CROSS BORDER
The critical role of culture in pharmaceutical operations
Marvin Bower, former managing director of McKinsey & Company –
A definition of corporate culture
“It’s the way we do things around here”
CORPORATE
Hofstede’s definition of culture:
“Culture is the collective programming of the
mind that distinguishes one group or category of
people from another.”
Some western cultural concepts related to disease
• A high expectation that disease can be cured or at least
“managed”
• The need to leave the doctors surgery with a
prescription.
• The belief that medicines should be powerful but free of
risk
• Belief that physical disease is separate from emotional
and spiritual dimensions
• A belief that mental diseases are not as “real” as somatic
disease.
One mans meat is another mans fish (Fr: poisson)
• Co-trimoxazole suspension
– Roche product sweet, pink, cherry-flavored
– Teva’s first US generic was based on the local (Israeli)
formulation which was anise flavored
• Tylenol extra strength adult syrup
– An unpleasant bitter peppermint flavor
– A generic formulation with taste masking was rejected by
US marketing as non-equivalent
• EP/USP description of Drug substance: white to off white is
acceptable but Japan will not accept off-white as a
descriptive
• J&J’s attempt to launch a black Elastoplast as a “skin
coloured product for the African market” failed
Packaging
• Obviously the art work will reflect the appropriate cultures of the target countries
• But this can actually produce some more complicated issues as for example:-
– Different shelf life due to the US packaging (bottles with desiccant) versus the European preference for blister packs.
• “The split tablet, when stored in standard high-density polyethylene
pharmacy bottles and caps (no seal), should meet established stability
requirements for a period of 90 days at 25º +/- 2º C:60% +/-5% Relative
Humidity”.
Why do they require 90 days stability?
Europeans naturally
break one tablet, take
one half now and the
other half at the next
dosage point.
The Americans take the
whole of the prescription
and break all the tablets.
Mitigating the Risks of Ethanol Induced Dose Dumping from Oral
Sustained/Controlled Release Dosage Forms FDA meeting Oct 2005
• Palladone (hydromorphone hydrochloride
extended release) Capsules was approved by the
United States Food and Drug Administration
(FDA) on September 24, 2004,
• Soon after the approval the FDA requested
Purdue Pharma LP to withdraw the product from
the market due to serious safety concerns based
on new data showing that when Palladone was
taken with alcohol, the extended release
mechanism was harmed leading to dose‐dumping.
As a result the FDA introduced dissolution in
alcoholic media for a wide range of products
Irrespective of the fact that the label says quite clearly
DO NOT DRINK WHILE TAKINGEEEE
The FDA dissolution requirements
• Due to concerns of dose dumping from this drug product when
taken with alcohol, please conduct additional dissolution testing
using various concentrations of ethanol in the dissolution
medium, as follows:
– Testing Conditions: 900 mL, 0.1 N HCl, apparatus I (basket) @ 200
rpm, with and without the alcohol (see below):
• Test 1: 12 units tested according to the proposed method (with 0.1 N HCl),
with data collected every 15 minutes for a total of 2 hours.
• Test 2: 12 units analyzed by substituting 5% (v/v) of test medium with
Alcohol USP, and data collection every 15 minutes for a total of 2 hours.
• Test 3: 12 units analyzed by substituting 20% (v/v) of test medium with
Alcohol USP, and data collection every 15 minutes for a total of 2 hours.
• Test 4: 12 units analyzed by substituting 40% (v/v) of test medium with
Alcohol USP, and data collection every 15 minutes for a total of 2 hours.
Both test and RLD products must be tested accordingly and data must
be provided on individual unit, means, range and %CV on both strengths.
900ml of
40%
alcohol
is
almost a
full
bottle of
Vodka
Waivers for AIDD dataAn Eu regulatory responses
• Q. Concomitant intake
with alcohol is unlikely
if contraindicated in
labeling. In the unlikely
event of concomitant
intake, the
consequences are not
serious (e.g. the dose
is not different to a IR
dose).
• A: Where incompatibility
with alcohol is evident, it
is currently sufficient to
address safety or other
concerns by the inclusion
of appropriate warnings in
the product literature
unless serious concerns
are raised with respect to
efficacy and safety
Cultural issues are of ever increasing importance
CRO &
CMO
COST
SAVING
CONSOLIDATION
ACQUISITION
ALLIANCES
MERGERS
CULTURAL
ISSUES
Schein’s model of organisational culture
Artefacts, Creations
Technology, Art
Visible and Audible behaviour patterns
Values
Basic Assumptions
Relationships to the environment
Nature of reality and truth
Nature of human nature
Nature of human activity
Nature of human relationships
Three levels of culture
Visible, but not always
obvious, recognized initially, or
associated with values
Generally a higher level of
awareness of what is valued in
the organization
Invisible, not usually stated,
taken for granted
Cultural influences
National
culture
Professional
subculture
Organisation’s
History
Organisationals
ubculture
Generation
culture
How corporate cultures are created
Philosophy of
organisation’s
founders
Philosophy of
organisation’s
founders
Staff
selection
criteria
Staff
selection
criteria
Top
management
Top
management
Social
interaction
Social
interaction
ORGANISATION
CULTURE
ORGANISATION
CULTURE
STRONG
CULTURE
MODERATE
CULTURE
[STABLE]
WEAK
CULTURE
MODERATE
CULTURE
[INTENSE]
STRONG
STAFF
COMMITMENT
TO VALUES
WEAKLOW %age of staff sharing values HIGH
CULTURAL STRENGTH MATRIX
Know what you
are up against
Corporate cultures
• Strong Characteristics
– Conduct business according to a clear, widely-understood philosophy
– Considerable time spent by management communicating and reinforcing values
– Values are widely shared and deeply rooted
– Have a well-defined corporate character, reinforced by value statements
– Careful screening/selection of new employees to be sure they will “fit in”
• Weak Characteristics
– Lack of a widely-shared core set of values
– Few behavioral norms evident in operating practices
– Few strong traditions
– No strong sense of company identity
– Little cohesion among departments
– Weak employee allegiance tocompany’s vision and strategy
Culture change is one of the toughest managerial tasks
Organisational approaches to cultural differences
Minimise frictions from
cultural differences, often
associated with ethnocentrism.
Ignore cultural differences
associated with ignorance.
Identify, appreciate
and utilise
cultural differences.
IGNORE IT
LIVE WITH IT
USE IT
SEMIOTICS-The study of cultural signs
• How is the space allocated?
• Where are the offices located?
• How much space is given to
whom?
• Where are people located?
• What is posted on bulletin
boards or displayed on walls?
• What is displayed on desks or
in other areas of the building?
– In the work groups?
– On lockers or closets?
• How are common areas
utilized?
• What do people write to one
another?
– What is said in memos or email?
– What is the tone of messages
(formal or informal, pleasant or
hostile, etc.)?
– How often do people
communicate with one another?
– Is all communication written, or do
people communicate verbally?
• What interaction between
employees do you see? How
much emotion is expressed
during the interaction?
Take a walk around the building, and look at some of the physical signs of culture.
Why cultural factors are frequently considered unimportant
• Globalisation
– McDonalds can do it so anyone can
• Lack of appreciation by Management
– Focus on the merger
– Managers are global and special so don’t see it
– Or they are local and don’t see it
• Cultural blindness
– It is only recently beginning to attract serious attention
Actually McDonalds couldn’t do it
INDIA
• The original launch was in line with a
strategy of “product identity”
• Instantly recognizable with repeat of
previous successes in new
geographies
• A failure until they removed beef and
concentrated on chicken and lamb,
increased dramatically the vegetarian
option-introduced separate cooking
and purchasing for “pure” vegetable
sources
Leadership Across Cultures
• Leadership styles may vary among different
countries or cultures.
– European managers tend to be more people-oriented
than American or Japanese managers.
– Japanese managers are group-oriented, while U.S
managers focuses more on profitability.
– Time horizons also are affected by cultures.
• U.S. firms often focus on short-run efforts and results.
• Japanese firms have a longer-run perspective.
• European firms fall somewhere between the U.S. and
Japanese orientations.
Cultural Blindness
• Cartwright “the rationale as to why Anglo-American
researchers appear to have attached less significance to
national culture than their European colleagues isE.
– Both are individualistic cultures [minimum government
interference]
– Unlike many of the countries in Europe the US and UK do
not have multiple land borders, nor have they seen these
boundaries change significantly over time
– As multicultural societies they are regarded as having
successfully assimilated and absorbed into their
membership individuals from a variety of different national
and cultural backgrounds
Cultural attitude to quality
• An IBM firm in Windsor, Ontario, ordered a shipment of
components from a Japanese firm, specifying the Acceptable
Quality Limit as three defective components for every 10,000
parts.
• In a covering letter from the Japanese supplier to the IBM firm
that accompanied the order the Japanese company explained
how difficult it was to produce the defective parts and said:
– “We Japanese have hard time understanding North
American business practices but the 3 defective parts per
10,000 have been included and are wrapped separately.”
“Hope this pleases.”
Human error behavioural approaches
• Conventional approach
– Processes and SOP’s
– Training
– Environment
• At risk cultures [risk believed to be
insignificant or justified]
– Remove incentives for at-risk
behaviour
– Create incentives for healthy
behaviour
– Increase situation awareness
• Reckless cultures [disregard of
unjustifiable risk]
– Remedial action
– Disciplinary action
An example-Global QA
If you have a global approach
to quality assurance and in
particular QUALITY RISK
MANAGEMENT you cannot
expect to use the same tools
for companies (countries)
that have different risk cultures
Insensitivity to cultural issues
• Executives
– Tend to be international
– Negotiate with other Executives
• Managers
– Professionally experienced but not exposed to other cultures
– If dealing with cross-border alliances this can even affect professional
issues [cGMP US, Eu, WHO, Russia]
– Greatly influenced by local upbringing
• US-perception and individualism
• CEE-Centralisation
• China-Conformity
Some examples of cultural issues during negotiations
• Cancellation of meetings with no apology or explanation
• Failure to understand the sense of time management that
different cultures have
• The habit of communicating with others in a local language;
misinterpreted as a sign of mistrust
• Lack of documentation—most things are kept in the head
Japanese regard the contract only as the beginning of a business
relationship during which the terms of the contract are open for renegotiation
In USA this attitude appears to be completely unethical
The Japanese regard the USA approach as unethical in that they try and
enforce a contract although the circumstances have changed
Communication
Intent v. Impact
SENDER RECEIVER
INTENT IMPACT
Culture,
Gender,
Age,
Education,
Skill,
Experience,
Knowledge,
Style,
Perceptions,
Attitudes,
Culture,
Culture,
Gender,
Age,
Education,
Skill,
Experience,
Knowledge,
Style,
Perceptions,
Attitudes,
Culture,
Communication
• LINGUISTIC– Although the negotiating
language may be common
often it is not the natural
language for either of the
parties
– Sentence construction in
one language can give the
wrong meaning in another
even though the translation
is correct
– Be careful of idiomatic
sayings
• CONSTRUCTION– Direct, clear and precise
• US, German?, Israeli
– Indirect, diplomatic and
reserved• Japanese, British, Indian
– Complex• Slavic
Please
revert
Please send back
your changes,
revisions and
comments
Cultural issues and language
• Training is a prerequisite
of all cGXP systems
• The regulatory authorities
are asking the question
“trained or really trained?
• But what about training
via translation-are you
translator friendly
• Obviously language is significant.
– The return trip (almost uniquely UK
English)
– SOP’s in English in Puerto Ricoh
– Colloquial expressions
– Jokes
• How do you check that your audience
really understands?
– Beware of judgments derived from
observation of physical reactions
• Smiling and nodding are not the same in
all cultures (India, Bulgaria)
MS Word now lists 17 different types of English
Oops
• An advertisement for the
new Executive Director of
the EMA resulted in the
process being delayed
because the translation in
German used the word
Physiker instead of Arzt.
• In a clinical trial on
arthritis in the quality of
life questionnaire
“Shampoo your hair” had
to be changed to “wash
your hair” because both
soap and shampoo were
commonly used in the
country where the trial
was being conducted
Silence
• Japan – acceptable as a moment for serious thought
• Europe – produces a feeling of discomfort
• USA – a sign of disagreement
Significant silence [the call center issue]
It is not just language
• Many western presenters
are told to make their
presentations interactive-
get audience participation
– But actually not all
cultures respond well to
this and forcing this may
well destroy the
atmosphere needed for
effective training
• For example I have found
that in CEE simulations
and role play are not well
received (a possible hang
over from the communist
era)
• “We are very happy to have you and we are excited about your session.”
• “I'm so pleased. Is there anything in particular you would like to discuss tomorrow?”
• No, that is up to you, only, please don't walk in and tell us that you are interested in hearing what we have to say. One of your colleagues from the U.S. always does that.
• We are tired of talking to each other. We want to take advantage of your presence and hear what you have to tell us.
Hofstede’s Dimensions of National Culture
Geert Hofstede™ Cultural Dimensions- http://www.geert-hofstede.com/
PDI-Power distance ratio
The degree to which the less powerful
members of a society accept and expect that
power is distributed unequally. People in
societies exhibiting a large degree of power
distance accept a hierarchical order in which
everybody has a place which needs no
further justification
IDV-Individualism v collectivism
A preference for a loosely-knit
social framework in which individuals
are expected to take care of themselves
and their immediate families only rather
than a preference for a tightly-knit
framework in society in which individuals
can expect their relatives or members of a
particular in-group to look after them.
MAS-Masculinity v femininity
A preference in society for achievement,
heroism, assertiveness and material reward for
success. Society at large is more competitive.
UAI-Uncertainty avoidance
The degree to which the members of a
society feel uncomfortable with uncertainty
and ambiguity.
LTO-Long term orientation
People believe that truth depends very much
on situation, context and time. They show an
ability to adapt traditions to changed conditions,
a strong propensity to save and invest,
thriftiness, and perseverance in achieving results.
0
10
20
30
40
50
60
70
80
90
100
PDI IDV MAS UAI LTO
UK
USA
0
10
20
30
40
50
60
70
80
90
100
PDI IDV MAS UAI LTO
RUSSIA
USA
0
20
40
60
80
100
120
PDI IDV MAS UAI LTO
CZECH
SLOVAK
Hofstede comparisons
0
10
20
30
40
50
60
70
80
PDI IDV MAS UAI LTO
GERMANY
INDIA
0
10
20
30
40
50
60
70
80
90
100
PDI IDV MAS UAI LTO
CHINA
USA
US training Russian FDA on GMP
• A US partnership made up of Lilly, the Chao
Center and the Parenteral Drug Association
(PDA), has been formed to spread global
manufacturing standards throughout Russia.
– Training will aim to improve Rozdravnadzor’s
[Russian FDA] understanding of good
manufacturing practices
• Officials from Rozdravnadzor and the
Russian Inspectorate will attend hands on
training sessions at manufacturing
simulation facilities at Lilly, the Chao Center
and the PDA in the US.
0
10
20
30
40
50
60
70
80
90
100
PDI IDV MAS UAI LTO
RUSSIA
USA
HOW BIG IS THE PROBLEM?
• How different are the cultures?
• What is the commonality of purpose of the two
companies on the project?
• How non conflictual are the partners?
• How time critical is the project?
And remember both
sides are part of the
cultural divide
KNOW YOURSELF
The French book-
1000 ways to cook Elephant
The English book-
Elephants I have shot on Safari
The American book-
How to Make Bigger And Better Elephants
The Japanese book –
How to Make Smaller And Cheaper Elephants
The Greek book –
How to Sell Elephants for a Lot of Money
The German book –
A Short Introduction to Elephants, Volumes 1-6.
The Swiss book –
The Country Hannibal Went Through With His Elephants
The Canadian book –
Elephants: A Federal or State Issue? The Swedish book –
How to reduce your taxes with an elephant.