PHARMACEUTICAL PRODUCTION

Sandra Masanés Solid Bulk Manufacturing Manager

ABOUT MERCK Merck  is  the  world's  oldest  pharmaceu4cal  and  chemical  company.  Merck  family  started  their  tradi4on  in  the  pharmaceu4cal  industry  in  1668  in  Darmstadt  (Germany)  with  the  Angel  Pharmacy,  founded  by  Friedich  Jacob  Merck.    

Nowadays,  Merck  is  present  in  67  countries  and  with  around  40,000  employees,  Merck  is  s4ll  innova4ng  to  improve  and  construct  the  future.    The  founding  family  remains  the  majority  owner  of  the  company  to  this  day.      

At  the  end  of  the  First  Wold  War,  Merck  lost  his  companies  in  the  foreign  countries,  Merck  &  Co  among  them,  that  became  an  american  company  completely  independent.  

Since  1924  Merck  is  present  in  Spain,  currently  with  3  sites  and  900  employees:  •  Pharmaceu4cal  and  Chemical  Plant  (Mollet  del  Vallés,  Barcelona)  •  Biotechnological  Plant  (Tres  Cantos,  Madrid)  •  Central  services  (María  de  Molina,  Madrid)  

PHARMACEUTICAL PRODUCTION INDEX

-  Pharmaceutical Production : General Overview -  Bulk Manufacturing examples -  Tasks and Responsibilities -  Helpful tools :

v  Lean Manufacturing : 5S examples v  Performance Management : Dashboard v  KPI (Key Performance Indicators) v  Meeting cascading v  Problem Solving

-  Education and Soft Skills -  Questions

PHARMA PRODUCTION : General Overview

• From  the  receiving  of  the  raw  materials  in  the  warehouse  to  the  weighing  up  of  the  components  of  the  formula4on  for  each  product  

Dispensing  

• From  the  receiving  of  the  components  of  the  formula4on  of  each  product  to  the  obtaining  of  bulk  product  (pharmaceu4cal  dosage  form)  

Bulk  Manufacturing   • From  the  receiving  of  the  

bulk  product  to  the  terciary  packaging  (boxes  to  be  send  to  the  warehouse)  

Packaging  

BULK MANUFACTURING

BULK MANUFACTURING Tasks and responsibilities

-­‐  Recep4on  of  the  raw  materials  /  intermediate  containers  in  the  manufacturing  area.    -­‐  Manufacture  the  product  following  the  instruc4ons  (MBR  :  Manufacturing  batch  

records).    

-­‐  Clean  equipments  /  installa4ons  according  to  established  frequency  and  with  validated  cleaning  methods.  

 -­‐  Report  and  collaborate  to  fix  any  posible  devia4on  to  the  established  instruc4ons  if  

any  (breakdowns  of  equipment,  in-­‐process  controls  not  conforms,  etc..).  

-­‐  Agree  and  follow-­‐up  and  the  monthly-­‐yearly  produc4on  with  Demand  Planning  

-­‐  Con4nuous  training  of  people  working  in  manufacturing  produc4on  (Operators,  supervisors,  technicians).  

 

 

 

BULK MANUFACTURING Tasks and responsibilities (cont.)

 -­‐  Update  technical  documenta4on  to  assure  the  op4mum  performance  of  the  

department  à  Manufacturing  batch  records,  cleaning  methods,  equipments  instruc4ons,  SOP  (Standard  Opera4onal  Processes).  

 -­‐  Collaborate  with  Pharma  Technology  or  Galenical  department  in  technical  trials  and  

process  valida4ons.  

-­‐  Collaborate  with  Engineering  and  Maintenance  with  new  equipments  start-­‐up  (edit  URS  requirements,  IQ,  OQ,  PQ  protocols  and  reports,  preven4ve  and  correc4ve  maintenance,…)  

 -­‐  Propose  and  implement  tools  /  investments  to  op4mize  or  improve  the  daily  work    -­‐  Manage  and  monitorize  appropiate  KPI  (Key  Performance  Indicators)  according  to  the  

priori4es  of  the  department.  

-­‐  Personnel  management  à  Conflict  management.  Comunica4on  with  impact.  Feedback  coulture  

-­‐  …….    

BULK MANUFACTURING Helpful Tools

-  Lean Manufacturing : 5S examples -  Performance Management -  Meeting cascading -  Problem Solving

Lean Manufacturing -­‐  LEAN  MANUFACTURING  à  Several  methods  and  tools  to  help  opera4ons  to  be  

developed  in  a  flexible  and  dynamic  way,  without  any  waste,  highly  rentables  and  inside  a  clean  and  organized  environment.  

5S  is  an  organiza4ve  method  in  the  working  place  focused  in  remove  waste,  basically  in  4me.  

5S examples : Before and After

Performance Management : Dashboards Performance  management  is  not  only  widely  used  to  track  the  daily  work,  adherence  to  what  was   planned   and   help   to   iden4fy   risks   and   improving   opportuni4es   (Shopfloor  Dashboard),  but  also  to  select  appropriate  KPI   (Key  Performance   Indicators),  organize  mul4disciplinary  problem  solving  sessions,  propose  new  investments,  etc.  

Follow-­‐up  KPI  

Iden4fied  risks  and  

recurrences   Daily  Performance  

KPI : Key Performance Indicators Key  Performance  Indicators  are  quanAfiable  measurements  that  help  an  organizaAon  to  define  and  measure  progress  toward  established  goals.    PRODUCTION  INDICATORS    

-­‐  OUTPUT  :  Weekly  /  Monthly  basis  -­‐  ADHERENCE  TO  PLANNING  

QUALITY  INDICATORS    

-­‐  Number   of   DeviaAons   and   classificaAon   on   the   root   cause   :   Human   mistakes,  equipment  breakdowns,  suppliers,….  

-­‐  Complaints  from  the  market  

ENGINEERING  /  MAINTENANCE  INDICATORS    

-­‐  Recurrent  breakdowns    HUMAN  RESOURCES    

-­‐  AbseenAsm  percentage  

Performance Management : Meeting cascading Daily  

Site  Director  

Department’s  Head  

Technicians  

Weekly   Every  two  weeks  Every  three  months  

Supervisors  

Operators  

 Sec4on’s  mee4ng      MS  y  AS  30  min  

Produc4on  daily  mee4ng  15  min  

Projects  follow-­‐up    1h  

 Informa4ve  weekly  mee4ng  20  min  

One-­‐to  –One  

mee4ng  1,5h  

     

Feedback    (1h  per  shim)          

Other  departments  

Overlap    15  min  

Monthly  

Engineering  /  Produc4on  follow-­‐up  1h  

 Pharma  

Produc4on  mee4ng  

(Informa4ve  sessions)    1,5h    

EHS  –  Produc4on    1h  

Monthly  planning    (SCH-­‐Produc4on)  1h  

Pharma  Produc4on  follow-­‐

up  (All  departments)  

 1h  

Problem Solving Sessions Sessions   with   a   mul4disciplinary   team   to   fix   a   problem   ac4ng   on   the   root   cause   or  improve  a  concrete  issue  to  avoid  waste  on  the  processes.    

5  Why’s  à  Ask  un4l  you  get  the  root  cause  of  a  problem  to  avoid  recurrences.  

3. Why wasn’t there enough oil?

The oil pump doesn’t pump enough oil because shaft was worn

2. Why did the overload fuse blow?

There was not enough oil on the shaft

1. Why has the machine stopped?

The overload fuse has blown

Because the oil strainer is blocked with metal swarf

4. Why doesn’t the oil pump work properly?

No preventive maintenance or weekly cleaning performed

5. Why is the strainer blocked?

Problem Solving Sessions Fishbone  diagram  à  Normally  for  more  complex  problems.  Brainstorming  of  a  mul4disciplinary  team  based  on  6  “spines”  from  a  central  “bone”  :  Methods,  People,  Machine,  Environment,  Material,  Process.  The  objec4ve   is   the   same   :   iden4fy  and  fix  the  root  cause  of  a  problem  to  avoid  recurrences.  

Education and Soft skills EDUCATION  &  BACKGROUND    -­‐  Academic  degree  in  science  (Pharmacy,  Chemistry,  Biology)  -­‐  GMP  training  -­‐  Fluent  in  English  -­‐  Knowledge  in  Lean  Manufacturing  (Green  Belt/Black  Belt)  -­‐  Knowledge  in  Galenical  /Pharmaceu4cal  Technology  -­‐  Knowledge  in  Pharmaceu4cal  /  Chemical  installa4ons  and  u4li4es    SOFT  SKILLS    -­‐  Flexible    -­‐  Open  minded  -­‐  Proac4ve  -­‐  Good  management  skills  -­‐  Ability  to  work  under  pressure  -­‐  Team  leader  -­‐  Good  communica4on  skills  -­‐  Focused  on  results