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Espacios. Vol. 37 (Nº 11) Año 2016. Pág. 21

Practices and processes for new medicines innovation management in the Brazilian pharmaceutical industry: a multiple case study

Práticas e processos de gestão da inovação de novos medicamentos na indústria farmacêutica brasileira: um estudo de caso múltiplo

Sergio Hideo YAMAGUISHI 1; Desiree Moraes ZOUAIN; Renata BAZANTE-YAMAGUISHI

Recibido: 19/12/15 • Aprobado: 25/01/2016

Contenido

1. Introduction

2. Methodology

3. Results and discussions

4. Conclusions

References

1. Introduction

The growth of the pharmaceutical industry in Brazil was promising in the early twentieth century and it was linked to the discovery of new biological products by successful companies and technology and science institutions. Nevertheless, this situation changed as the technological evolution pointed to chemical synthesis, since there was no industrial base in the country. This new technological paradigm led the Brazilian government to develop actions to attract foreign investment and to seek more intensive and accelerated industrialization in this sector. However, the focus of this effort was the production and commercialization of pharmaceutical products, rather than researching, development and producing active pharmaceuticals ingredients (Urias 2009).

Over decades there has been great progress in this Brazilian industrial sector, making the country to reach the 10th position among the world's major markets. However, the observed rate of innovation remains low, since multinational companies conduct most of the investments in research and development (R&D) at their headquarters (Hasenclever et al. 2010). Some commercial factors such as the ease to copy innovative products and efforts focused on substitution of importation through reverse engineering, practiced by most of national laboratories, have undermined the future of innovation in this sector (Avila 2004).

The regulation of industrial property protection in Brazil was, in turn, a factor of great impact in the local market and for business strategy. Created in 1996, the law that regulates the protection of industrial property (Law No. 9279/96), culminated in a strategic shift in national pharmaceutical companies as they were prevented from copying the imported products.  In this sense, the laboratories had to develop new strategies for business (Cantalice 2009; Hasenclever et al. 2010; Santos and Pinho 2012).  However, in a recent study, Rosina (2011) concluded that the current patent regulatory structure, for not offering alternatives to monopoly as fostering of innovation, is more harmful than beneficial to the development of the Brazilian pharmaceutical sector, being necessary to develop alternative models of protection that can coexist with the current model.

During the 90s, major national laboratories underwent a significant intensification of technological effort, however, taking into account the competition on an international level, these efforts are still considered small and modest impacts (Santos and Pinho 2012). These efforts were focused on incremental innovation, as diagnosis by Radaelli (2012) which included 25 actors, namely, the government, affiliated entities, universities, research centers and pharmaceutical companies of national capital.

The Brazilian pharmaceutical industry has evolved over the last decade by applying the concepts of open innovation as a competitive strategy (Estado 2009). However, the innovation model, seen in selected companies, has adaptations for reasons of cultural issues and maturity of the company, so that the flow of creative ideas occurs only in the direction of the external environment to the internal of the company (Yang 2010). Andrade (2010), in turn, demonstrated that the outsourcing of research activities can accelerate innovation of medicines, since it allows to access technologies that would not be accessible otherwise. Nevertheless, Pitassi (2014) found low usage or lack of understanding of the assumptions of open innovation in selected Brazilian companies, which consistently use the R&D in the design and implementation of their innovation strategies.

As noted, there are several works whose theme encompasses innovation in the Brazilian pharmaceutical sector as per different purposes in their studies, however, it is noted a lack of publications where the activities practiced in innovation processes are explored and understood in more detail. Thus, this work will contribute in an unprecedented way, in identifying those details that are embedded in the organizations.  And as a result of a multiple case study, a set of strategies for innovation management will be proposed to the Brazilian pharmaceutical sector.

The aim of this article is to: (i) Identify how internal innovation processes occur and are managed in the Brazilian pharmaceutical organizations; (ii) Propose a list of best practices as per researcher observation; (iii) Indicate management strategies that would help other organizations getting better results in new product innovation. Note that the term "organization" is been used throughout this article and it can comprise a private company, a public institution or a technology park.

2. Methodology

2.1. Multiple case study

The methodology for this work considers a multiple case study in exploratory level with qualitative approach. The application of multiple case studies is presented as a more effective method when the form of the question to be answered is made ​​with "how", according to Yin (2010). However, the case study will be based on a structured interview, containing a standardized protocol (research instrument), as recommended by Gil (1989), and this will also include questions such as "what" and "which". It is noteworthy that the present work does not aim to understand the "why" of the facts.

Then a protocol was developed for the case study, containing questions formulated from the model of the innovation process, according to Tidd, Bessant, and Pavitt (2005). It was organized in two hierarchical levels: dimensions and sub-dimensions of the innovation process (Table 1) and has 34 open questions in order to understand specifically how the processes for managing innovation occur in the studied organization, being asked, where possible, an example to demonstrate the practical use and the result obtained by them. In order to contextualize the question, an explanatory note was developed for each question, aiming also to stimulate good understanding of it and standardization of response.

Table 1. Dimensions and sub-dimensions of innovation processes

A review of this protocol was conducted during the planning phase, with support of three experts in the field of qualitative research involving case studies and innovation subject. The objective of this review was to determine whether the protocol would answer the research questions and objectives. The comments and suggestions were received and incorporated, generating changes of low complexity and impact to its overall structure.

2.2. Complementary theory used in the research

Other theories have been used to support the present research. Bill Abernathy and Jim Utterback (1978) contributed by presenting an innovation process of a product or technology life cycle. Jensen et al. (2007) developed two distinct modes of innovation: STI (science, technology and innovation) is based on the production and use of codified scientific and technical knowledge and DUI (doing, using and interacting) is an informal process based on group experience and practical knowledge. Hargadon and Sutton (2000), for example, concluded that the best innovators followed a systematic process called 'knowledge-brokering' by using old ideas as raw material for a new one and so on. Hansen and Birkinshaw (2007) proposed a value chain of innovation, and highlighted it shall be seen as a process giving the executives an end-to-end view of their innovation efforts. Also in terms of innovation processes, the stage-gate processes create a clear and concise structural environment that a new idea must pass to become a commodity giving greater clarity and understanding (Cooper, Edgett, and Kleinschmidt 2002 and Davila, Epstein, and Shelton 2007). Von Hippel, Thomke, and Sonnack (1999) reported about how 3M implemented the process of lead users. This is based on the concept that a product is not designed by the manufacturer but by the users-experts. Chesbrough (2003, 2006) suggests breaking the paradigm of the companies using the traditional vertical model of development, where the department of R&D leads all innovation activities within the organization, and presents the Open Innovation as an alternative. Open innovation is defined as the use of knowledge from internal and external to the organization with the purpose of accelerating internal innovation sources, and expand the market for external use of innovation. Thomke (2002) addresses the issue of product testing and how introducing new technologies could bring many challenges since the organization of R&D is structured to the way new knowledge is created. Kim and Mauborgne (2002) emphasize the importance of knowing how to identify which businesses ideas have commercial potential and highlight the implementation of a tool called 'map of utilities', where each new idea can be evaluated.

2.3. Selection of research units

The research strategy took into account that each organization would represent a case, such as the unit of analysis, understanding that each organization has particular form for internal innovation processes. Thus, it was possible to make comparisons between the selected cases, allowing stratified analyzes (type of business, national origin, public or private capital and market segmentation).

The decision for selecting the research universe considered high variety of organizations: national and multinational companies; research institutes and a technology park (Table 2).

Table 2. Selected research units

3. Results and discussions

A synthetized summary of the content of the interviews are presented in the following paragraphs and was structured and organized by organization, dimensions and sub-dimensions of innovation which enables initial comparison between organizations in terms of innovative processes, organizational structure and strategies applied. This chapter is organized in three subsections which each one is correspondent to the objectives of this research.

3.1. Innovation processes

Case 1: Biolab

The process of managing innovation in Biolab aims to obtain new prescription drugs, within existing market segment and specifically focused on products for the treatment of chronic diseases, and in rare exceptions, an innovation creates a new product line. They conduct prospection of opportunities through a Patent area that performs the searching of patents that are about to expire; the advancement of new drugs in clinical trials and through statistical market data. Each project goes through a study of economic and financial viability, regulatory, marketing and galenic and medical development. Once approved by the board of directors and shareholders, this project joins the company's portfolio and goes to final development. The process for new product development is bounded by the local regulatory agency and the involvement of actors is conducted from basic research to the pre-product development. In the development phase the internal researchers are the main actors. During this phase the team is determined by product line and is composed of one representative of each sector of the company. The project manager has a fundamental role because accompanies the project plan and reports during weekly meetings with the vice-presidency. Biolab uses a project management system called "Sigespró" which controls the project at all stages of product development. Once the product is submitted for registration, the preparation of the marketing plan is initiated. It indicates the revision of the launch and all associated logistics strategy. The company uses the database of consultants to define their tactics of advertising and marketing to physicians. The change process also includes the marketing plan, the adequacy of the structure of production, in addition, all projects are supported by Knowledge Management area that assists in finding information from competing companies and products, strategy and guidance internal processes of innovation, knowledge transfer and retention of staff to prevent recurrence of project failure.

Case 2: Butantan Institute

The Butantan Institute is dedicated to the production of vaccines and this fully meets the demands of the Ministry of Health through the PNI. The production of serum is relatively low, but the institute needs to keep minimum inventory for national distribution. Technological and market trends are obtained by its researchers, their network of contacts, technical and scientific partnerships. These trends are discussed in national perspective, taking into account the technical, political and commercial factors. The new projects are evaluated through a tool of feasibility analysis that considers only technical and scientific aspects and all investment in research is accomplished through fostering agencies, and the creation of new projects depends heavily on the influence of the researcher who is leading. The process of project management has certain deficiencies and monitoring the status of each project is not carried out effectively. The new projects follow a structured process and are best monitored through meetings, discussions and reports. In terms of collaboration, the institute count with the Laboratories of Medical Investigation (LIM's) to exchange experiences with other researchers. New research projects are now under the project management office and most have defined the key milestones and training of the team is part of researcher's responsibility, except in the case of an institutional project. Once the product is developed and approved for use, it is available through the Public Health System (SUS) and PNI. In this respect, the distribution centers, the federal government and health centers, provide full support to the initiatives of release. The disclosure, distribution and definition of demand with the institute are all responsibilities of PNI. About learning, it is noteworthy that the institute considers the use of the same team to avoid failures in future projects, even if only to make appointments in the beginning.

Case 3: IPEN

The R&D of radiopharmaceutical products, which are conducted by Radiopharmacy Center, count with the support of the National Nuclear Energy Commission (CNEN), International Atomic Energy Agency (IAEA) and Foundation for Supporting Research of the State of São Paulo (FAPESP), universities, hospitals and clinics. Efforts have been concentrated on development in three general lines of work: radionuclide generators and methods of production of radioisotopes in the reactor and cyclotron; labeled molecules for use in diagnosis and therapy, and lyophilized new reagents for labeling with technetium-99m (IPEN 2014).

IPEN has monopoly on radionuclides and radiopharmaceuticals of long half-life as a matter of control of local market, technology and radioactive raw materials. Still, the center continues to invest following technological trends of the international market, observed through scientific publications, participation in events and contact with other research centers. The organization's strategy is updated every six months when it is possible to compare new technologies in relation to the market opportunity. The construction of project portfolio is a structured process that considers the importance and benefits of the project to the center, but lacks a business case tool. Projects of R&D and nationalization of products are led by a researcher who has an internal team (chosen according to his experience, area of​​expertise and availability) and supported by the nuclear physician. Only the list of priority projects of the center are under constant monitoring; it is still not a very structured process and does not count with a tool for optimizing the time of development, moreover, the work of R&D is based on empirical testing and laboratory analysis. During the development phase, information is obtained solely through clinical trials, which can be seen as some kind of response or reaction to the new product. In terms of marketing planning, the institute defines market which will suit, depending on the logistics to reach more distant regions of the country, based on the experience derived from previous projects. To support the learning process of the team, it uses physical files, and when it involves a new product, the project is accompanied by a document for 'transposition', enabling the transfer of knowledge for productive activities.

Case 4: MSD

The company is recognized as MSD in all countries where it operates, except in the United States and Canada, where it operates as Merck. Through medicines, vaccines, biologic therapies, consumer and animal health, the company operates in more than 140 countries. Present in Brazil since 1952, the subsidiary is present in the market through human health, animal health, consumer products and clinical research (MSD 2014).

The Brazilian subsidiary of MSD focuses their innovation activities in launching new products in the local market. Additionally, through an area of ​​Market Intelligence, the company monitors the activity of clinical research, statistical trends observed in each segment and performs prospecting opportunities. Very important information about their products comes from a group formed by the most reputable physicians in each specialty area and Marketing is who captures the major opportunities. Following determination of the headquarters, the local subsidiary searches for partnerships within the segments, in order to concentrate efforts and synergy with the existing sales structure. Innovation projects are examined through a business case where financial, marketing and strategic factors are considered. The conduct of the process is the responsibility of the product manager with support from Business Development area. In addition, new designs are evaluated using the method of profit and loss and are included in the existing project portfolio composition allowing revision of priorities. The model of project management is structured in terms of steps, sequence and areas involved and with the participation of a fixed team of Medical, Regulatory, Price and Supply areas, which are coordinated by the Business Development area. There is a process that identifies, making more effective management of each project. There are biweekly meetings with staff and monthly meetings with the board to monitor the status of each project and discuss possible actions, problems or reprioritization. In the launch phase, the ​​Sales area, which is the most affected in the change process, includes in training activities, review of team structure and script for visiting of propagandists. After launch, the product can be made available through free sample or a complete treatment to the patient. The second aims to demonstrate efficacy of the drug for the government, aiming sale by SUS. At the end of the project, the team conducts a brainstorming section to check for errors and successes enabling continuous improvement.

Case 5: Technology Park of Life

Technology Park of Life operates in the development of new products in the life sciences areas with the initiatives of external researchers who are seeking support from academic or industrial infrastructure. Each R&D project is submitted to a feasibility analysis in which is verified the timeline to launch and return on investment. The park has a strong presence in the state of Rio de Janeiro, across 14 locations, and has conducted scanning for exploring opportunities in product development and new partners. There is monitoring of scientific publications and events, such as conferences however, the application of new technologies depends on the researchers and projects developed internally.  Technological trends are discussed during meetings with academia, research centers and partner companies in coordination with Executive Group of the Life Sciences Industrial Complex (GECIV). The park has a business office that assists in marketing and financial analysis, facilitating obtainment of human resources, infrastructure and investment partners through the park or through the funding agencies. The new projects are evaluated by a multidisciplinary team in which the technical and market aspects are taken into account. This analysis includes marketing, financial, resources and infrastructure aspects and it is prepared by the owner of the technology itself. In terms of implementation, each project has a multidisciplinary team (technical and management) and project milestones are defined according to the scope of the project, enabling identify what expertise is required. In respect of launching process, park structure assists in defining the marketing strategy since the beginning of the project and often monitors throughout development phases. Knowledge management in the park is a point of utmost importance and is spread by the practice of transforming the learning obtained in partnerships through new tools or methodologies work. This knowledge is documented and disseminated through internal seminars.

3.2. Best practices

The selected best practices are organized by the dimensions and are being presented in Table 3. They were observed from the studied organizations and consequently those were selected based on the perspective and experience of the research group since they were realized as the most relevant practices in managing innovation from the research units. They are supported by a justification in order to support the selection. From that presented, a set of strategies to obtain better performance on managing innovation are supported and finally recommended.

Table 3. Top 10 - Best practices observed in the research units studied

3.3. Initial discussion on the strategies

The dominant strategy in the surveyed organizations is based on incrementalist strategy. According to Tidd, Bessant and Pavitt (2005) the 'incremental' claim that the full knowledge of complexity and change is impossible to be achieved. That is, the ability to understand the present and predict the future is limited. In this context, organizations recognize that they have only a very imperfect knowledge of their setting, their own strengths, weaknesses, possible indicators and directions of future changes. Therefore, organizations must be prepared to adapt their strategy face of new information and knowledge, which must consciously seek to obtain. In the other hand, rationalists strategies, which were based on military inspiration, include the step of understanding and analysis of surrounding (strengths, weaknesses, opportunities and threats); define the following strategy, then implement the strategy defined. Tidd, Bessant, and Pavitt (2005) suggests that incrementalist strategy, under circumstances of high risk and uncertainty, the more efficient procedure is: take steps towards a deliberate objective; measure and evaluate the effects of such measures and then set the goal and decide on the next step.

A fact that corroborates this prerogative is that the surveyed organizations use to develop copies of foreign products in order to nationalize production (IPEN) or launch an improved copy as soon as possible, in an attempt to reduce the distance to the innovative product (Biolab), to reduce uncertainty, high costs and risks, allowing of the tendency of organizations to adopt a technological imitative behavior. Organizations that developed maturity are gaining greater market share. Biolab, for example, is among the 10 largest pharmaceutical companies in the country, accounting for 2.13% of the market (Biolab 2014).

The evolutionary theory is also a relevant support for the incrementalist strategy discussed in this section. Nelson and Winter (1982) initiated a line of research incorporated in evolutionary biology. It discards any principle of invariant (or substantive) rationality of economic agents. The concept of maximization is not useful, because it involves many variables that cannot be known in advance by the entrepreneur. There is a need to develop a view of the firm composed of separate individual and provided with the cognitive characteristics. The rationality of agents cannot be pre-defined, as it is the result of learning along the interactions with the market and new technologies. According to evolutionists the development of the firm and its ability to respond to changes depend on the following  factors: learning and routine; path dependency (the firm may not deviate from its path of successful manner unless by changes in economic conditions or the nature of technology); it is necessary to know the nature of barriers to entry, the regulations, the degree of competition and exploring the possibilities of economies of scale and scope; core competence (set of differentiated technological skills, complementary assets and routines).

4. Conclusions

4.1. Key observations from research

In general, the innovation projects in organizations that carry out R&D activities in the country (e.g. Biolab, IPEN, Butantan and Life Technology Park) follow a similar procedure described above, on the fact that the development of a new drug, even if it is a copy, it is an empirical and full of uncertainties process by which the clinical research process itself determines the need to run it at different stages before being considered approved by regulatory agency (pre-clinical, phase I, II, and III). ANVISA (2014) reports that 90% of the substances studied in pre-clinical (animal testing) are eliminated because they do not demonstrate sufficient pharmacological or therapeutic activity or are too toxic in humans. In phases I, II and III (testing in humans) the goal is to discover or verify the pharmacodynamic effects, pharmacological, clinical, or adverse reactions of the product under investigation, in order to determine its safety and efficacy.

Another key factor to choose the strategy to be adopted by the organization depends on the own core competencies. Prahalad and Hamel (1990) define core competencies are intangible resources that: in relation to competitors are difficult to be imitated; in relation to markets and customers are essential resources to enable the company to provide differentiated products or services and in relation to the change and evolution of the company's own process are the fundamental factor of greater flexibility that allows the exploration of different markets. It could be translated such as quantity and quality of internal investigators; successful experiences and results in research, development and innovation; appropriate organizational structure for managing innovation includes: knowledge, industrial property, project, market intelligence and regulatory management. A pattern observed in field research indicates that public research institutes (e.g. IPEN and Butantan Institute) have greater technical and scientific expertise through their teams of internal researchers and external partnerships. These organizations must have strategies based on solid partnerships with other research institutes, universities or companies and leverage their intellectual capacity and infrastructure to implement research projects and innovative product development with relevance to the country. They also need to adopt project management techniques in order to fulfill the gap identified in the fieldwork. By improving in terms of organizational structure and applying methods and tools, the organization will increase its performance and delivery of innovations projects, while becoming more competitive.

Technological Park of Life, through its technological partners, has technical and scientific skills, similar to IPEN and Butantan Institute by also own a research institute and maintain manufacturing operations of antivenoms, vaccines and drugs. However, the main difference is the Park's infrastructure and support in managing new innovation projects offered to researchers and companies seeking partnerships or incubation. Its core competencies are related to its vast network of universities, foundations, development agencies, related associations, government and associated companies. In general, technology parks should establish their own strategies based on technical and scientific expertise and their management structure (projects, industrial property, marketing and knowledge management). These two parts shall be tuned to support during the planning and implementation. The infrastructure available in a technology park should be the main aspect to be taken into account in a partnership project with a company or researcher interested in being 'incubated'. The strategy must be outlined to enable the infrastructure and expertise to be available to potential candidates interested in developing innovation projects.

For companies of national capital (e.g. Biolab), it is suggested to adopt a solid organizational structure combined with a strategy of copying competitors' products in development for the company to get greater results with less level of investments in facilities and R&D activities. The company must observe their marketing skills to perform the search for new product opportunities within existing product lines to maximize the synergy of the Sales team, for example. In general, a national laboratory should focus on performing incremental innovations, rather than radical innovation, because the first allows for greater understanding and learning for staff while working in the evolutionary process of the team and the company, which can be established a virtuous cycle, so that the strategy can support the search and retrieval of innovative products, enabling the creation of spaces and opportunities (competitive advantage) and generate monopoly profits, causing the company to follow its path of innovation.

A subsidiary of multinational installed in the country (e.g. MSD) must have an organizational structure that supports the launch of new imported products as soon as possible, allowing faster return of high investments in R&D performed by the headquarters.  The local strategy should include prospecting for opportunities to develop new businesses through partnerships with other companies or research institutions. For each new innovation project, the subsidiary must have a scoring process so that the alignment with the established strategy can checked. Moreover, it is also important to note what skills of subsidiary in the existing product lines to maximize the synergy of internal support teams. Once the strategy is clearly defined, the company must fit it in terms of organizational structure so that the projects are implemented efficiently with adequate support for retention of the knowledge acquired, allowing the processes of evolution and maturity occur in the organization.

4.2. Final considerations

The first goal of this article is to answer "how internal innovation processes occur and are managed in the Brazilian pharmaceutical organizations". The research presented the process flow for each of the organizations and based on that some patterns can be verified. In general perspective, we can concluded the private national or multinational companies, regardless of their different roles on the R&D in the country, present well-structured project management; apply mechanisms of prospection for searching opportunities in the market; focus on marketing and concentrate their efforts on the physicians. In the other hand, public institutions, in general, concentrate effort on R&D activities and perform more technical and scientific partnership; present deficiency on project management; progresses are highly dependent on researcher-leader; decisions are heavily based on technical and scientific aspects; funding is based on public model. However, technology parks could meet, respecting the proper proportions, both positive aspects from private companies and public institutions while they have structured project management, apply mechanisms of prospection; count with scientific and technical support from academia; use public funding system; among other aspects.

The second goal of this article is to "propose a list of the best practices as per researcher observation". The research showed there are several opportunities for improving the performance of innovation by implementing methods, procedures and practices as highlighted in the research. The main challenge for the organization is to focus on their core competence and then complement their potential 'gaps' in terms of organizational structure or practices. This article has presented five different organizations with different sizes, origins, types and innovation focuses, but each of them have presented their strengths and weaknesses allowing that initiatives, as stated as 'best practices' can be implemented. In summary, public research institutions should implement project management structure, techniques and tools. Private companies should start / continue focusing on copying innovative products to provide evolution on their innovation trajectory while prospecting for opportunities of partnership. While technology parks meet both benefits of public research institutions and private companies, they should extend and maintain their network to allow technological infrastructure for incubation of new research projects. This framework is the main contribution of this research study.

The last goal of this article is to "indicate what management strategies would help other organizations to obtain better results in new pharmaceutical product innovation". The research indicates that the dominant strategy in the surveyed organizations is based on incrementalist strategy, supported by the fact that the organizations surveyed rely on development of copies in an attempt to reduce uncertainty, high costs and risks in a trend toward technological imitative behavior. It is worth to emphasize that the success of the innovation effort of an organization depends on the existence of technical training, organizational skills (in respect to internal aspect of the firms) and relational (in respect to relations between firms). The relationship between existing skills and the potential to generate results is an important element in guiding the strategies of the organization. Once the strategy is clearly defined, organizations must fit in terms of organizational structure so that the projects are implemented efficiently and with adequate support for retention of the acquired knowledge, enabling its innovative trajectory follow a continuous process and gradual evolution and maturity.

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1. Autor correspondente. Email: S_yamaguishi@yahoo.com.br