applying “lean” – global regulatory approvals & maintenance (part 1) · 2013. 5. 2. ·...

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W H I T E P A P E R

Applying “LEAN” –

Global Regulatory Approvals & Maintenance

(Part 1)

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“LEAN” for Regulatory – Part 1

The “LEAN Way” for Global Regulatory Approvals

Lean thinking is not a manufacturing tactic or a cost‐reduction program, but a management Strategy

You are not alone in the quest for bringing your products to market and improve the quality of life for

millions! Pharmaceutical companies across the world are making efforts and investing in building

efficiencies by integrating their systems, people and knowledge to bring quality medicine in to the market.

In the pursuit of building agile regulatory framework to support business goal companies have structured

their regulatory teams globally with limited control on global submissions and in-turn approvals.

This white paper focuses on building lean regulatory framework for successful global submissions and faster

approvals.

Lean journey should begin with driving out waste so that Regulatory associates efforts add value and help

in authoring compliant dossiers, enhance reusability of components and augment faster approvals globally.

Identifying value-added and non-value-added steps in every process is the beginning of the journey toward

lean framework. For lean principles to take root, leaders must inculcate an organizational culture that is

receptive to lean thinking.

The commitment to lean must start at the very top of the organization and all associates should be

involved in helping to redesign processes to improve flow and reduce waste. Whether building a car or

compiling a dossier, associates must rely on multiple, complex processes to accomplish their tasks and

provide value.

Waste of time in getting the approval is the biggest cost to the company and it can decrease value.

This paper highlights how pharmaceutical companies can bring in Lean Principles in the way they approach

Health Authorities globally for regulatory approvals.

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Introduction

Pharmaceutical industry is not transforming fast enough to address the persistent decline in bringing new

drugs into the market. Alternative models are being explored in an effort to jumpstart transformation. One

such model is to transform from a Fully Integrated Pharmaceutical Company to a Fully Integrated

Pharmaceutical Network. Except for a few, most departments, (Chemistry (manufacturing), Clinical, Non

Clinical, Logistics, IT, Marketing, etc.) have this network already built. On the contrary, in spite of the cost

benefits and business benefits, some companies have been cautious in building these networks around

some of the vital functions like IP, Regulatory Affairs, as they are the most vital functions that drive R & D

efforts of the company to the market successfully.

Companies world over have realized that to survive in today’s challenging economic climate, they must

have a global strategy in place to target markets. They are now looking to create new revenue streams or

supplement existing ones. Selling products in rapidly growing emerging markets (Asia, Latin America, the

Middle East, and Africa) presented many opportunities to extend a drug’s lifecycle and profitability.

However opportunities in emerging markets have also brought in many challenges as local regulatory

requirements in each country are governed by their regional compulsions. Reason, the regulations were

written to safeguard the needs in those countries and the regulations had evolved independently of one

another. Consequently, there is an enormous amount of diversity in the regulations, laws, and procedures

for registering new pharmaceutical products.

ASEAN

SADC

GCC

PANDRH

APEC

US

EU

Regional Regulatory Network

Government

Issues Healthcare

Laws

Health Authority

Issues Guidelines &

Guidance

Pharmaceutical

Industry

Develop & Market

Product

National Regulatory Framework

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Pharmaceutical companies slowly realized that the key to success in these markets largely depended in

obtaining timely marketing / clinical approvals from regulators for which local regulatory knowledge had

become the key. The companies were in a fix as they did not know whether they had to standardize or

“harmonize” the application while approaching health authorities for market approval of their products. As

there was tremendous regional pull on local requirements, companies were left with no option but to

strengthen their regulatory departments or outsource to local regulatory affairs consulting firms. During

this phase unfortunately, the companies did not forsee the growing complexities within their team

structure and the lags they were building which went on to become obstacles in their overall structure.

Over the years, the ICH and several regional harmonization initiatives (RHIs) in non-ICH countries

(Association of Southeast Asian Nations (ASEAN), Asia-Pacific Economic Cooperation (APEC), the Gulf

Cooperation Council (GCC), the Southern African Development Community (SADC), and the Pan American

Health Organization (PAHO)) have worked closely with one another (via ICH’s Global Cooperation Group)

and, more recently formed a joint working group with the goals of

• Reducing country and regional differences in technical requirements that impact the availability

and cost of new medicines

• Promoting the international movement of pharmaceuticals that are safe, effective, and of high

quality, and

• Promoting the conduct of human clinical trials and data collection that meet international

standards.

Even though it is unclear whether global harmonization would be a reality there is definite progress; the

initiatives that are being taken regionally is a good sign for the industry. During the years regulatory

landscape had changed and companies have moved to building regional hubs and networks with no

evident intention of becoming lean and compliant. Inflection points in the regulatory landscape had

changed over the years; they were predominantly driven by market expansion, advent of various IT

applications and finally the standards enforced by various stakeholders (FDA, EMA, PMDA, regionally

harmonized groups and others). The last few years in the regulatory landscape can be classified into three

different phases.

• Phase 1: Companies started expanding into multiple geographies and so regulatory departments

had seen unorganized growth

• Phase 2: Influence of IT application like eCTD, Tracking Tools & Regulatory Intel, during this phase

IT had changed the life of regulatory associate in meeting global needs

• Phase 3: Global Submissions with Lean regulatory teams by building Regulatory Centre of

Excellence.

In the first phase there was growing need from the business function for registering products in multiple

countries, so regional RA teams were strengthened. Local customization of dossier was done at the

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regional level, as a result pharmaceutical companies were forced to maintain large regulatory departments

across the geographies this has resulted in confinement of knowledge at the regional level without being

precluded to the central team hence prevented reusability of the submission package.

Second phase was driven primarily with the advent of IT and push from authorities for submission of

applications in the electronic format and partially due to the harmonization of regulatory requirements

over the past few years.

To help pharmaceutical companies meet the new regulatory submission standards set by authorities and to

successfully launch or expand therapies into new markets many of the shelf RIM applications (eCTD,

tracking tools, document management, and BI applications) had come into market. They have changed the

face of the regulatory departments. To a large extent these applications could fix the gaps and changed the

way regulatory teams started functioning. RIM infrastructure enhanced visibility of global submissions,

tracked the status of submission components from initial submissions to post-approval, tracked progress of

health authority queries and responses, assisted in capturing knowledge, connected central and regional

regulatory teams, structured their change protocols and in short strengthened Leadership in taking better

decisions.

RIM framework offered integrated solution with the functionality to create any submission format (eCTD,

NeeS, ACTD and paper) as well as comply with evolving country-specific guidelines from within the same

application. RIM offered a central platform for global collaboration on all data and documentation during

the submissions process, shortening the submissions cycle and time-to-market.

Phase 3: LEAN way for Global Regulatory Approvals

Another market factor impacting life sciences companies is the drive to decrease the total cost of

ownership of regulatory applications. Lack of optimization in both infrastructure and business processes is

making it difficult to take full advantage of business process optimization offered by RIM environment. It’s

time for companies to think beyond to bring in efficiency by optimizing the RIM environment and achieve

goal of getting faster approvals in global market.

LEAN way for Global Regulatory Approvals is an interesting concept which when meticulously implemented

can drive regulatory teams in augmenting their business goal of entering global markets with speed.

There is common misconception that LEAN is about cutting teams. It is not cutting teams it is: Least

number of associates who can effectively produce quality dossiers/negotiate with authorities to

successfully obtain approvals in new markets /molecular entities/indications

LEAN is about building scalable structure, driving out waste, with right RIM environment supporting

process, with flexible network of service providers who can augment company’s goal of faster approvals.

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What is LEAN?

The concept called “lean management” or “lean thinking” is most commonly associated with Japanese

manufacturing, particularly the Toyota Production System. Much of the Toyota way focuses on what

managers should stop depending on, say “mass inspection to achieve quality” and, instead, should focus on

improving the production process and building quality into the product in the first place.

The core idea of lean involves identifying the value of any given process by distinguishing value added steps

from non-value-added steps, and eliminating waste (or muda in Japanese) so that every step adds value to

the process.

To maximize value and eliminate waste, leadership must evaluate processes by accurately specifying the

value desired by the associate; identifying every step in the process (or “value stream,” in the language of

lean) and eliminating non-value-added steps; and making value flow from beginning to end.

When applied rigorously and throughout an entire organization, lean principles can have a dramatic affect

on productivity, cost, and quality.

To remain LEAN companies need to answer following few questions.

• Leadership Commitment

• LEAN Process

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• Initiatives and Innovation

• RA team framework, team structure and geographical presence

• What are the critical Information Technology needs

• Network of service providers

Note: Based on the current figures across different industries companies had taken at least 1 to >7 years to

inculcate Lean Principals and bring in efficiency to derive value.

Leadership Commitment:

Introducing lean thinking in an organization requires major change management throughout the

organization, which can be traumatic and difficult. Strong commitment and inspiring leadership from

senior leaders is essential to the success of an effort this challenging. Those at the very top of the

organization must lead it. It cannot be done piecemeal, but must be a whole-system strategy. There is no

single solution and it cannot be done only by middle managers or frontline workers.

Senior management must be a vocal, should champion and, create an environment where it is permissible

to fail, set stretch goals, and encourage “leaps of faith.” Leadership team should understand that

organization’s culture is set of values and beliefs that guide people to behave in certain ways. Leaders who

wish to change their organizational culture cannot do so by edict. They must intervene and require people

to behave differently, allowing them to experience a better set of results.

One of the challenges of implementing lean is that it requires people to identify waste in the work in which

they are so invested. No associate would even think that his work is not adding value and is wasteful; such

an idea can be very painful and difficult to accept. So success of the creating LEAN would largely depend on

the direction that Leadership would bring in.

Process:

A process is a set of actions or steps, each of which must be accomplished properly in proper sequence at

proper time to create value. A perfect process creates precisely the right value because every step

valuable, capable, adequate, flexible, and linked by continuous flow. Failure in any of these dimensions

produces some type of waste.

The Toyota way identifies seven categories of waste: overproduction, waiting, transporting, processing,

inventory, motion, and correction. A perfect process not only creates value, but it is also satisfying for

people to perform; managers to manage, and customers to experience.

Getting Started To create the perfect process, begin by identifying the key processes (Global Submission) in

your organization. Identify the person responsible for each process as a whole, how it works, and how to

make faster and compliant submissions. Caution should be prevailed in appointing the right person for the

process as it requires attention and relentless pursuit of driving waste out of the process.

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Sustainability of the process depends on the entirety and on the understanding of its logic. The best way to

create vision and understanding is to directly involve participants in improving the process. This is most

often done by bringing together key participants from a chosen process.

Developing compensation mechanisms, or use a productivity-based compensation system is also a good

measure to drive process improvements.

An intensive four- or five-day session focused solely on analyzing current processes and implementing

changes can be organized. For each key process identify, a kaizen team (Kaizen means continuous,

incremental improvement of an activity to create more value with less muda) and assist them in mapping

the process as it actually operates (not how it is supposed to operate), specifying value from the standpoint

of the customer (external or internal), as well as waste in steps or between steps. Physically walking

through the process steps can be very illuminating.

An example of a process map:

MAA roll out has been taken as an example, and the process has been explained below. There can be many

dependencies during the authoring phase of a dossier. RA associate is depended on different stakeholders

for different sections of the dossier.

MAA Roll Out Current Process Map:

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As depicted in the above chart during the strategy phase, central RA team works closely with regional

affiliates to understand the regional requirements after which the team coordinates with Authors and

prepares appropriate strategy in compiling or customizing the dossier. During this phase if the

requirements are not captured well and are not shared with Authors they can lead to waste of effort. As a

result there can be many challenges, as the dossier can go back and forth for necessary changes. Also at

every stage there might be a possibility for Authors going back to Affiliates for information which is

depicted with dotted arrows.

Once the requirements are gathered, work package is developed, dossier back bone is defined and core

dossier is developed, Module I is completed and if any regional translations are to be done they are done

and finally sent to the Regional Affiliates for their review, comments and submission.

Regional Affiliate based on the quality of the dossier either can submit “as is” or incase of gaps they can

rework on specific sections and finally submit the dossier. Based on the quality of the dossier it can be

approved or more queries can come up for the final approval.

Submission Manager

Author

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In the above process map there are many dependencies which are closely integrated and are not visible.

Timelines can take a drastic hit incase if those dependencies are not incorporated and planned. During the

compilation phase there will be some wait time for getting the documents from various departments; one

such example can be latest stability data from the plant. In the given context if the data does not come in

time, associates many not see this as their wasted time, and may not stop to wonder why data is not

coming. But if the data is always available, associates do not have to spend time in following up with the

stakeholders and in fact can plan their time more appropriately.

LEAN thinking can envision and map the future state by asking how the process should be changed to

move toward perfection. This is known as a “future state process map”, process map below can show a

future state process. Note that the ideal future state eliminates most of the wasted time between steps,

allowing workers to complete the same task by less than a month.

The details of these sample maps are less important than the ideas they represent. The format of a process

map can vary according to the mapmakers’ preferences. The important thing about a process map is that it

is explicit about the flow and value of the process.

MAA Roll Out Future Process Map:

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In the new process after the submission process is developed, authors can closely work with submission

manager’s right from the early stages of requirement gathering. As authors are capturing the requirements

in the early stages they can be more confident and probability of going back and forth to the Regional

Affiliates will be less.

Authors being involved right from the early stage can also give confidence and assist them in using

reusable components of the available dossier and make the necessary customization where ever possible.

For example from ICH CTD to ACTD there are many reusable components which can be used “as is”. On

further breakdown of the process this phase can be further LEANER.

Submission Manager

Author

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Reducing slack in this process can bring agility in the process and assist in developing regulatory compliant

dossiers in much lesser time. Using the future state process map, staff can be reorganized if necessary to

match the requirements of the process.

Network of Service Providers:

The ability for transformation and implementation of these initiatives quickly dissipate with the size of the

global entity and the number of moving parts. The effort and risks involved in the many trade-offs that will

occur throughout the development of a common business model, and the corresponding changes require

more than a cursory understanding of the current state within each business/region involved. It is

important for the RA department to realize what process is adding value and what process is creating

waste. By working with network of service providers can waste be converted into value is what

organizations should constantly question. Some of these questions can be:

• Strategic change: How will the new structure or assets enable enhanced value generation?

• Tactical change: What types of new changes are needed to succeed in new markets?

• Operational change: How will we operate differently once the new businesses/assets are

assimilated?

Based on the above three attributes companies can decide on the network of partners, working with

partners may also represent an attractive option to gain experience, optimize cost, and enhance

productivity.

Consolidating disparate systems that have proliferated and people who are spread throughout during

expansion into multiple markets is now a high value-adding proposition for companies seeking to boost

business performance and operational efficiency. LEAN approach is an effective means of creating

harmony across a global enterprise, with the primary emphasis on driving synergies operationally. These

synergies are typically enabled through business process redesign and enterprise system harmonization.

LEAN approach for creating common global business operating model and solution template that can be

leveraged across the global enterprise enables the transformation and harmonization of critical business

processes, along with underlying goal of achieving speedy marketing approvals.

applying “lean” – global regulatory approvals & maintenance (part 1) · 2013. 5. 2. ·...

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