Product lifecycle management in pharmaceuticals

Abstract

A product lifecycle is the succession of stages from the product’s birth until its final withdrawal from the market. While each stage brings significant changes, a succession of strategies for the management of product lifecycle is required. The product lifecycle management creates and manages a company's product-related intellectual capital starting from an idea to its final retreat. In pharmaceutical industry, it benefits through enhancing the lifespan of patent and pricing strategies. Improved patient compliance, revenue growth, expanded clinical benefits, cost advantages life extension exclusivity and quicker market launch are amongst the main applications of product lifecycle management. To fabricate an effective and fruitful product lifecycle management program many attributes are considered. The chief ones are: early start; strategic planning clear leadership; supporting knowledge and skills, preparedness for changing rules of government and organizations.The present manuscript focuses on product lifecycle management, its applications and the key considerations for a successful product lifecycle management.

Keywords

Pharmaceuticals product lifecycle return of investment product lifecycle management strategy

Introduction

During the last years, the period of true marketing exclusivity for pharmaceuticals has shrunk dramatically. Today’s pharmaceutical industry is facing tremendous pressure when a blockbuster drug patent expires owing to short drug lifecycles, strong competition, heightened health authority scrutiny, rising development costs coupled with lower drug prices and the need for the latest technologies.^1,2

As a concept, product lifecycle management (PLM) has existed for many years originating in electronics and automotive sectors. It allows a company to actively manage the way in which a product is being sourced, manufactured and planned throughout its lifecycle. PLM is a strategic approach for creating and managing a company's product-related intellectual capital starting from its initial conception to retirement. PLM improves a company’s product development processes and its ability to use product-related information to make better business decisions and deliver greater value to customers.^3,4

Many manufacturers pursue lifecycle management tactics in reactive manner. Franchise can be sustained if brand equity (and prescriptions) can be transferred to a follow-on or derivative product, even a reformulation or new delivery system. This is generally done through secondary patents or second generation patent. These patents seek to protect a drug after the original patent on that drug expires. Thus, patent lifecycle management is a part of PLM. Switching a prescription drug to an over-the counter drug is also another tactic to have an edge over generics. But these tactics, despite great efforts, at some point give way to generics although they enhance the return of investment.^5,6

The PLM program should be based on the development and implementation of intellectual property (IP). Rapid changes in markets, technologies, regulations and laws and new competitor products and offerings make lifecycle management programs highly dynamic. Thus, PLM strategies should be constantly reassessed for new opportunities. The PLM program has become an increasingly more challenging due to recent developments in the U.S. courts and potential legislative changes Hence, companies should not only constantly reassess their strategies but overall approaches towards PLM.⁷

Pharmaceutical companies are now determined to extend the life of their drug beyond patent expiration, devising strategies to manage the lifecycle of their most important medicines that begin in the clinical phases. PLM has become a necessity to the continued success of pharmaceutical companies. Companies that have instituted a comprehensive lifecycle management strategy and a detailed plan to guide their progress toward their goal are reaping financial and clinical rewards. Successful PLM involves the continued development of scientific, technical, regulatory and marketing strategies that enhance the value and extend the life of medicines.⁸

It is of critical importance that IP protection permits the innovators of successful products to recoup their investment. With rising development costs, the pressure to utilize IP protection to the fullest extent permitted has become even greater. Thus, the most successful innovator companies have developed sophisticated IP strategies. For the purpose of pharmaceuticals, PLM does not mean a way to protect their innovation through different patents or obtaining patent term extensions to take the benefit of all available protection. It also means to co-ordinate worldwide IP litigation strategies to achieve the desired result at a global level. Successful PLM enforcement strategy involves three distinct but interrelated laws: patent law, regulatory law and competition law. An integrated approach of all three aspects is necessary. An understanding of the regulatory process by which drug products obtain their marketing authorizations and prices is fundamental; however, patent litigation is the key ingredient. To make a rather crude analogy, if PLM strategy is considered a road vehicle, regulatory information is the steering, patent litigation the engine and competition law both the seat belt and the brakes. PLM requires firm grip over these three laws and technical expertise necessary to make the most informed decisions in litigation. This is more important for secondary patents, for example, patents protecting a route of chemical synthesis or a particular tablet composition. If the patent protects the new chemical entity, a technical analysis for the purpose of elucidating infringement need only to determine whether the active substance is present or not. For a secondary patent, the analysis could be required to assess whether a competing synthetic process or tablet composition is the same or equivalent to that protected by the patent.

The interplay, between the laws and the technical foundations, is of critical importance to strategy. For example, an understanding of the regulatory drug approval process for generic medicines enables accurate assessment of the progress of generic competition. This includes an understanding of the intensity of any given generic threat. Understanding the regulatory approvals process not only enables accurate assessment of threats but also the identification of the most suitable trigger point for entering into pre-action correspondence or commencing litigation proceedings. Trigger points for litigation can be evaluated by comparing the timeline of the drug approvals process, from filing the application to launching on the market, with the timeline for obtaining injunctive relief in the country concerned. It has to be always borne in mind the need to prove the infringing activity, or threat of infringing activity to the level required by local law.⁹

PLM was evolved in the 1990s and has played an important role for manufacturing companies. During the last two decades, changes have taken place due to modified regulations, technological advancements and globalization.¹⁰ In the last decade, PLM was viewed by industry as a tool to extend lifecycle of products while regulators found it a kind of antitrust activity to create monopoly. However, the previous decade has witnessed the transformation in their views. In the present scenario, the industry considers PLM as a core process to integrate its other business activities, whereas the regulators support the industry to adopt PLM in a proactive way to improve the innovation and quality of product.¹¹

In the present manuscript, an attempt has been made to study PLM, its applications and key considerations for a successful PLM.

Lifecycle of a pharmaceutical product

All products and services have a certain lifecycle. The lifecycle is the period from the product’s first launch into the market until its final withdrawal. In general, product lifecycle is split up in five different phases; however, the lifecycle of a pharmaceutical product is longer and more complex due to loads of data, growing product complexity, regulatory oversight and validation, time to market pressures, increasing quality requirements and increased branded and generic competition.⁴ Therefore, the pharmaceutical product lifecycle can be divided into six phases (product approval phase is the additional one in comparison to other product’s lifecycle):

Product development

Product approval

Product introduction

Product growth

Product maturity

Product decline

Significant changes occur during each phase reflecting the product’s behavior into the market, i.e. the sales which introduce the product into the market.^4,12^–¹⁴

A Product lifecycle of a fictitious product in terms of sales cost and profit is given in Figure 1.¹³

Figure 1.

A product lifecycle of a fictitious product in terms of sales, cost and profit.¹²

Product development phase

As and when a company finds and develops a new product idea, the product development phase begins.^12,14 Those products that survive the rigorous preclinical and clinical trials are then subjected to approval from regulatory authority before their placement into the marketplace.²

Product approval phase

All preclinical and clinical data are collected and subsequently submitted in appropriate form(s) to the regulatory authorities along with the quality data and the description of the manufacturing process for review. A continuum of communication with the regulatory personnel is required during this phase. Drug approval is granted only if the regulators found that the data prove the quality, efficacy and safety of the drug. It is the most crucial phase because without the approval from the corresponding regulatory body, no drug can undergo commercialisation.²

Introduction phase

It includes the product launch with its requirements so that it will have maximum impact at the moment of sale. In this phase, distribution arrangements are introduced. Commonly large expenditure on promotion and advertising (in case of pharmaceuticals – only when permitted) is made and quick but costly service requirements are introduced. A company spends a lot of money. However, only a small proportion of that is received back.

Growth phase

This phase provides the satisfaction of witnessing the product’s take-off in the marketplace. This is the appropriate timing to focus on increasing the market share. When a product has been introduced first into the market, it is able to gain market share relatively easily. Promotion and advertising continues up to some extent in this phase. In this period efficiencies, product availability and services are developed and improved. The major factors in gaining customer confidence include cost efficiency, time to market, pricing and discount policy.

Maturity phase

When the variations of the main product saturate the market, the product enters the maturity phase. This period can provide the highest returns from the product. New brands are introduced during this phase even when they compete with the company’s existing product. This is the actual time to extend the product’s life. Changes in the pricing and discount policies are frequent. Scope of promotion and advertising relocates from getting new customers to product differentiation in terms of quality and reliability.

Decline phase

The decision for withdrawing a product appears to be a complex task and there are a lot of issues to be resolved before deciding to move it out of the market. Companies often retain a high price policy for the declining products to increase the profit margin and gradually discourage the few loyal remaining customers from buying it. It is the time to start withdrawing variations of the product from the market that are weak in their market position. The prices must be kept competitive and promotion should be withdrawn at a level that will make the product presence visible and at the same time retain the loyal customer. The basic channel should be kept efficient abandoning the alternative channels.¹²^–¹⁴ Various conditions and steps to be taken in different phases of a product’s lifecycle are illustrated in Table 1.

Table 1.

Various conditions and steps to be taken in different phases of a product’s lifecycle.^12,13

	Development phase	Approval phase	Introduction phase	Growth phase	Maturity phase	Decline phase
Sales	Zero	Zero	Low sales	Rapidly rising sales	Peak sales	Declining sales
Costs (per customer)	Very high	High	High	Average	Low	Low
Profit	Negative profits	Negative	Negative profits	Rising profits	High profits	Declining profits
Customers	Zero	Zero	Few	Growing number	Stable number beginning to decline	Declining number
Competitors	Almost not there	Almost not there	Early entry of competitors into the market	Price and distribution channel pressure	Establishment of competitive environment	Some competitors are already Withdrawing
Strategic Goal	Make the product known and establish a test Period	Make the product approved atthe earliest	Acquire a strong market position	Maintain your market position and build on it	Defend market position from competitors and improve your product	“Milk” all remaining profits from product
Product	Limited number of variations	Product under approval	Introduction of product variations and models	Improvement – upgrade of product	Price decrease	Variations and models that are not profitable are withdrawn
Price goal	High sales to middle men	Depend upon regulatory bodies	Aggressive price policy (decrease) for sales increase	Re-estimation of price policy	Defensive price policy	Maintain price level for small profit
Promotion goal	Creation of public – market product awareness	Depend upon regulatory bodies	Reinforcement of product awareness and preference	Reinforcement of middle men	Maintain loyal to middle men	Gradual decrease
Distribution Goal	Exclusive & selective distribution through certain distribution channels and creation of high profit margins	Not applicable	General & reinforced distribution through all distribution channels available	general & reinforced distribution with good supply to the middle men with low margins of profit for them	General & reinforced distribution with good supply to the middle men with low margins of profit for them	Withdrawal from most channels of distribution except those used in the development phase

Product lifecycle management

There is a continuous rise in need for PLM due to following reasons:

Decline in research and development productivity

Escalation in average development costs

Narrowing of return of investment

Competition is soaring high

Competition from generics

Dispersing markets

Decline in research and development productivity

The research and development pipelines are drying up quickly. This can be estimated by the fact that the number of new medicines approved by the US Food and Drug Administration (FDA) in 2010 is about half of those approved in 1996. This implies that the industry is running out of new blockbuster drugs in the near future. There are a number of blockbuster drugs produced by many big and small companies in the last few decades, but now the blockbusters are, one by one, coming to the end of their patent protected lives.¹⁵ A decline in research and development productivity in new medicines from 1996 to 2010 is illustrated in Figure 2.¹⁶ One of the reasons for this could be the high failure rates due to more stringent regulatory environment requiring new and more demanding hurdles to be cleared by the new drug candidate to enter the market.

Figure 2.

Decline in R&D productivity in new medicines.¹⁶

Escalation in average development costs

The average sum of money required to develop a drug is very high. At the same time, sufficient funds are required to get it approved.^15,17 The average drug development costs may vary in accordance with drug group, choice of strategy and type of therapy from US$500 m to US$2000 m. For example, drugs designed to treat respiratory disorders such as asthma have an expected capitalized cost per approved drug of US$1.3 billion while for drugs treating genitourinary disorders, it is US$635 m.^18,19 A recent Tufts CSDD study has shown that the average capitalized cost to bring one new bio-pharmaceutical product to market (including the cost of failures) is $1.24 billion, in 2005, while for conventional pharmaceutical products, the same is $1.32 billion.²⁰ With such development costs, it is expected that only the leading and well-heeled players can afford to take a drug all the way from initial discovery through to commercialization.¹⁵

Narrowing of return of investment

Modern patent protection was designed to safeguard IP and allow companies to recoup costs incurred during the research and development. The period of time, however, for pharmaceutical companies to maximize the return on investment (ROI) has narrowed.¹⁷ Tufts CSDD has shown that the average time required to take a product from the start of clinical testing to regulatory approval is 7.2 years. For example, clinical development times range from as short as 5.2 years for AIDS antiviral agents to a long period of 7.9 years for anti-neoplastic agents. If the average time to obtain regulatory approval for neuro-pharmacologic and cancer drugs is 1.7 and 0.8 years, respectively, the total time to take a candidate drug from the start of human testing to market is about 9 years (excluding the preclinical, animal testing phase, as well as discovery and research).²⁰ Thus, 12–15 years for drug development (including testing and regulatory approval) leaves only about 5–8 years from the patent exclusivity period of 20 years, for commercialization. The majority of revenues are usually achieved during this period of exclusivity.¹⁷

Competition is soaring high

There is always a cutthroat competition for launching newer products into the market. The companies are running eagerly for success and approval processes have become streamlined.¹³ Thus, the period of exclusivity, which is the period to harvest ROI, has been shortened from years to only a few months, as in case of Vioxx.¹

Competition from generics

Today, generic companies are stronger and more sophisticated compared to earlier times, and generic products are entering the market in early stages of the lifecycle, in some cases, earlier than patent expiry. Since generics are cheaper than their branded competitors, their market share, in prescription terms, is much higher, the research and development-based industries face competition in a dual mode, i.e. competition from the same field players as well as generic companies.¹⁵

Dispersing markets

In earlier times, the physician was the main customer in the prescription-drug pharmaceutical industry. Thus, pharmaceutical companies had a relatively simple approach to promoting and marketing prescription drugs. However, presently pharmaceutical companies increasingly need to address a networked audience comprising: payer organizations and influential advisory functions, increasingly knowledgeable consumers and other stakeholders such as nurses as well as the traditional physician base.¹⁵

Declining research and development productivity, rising costs of development and shorter exclusivity periods have increased the average cost of launching a successful new drug.²¹ Taking these points into consideration, it can be easily sought out that extending the lifespan of proven drugs by branded companies is a rising need and can be fulfilled to a greater extent by PLM.

Applications of PLM

PLM not only benefits through enhancing the lifespan of patent but also pricing strategies. Thus, PLM provides benefits to both large and small industries. The financial health of large, brand-name pharmaceutical companies relies heavily on portfolios of drugs grossing in excess of one billion dollars annually. Research and development of these blockbuster drugs require a tremendous investment of resources. According to the Pharmaceutical Research and Manufacturers of America (PhRMA), only one of every 10,000 potential medicines investigated by America’s research-based pharmaceutical companies makes it through the research and development pipeline and is approved for patient use by the US. In general, FDA approval takes an average of 10 to 15 years of research and development and may cost over $1.3 billion. Thus, it is very important for these industries to incorporate PLM.^19,22

Applications of PLM include:

In improving patient compliance

For providing revenue growth

To gain clinical benefits

For quick to market launch

For obtaining cost advantages

For life extension exclusivity²³

PLM benefits through:

Revenue acceleration

Unit profit enhancement

Improved innovation and quality

Lower costs and improved productivity

Revenue acceleration opportunities provide:

Enhanced market penetration for a new indication

Ways to meet the threat posed by generic drugs by tracking them.

Greater market penetration through product line extension driven by prescriber/patient feedback

Delivery changes to bulk drug or dosage form manufacturing processes that possess a novel patent, thereby conferring additional patent protection once generic competition occurs.

Marketers to differentiate the product, reducing the effect of generic erosion after patent expiration.

Significant improvements to the manufacturing or supply process that reduces the cost of goods, thereby preserving unit margins or enabling more competitive product pricing.

Market variants through technology transfer to regional manufacturing sites, enhancing local market acceptance and deeper penetration while reducing stock complexity that would otherwise drive up costs at high-volume facilities.

Unit profit enhancement opportunities provide:

Technology transfer to sites that give economies of scale or enable cost reduction in some way, such as lower inventory, lower stock expiry, better capacity use; or relocating bulk active or dosage form manufacture to a low-tax or low-fixed-variable-product costs environment

Optimization of manufacturing processes in situ that drives down cost of goods, such as yield or process robustness or reduction in raw material costs.¹

Key considerations for successful PLM

There are a number of factors that have been selected in a benchmarking study for the purpose of successful PLM.¹⁷ These factors are

Early start

Strategic planning

Establish clear leadership

Knowledge and skills to support the process

Preparation for the changing rules of government and organizations

Focus on profitability throughout the lifecycle

Monitoring and gauging of the success of the processes implemented.

Early start

PLM approach needs to be proactive and not as a late-stage attempt to fend off generic competition. In practice, product lifecycle activities are rarely considered early enough for companies to execute them to the best effect, but in principle companies should develop a roadmap in a molecule’s early life to track the rise and falls of a molecule through various stages of development. Such a molecular mapping optimises its marketing potential. For example, Humira (Adalimumab) was approved by US FDA in December 2002 for rheumatoid arthritis. In the development phase of the first indication, work to develop follow-up indications was started. Abbott Laboratories also initiated to understand the effect of Humira in other autoimmune diseases. As a result, Humira was approved for treating psoriatic arthritis in 2005 and Crohn’s disease in 2006. Similarly, Eli Lilly and Company had instigated mapping lifecycle management from discovery and developed antipsychotic Zyprexa for multiple indications. Zyprexa was approved in 1996 for manifestation of psychotic disorder, in 2003 for treatment of depressive episodes associated with bipolar disorder and in 2004 for long-term treatment of bipolar disorder.⁸

Strategic planning

The main purpose of PLM is to maximise the profitability of a product over its lifecycle. Since the PLM is becoming more crucial to the industry’s future, pharmaceutical companies need to move from viewing lifecycle management as a collection of reactive strategies to viewing it as a key organizational capability – an integrated set of governance mechanisms, rigorous processes, people skills and knowledge, supported by transparent product and portfolio information and performance indicators. By concentrating their efforts in the following areas, pharmaceutical firms can develop a more integrated approach to lifecycle management and take advantage of every opportunity to increase product profitability.¹⁵

The companies have established dedicated multi-functional PLM teams to drive early planning, monitor progress and benchmark efforts. They have also planned for PLM in the context of their broad business goals and product portfolios, evaluating the ROI of PLM opportunities with alternative investments in new research and development, strategic acquisitions and the like.²²

For example, Abbott Laboratories has redecorated its lifecycle management team’s organisation by including a central data repository for all teams to access the same information for all molecules development and clinical testing.⁸

Establish clear leadership

A company should thrive to establish its leadership in the market as well. Thus, establishment of clear ownership for lifecycle management and accountability for key actions in the lifecycle plan is the main necessity for a company. A small team should carry out strategic programmes based on rational analysis of problems and an innovative approach to solve them. In addition, the lifecycle strategy should be supported by individuals with the right combination of influence and negotiation to challenge internal barriers and drive performance against hard targets.^15,24

A successful example for this is of Pfizer’s Lipitor which generated global revenues of $13.6 billion, leaving a benchmark in pharmaceutical history. Lipitor was launched in 1997 (US, EU) and in 2000 (Japan). Pfizer extended its lifecycle by introducing (Lipitor plus Norvasc). In November 2011, it lost its patent protection but is still going well with strategies like price reductions (up to 80%).²⁵^–²⁷

Knowledge and skills to support the process

A successful PLM program is fabricated around a firm vision of the underlying product and its fit within the product line, franchise or company, as well as an exhaustive understanding of the overall competitive landscape in which the product is marketed.⁷

Thus, the collection of PLM options must be thoroughly scrutinized and assisted by a complete understanding of the complex dynamics that affect a product during its market life. No PLM option can be successful without sufficient knowledge and skills to support the process. For example, without thorough knowledge of a drug’s pharmacokinetics, its safety and toxicity profile, the indications for which it is being targeted and the first generation product’s format and treatment regimen, it is impossible to determine the potential of product for PLM through reformulation, expanded indications, over-the counter (OTC) switch and/or fixed dose combination.²⁴

Preparation for the changing rules of government and organizations

The governance and organizations have crucial influence on PLM. In general, the political winds are at the back of the generics sector. There is a huge pressure to keep low prescription prices. As the FDA is becoming more concerned with safety and patient outcomes, it has imposed more difficult hurdles regarding new product approvals. The new product manufacturers are always closely watched by third party payers. For the purpose of reimbursement, the cost-effectiveness and patient benefits should be closely proven.^17,24 Thus, the PLM plan should be flexible enough to take on such challenges. For instance, when bilingual labeling (i.e., the label should contain all the necessary details in both English & Hindi) was made mandatory in India, it created ambiguity in the market. There were doubts regarding readability of content (especially on ampoules) and opposition from southern states. Though a relaxation period of 6 months was provided, it was still a difficult task as excess of expenditure on reprinting of labels was required.

Some companies put only the name of medicine in Hindi while some others carried out all details in both languages, but only on the medicine box and kept only the drug’s name in Hindi on the immediate pack. However, later due to efforts from some pharmaceutical industry associations, Indian Pharmaceutical Alliance (IPA) and Confederation of Indian Pharmaceutical Industry (CIPI), the decision of bilingual labeling was retracted from mandatory to only voluntary.²⁸^–³¹

Focus on profitability throughout the lifecycle

PLM strategies decisions are based on top-line growth – certainly a key driver of profitability, but by no means the only one. Simultaneously, focus on profitability does not, in any means, indicate that the quality, safety or efficacy of a drug will be compromised. Lifecycle management activities focused on managing cost are now rarely considered. Obviously, the cost base of the product becomes particularly important late in its lifecycle when generic is prevalent. When cost pressures do not seem to be an issue, the decisions concerned with the cost of the product need to be taken well in advance. There should be other secondary objectives which will eventually lead to profitability such as the enrichment of number and type of customers (through target population expansion or indication expansion), which will directly increase the sales and fetch higher revenues to that firm.¹⁵

Monitoring and gauging of the success of the processes implemented

Since PLM is a dynamic process, the plan must be constantly reassessed against the contemporary market and aggressive milieu and be evolved in accordance.⁷ In order to analyze whether a PLM option is successful upon implementation and to see the current position of the firm, a simultaneous monitoring of the process and measurement of its success is a very important aspect as it provides the plot for doing much better. Comparative pharmaco-economic analysis plays an increasingly important role in positioning the product with institutional, governmental and commercial payer organizations on its launch. Keeping a track record of the progress will always provide guidance about what to do next.^17,24

Conclusion

PLM, a strategic approach for managing a company’s product-related intellectual capital that existed for many years in electronics and automotive sectors, can now be applied in pharmaceutical sector as well to sustain the franchise of an innovator pharmaceutical company and increase its return of investment. PLM benefits both large and small industries and can be applied for improving patient compliance, providing revenue growth, gaining clinical benefits obtaining cost advantages, life extension exclusivity and quick to market launch. For a successful PLM, an early start, a strategic planning, a clear leadership and supporting knowledge and skills are required. Preparation for the changing rules of the Government and related organizations, the focus on profitability throughout the lifecycle, the monitoring and gauging of the success of the process are must for taking this approach to higher levels of success.

Footnotes

Funding

This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

Conflict of interest

The authors declare that they do not have any conflicts of interest.

Author's Biographies

Vandana Prajapati is M. Pharm. research scholar at M. D. University, Rohtak and has drug regulatory affairs as the area of specialization. She possesses a Bachelors degree in Pharmacy.

Harish Dureja is Associate Professor in Pharmaceutics at Department of Pharmaceutical Sciences, M. D. University, Rohtak. He possesses a Doctorate degree in Pharmaceutical Sciences.

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