dosing lines: tablets, capsules
and sachets.
• Manufacturing eGuide with
process synoptic and product
specs.
• Check-in process unit and assets.
• Registration of conditioning
material and empty drum carriers.
• Units registration of bags and
drums with barcode labels.
• Control of dose weigh.
• Waste reporting and mass yield
calculation of batch.
• Dosing batch report.

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Production supervision
• Support during execution of
manufacturing orders.
• Exception management.
• Review of Production reports.
• Verification and acceptance of
incidences.
• Production report approval.
• Order / Batch release to next step.

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• Technological infrastructure update
(equipment, hardware & software)
• Standard life sciences MES
package but customizations
required
• Logistics System integration.
• Minimal interferences with plant
production planning.
• System Qualification and Validation
for regulatory compliance.
• External plant personnel.
• Communication with legacy
equipments, systems and
installations.
• International supplier with a
recently new local integrator.
• Standardization and
homogenization of the system
among the processes.
• Project scope spitted in 3 phases
for shorter milestones, visible
results:
(1º) QC / Sampling,
(2º) Weigh & Dispense,
(3º) Formulation and Dosing.
• Specialized consultancy:
intensive work vs constant work,
consultancy costs vs training costs.
• Evaluation of the real effort with an
assumable planning for everybody.
• Creation of a multidisciplinary
human team for the project.
• Certified technical training and
practical learning by doing.
• Analysis of requirements in depth.
• Realignment with the standard
MES product functionality to reduce
customizations.
Challenges and solutions

35. 35
1. Traditional manufacturing operative in question
2. Common manufacturing guide context
3. Implementation of a Manufacturing eGuide
4. Who & how make MeG real?
5. Almirall’s way to operations excellence
6. Continuous improvement …
7. Questions & answers.
Improving operations
performance through eGuides

36. 36
• for the definition:
• Assets specifications, set-up instructions and parametrization.
• Shopfloor devices & equipment interface (for automated plant
data collection, conection to field instrumentation, etc.).
• for scheduling:
• ERP system interface of work order, inventory, reporting material
quantities of production, consumption and scrapts.
• for execution:
• Data entry of production, consumption and scrapts of material.
• Asset set-up based on specifications.
• Automated plant data collection for step action and data logging.
• for analysis:
• Raw material lot traceability during operations (work in process).
• Product genealogy, Inventory reports, Work order event logs.
• Audit trail reporting.
Continuous improvement ...
enhanced functionality

37. 37
• Common model and services available
• Modular and scalable system’s architecture
Using
• Dynamic order priority and route sequencing
• Human resources tasks management
• Shopfloor interface to equipment and HMI.
Using
• Real time inventory management
• Definition of materials, substitutes y secondary prod.
• Bill of Material (BOM)
Using
• Manufacturing centralized model
• Implementation of Standard Operational Procedures
• Certification of critical events
Using
• Current Work Order in process management
• Production events recording
Using
Current production vs. plan
compliance
Process and production
consistency improvement
Inventory performance
improvement
Order “Lead Time”
reduction
Using an incremental
approach to the operational
improvement
Continuous improvement ...
bigger scope

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• ANSI/ISA-95: Enterprise-Control System Integration.
• GAMP5: Good Automated Manufacturing Practice. Guide
for Validation of Automated System.
• CFR Title 21 FDA Part 11 – Electronic Records; Electronic
Signatures (USA CFR regulation).
• Guidance for Industry Parte 11, Electronic Records;
Electronic Signatures – Scope and Application
(August 2003).
• Risk Based Approach to Compliant Electronic
Records and Signatures (ISPE, October 2005).
Continuous improvement ...
regulatory compliance

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The manufacturing operations eGuide
is a key to success of plant continuous
improvement strategies,
helping in the daily tasks of all human
resources responsible for manufacturing,
sharing essential information
across plant areas and
enabling regulatory compliance.
The IT “facilitator” of plant
human resources
MeG

40. 40
1. Traditional manufacturing operative in question
2. Common manufacturing guide context
3. Implementation of a Manufacturing eGuide
4. Who & how make MeG real?
5. Continuous improvement …
6. Almirall’s way to operations excellence
7. Questions & answers.
Improving operations
performance through eGuides

41. 41
INLEAN
C/ Jordi Girona, 1-3,
Parc UPC – K2M
08034 Barcelona, SPAIN
Tel. +34 93 494 1411
www.inlean.com
linkedin.com/in/davidbadia
twitter.com/davidbadia
david.badia@inlean.com
David Badia
Improving operations
performance through eGuides
Thank you!