"If anything in life is constant, it is change." - Bryce's Law

INTRODUCTION

Like so many of you, I am often mystified as to why there is so much trouble in the middle East. We could easily blame it on religious fanaticism, be it Christian, Jewish, or Muslim. Perhaps. But I tend to believe it can primarily be attributed to change (or the fear of it). In this part of the world, there is great suspicion over the cultural differences between religious groups. Each side fears if they make peace and accept the other parties, it will have an adverse affect on their culture which is something they simply will not accept. In their minds, each believes they follow the "true calling" and will not tolerate any di

According to USFDA, a combination product is one composed of any combination of a drug and device; biological product and device; drug and biological product

scussion to the contrary. Frankly, I do not think anyone is trying to change the moral conviction of the other; nonetheless, the fear remains.

We see similar examples of the fear of change, on a much smaller scale, in business, the volunteer non-profit organizations we participate in, and in society in general. Change is a fact of life. Change happens every day before our eyes in the most subtle ways. Change is constant. And instead of resisting change, we should learn to understand it and learn to cope with it. Refusal to deal with change is simply denying reality. For example, I see substantial changes in the schools my children attend, not just the difference between my generation and theirs, but the changes

; or drug, device, and biological product and fixed dose combination would include two or more combinations of drug.

Examples of combination products may in

in their own schools in the short time since they have been going to school. I have also witnessed substantial changes in the workplace since I entered it in the 1970's.

In the systems world, IT departments should readily understand the nature of change for they typically devote 80% of their work effort on modifying and improving corporate systems. As an aside, I find it rather amusing that systems people, who are supposed to be the merchants of change, are often the most resistant to it themselves.

It would be nice to believe change always represents progress. Not necessarily. Change can also be counterproductive if a new convention is introduced that doesn't improve the status quo. This is probably the bigges

lude drug-coated devices, drugs packaged with delivery devices in medical kits, and drugs and devices packaged separately but intended to be used together.

cause for the fear of change; that it will not improve our livelihood but, instead, cause a decline in our way of life.

Change is not a technical problem as much as it is a people problem. Implementing changes to our mechanical devices is nothing compared to how the human being must deal with the device.

WHAT CAUSES CHANGE?

There are fundamentally three reasons for change:

• Political/Government influences - representing new or modified laws, rules and regulations to be implemented either dictated to us or by majority rule. This is closely related to...
  
  
• Cultural influences - society, fashion, religion, customs and language, even the physical environment affects change. For example, the use of our verna

here is enormous increase in the number of combination products entering the market in the recent years. Combination products have proven advantages but fixe

ular or our personal appearance represents subtle changes in attitudes and morality. Mother nature, with its tempest of storms, affects how and where we live. The evolution of technology falls into this category as well. For example, consider how the PC, cell phones, video players, and the Internet have affected our lives over the last few years. We now live in a fast-paced world where we expect everything on demand.

Competitive/Economic Influences - in order to succeed in life, it is necessary to evolve and improve in order to win. Do we really want to just "Keep up with the Jones'" or do we want to get ahead of them? Economics also influences our way of life and represents our safety blanket. For example, if we do

d dose combinations are still in the process of convincing regulatory authority on their advantages over the single ingredient formulations.

Combination pro

not feel economically stable, we will alter what we are doing in life to safeguard our family and ourselves.

As an aside, these three agents of change greatly influence our information requirements. Those who understand this will adapt accordingly and be masters of their destiny. Those that do not, will fall behind.

There are three degrees of change:

• Subtle - representing minor changes occurring daily which we accept (either gladly or grudgingly). Subtle changes can be as insignificant as a change in our speech, form of address, a new hair style, etc. We will either like and embrace such changes or we will simply tolerate them.
  
  
• Moderate - representing significant modifications to the status quo. This in

ucts have become life saving products for the pharmaceutical companies who doesn’t have many innovative molecules in their product pipeline and have been inc

ludes such things as upgrades to our systems and procedures, changes to our policies, and material changes affecting our way of life. Moderate changes are either mandated or requires some tact or diplomacy to implement.

Radical - represents changes upsetting the status quo. This includes complete overhauls of systems, the introduction of totally new ways of conducting business, and such things as mergers, diversifications, closings, and divorce.

Understand this, resistance to change grows as we move from subtle to radical. Subtle changes are those we understand and readily adapt to, but unending changes turning our world upside-down will not always be greeted with enthusiasm.

"Living without change would be

inconceivable and unbearable. At the same time few of us would care to go on living in the midst of ceaseless, chaotic, completely unpredictable change." - Hadley Cantril

WHY DO WE RESIST CHANGE?

Let us now consider the fundamental reasons why we resist change:

• We are creatures of habit. We long for stability in our lives which represents a comfort zone we want to live in. Any proposed change to this comfort zone is greeted with suspicion. This is perhaps the biggest reason for resistance to change.
  
  
• Fear of the unknown. Going into a dark room is difficult even for the bravest of souls. As human-beings, we have a natural tendency to want to be in control of our actions and behavior. As suc

nation products and maximize the revenues. But the companies involved in this practice are overlooking that they are burdening the patients both economically

, the unknown is terrifying and causes us to invent rationales for why we shouldn't do something; even worse, ignorance leads to fabrications of the truth and gossip.

Human emotion. Humans are capricious, and tend to do only what pleases them. We may elect to cooperate or stubbornly resist for no apparent reason. As such, we must recognize man as a political animal who will only do those things they feel are in their best interest. We do not like our authority or territory challenged whereby we might lose control. Consequently, we will sabotage any change coming our way.

Ignorance. We are either unaware a problem exists or that a better solution can be found. Many people are comfortable operating in a stat

and physically. They need to rightly judge the benefits of the combination products and they have to even look at the risks involved when combining the produ

of ignorance, they do not want to know about problems or anything affecting their environment.

Combinations of the above.

A person's age also affects resistance to change. As we get older we become more set in our ways and less likely to accept change. In contrast, younger people are much more adaptive to change. A lot of this has to do with the fertility of the mind. Our most creative and energetic years are in our youth where we believe the sky is the limit. This is why the military wants young soldiers for they believe themselves to be fearless and want to prove themselves to their superiors and family. In other words, they have not yet learned they are not indestructible. But after they have been b

ts. Some of the combination products were well accepted by physicians while others suffered. Companies involved in development of combination products are fi

rned a couple of times, they start to become jaded and start to challenge the rationale for why they are asked to perform certain tasks. Further, the military realizes younger minds can be shaped more readily than older ones.

IMPLEMENTING CHANGE

As we all know, implementing change is not a simple matter. A lot depends on the perceptions of people. If we believe a change to be worthwhile, we will readily accept it; if not, we will bitterly resist it. As humans, we act on our perceptions which is not necessarily synonymous with reality; it is how we believe something to be regardless if it is true or not. Hitler and Joseph Goerbels were acutely aware of this phenomenon and distorted people's perceptions in or

ding difficulty in defining their combination products and facing various challenges from selecting a combination to marketing it.

Following aspects would a

er to bring about sweeping changes in Germany. Both the press and politicians in general are also astute in this regard and attempt to influence public perceptions, thereby bringing about the changes they champion. Advertising agencies are also aware of this, as should business and non-profit groups interested in bringing about change.

Before we turn everyone into propaganda ministers though, let us consider the fundamentals for altering perceptions which is commonly referred to as the three canons of discourse: ethos, pathos, and logos, representing emotional appeals at ethical, emotional, and logical levels. We deliver these arguments through media appealing to our senses and intellect and "voila" you have the recip

dd to the challenges in developing combination products:

Which markets to tap where the combination products can do fairly well?
Which combination prod

for manipulating perceptions:

Rhetorical Argument (the message) X Media = Perception

Before we try to sell people on a particular change, we have to weigh the impact on its effect (subtle, moderate, or radical) versus the costs and benefits involved. "PRIDE" Special Subjects Bulletin Number 19 ("The Elements of Cost/Benefit Analysis" - Apr 11, 2005) includes a description for performing a Cost/Benefit Analysis.

We must recognize from the outset the cost of change is proportional to resistance to it. The higher the degree of change ("subtle" versus "radical"), the more costly it will be to implement.

Regardless of the scope or degree of change, in order for it to be successfully implemented, it must become a natural pa

cts are meaningful and rational?
Which therapeutic categories to select?
Which Combinations can address unmet needs of the patients?
Do combin

t of our lives (our culture). In other words, we have accepted the change and alter our lives to implement it. If we fail to adapt to it, the change will not take affect in the manner we had hoped. Let me give you an example, years ago my wife worked for a large jet engine manufacturer in the mid-west where she ordered specific parts for the assembly line. A lot of the ordering was done manually using index cards and paper forms. The company believed this to be antiquated and ordered the design of a new Order Processing System. Millions of dollars were spent on the project for a new "state of the art" system. As the system neared initial start-up, the order processing staff was given rather cryptic training in

tions increase the patient compliance?
What would be the developing cost?
How to tackle the risks encountered during combination product developmen

the use of the system. The system may have been a good one, but the developers underestimated the human element of change. So much so, when system startup came, the order processing staff simply ignored the new system and continued with their index cards and manual forms. This was a major setback for the systems people. What had they done wrong? Three things: first, they didn't solicit support for the project from the order processing staff in the early stages of the project, nor did they have a representative from the staff participate in the project; Second, the training of the staff was done badly (cryptic instructions were given instead of offering education in terms the staff could understand), and; Thi

t?

As combination products don't fit into the traditional categories of drugs, medical devices, or biological products, the USFDA is in the process of devel

d, the systems department failed to provide adequate technical support during system startup. Consequently, the order processing staff ignored the new system, went back to their old ways of doing things, and sent the systems staff back to the drawing boards.

Anytime we are interesting in introducing any major change, there are three things we must do:

1. Solicit support from the people who will be affected by the change thereby getting them "on board."
   
   
2. Train them effectively (in terms the staff will understand).
   
   
3. Follow-up and support the people until the change becomes a natural part of the culture.

By doing so, we set at ease concerns people have about the merit of the change. If this is not d

ping new procedures for reviewing their safety, efficacy and quality.

Professional from academic institutions, pharmaceutical industries, health care indust

ne, people will either ignore the change, or even worse, deliberately sabotage it.

Implement as much change as the people affected can assimilate. Too much change may be too difficult for people to cope with. In this event, stage your changes over times. Always remember, "You eat elephants one spoonful at a time."

TREND ANALYSIS

The Implementation of change is considered so important by some companies, they will track the frequency of changes and the degree of severity by either maintaining logs or plotting time lines (or both).

Such analysis is useful for spotting trends. If there is increased frequency of change, a manager should be asking questions as to why. Perhaps there is something fundamentall

y and representatives from various regulatory agencies are working out to design the regulatory requirements for manufacture and sale of combination products

wrong with the product or object we are managing.

THE NEED FOR CHANGE CONTROL

People will tolerate a certain amount of change, but complete chaos, where change occurs rapidly and unpredictably, is difficult for anyone to tolerate. "Controlled" changes, on the other hand, are more palatable to accept. To do so, we have to itemize and prioritize a backlog of anticipated changes and implement them under structured conditions as time and costs permit, thereby adding "rhyme and reason" to changes as opposed to helter skelter.

Taking control over the implementation of changes (or "Change Control") is essential in order to move from a "reactive" management style to a "pro-active" style. In other words, we take charge

.

As there is an increasing trend of the combination products companies manufacturing such products should be able to tackle the problems involved in the de

f change as opposed to changes taking charge of us.

CONCLUSION

Change is a fact of life and as such, we must either learn to adapt to it or perish. In fact, it is our duty to change, to aspire, to progress, to seek perfection and evolve. Change is natural.

Change impacts the lives of people and, as such, affects their emotions and insecurities. To implement change requires an appeal to the perceptions of people in terms of how it will improve their livelihood. If the change is misunderstood or if it is perceived as something having an adverse effect on the status quo, it will be steadfastly resisted. However, if a change is pitched properly, not only will people welcome it, they will help implement it for

elopment. They need to be wiser in analyzing the market trends and the regulatory requirements.

Companies that provide selfless information through particip

you.

Implementing change means overcoming fear and establishing trust. And remember, bite off only what your people can chew. Since change is an evolutionary process, stage your changes over time. As one part of your overall plan is implemented, phase in the next.

Finally, I will leave you with this quote from Machiavelli's, "The Prince" written in 1513:

"It must be remembered that there is nothing more difficult to plan, more doubtful of success, nor more dangerous to manage than the creation of a new system. For the initiator has the enmity of all who would profit by the preservation of the old institution and merely lukewarm defenders in those who would gain by the new ones."

I guess some things never change

tion in industry events and feedback to regulatory authorities would be able to face the challenges and will be successful in developing combination products