BRISTOL-MYERS SQUIBB IN AQUITAINE, FRANCE

1
Depuis KEY
1995,
Bristol-Myers AN
Squibb
a
P02/03
FIGURES P04/05
INTERNATIONALLY-ORIENTATED
CENTRE OF EXCELLENCE P06/07 AN ONGOING INVESTMENT
investi
plus
de
200
millions
d’euros
en
POLICY P08/09 QUALITY, THE No. 1 PRIORITY P10/11 HUMAN RESOURCES AND THE ENVIRONMENT: WHAT ARE THE GOALS?
Aquitaine. Des investissements dans tous
les domaines d’activité, qui font du site
d’Agen un outil hautement performant.
UNE STRATÉGIE D’INVESTISSEMENT
GLOBALE
Tous les secteurs ont bénéficié, au fil des
années, de cette politique systématique.
Les lignes de conditionnement, très
automatisées, d’où sortent les produits
finis. Le contrôle qualité, avec la mise en
fonctionnement en 2008 d’un laboratoire
de contrôle ultramoderne. Le système de
stockage, avec la construction en 1997
d’un nouveau magasin grande hauteur,
qui a vu sa capacité accrue en 2002. Et la
fabrication, où sont réalisés les mélanges
des différents composants nécess
BRISTOL-MYERS SQUIBB
IN AQUITAINE, FRANCE
02
KEY FIGURES
KEY FIGURES
BRISTOL-MYERS SQUIBB IN AQUITAINE, FRANCE
1,400
EMPLOYEES IN GASCOGNE SITE (870),
GUYENNE SITE (400) AND AT THE
LOGISTICS CENTRE (130)
IN 1994 UPSA BECAME A 100% SUBSIDIARY OF BRISTOL-MYERS SQUIBB. Primarily dedicated to pain relief, in particular in an
effervescent pharmaceutical form, Agen has since doubled its production capacity thanks to an ongoing investment policy. It is now
Bristol-Myers Squibb’s leading plant worldwide in terms of volume, as well as the biggest private employer in the Lot-et-Garonne
department (47).
40 %
900
OF PRODUCTION EXPORTED
SUPPLIERS, OF
WHICH 30% ARE LOCAL OR REGIONAL,
FOR AN ANNUAL TURNOVER OF AROUND
40 MILLION EUROS
400
200
MILLION BOXES PRODUCED IN 2011,
I.E. 50% OF THE VOLUMES OF BRISTOLMYERS SQUIBB WORLDWIDE
MILLION EUROS INVESTED
OVER 15 YEARS
3,600
ESTIMATED INDIRECT JOBS GENERATED
BY THE SITE
27
AUTOMATED PACKAGING LINES
343
FINISHED PRODUCT REFERENCES
03
04
CENTRE OF EXCELLENCE
AN
INTERNATIONALLYORIENTATED
CENTRE OF
EXCELLENCE
KEY PRODUCTS MANUFACTURED
AT THE AGEN SITE
PAIN
Dafalgan® 500 mg scored effervescent tablets
Dafalgan® 500 mg capsules
Dafalgan® 1 g film-coated tablets
Dafalgan® 1 g effervescent tablets
Dafalgan® paediatric oral solution 3%
Dafalgan® 80 mg, 150 mg, 250 mg effervescent powder
for oral solution in sachets
Dafalgan® 80 mg, 150 mg, 300 mg suppositories
Dafalgan adult 600 mg suppositories
®
Daflagan codéine® scored effervescent tablets and film-coated
tablets
MILESTONES
Efferalgan® 500 mg scored effervescent tablets
D 1935
Dr. Camille Bru founded Laboratoires UPSA
(Union de Pharmacologie Scientifique
Appliquée / (Union of Applied Scientific
Pharmacology)
Efferalgan® 1 g effervescent tablets
Efferalgan 500 mg tablets
®
Efferalganodis® 500 mg or dispersible tablets
EfferalganVitamineC® 500 mg/200 mg effervescent
tablets
Actiskenan®, 5 mg, 10 mg, 20 mg et 30 mg, capsules
D 1951
Creation of the first manufacturing plant
(Guyenne)
Skenan® LP, 10 mg, 30 mg, 60 mg, 100 mg et 200 mg,
prolonged release micro granules in capsules
D 1970
Creation of the second plant (Gascogne)
Aspirine 500 mg Vitamine C Oberlin® scored effervescent
tablets
D 1985-1989
Aspirine UPSA® Vitaminée C effervescent buffered, scored
effervescent tablets
Construction of effervescent production
tower No. 1
D 1994
UPSA becomes a 100% subsidiary of
Bristol-Myers Squibb
D 1997
• Construction of the warehouse for raw
materials and packaging components
• Creation of the product development
laboratory
Aspirine UPSA® 500 mg et 1 000 mg effervescent tablets
OVER-THE-COUNTER MEDICATION
Citrate de bétaïne UPSA® 2 g (Betaine citrate), sugar-free,
effervescent tablets sweetened with sodium saccharin
Donormyl® 15 mg scored effervescent tablets and scored
film-coated tablets
Fervex®, Fervex® sugar-free and Fervex® children, granules
in sachets
Mucomyst® 200 mg, oral powder in sachets
Mucomyst® 200 mg/5 ml, powder for oral suspension
Niflugel® 2,5%, gel
Nifluril® 250 mg capsules
Nifluril® adult 700 mg suppositories
D 1998-2000
Nifluril® children 400 mg suppositories
Tower No. 3 put into production
Polysilane UPSA® (dimeticone), oral gel in tube and single-dose
sachets
D 2007-2008
The new Quality Control laboratory
and granulation module # 5.4 put into
operation
Upfen® 200 mg scored tablets
Vitamine C UPSA® 500 mg chewable tablets
Vitamine C UPSA® 500 mg exotic fruit, chewable tablets
Vitamine C UPSA® 1 g effervescent tablets
D 2010
Tower No. 6 and granulation module
# 5.3 put into production
01_ Quality Control
operation
01
CENTRE OF EXCELLENCE
BRISTOL-MYERS SQUIBB IN AQUITAINE, FRANCE
BRISTOL-MYERS SQUIBB’S LEADING
PRODUCTION SITE WORLDWIDE
The largest production site (in volume)
of Bristol-Myers Squibb, an international
American pharmaceutical company, is in
Aquitaine. When UPSA joined the group
some 60 years after its creation, Agen was
already a benchmark in pain relief. Today,
1.8 million boxes of medicine leave the
production lines daily, which represents,
all types of products combined, an annual
production of 18,000 tonnes of medicine,
making Agen the global leader in the
production of effervescent drugs.
PAINKILLERS AND DIVERSITY
OF DOSAGE FORMS
Since the outset, the Agen site has
effectively been dedicated primarily to
painkillers. Paracetamol, aspirin, codeine
combined with paracetamol and morphine
derivatives help to relieve all types of pain,
in many pharmaceutical forms: effervescent
tablets - the emblematic dosage form of
the Agen manufacturing plant - but also
uncoated and film-coated tablets, capsules,
suppositories, sachets and oral solutions.
This variety of dosage forms meets the
needs of all patient populations: infants,
children, adults and the elderly.
INNOVATIVE DOSAGE SOLUTIONS
FOR THE BENEFIT OF PATIENTS
Developing dosage solutions is another
key activity of the Agen section. Created
in 1997, the product development laboratory
is dedicated to perfecting new formulae.
Latest innovation: the launch in 2010 of a
new analgesic tablet, 10% smaller than the
old formula and film-coated to make it easier
to swallow and thus facilitate observance
for relief of chronic pain, to the patient’s
benefit.
05
”AGEN, A WORLDWIDE
BENCHMARK IN PAIN
RELIEF”
A LOGISTICS HUB, DISTRIBUTION
AND EXPORT PLATFORM
Logistics is the site’s third-leading activity.
Agen effectively supplies painkiller products
to all of Bristol-Myers Squibb’s French and
international customers. What are the goals?
In France, ensuring the smooth-running
supply of 23,000 dispensing chemists,
3,000 hospitals and clinics and 30 wholesale
distributors, which involves storing millions
of boxes, recording customer orders and
ensuring shipments at the highest level of
quality. Not to mention exports, mainly to
Europe and Africa: 40% of the 400 million
boxes produced annually are exported.
Orders are honoured within a timeframe
of two to four days, which is reduced to
24 hours for deliveries weighing less than
30 kg.
OVER-THE-COUNTER MEDICATION,
ANOTHER OF AGEN’S SPECIALITIES
A total of 343 finished product references
leave Agen’s packaging lines. In addition
to the 246 pain relief products, there is a
wide range of OTC medication intended for
the minor ailments of everyday life such as
colds, coughs, flu-like symptoms or digestive
problems.
06
INVESTMENT STRATEGY
01
INVESTMENT STRATEGY
BRISTOL-MYERS SQUIBB IN AQUITAINE, FRANCE
02
01_ Packaging Operator
05
02_ The high-bay
warehouse has a 16,000
pallets storage capacity
03_ 80 employees work
in the Quality Control
Laboratory since 2008
AN ONGOING
INVESTMENT
POLICY
04
07
04_ Operator in production
tower No. 6
05_ Production towers
unique in the world
06_ The clover, symbol
of UPSA
03
06
Since 1995, Bristol-Myers Squibb has
invested over 200 million euros in
Aquitaine in all fields of activity that
make the Agen site a very high-performance tool.
A COMPREHENSIVE INVESTMENT STRATEGY
MILESTONES
15 YEARS OF INVESTING
IN AQUITAINE
Since Agen’s integration into Bristol-Myers
Squibb’s manufacturing operations, the
investment policy has involved the entire site.
The following have been put into operation:
D 4 production towers
D 2 granulation modules
D 14 new packaging lines
D 1 new quality control laboratory
D 1 product development laboratory
D and a huge high-bay warehouse for storage
and supplying the workshops with raw
materials and packaging components.
All sectors have benefited from this systematic policy over the years. Highly automated
packaging lines where the finished products
emerge. Quality control with an ultra modern
control laboratory put into operation in 2008.
The storage system, with the construction
of a new high-bay warehouse in 1997, the
capacity of which was increased in 2002.
And a manufacturing unit, where the mixes
of the different components required for
producing each drug are carried out. At the
Agen site, there are two types of manufacturing equipment: granulation modules, which
operate on a horizontal process, and the
production towers.
FOUR NEW EFFERVESCENT PRODUCTION
TOWERS
These production towers, unique in the
world and symbols of the Agen site’s
identity, rely on a very special layout, which
uses gravity to transfer the product from
one step of the process to the next one. This
vertical process has proved the best way
to handle very large volumes. The concept
of the towers, opened in 1985, was later
duplicated with the start-up of new towers
to meet increasing customer demand.
Tower No. 6 being put into production
highlighted 2010.
INCREASING PRODUCTION CAPACITY AND
MANUFACTURING PERFORMANCE
Since its integration with Bristol-Myers
Squibb, the Agen manufacturing centre has
doubled its production capacity in fifteen
years and improved its performance level.
The most recent production towers and
granulation modules are characterised by
greater flexibility, which makes it possible
to shift more easily from the manufacture
of one product to another.
IMPROVING WORKING CONDITIONS
Other objectives of this ongoing investment
policy: continuously improving quality
and working conditions, complying with
the pharmaceutical and environmental
regulations in force and implementing
training programmes to promote the
acquisition of new skills.
08
QUALITY
QUALITY
BRISTOL-MYERS SQUIBB IN AQUITAINE, FRANCE
09
5
01_ Quality Control Laboratory:
preparation of a gas chromatography
analysis
6th floor: Raw material storage
02_ Many automatic control devices
on packaging lines (cameras and
barcode readers) support the respect
of a crucial priority
5th floor: Automatic weighing
3
QUALITY, THE
No. 1 PRIORITY
4th floor: Granulation
3rd floor: Cooling
2nd floor: Grading
01
1
2
4
6
1st floor: Final mix
7
8
9
Ground floor: Supervision of the operation
02
QUALITY: A VITAL REQUIREMENT
FOR BRISTOL-MYERS SQUIBB
Quality is vital because the company operates
in a public health field at a very high technical
level and is governed by regulatory constraints.
The implemented operation is based on three
major levers:
D rigorous and selective purchasing processes
D systematic inspections at every stage of
the production cycle (see diagram): up to
60 inspections per drug!
D regular audits of all management systems
with regard to quality and practices within
the units, carried out by Bristol-Myers Squibb
and AFSSAPS(1).
(1) French Health Products Safety Agency
On reception, all the raw materials
and packaging items are given a batch
number and pallet number. The pallets
are transferred to the sampling units.
packaging components received with the
specifications described in the registration
file, the corresponding pallets are released
by the computer system and become
available for use in production.
D 2 SAMPLING
D 4 DESTOCKING AND SUPPLYING THE
D 1 RECEPTION
Without interrupting the supply chain,
samples of raw materials and packaging
components are taken for analysis by
the Quality Control Department.
D 3 STORAGE IN THE HIGH-BAY
WAREHOUSE
The pallets are transferred to the high-bay
warehouse (7 levels, 16,000 locations)
under a “quarantine” status. A computerised system manages all of the storage locations and is interfaced with the
Enterprise Resource Planning system and
Quality Management System.
Once the Quality Control laboratory
has tested samples and confirmed the
compliance of the batch of material or
WORKSHOPS
This consists in delivering the components
necessary to produce a pharmaceutical batch
to the production workshops. Destocking
is carried out based on production orders
and thanks to the software that manages
the storage locations; traceability is
guaranteed.
D 5 MANUFACTURING
Effervescent tablets combine an organic
acid and a carbonate base. On contact
with water, this combination produces a
chemical reaction resulting in an off-gassing
of carbon dioxide. A complex process,
organised on six levels, continues through
all the manufacturing stages.
D
6th floor: after being routed by pneumatic
conveyors the raw materials are stored.
5th floor: the various components, sodium
bicarbonate, citric acid, the active principle
and sorbitol are weighed very accurately.
4th floor: after being weighed the different
components are mixed, granulated and
dried.
3rd floor: the temperature of the granulated
powder is reduced to 20° in a cooler.
2nd floor: when cooled, the powder must
be calibrated to obtain the desired granulometry.
1st floor: the last operation where additive
products, flavouring and compression lubricants are added to obtain a pharmaceutical
batch that is homogenised in the final mix.
Ground floor: This fully automated production
unit is controlled by a Tour Operator, who
oversees the smooth running of the different
operations and ensures good manufacturing
quality of their production unit.
D 6 PACKAGING
The granules obtained after the manufacturing stage are conveyed to the tablet
presses. The three operations: compression, primary packaging (where the product
is placed in its protective envelope: tube,
strip, blister pack, sachet) and secondary
packaging (the drug is introduced into a
box together with its instruction leaflet)
are performed continuously without
reloading
Many automatic control devices on packaging lines (cameras and bar code readers
for each item printed), combined with
periodic inspections entrusted to the
vigilance and professionalism of the operators and production technicians, ensure
the product meets quality standards.
Boxes are grouped automatically in crates
and then transferred by conveyor to the
pallet area, located outside the white area.
D 7 PALLETISATION
In a specific area, pallets of finished goods
are filmed and identified, thus establishing
perfect continuity in product traceability.
D 8 BATCH ACCEPTANCE
Each batch record is subject to final
inspection by Quality Assurance. This
operation ensures that the entire
production and control process was
conducted in accordance with established
procedures and the patient will have
medicines with the pharmaceutical
guarantees of quality described in the
registration file.
D 9 SHIPPING
The products are transported to the
Bristol-Myers Squibb Agen distribution
centre, which organises the shipment
to pharmacists, hospitals, wholesalers,
subsidiaries or direct export customers,
the latter involving more than 100 destinations around the world.
10
HR AND ENVIRONMENT CHALLENGES
BIGGEST PRIVATE EMPLOYER
IN LOT-ET-GARONNE
HUMAN RESOURCES
AND THE ENVIRONMENT:
WHAT ARE THE GOALS?
01
11
04
For the biggest private employer in the Lot-etGaronne department and one of the biggest in
the Aquitaine region, the human resource goals
include, in particular, training and recognition of
diversity. 30,000 hours of training is provided,
on average, each year to employees of the
Agen site, the equivalent of 3.5 to 4% of
the payroll: training on new equipment of
increasing technical complexity, but also
on safety and security and learning good
practices in pharmaceutical manufacturing
with a specific section designed to promote
the continued employment of older workers,
in addition to arranging work schedules, such
as the possibility of no longer having to work
night shifts in the workshops that run in three
eight-hour shifts.
02
KEY FACTS
BREAKDOWN OF THE WORKFORCE
62% MEN AND 38% WOMEN:
D 53% WORKERS
D 34% EMPLOYEES, TECHNICIANS,
SUPERVISORS
D 10% MANAGERS
D 3% TRAINING AND PRE-QUALIFICATION
CONTRACTS
D AVERAGE SENIORITY: 13 YEARS
HR AND ENVIRONMENT CHALLENGES
BRISTOL-MYERS SQUIBB IN AQUITAINE, FRANCE
TAKING ACCOUNT OF THE IMPACT ON THE
ENVIRONMENT
RENEWABLE ENERGIES AND PROTECTION OF
WATER RESOURCES
The Agen site’s environmental policy is
part of the 2015 Sustainability programme,
which sets targets for reducing greenhouse
gas (GHG) emissions and consumption of
resources. Bristol-Myers Squibb was the
first company in the department to obtain
ISO 14001 environmental certification, which
has been confirmed regularly since 2001
(last follow-up audit in January 2011).
Agen was one of the first sites in the
Aquitaine region to sign a “kWh Equilibre”
contract with EDF (Electricité De France,
French Electricity Company) in 2004.
Bristol-Myers Squibb agreed to pay 15% of
its annual electricity consumption at a price
higher than the base price to encourage
production from renewable energy sources.
(A commitment guaranteed by Observ’er,
an international independent verifier
organisation).
BILAN CARBONE® AND GREENHOUSEASG
(GHG) REDUCTION
SUCCESSFULLY INTEGRATING PEOPLE
WITH DISABILITIES
Bristol-Myers Squibb takes a proactive
approach to integrating people with
disabilities. The signing of a three-year
agreement and the establishment of
disability referents has helped to increase
their overall employment rate at the Agen
site from 3% in 2007 to 5.15% in 2010.
03
In 2010, Bristol-Myers Squibb extended its
Bilan Carbone® initiative, already conducted
for its head office in Rueil-Malmaison and
the medical visit activity, to the Agen site
as well as to the drug distribution activity.
The objective is to reduce GHG emissions
by 15% between now and 2015.
Optimizing the consumption of the cooling
towers at the Gascogne site, recovering
rainwater, replacing certain water circuits
lost through closed circuits and optimising
some of the manufacturing processes
has reduced water consumption by 50%
in 5 years. The result of the sorting and
recovery policy based on a new sorting
platform is that 60% of waste is now
recycled as against 30% in 2008.
05
01_ Packaging operators
02_ Agen site has chosen
to use an electric vehicle for
its Waste Management
03_ Water cooling tower
04_ Employee of the GOTC
(Global Order to Cash)
Customer Service
05_ Fluid supply pipes
249081104 – 2011/09
304, avenue du Docteur Jean Bru - 47000 Agen, France
Tel: (+ 33) 05 53 69 84 44
BRISTOL-MYERS SQUIBB FRANCE
3, rue Joseph Monier - 92500 Rueil-Malmaison, France
Tel: (+ 33) 01 58 83 60 00
BRISTOL-MYERS SQUIBB FRANCE WEBSITE
www.bmsfrance.fr
INSTITUT UPSA DE LA DOULEUR WEBSITE
www.institut-upsa-douleur.org
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Cover picture: Aurélie, Quality Control Technician
Design: Burson-Marsteller - Photos credits: Photothèque Bristol-Myers Squibb - Vincent Colin - d.lutz@balloide-photo.com - © Patrick Allard / Agence Réa BRISTOL-MYERS SQUIBB - UPSA SITE