|
Background: Uptake of super generic or hybrid pharmaceuticals has decelerated despite their important economic potential for the generic pharmaceutical industry. The aim of switching to these product portfolios was to enable product differentiation; however, these strategies are influenced by new semantic challenges, which have hampered the promotion of value-added pharmaceuticals or super generics in recent years. |
Submitted: 2 October 2014; Revised: 25 February 2015; Accepted: 10 March 2015; Published online first: 20 March 2015
Previous studies comparing brand-name drugs with generic drugs have focused on cost-reduction rather than clinical outcome. The focus of this study is on the improved product itself and how this improvement contributes to promotion of the product. Improvements can include a new dosage form, a route of administration, a new indication, or a combination of these. In such cases, the product cannot be considered as a simple generic. For such a product, new data supporting any new features must be generated.
In the US, drugs approved under 505(b)(2) can rely, in part, on data from existing reference drugs. This means that they can be developed and achieve US Food and Drug Administration (FDA) approval in as little as 30 months, with only a fraction of the number of required clinical trials and at much lower cost. Additionally, unlike generic drugs approved under section 505(j), in which exclusivity can be held for only 180 days, the 505(b)(2) applicant may qualify for 3, 5, or 7 years of market exclusivity, depending on the extent of the change to the previously approved drug and the type of clinical data included in the new drug application (NDA).
According to some of the producers interviewed, using 505(b)(2) as the foundation of a drug development programme is a fast and cost-effective strategy that has proved its functionality. An alternative to spending important sums on developing blockbusters is to concentrate on developing products for niche markets that may have smaller market potential, but that can be approached with dramatically lower development costs using the section 505(b)(2) pathway for FDA approval [1].
Given that the large pharmaceutical companies are developing ‘fewer’ innovative small molecules, the decrease in innovative products results in fewer generic drug targets and challenges the sustainability of the generics industry. The importance of developing products via 505(b)(2) has motivated generic pharmaceutical manufacturers to find solutions for product differentiation and sustainability of this industry.
Furthermore, an evolution in nomenclature for differentiated generic drug products has been observed in the past four years.
In the present study of terminology used in generic pharmaceutical innovation, we aimed to assess the possibility of real ‘product innovation’ and how generics companies could organize this ‘innovative’ activity.
In the intervening years, it seems that little progress has been made by pure generic drug companies in this area. We question whether the inclusion of the term ‘generic’ in super generic or value-added generic may in fact partially contribute to this lack of success because, intuitively, the terms ‘generic’ and ‘innovative’, may appear to be oxymoronic.
In this study, we analyse the change in usage of terms such as super generics, value-added generics, new therapeutic entities, and premium generics.
Data collection
A qualitative approach was taken for this study. A semi-structured format was selected because structured interviews often produce quantitative data. Semi-structured interviews are generally organized around a set of predetermined open-ended questions, with other questions emerging from the dialogue between interviewer and interviewee. This iterative process of data collection and analysis eventually leads to a point in the data collection at which no new categories or themes emerge. This is referred to as saturation, signalling that data collection is complete.
Semi-structured interviews were conducted with managers, industry consultants, lawyers and researchers to collate their views and perspectives, and to enable their experiences in this area to be shared. Between April 2013 and June 2014, 10 interviews were conducted (the number of people who agreed to be interviewed). The length of interviews varied between 45 and 90 minutes. They were conducted in Europe, India and USA.
The interviews were conducted according to a predefined questionnaire; however, new topics would sometimes emerge during the interviews. The questionnaire focused specifically on ‘super generic’ products and how semantic alternatives may influence marketing strategy. The questionnaire was arranged into two parts: a survey about the history and background of super generics and a questionnaire about the evolution of the use of super generics as product types in published research. Questions in parts one and two of the questionnaire are presented in Table 1.
The semi-structured interviews enabled new and up-to-date information to be collected on changes in the super generic phenomenon, thereby filling knowledge gaps in published articles and reports. They were useful for opening discussions with professionals and obtaining different versions of this story. Such details could not be easily discovered by using a non-qualitative method. Qualitative research data are based on human experience, and are therefore powerful and sometimes more compelling than quantitative data. Subtleties and complexities about the research subjects, topic, or both, are often discovered that are sometimes missed by other forms of enquiries.
‘Open-ended’ questions are not necessarily worded in exactly the same way with each participant. Participants are free to respond in their own words, and these responses tend to be more complex than simply ‘yes’ or ‘no’ answers used in quantitative methods.
The same procedures in interview and data collection were used as the first article of this series about the strategic importance of super generic pharmaceutical and the new era for the generics pharmaceutical industry.
Interviewees were classified by an extract of their name in our node list. This kept their identity anonymous and is a quick and simple way to label the interview contents.
On the platform of professional groups on LinkedIn, professionals in the pharmaceutical industry were identified, and debates and discussions related to current changes in marketing super generics were initiated.
A literature review was conducted using databases, such as MEDLINE, PUBMED, Google Scholar and other research engines, to collect the relevant articles published in English, French and German between 2004 and 2014. To obtain better results, other published articles and reports related to the subject were also investigated in our literature review, for instance, the IMS reports. The search strategy was developed using 11 search terms [2] relevant to semantic challenges and generic pharmaceutical product re-innovation. The following search terms were used: ‘innovative generic medicines’, ‘super generic pharmaceuticals’, ‘premium generics’, ‘specialty generics’, ‘value-added generics’, ‘new therapeutic entities’, ‘improved therapeutics’, ‘pricing strategy’, ‘marketing strategy’, ‘drug delivery system’, ‘505(b)(2) approvals’. Inclusion criteria were generic medicines, super generic and value proposition.
More specifically the literature review has enabled us:
The challenge of post-patent expiration is characterized by high-price competition between generics manufacturers. If companies were to invest in a smaller number of value-added generics rather than a large number of conventional generics, they may obtain better returns on investment.
Despite the efforts of several generic pharmaceutical companies, the product innovation potential of generics manufacturers is not always transparent in pharmaceutical and pharmacoeconomic literature.
In 2004, Kermani [3] pointed to the ‘involvement’ of some generics companies in innovative research and development. In this context, innovation is applauded because of the dynamic it may bring to the market, for further financial benefits it will bring for the manufacturers, and also because ‘the effective drug treatment can lessen the economic burden of major diseases’. Health-economic evaluations are related to these results because, ‘improved treatments’ could provide better disease management, shorter hospitalization rates, reduced mortality, and savings for healthcare systems.
Other authors have acclaimed the importance of value-added generics as a new model [4].
The value-added model contains ‘value’ for the business models of such companies that launch an innovation adventure. Here, our attention is focused on the innovation as a ‘value’ profile for the generic pharmaceutical industry.
According to the economic literature, the innovator is the unusual businessman who is able to combine capital, labour and resources to develop a new product, a new service or a new form of business organization [5, 6].
Product innovation is only one part of the story. Innovative change can occur through improvements in the production process, raw material and intermediate inputs, enhancing the efficiency of the management system, and risk reduction [7].
For innovative generics manufacturers, improved therapeutics and pricing, and the return on investment in innovative activities, is just as important as producing a high-quality product. Is innovation rewarding enough for generics manufacturers? Access to a higher pricing system is important for companies using this strategy. With increased pressure on health funds and Health Maintenance Organizations, it is more difficult for a product to make it onto an approved list or reimbursement programme.
Where a product is presented as a line extension of a branded product, there is tacit assumption of added value (whereas it may simply be a case of life-cycle management related to patent expiry). When a generic drug company presents essentially the same product under the designation of super generic, generic plus or added-value generic, it may well be that the reimbursement barrier is raised or even becomes insurmountable.
For example, Actavis has recently reported a negative recommendation from the FDA Advisory Panel for their fixed-dose combination of Valsartan and Nebivolol [8].
The panel vote was split, with six rejecting and four in favour of the product. This narrowest of margins raises the question of whether the vote might have been different had the application been made by a traditionally recognized innovator company and whether there is a subconscious mindset that assumes that generic companies cannot really add value to existing products. The mechanism of application via an NDA, however, would have been the same. It is also still only a recommendation, which is not binding by FDA.
In the most recent cycle of innovation in the generic pharmaceutical industry more acceptable innovative activity included ‘re-innovated’ products emerging from new technology platforms, change in the managerial mindset, and evolving business models [9]. This innovative character aims to satisfy the patients’ unmet medical needs [10].
Increasing access to new technology platforms can enable generic manufacturers to become more active and find new financial returns on their investments in several therapeutic areas, such as pain therapy, respiratory, oncology, geriatrics, and paediatrics.
Labelling challenges of re-innovated products, reminds us of the difficult discipline of integrating ‘newness’ into the ‘old’ product. The only issue that can save the re-innovated product is a real integration of ‘value’ and the satisfaction of unmet medical needs.
Identifying this value in improved generics has become a real marketing strategy in recent years.
Labelling ‘re-innovated’ products: the semantic challenge
A semantic shift has been observed in the designation of super generics in the pharmaceutical literature. Labels such as ‘re-innovated’ products, ‘value-added generics’, ‘new therapeutic entities’, and ‘enhanced therapeutics’, all indicate a subconscious search for a ‘non-generic’ identity and a move away from being simply a ‘generic extension’.
In one of our interviews a pharmaceutical research and development scientist commented:
‘The use of the term super generic, to my view is just a change in the communication strategy (the word super generic has a ‘generic’ component, by eliminating this component you stress the innovation part …’ (2014).
A marketing manager described the issue from another perspective: the absence of a clear product definition and pricing challenges:
‘… I think that the problem is that there is no clear definition of products that are derived from existing drugs/generics; therefore, we see a trend towards the terms used by FDA (505(b)(2) and EMA (Art 10.3). Especially, the pharmaceutical companies want to move away from the term ‘super generics’ as it has the connotation of still being a ‘generic’ and as such it can easily be put under the generic pricing.’(2014).
That is why, in some recent articles, the label ‘super generic’ is avoided because the product in question is a ‘hybrid’ version.
The hopes and expectations related to super generic products are numerous. Apart from economic and financial results that they may generate for the manufacturers, they bring about hope for patients in search of ‘value-added medicines’ that may satisfy their unmet medical needs.
Recently used nomenclature relating to re-innovated pharmaceutical products is presented in Table 2.
The challenge of ‘value’ integration: satisfying ‘great expectations’?
The demand for ‘new medicines’ is increasing. Patients demand ‘new’ but ‘efficient’ and accessible pharmaceuticals; however, solving this equation requires innovation.
The urge of pharmaceutical companies to move away from the terms ‘super generic’ and ‘generic’, indicates that they want to avoid the connotation of still being a ‘generic’ and as such prices can be set at generics levels. That is why Teva brought forward the term ‘novel therapeutic entity’ to indicate the novelty of the product and to align it with the term ‘new chemical entity’.
New therapeutic entities and new chemical entities are also similar.
It seems that all these new labels aim to target new market segmentation and change the concept of ‘new product’. Therefore, ‘value creation’ is reinforced by the gap created between the ‘generic’ and ‘re-innovated’ drug products. In this way, they seek to maximize the expected economic returns at a reduced level of risk in a new product pipeline.
Super generic products may also be seen as linking innovation with affordability [16] for patients. As several versions of a known drug can cause confusion for prescribers and patients, the clear description of the drug category, dosage and means of administration require clear and precise labelling to ensure the prescribers and patients correctly use the innovated dosage form.
‘Innovation’ is taken into account by super generic producers, but it is undoubtedly a complex function of patients’ needs, providers’ capabilities, regulatory frameworks, incentive mechanisms, and intellectual property rights and, of course, the availability of appropriate funding. In the case of re-innovated pharmaceuticals, the ‘value’ proposition to patients and health organizations is the principal business argument with the investment affording an appropriate return. According to Porter (2011): the most important thing about ‘value’ is that it should drive innovation and improve health outcomes.
Furthermore a ‘shared value’ perspective as Porter [20] refers to, focuses on improving, growing techniques and strengthening the local cluster of supporting suppliers and other institutions to increase efficiency, product quality and sustainability. This leads to a bigger part of revenue and profits.
The innovative technology platforms are one of the main tools that can help the pharmaceutical manufacturers to achieve this goal.
Risk reduction and the creation of new market segments are among the targets followed by super generic producers in the search of ‘value creation’; in this framework, even quality by design can be considered as a marketing tool.
‘The market leaders follow the quality by design approach, multifunctional excipients, modifying dosage form, and reforming the release pattern to develop the value added therapies which creates a new segment and uplift the growth in generics market and even assures better quality and economic viability.’
In a more technical discussion, the commercial use of quality by design (QbD) may not have a positive effect on quality, even if the method is scientific and with the intention of providing better results [21].
The commercial use of QbD may divert the industry from taking real innovative initiatives [22]. The quality approach may bring added value and can create ‘value’ itself in the business model but it may be assessed [9].
Quality by design is a concept for planning the quality and to meet customer expectations for ‘value’. The focus of this concept is that quality should be built into a product with a thorough understanding of the product, the process by which it is developed and manufactured, alongside knowledge of the risks involved in the manufacturing of these products and how best to mitigate them.
‘The focus of the QbD exercise is process understanding. One can use many approaches to gain process understanding. The most effective approach is statistically designed experiments. Constructing a design space using any other approach will be costly and provides low-quality models. The greatest challenge is identifying the candidate experimental variables.’
The QbD can be considered as a business argument for developing high quality, low-risk products:
…QbD is perfect as to this aiming (manufacturing of the super generics), especially when the active pharmaceutical ingredient is already available and characterized, pursuing a QbD approach for an improved product. Targeting the specific needs of patients, e.g. ease of ingestion, storage and handling procedures, improved robustness.
If a company simply uses a QbD model as a quality approach, then they are using a ‘strategy’ for making a good product or process design decisions (which would be classified in the area of managerial decisions). The use of quality tools in a structured way improves the business competitive standing by lowering risk and costs in all the dimensions, e.g. regulatory, production, customer value and business.
FDA has fully implemented QbD for abbreviated new drug applications as of January 2013. Manufacturers of generics, therefore, have to pay more attention to quality and adopt QbD.
Patient expectations can be satisfied, either in mature markets or the promising emerging markets, by providing ‘shared values’, see Figure 1.
As generics manufacturers mature and seek ideas for product differentiation, they are becoming more creative and more ‘value-creation’ conscious. In this way, they attempt to move away from short-term financial performance towards the most important customer needs that will determine their long-term success.
Product examples resulting from ‘value-creation’ strategy
The use of new technology platforms can indeed be viewed as a search for value creation and quality product ‘culture’. Examples are discussed below.
The nasal sumatriptan
Sumatriptan allows the same blood levels of the drug to be achieved in 2–3 mins, compared with the currently marketed Imitrex, which takes 60–120 mins [23].
Human clinical trials have shown that the Intravail® formulation of sumatriptan achieves therapeutic drug levels at about 2–3 mins, 20–30 times faster than the currently marketed non-injectable sumatriptan products. For comparison, the most widely used triptan formulations, namely sumatriptan nasal spray or tablet formulations, both reach maximum blood levels of the drug in about 60–120 mins, thus delaying onset of relief. The total triptan market exceeds US$3 billion annually, with sumatriptan comprising approximately US$2 billion of the total.
Chronic respiratory diseases (complex re-innovated product)
According to Schubben et al. [24], pulmonary powder inhalation treatments, such as caperomycin oleate, is superior to sulfate salt and has a favourable risk–benefit profile for the future treatment of tuberculosis. By using more efficient and convenient treatments, the adherence to drug therapy can be increased, and this is an opportunity to enhance therapeutic outcomes.
The complexity of inhalation products makes it more difficult to develop generics versions (substitutable and interchangeable). Under Article 10.3 hybrids or 505(b)(2), the development of orally inhaled products can be approved. Cost-effective versions like this have good marketing opportunities in emerging markets.
The development of orodispersible tablet technology
The development of orodispersible tablet technology is becoming more important because of increasing demand and the availability of technology that allows its manufacture using conventional equipment. This technology is more convenient for the patient and has the ability to increase market share owing to product differentiation [25].
Intranasal diazepam as an alternative to diastat rectal gel, developed by Neurelis
Intranasal diazepam (NRL-1) is a proprietary formulation of diazepam delivered via an already marketed nasal sprayer, that is being developed for the management of children and adults who require intermittent use of diazepam to control bouts of acute repetitive seizure activity. In clinical trials, NRL-1 has demonstrated high bioavailability, low variability from dose to dose, and was well tolerated. Most patients who experience acute repetitive seizures, however, are currently seen in emergency rooms and treated with intravenous benzodiazepines [26]. Most of these patients are admitted to hospital. Intranasal diazepam has the potential to provide a superior alternative to either rectal administration of Diastat® or the need to visit the emergency room for intravenous administration of drugs.
The acceptance barrier for the super generic has been raised considerably owing to pressure on health funds. For example, in the US, Express Scripts and CVS Health have recently removed two combination products [27] from their reimbursement list [28]. These are Duexis and Vimovo; both are combination drugs and their ingredients are available as generic individual monotherapies. Duexis comprises the pain reliever ibuprofen, the active ingredient in Advil and Motrin, and the heartburn remedy famotidine, Pepcid®. Vimovo is another pain drug and stomach combination drug, naproxen (Aleve) and esomeprazole (Nexium). These two products both belong to Horizon Pharma and the removal of such products will require companies looking for differentiation to refocus their targets. In the case of Vimovo, Horizon has advised that they have been awarded additional [29] patent claims, but anticipate that the removal of the product from reimbursement will reduce income and they will be looking at alternate means for promoting such products as speciality pharmaceuticals or even rising prices [30].
In this paper, the ambiguities in designations of the super generics are discussed, and differences between them are explored through interviews and literature review. These new versions may have different periods of exclusivity in different jurisdictions, and that is one of the reasons that designation is so important [31, 32].
For the 505(b)(2) pathways commonly used by super generic producers, more products were approved in 2012 through 505(b)(2) development in the US [31]. This is because the super generic pathway can be applied to a wide range of development scenarios. Bringing modified version of an existing drug to market, although potentially much faster and less costly than starting a new drug, is still a demanding process, requiring a complete understanding of marketing challenges around product designation [31–33].
The super generic or value-added generic created a new product strategy and opened a new pathway towards sustainability in the market. The benefit of this product differentiation is not only focused on higher financial outcomes, albeit at higher risk for the companies, but also, most importantly, on providing a range of affordable alternatives to patients.
In this changing perspective for the generics industry, using the ‘generics’ designation for improved therapeutics seems to present an obstacle to generating higher revenues. Nowadays, the major generics manufacturers need to demonstrate their potential for going far beyond generics activities. The need for generics manufacturers to differentiate in the generic pharmaceuticals market is driven by the necessity to move away from the classic International Nonproprietary Name market with low margins and falling prices.
Even if switching to super generics seems to be ‘hard’, these differentiated versions are addressing unmet patient needs and may provide value to payers and justify a higher than generics price.
These pharmaceutical products occupy a space between innovative and generics, ‘the third sector’, and is forecasting now at US$24 billion and reaching US$32 billion global sales by 2018 [33].
Another important concern here is prioritizing patients’ needs as a ‘value’. This can contribute to progress in the context of ‘patient centric’ approach.
Super generic products are introduced to market as innovative or re-innovated pharmaceuticals. The other dimensions of super generics include a cost-saving paradigm [34], patient compliance providers, and pharmaceutical growth generators [35].
In spite of their high economic and therapeutic values, the use of super generics seems to have decreased and interest partly diminished. Even if the use of 505(b)(2) as a regulatory pathway in the US can provide market exclusivity, semantic challenges around the use of ‘generic’ drug for the product category can be the main drawback.
If innovative generics companies can invest in generics and re-innovated, improved therapeutics, they may take a big step towards new chemical entity development, and, in the long run, may benefit from the both types of products by value proposition. The semantic challenge can be observed as a strategic marketing for these products.
Acquiring higher reimbursement prices can become reality if, and only if, any agreed price increase matches the effectiveness of the value-added product. If it is innovative and reduces the risks, then payers may accept a higher price.
These improved versions offer other benefits. For example, encouraging payers for better alternatives; providing different affordable pharmaceutical treatments to patients; designing products that meet more precisely the needs of patients; and improving the standards of incremental product innovation and life-cycle strategy.
Value integration strategies, however, may also include educating prescribers to better choose their target treatments; and communicating with patients to inform them of alternatives that may be more convenient to administer, and with similar or improved clinical outcomes.
The author wishes to thank the English editing support provided by Ms Maysoon Delahunty, GaBI Journal Editor for this manuscript.
Disclosure of financial and competing interests: Dr Malcolm Ross is Managing Director of Generapharm Consulting, Basel, Switzerland. The authors have indicated that they have no conflicts of interest with regard to the content of this article.
Provenance and peer review: Not commissioned; externally peer reviewed.
Malcolm Ross, BPharm, PhD, Switzerland
References
1. Phelps KV. Taking the 505(b)(2) route. Drug Discovery & Development. 9 August 2012 [homepage on the Internet]. 2015 Feb 24 [cited 2015 Feb 25]. Available from: http://www.dddmag.com/articles/2012/08/taking-505b2-route
2. Robinson D, Reed V, editors. The A Z of social research jargon. Aldershot, UK: Ashgate; 1998.
3. Kermani F. Generics companies: aspiring to innovate. Journal of Generic Medicines. 2004;1:4(336-46).
4. Sommerfeld TL. Generic appeal to innovation pharma. Journal of Generic Medicines. 2007;4:4(259-66).
5. Stopler W. Joseph Alois Schumpeter: the public life of a private man. Princeton: University Press; 1994.
6. Schumpeter J. The Theory of economic development. Harvard Economic Studies 46; 1934.
7. Wechsler J. New era for generic drugs. 1 November 2014. BioPharm International. [cited 2015 Feb 25]. Available from: http://www.biopharminternational.com/new-era-generic-drugs-2
8. Actavis. FDA Advisory Committee recommends against approval of Actavis’ Nebivolol/Valsartan fixed-dose combination NDA for treatment of hypertension. 9 Sep 2014 [homepage on the Internet]. [cited 2015 Feb 25]. Available from: http://www.actavis.com/news/news/thomson-reuters/fda-advisory-committee-recommends-against-approval
9. Barei F, Le Pen C, Simoens S. The generic pharmaceutical industry, moving beyond incremental innovation. Generics and Biosimilars Initiative Journal (GaBI Journal). 2013;2(1):13-9. doi:10.5639/gabij.2013.0201.011
10. New Pharma Thinkers. Barei F. The assessment of innovation in generic pharmaceutical industry, a qualitative review. 18 September 2012 [homepage on the Internet]. [cited 2015 Feb 25]. Available from: http://www.newpharmathinkers.com/super-generic-innovation/
11. Ross M. Innovation strategies for generic drug companies: moving into super generics. IDrugs. 2010;13(4):243-7.
12. Stegemann, et al. Improved therapeutic entities derived from known generics as an unexplored source of innovative drug products. Eur J Pharm Sci. 2011;44(4):447-54.
13. Stegemann, et al. Developing and advancing dry powder inhalation towards enhanced therapeutics. Eur J Pharm Sci. 2013;48(1-2):181-94.
14. Cheng C, Shiu E. Re-innovation – what is it and what could influence its performance? Academy of Marketing Conference; 2006: London, UK. Conference Paper No. 254.
15. Rothwell R, Gardiner P. Re-innovation and robust designs: producer and user benefits. Journal of Marketing Management. 1988;3(3):372-87.
16. Sainkoudje, SI. Analyse de la procédure 505(b)(2) de la réglementation américaine relative aux demandes d’autorisation de mise sur le marché de médicaments génériques innovants et comparaison avec les procédures similaires en Europe et en France. Université Rennes 1, Faculté de la pharmacie.
17. Teva Pharmaceuticals Industries Ltd [homepage on the Internet]. 2015 Feb 24 [cited 2015 Feb 25]. Available from: http://www.tevapharm.com/RandD/Documents/BioMed/RandD.pdf
18. U.S. Food and Drug Administration. Guidance for Industry. Applications covered by section 505(b)(2). Draft guidance. October 1999 [homepage on the Internet]. 1999 Oct 4 [cited 2015 Feb 25]. Available from: http://www.fda.gov/downloads/Drugs/Guidances/ucm079345.pdf
19. Daiichi Sankyo. Daiichi sankyo launches new generic drugs through its Daiichi Sankyo Espha subsidiary. 20 June 2014 [homepage on the Internet]. 2015 Feb 24 [cited 2015 Feb 25]. Available from: http://www.daiichisankyo.com/media_investors/media_relations/press_releases/detail/006145.html
20. Porter ME, Kramer MR. Creating shared value. Harvard Business Review. 30 November 2011 [homepage on the Internet]. 2014 Apr 17 [cited 2015 Feb 25]. Available from: http://adamantconsult.com/wp-content/uploads/2014/05/11-porter-creating-shared-value-ss-highlights.pdf
21. Trivedi B, et al. Quality by design in pharmaceuticals. Int J Pharm Pharm Sci. 2012;4(1):17-29.
22. Cosby ST. Process analytical technology in biopharmaceuticals. Massachusetts Institute of Technology; 2013. 2013 May 9 [cited 2015 Feb 25]. Available from: http://dspace.mit.edu/bitstream/handle/1721.1/80911/857788914.pdf?sequence=1
23. Maggio ET. Absorption enhancing excipients in systemic nasal drug delivery. Journal of excipients and food chemicals. 2014;5(2). Available from: https://ojs.abo.fi/index.php/jefc/article/download/756/1030
24. Schoubben A, Blasi P, Marenzoni ML, Barberini L. Capreomycin supergenerics for pulmonary tuberculosis treatment: preparation, in vitro, and in vivo characterization. Eur J Pharm Biopharm. 2013;83(3):388-95.
25. Swapnil SG, et al. A review on: Orodispersible Tablet Technology – a novel approach to develop the supergenrics. International Journal of Pharmaceutical Science Research. 2014;26(2):231-6.
26. Neurelis regains rights to Intranasal Diazepam Program. [cited 2015 Feb 25]. Available from: from: http://www.lelezard.com/en/news-4322972.html
27. Controlled Release Society. CRS Newsletter [homepage on the Internet]. 2011;28(1). [cited 2015 Feb 25]. Available from: http://www.controlledreleasesociety.org/publications/Newsletter/Documents/v28i1.pdf
28. Langreth R. More medicines goes off limit in drug price showdown. Bloomberg Business. 25 November 2014. [cited 2015 Feb 25]. Available from: http://www.bloomberg.com/news/2014-11-25/more-medicine-goes-off-limits-in-drug-price-showdown.html
29. Complete response letter from FDA, positive opinion on drug, technical update, financial result release, and clinical trial results – research reports on Acelrx, Horizon, Gilead, Abbvie and Exelixis [press release]. Market Watch. 31 July 2014. [cited 2015 Feb 25]. Available from: http://www.marketwatch.com/story/complete-response-letter-from-fda-positive-opinion-on-drug-technical-update-financial-result-release-and-clinical-trial-results-research-reports-on-acelrx-horizon-gilead-abbvie-and-exelixis-2014-07-31
30. Helfand C. Doom for combo meds? Expresse scripts, CVs dump horizon pharma two-in-one drugs. Fierce Pharma Marketing. 30 July 2014. [cited 2015 Feb 25]. Available from: http://www.fiercepharmamarketing.com/story/doom-combo-meds-express-scripts-cvs-dump-horizon-pharma-two-one-
31. Phelps K. (B)(2) or not (B)(2) – That is the Question, 505(b)(2) can result in product approval with lower risk, reduced costs, and faster time to market? Contract Pharma. 6 November 2013. [cited 2015 Feb 25]. Available from: http://www.contractpharma.com/contents/view_experts-opinion/2013-11-06/b2-or-not-b2-that-is-the-question/
32. Szejtili J. Cyclodextrin complex generic drugs are generally not bio-equivalent with the reference products: therefore the increase in number of marketed drug/Cyclodextrin formulations is so slow. Journal of Inclusion Phenomena and Marocyclic Chemistry. 2005;52(1-2):1-11.
33. Vaczek D. Finding value in generics with a twist. Medical Marketing and Media. 5 November 2013. [cited 2015 Feb 25]. Available from: http://www.mmm-online.com/finding-value-in-generic-drugs-with-a-twist/article/381633/
34. Garud SS. (2014), Super generics a cost-saving paradigm. IJPRD. 2011;5(11):57-66.
35. Kumar L, Deshpande A, Page A. Super generics/improved therapeutic entities: an approach to fulfill unmet medical needs & extending market exclusivity of generic medicines. International Journal of Pharmacy and Pharmaceutical Sciences. 2015;7(2).
|
Author for correspondence: Fereshteh Barei, PhD, Paris Dauphine University, Place de Maréchal de Lattre de Tassigny, FR-75016, Paris, France |
Disclosure of Conflict of Interest Statement is available upon request.
Copyright © 2015 Pro Pharma Communications International
Permission granted to reproduce for personal and non-commercial use only. All other reproduction, copy or reprinting of all or part of any ‘Content’ found on this website is strictly prohibited without the prior consent of the publisher. Contact the publisher to obtain permission before redistributing.
Source URL: https://gabi-journal.net/the-refinement-of-the-super-generic-concept-semantic-challenge-for-product-re-innovation.html
|
Background: Due to the declining innovativeness of the classic R & D model in the original pharmaceutical industry, the generic pharmaceutical industry is aiming to become an innovation generator itself. |
Submitted: 17 December 2012; Revised: 4 February 2013; Accepted: 11 March 2013; Published online first: 15 March 2013
Innovation is widely regarded as an instrument to create competitive advantage. Different types of innovation exist, including incremental innovation, re-innovation and radical innovation. Incremental innovation deals with creating minor improvements or simple adjustments in a product’s current state [1, 2]. Re-innovation has been defined as: ‘the process of innovation and product development that occurs after a new product is launched, building upon early success but improving the next generation with revised and refined features’ [3]. Finally, radical innovation refers to radical, new inventions that produce milestones, new products or services, and as a result lead to the development of new industries [4]. Today there is less radical product innovation in the original pharmaceutical industry. Moreover, the concept of ‘new product’ has also evolved by the application of strategies such as incremental innovation and re-innovation. In the past, radical or disruptive innovation changed the pharmaceutical market, whereas today generic pharmaceutical firms attempt to innovate in a less costly way in a shorter time with less regulatory obstacles due to the substantial R & D costs to achieve a radical new product. Incremental innovation and re-innovation meet these objectives.
The generic pharmaceutical industry is now evolving in an innovative way. Some firms are applying strategic changes in their management systems and business models and creating new product portfolios fortified with ‘super generics’, new chemical entities and novel drug delivery systems. A super generic drug is an improved version of an original drug which has lost product patent protection. The product patent for the original drug will have expired or have been circumvented by the company developing the super generics. The nature of the improvement may include drug delivery, manufacturing or reformulation technology. This kind of value-added version is manufactured in a re-innovation framework. This innovative design is between incremental and radical innovation. Companies producing super generics have a greater regulatory risk in gaining marketing approval compared to strict generics manufacturers [5]. Without getting into the details, there are three regulatory pathways for drug approval in Europe and the US.
The US Food and Drug Administration (FDA) does not recognize the term ‘super generics’. These products are also referred to as ‘added value generics, new therapeutic entities or hybrids’. These products differ from the original product in formulation or method of delivery. These products are improved formulation of a known product.
This group of generics needs a completely New Drug Application (NDA) in order to gain FDA approval. The regulatory pathway in Europe appears to be very similar to that in the US and was introduced within the Directive 2001/83/EC in November 2001 and in the Regulation (EC) No 726/2004. These products are not interchangeable with the brand-name drugs. Those regulatory pathways are summarized in Table 1.
With a NDA, innovative drug therapies are reaching the market in a specific dosage form for one or more clinically proven indications of which, after expiration of the patent or the data exclusivity, copies are launched using Abbreviated New Drug Applications (ANDA). Advanced therapies that emerged from launched molecules during their product life cycle have gained considerable attention as clinical practice provides evidence for additional therapeutic values; patient centric delivery systems show improved therapeutic outcomes or emerging technologies offer efficiency gains in manufacturing or access to emerging markets. The US and European regulatory framework has set reasonable regulations in place for these super generics or hybrid applications. While these regulations are relatively recent the pharmaceutical industry is just starting to use this route for its product development [6, 7].
However, super generics take an average of three to four years development time to registration, and enjoy reduced development and regulatory risks compared to new chemical entities. The end product may gain a significant price premium to conventional generics once marketing approval is received. Depending on the type of modification to the original formulation and whether the super generic drug is being developed for the same or a different indication will also have an impact on the level of additional research that is needed to gain approval for the reformulated product [8]. The quantity of issued patents highlights the technical knowledge and skill sets that are available in generic pharmaceutical firms. The success of these pharmaceutical firms has illustrated the possibility of changing from the classic model of ‘copy maker’ towards a model of creating new value-added products, manufacturing strategies and new business models [9, 10].
Meanwhile, the demand side for pharmaceutical treatments has also evolved. ‘New’ customers have emerged, i.e. a better informed, web data empowered generation of patients searching for cost-effective treatments. The generic pharmaceutical industry is reacting to this by applying new business models.
By applying a patient-centred and quality-based perspective into their business models, the generic pharmaceutical industry is attempting to offer new less risky and cost-effective products. The most important aspect is that innovation is no longer just about the product itself, it is also centred on how a company contributes to improving the health of patients. This process has required the out-licensing of innovative generic drug products and has also involved the establishment of new partnerships and alliances to better utilize technological platforms and manufacturing facilities [11]. As an example, Teva Pharmaceuticals acquired Ivax in 2006, Barr Laboratories in 2008, and Ratiopharm in 2010.
The aim of this article is to gain insight into re-innovation in the generic pharmaceutical industry by focusing on product innovation, and a business model based on value proposition employed by some of the innovative generic pharmaceutical firms. This is an alternative model between hybrid and classic R & D companies.
This research complies with the procedure of Paris Dauphine University not to require consent from an institutional review board when subjects cannot be identified. Also, there are no personal identifiers in the data files or in the results.
We applied a qualitative approach. Semi-structured interviews [12] were conducted because they offer the opportunity to ask experts about their views and experiences of the recent changes. In the absence of studies and documentation on this topic due to its novelty, we conducted interviews with managers, industry consultants, lawyers, physicians, pharmacists, patent attorneys, and researchers to gather more views and share their experiences in this area. We prepared two questionnaires; the original questionnaire was more focused on the intellectual aspect of innovation, trying to investigate about the type of innovation in this industry. In Table 2 we have presented a list of our sources in this qualitative research.
The questionnaire had three parts: the first part was about innovation strategy and how it has influenced the generic drug form; the second part was about innovation in their business model, and how do they boost their model by value proposition to customers; the third part was about innovation in the product portfolio and the reasons of product selection and the use of new technology platforms and new statistical methods to reduce risks and optimize product manufacturing in a shorter time to a quicker access to market. We checked the questions with two researchers who were specialists in survey design and we consulted with an American economist who conducts this type of research in order to validate our questionnaire, some of the questions were added during or after some interviews.
Some new topics emerged during the interviews.From April to October of 2011, a total of 20 interviews were conducted in Basel,Budapest, Paris, at the forum on ‘Biopharmaceuticals and Supergenerics’, and in Frankfurt. There are also some interviews that were conducted by telephone calls to Australia, India, UK and US.
We have also followed relevant forums and conferences in France, Hungary, and International Fairs like the CPhI Worldwide in Frankfurt, Germany, to get up-to-date information.
During the first forum on super generics in Budapest, Hungary, we discussed the regulatory aspect of this innovation in the companies manufacturing innovative products known as super generics, hybrid products and value added generics. In Frankfurt, we met for the first time the specialists we contacted via LinkedIn and by email. It was a unique occasion to meet and discuss with the representatives of the super generics manufacturers worldwide.
We studied almost every day every piece of news related directly or indirectly to our research coming from reliable references. This shows that quality by design (QbD) is a very important concept and that innovative generic drug firms may apply QbD not only to reduce the risk of product failure but also to respond to the demands of FDA.
Several economic and financial reports from Business Insight, Data Monitor, IMS, Ernest & Young, Markets and Research were also reviewed before and during the interviews. The companies that accepted participation in this research are: Mayne Pharma (Australia), Capsugel (Belgium), Biogaran (France), Gedeon Richter (Hungary), Dr Reddy (India) and Hanmi (Korea). The other participants were from drug development companies, consultancy companies, and formulation scientists. Other information was collected using the websites of the associations of generic drugs, such as the European Generic medicines Association (EGA); the generic drug industry association in France (GEMME, Association des professionnels du médicament générique); the American Generic Pharmaceutical Association (GPhA); and the International Generic Pharmaceutical Alliance (IGPA) as part of their insights into 2010 on the generics markets in Europe.
Data analysis
We have constructed a database of our data collected from the interviews. Interviews were recorded, transcribed verbatim and analyzed using the software NVivo 9.2 software according to the Matrix Framework approach. We used NVivo Dataset and survey to explore our findings. In practice we began by coding the ‘raw’ data at nodes representing themes in our text-data. Alternatively, we ran ‘Text’ search query or ‘Word’ frequency to identify common themes in survey responses before coding them. Matrix coding analysis helped us to associate the main results to the three main axes of our research work: Innovation in management system, Business model innovation and Product portfolio innovation. Framework matrices provided a way to summarize or condense the source materials in a grid. Subsequently, we launched questions and found patterns based on our coding and checked for coding consistency among interviewees. This method helped us to compare results, and to identify new perspectives of the survey results that could not be acquired without running the queries and coding the results.
Producing novel products is defined as the part of new product development strategy which explores the extension of existing innovations, which can only happen after the first generation of a new product is launched [13]. This is, for example, the case with the development of super generics and bio-superior products that follow on from reference biopharmaceutical products. Being built upon early successful products, re-innovative products are created through applying new platforms, new components, or new configurations with breakthrough technologies to previous products or manufacturing processes [14, 15]. The new re-innovated medicines are focusing on improving health outcomes for patients.
‘… In the past, successful pharmaceuticals stemmed from having good clinical trial data which companies owned and controlled. In the future, their success in the market will instead be evaluated by post marketing data resulting from patients’ satisfaction, of which they will no longer have sole possession …’ (Pharma Researcher, UK)
At the industrial level, through re-innovation attempts, generic pharmaceutical firms aim to minimize the new product failure rate [7], reduce the cost of developing a new product and decrease the lead time in bringing it to market. A pharmaceutical product developed and manufactured with less excipients and unit operation, while maintaining the product therapeutic performance compared to the originator, could be considered as an improved therapeutic entity as it reduces the overall costs of manufacturing that could lead to reduced healthcare spending [16].
Innovative generic pharmaceutical firms may apply QbD and design of experiment methods to optimize their production outcome and minimize the risk. Quality by design means designing and developing a product and associated manufacturing processes that will be used during product development to ensure that the product consistently attains a predefined quality at the end of the manufacturing process [17]. Statistical methods are becoming increasingly vital for pharmaceutical firms. Design of experiments is a tool for determining the relationship between the factors that have an effect on a process and the response of that process [18].
The re-innovative product (as compared to an incremental new product) can be defined as a product that provides new features, benefits, or improvements through existing technology. As such, re-innovation and incremental innovation are different in two aspects: 1) incremental products are improved only by incremental technologies while breakthrough technologies can be used in re-innovative products; and 2) incremental products must be based on the current platform but re-innovative products are either (mostly) based on a new platform or (occasionally) based on an existing platform [19].
‘… As to technology platforms, if for example you consider aerosolization as a platform, then using such a platform to create new, better forms of an existing entity are part of re-innovation …’ (US Manager, 2012)
Re-innovation by the generic pharmaceutical industry can be observed in drug product design, formulation, process development and manufacturing processes going back to the early stages of the product development cycle.
Some product examples are:
1-Abraxane, super generic form of Taxol (FDA, 2005), which uses albumin to deliver the chemotherapy, not Cremophor, and so avoids hypersensitivity and claims a greater tumour response rate than Taxol. The drug Abraxane (nanoparticle albumin bound paclitaxel) uses the approach of coating Taxol with albumin to reduce the side effects associated with standard Taxol (paclitaxel), making it possible to give it without steroids (which can be a rather bothersome issue for many patients, causing problems from severe insomnia to very high blood sugars and more) and also reducing some other Taxol-associated side effects like joint and muscle aches [20, 21].
2-SUBACAP is an improved version of the conventional itraconazole formulation used to treat fungal infections. In June 2012, Mayne Pharma announced that the UK Medicines and Healthcare products Regulatory Agency (MHRA) had reversed its previous decision on SUBACAP and advised that the SUBACAP marketing authorization application was approvable in the UK. Mayne Pharma is in the process of submitting the response to re-activate the ‘Decentralized Procedure’ to seek approval in Germany, Spain and Sweden. Following approval in these countries, the company will seek a second round of approvals in other European countries, including Belgium, Italy, Greece, Portugal and The Netherlands. The total European market sales of itraconazole in 2011 were US$85 million (companies communication and annual report 2012). SUBACAP provides enhancements to patients and prescribers with reduced inter- and intra-patient variability and therefore a more predictable clinical response enabling a reduction in active drug quantity to deliver therapeutic blood levels. Itraconazole is one of the broadest spectrum antifungal drugs on the market and can be used to treat both superficial fungal infections such as onychomycosis (nail infection) and systemic fungal infections such as histoplasmosis, aspergillosis and candidiasis which can be life threatening to immunocompromised patients [22].
Another example of novel technology platform used in super generic drug manufacturing is the application of nanoparticle technology to address challenges associated with the delivery of poorly soluble compounds. Re-innovation has, for example, led to the development of a tablet dosage form that incorporated candesartan cilexetil nanoparticles [23–28] to reduce dosage, reduce toxicity, improve bioavailability and enhance solubility. The original candesartan cilexetil is used for the treatment of hypertension. The major drawback in the therapeutic efficacy of candesartan cilexetil is its very low aqueous solubility leading to low and variable bioavailability. Low bioavailability may lead to variability in therapeutic response. The formulation change resulting from Design of Experiments and nanoparticle technology resulted in better solubility. Using Design of Experiments for process optimization resulted in a robust scalable manufacturing process with design space established for critical process parameters that can balance milling time, particles size and yield. Design of Experiments studies indicated that, out of the three parameters tested in the experimental design, disc speed, pump speed and bead volume were found to affect the critical product attributes either through non-linear, quadratic or interaction effects [29, 30].
The robustness of the model was validated based on confirmatory trials that indicated statistically no difference between predicted and experimental values. The rate and extent of drug dissolution from tablet dosage form incorporating drug nanoparticles was significantly higher than in the tablet containing micronized drug and marketed product.
The increase in drug dissolution resulted in significant enhancement in rate (Cmax) and extent of drug absorption (AUC).
The manufacturing process used is simple and scalable indicating general applicability of the approach to develop oral dosage forms of sparingly soluble drug.
The formulation approach used provides a viable approach to enhance dissolution and bioavailability of sparingly soluble compounds (BCS class II) that may translate into improved therapeutic outcome [23].
This innovative change is also illustrated by the following quote:
‘Super-generic [drug] products, mostly nano- and micro-sized drug delivery systems, focus on improving active principles which were previously commercialized in another formulation. These new formulations are certainly not bioequivalent in the generic [drug] industry’s sense of the term, they are therefore not generics. They are new, i.e. innovative, drugs, which can replace treatment with the previous entity.’ (Drug Delivery Manager, USA)
Another example of re-innovation in super generic drugs relates to the development of a per oral [29] dosage form for a sparingly soluble camptothecin analogue. This was achieved by formulating it as a drug complex [30]. This formulation approach addressed limitations of the currently marketed product that is only amenable for intravenous administration. The drug complex following oral administration demonstrated safety and efficacy comparable to marketed product in athymic mice with implanted tumours. The manufacturing process used is simple and scalable indicating general applicability of the approach to develop oral dosage forms of sparingly soluble drugs. An oral dosage form should result in lower treatment cost, better patient compliance and improved therapeutic outcome for better disease management [23].
In a recent compliance review for antihypertensive drug treatments it was found that some drug classes have significantly poorer adherence performance by patients than other drug classes. Only one third of patients were adherent to b-blockers and diuretics, while two thirds of patients were adherent to angiotension converting enzyme inhibitors and angiotensin II Receptor blockers [31]. Even an adherence of two-thirds of patients still remains at an unsatisfactory low level and leaves considerable room for improvement.
Modifying the release of drugs that have a short biological half-life by extending their release, circumvents high plasma peaks, reduces fluctuations in plasma levels and allows for a once-daily intake that can optimize therapy. This can avoid the daily oral intake for people with dysphagia or dementia. In this new business model, therapy is moving away from a clinical parameter oriented treatment to an outcome oriented disease management programme [32].
The low price of generic drugs threatens to undermine the sustainability of the generic pharmaceutical industry in regards to its low margins, number of competitors, increased requirements for pharmacovigilance, the mature markets in developed countries, and the post-patent cliff arena after 2015 [8]. Meanwhile, medical and technological changes push the pharmaceutical industry to implement new business models. These changes coincide with a growing demand from ageing populations, and better-informed patients who have a substantial need for individualized cost-effective treatments.
Several generic pharmaceutical firms have evolved their traditional business models into innovative models. These models are key to maintaining market position. They are focused on patients’ unmet medical needs and a high quality approach to the manufacturing process.
The innovative business models emerge from new management systems. The challenge of new management systems in these innovative generic pharmaceutical firms is on product innovation: how to manage a better organization to achieve a maximum product differentiation through value proposition to patients? How to optimize product quality? How to reduce manufacturing costs? How to reduce the time to market?
The generic pharmaceutical industry is evolving into a less generic, but more innovative format. In this respect, it should be noted that many generic pharmaceutical firms have the capacity to re-innovate. They have experience, good knowledge and the technical possibility to re-innovate. Alternatively, new alliances can provide the necessary financial resources for technical and marketing requirements.
Implementing re-innovation as a strategy strives to convert price-focused competition into product quality competition, this is central to an innovative business model. Some generic pharmaceutical firms are re-innovating their product portfolio by using new technology platforms, new components and new configurations. These attempts have mainly resulted in super generic drugs; value added products or hybrid products and biosimilars. These super generic drugs and improved therapeutic entities are an important source for innovation in drug therapy in the coming decades.
The so-called super generics are a promising alternative. The value added products resulting from re-innovation strategy by using new ‘technology platforms’, new components and new services will be a strategic element for affordable and individualized medicines.
According to our findings:
This research may be followed by further investigation in innovative business models adapted by an evolving generic pharmaceutical industry that has not yet been studied. A quantitative study of R & D investment and strategic alliances in an innovative generic pharmaceutical industry will reveal more.
Due to evolution in the pharmaceutical industry landscape, some generic pharmaceutical companies are restructuring their business models. In this new industrial design, some of the generics manufactures are re-inventing their product portfolio through a re-innovation strategy. New technology platforms, new components and new configurations are adopted to provide patient compliance and increase patient quality of life. Super generics, biosimilars, bio-superiors and value added versions are some of the new product alternatives resulting from this innovative evolution. The product itself is not the only target; the conversion of competition from price to product quality ensures the value proposition and provides product differentiation. New innovative product portfolios are the evidence that innovative generics companies are not only mastering incremental innovation but are also adopting re-innovation in their new strategies. In this perspective, biotechnology, nanosciences and nanotechnology are ‘strategic’ areas for its scientific and commercial development.
For patients, the innovative changes in product portfolios struggle to improve patient’s quality of life, reduce side effects and enhance efficiency by new product alternatives. These new product alternatives are developed by applying new technology platforms like nanotechnology. Enhancing drug solubility is often key to improving a product’s formulation. New nanotechnologiesa are now being used to solubilize drugs with the aim of improving bioavailability and activity, and reducing in vivo variabilityb.
The re-innovated product portfolios propose more personalized products according to patient’s unmet medical needs. Non-compliance can be attributed to poor taste, difficulty in administration or swallowing, and the inconvenience of multiple doses per day. Non-compliance is a frequent issue (see Cap Gemini Ernest & Young, Compliance Discovery Workshop, 2003). General reasons for non-compliance include: side effects/adverse events, lack of access, financial constraints and lack of communication or information, poor taste and difficulty to swallow (inconvenience in administration). Compliance is dependent on the class of drugs. Some of the new super generics have the advantage of a lower dose, they have the same positive effect provided by the original version, and have significantly reduced adverse side effects [33]. The importance of the oral route of administration [34] from both a clinician and patient acceptance point of view means there has been a vast amount of development and research in drug delivery via this route. Pharmaceutical devices will continue to drive patient compliance and acceptability. The convergence of microelectromechanical systems and nanotechnology with biological applications offers breakthrough in drug developments [35]. As such, improved therapeutic entities could bring innovation faster and at lower risk to society and help to improve health outcomes [36].
For further reading, please refer to references 37 to 47.
Competing interests: Professor Claude Le Pen is professor of health economics at Paris Dauphine University. He has also several organizational, scientific and governmental responsibilities. Professor Steven Simoens holds the EGA Chair ‘European policy towards generic medicines’. The authors have no conflicts of interest that are directly relevant to the content of this manuscript. This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Provenance and peer review: Not commissioned; externally peer reviewed.
Professor Claude Le Pen, PhD
LEGOS, Laboratory of Economics and Management of Health Organizations, Paris Dauphine University, Place du Maréchal de Lattre de Tassigny, FR-75775 Paris Cedex 16, France
Professor Steven Simoens, MSc, PhD
Department of Pharmaceutical and Pharmacological Sciences, Research Centre for Pharmaceutical Care and Pharmacoeconomics, Katholieke Universiteit Leuven, Onderwijs en Navorsing 2, PO Box 521, 49 Herestraat, BE-3000 Leuven, Belgium
References
1. Banbury C, Mitchell W. The effect of introducing important incremental innovations on market share and business survival. Strategic Management Journal. Special Issue. 1995;16 S1:161-82. doi:10.1002/smj.4250160922
2. Henderson RM, Clark KB. Architectural innovation: the reconfiguration of existing product technologies and the failure of established firms. Adminstrative Science Quarterly. 1990;35(1):9-30.
3. Rothwell R, Gardiner P. The strategic management of re-innovation. R & D Management. 1989;19(2):147-60.
4. Cheng C, Shiu E. Preconditions for product innovation in Taiwan: evidence from high technology firms, Asia Pacific Business Review. 2008;14(2):191-211.
5. Parrek A. A cost effective clinical trial procedures to ensure the smooth development and approval of super generics. 2nd Annual NextGen 2011: Super-generics Strategies. 27–29 April 2011, Mumbai, India. Data on file.
6. Nadler HL, Degraft-Johnson D. Demystifying FDA’s 505(b)(2), drug registration process. Regulatory Affairs Professionals Society (RAPS); 2009.
7. Stegemann S, Klebovich I, Anta I, et al. Improved therapeutic entities derived from known generics as an unexplored source of innovative drug products. Eur J Pharm Sci. 2011;44(4):447-54. doi:10.1016/j.ejps.2011.09.012
8. Buggle I. Marketing opportunities for supergenerics. Business Insight. 2010;38-46. Data on file.
9. Sommerfeld T. Strategic options for mid-sized generic players. Journal of Generic Medicines. 2005;2(4):308-15.
10. Kermani F. Generic companies: aspiring to innovate. Journal of Generic Medicines. 2004;1(4):336-46.
11. The significance and apparent repercussions of 2009–2015 pharmaceutical patent cliff. Bioassociate. Innovative Consulting; 2012.
12. Pope C, Mays N. Qualitative research in health care. 3rd ed. Blackwell Publishing: Oxford; 2008. p. 22-43.
13. Cheng C, Shiu E. Re-innovation – what is it and what could influence its performance? Academy of Marketing Conference; 2006: London, UK. Conference Paper No. 254.
14. Rothwell R, Gardiner P. Invention, innovation, re-innovation and the role of the user: A case study of the British Hovercraft development. Technovation. 1985;3(3):167-86.
15. Rothwell R, Gardiner P. Re-innovation and robust designs: producer and user benefits. Journal of Marketing Management. 1988;3(3):372-87.
16. Yu LX. Pharmaceutical quality by design: product and process development, understanding, and control. Pharm Res. 2008;25(4):781-91.
17. Anderson MJ, Whitcomb P. Design of experiments. In: Kirk-Othmer Encyclopedia of Chemical Technology. Wiley; 2010. p. 1-22.
18. Dosage forms and routes of administration [homepage on the Internet]. [cited 2013 Feb 4]. Available from: scribd.com/doc/22880389/Dosage-Forms-and-Routes-of-Administration
19. Nekkanti V, Karatgi P, Paruchuri S, et al. Drug product development and pharmacological evaluation of a sparingly soluble novel camptothecin analog for peroral administration. Drug Delivery. 2011;18(4):294-303.
20. Drug delivery innovations driving improved patient compliance [homepage on the Internet]. C2011 [cited 2013 Feb 4]. Available from: http://www.marketresearch.com/product/display.asp?ProductID=6481767
21. Abraxane bests taxol in response rate for nsclc: what might this mean? [homepage on the Internet]. 2010 [cited 2013 Feb 4]. Available from: http://cancergrace.org/lung/2010/03/20/prelim-abraxane-vs-taxol-rr-results/
22. Mayne Pharma reports final FY12 result. Melbourne, Australia: Australian Securities Exchange. 2012 Aug 21 [cited 2013 Feb 4]. Available from: http://www.asx.com.au/asxpdf/20120821/pdf/4284tjk7gfxtsc.pdf
23. New formulation technologies to fast track development of super generics. Pillai R. Dr Reddy’s Laboratories, 2011. Data on file.
24. Basa S, Muniyappan T, Karatgi P, Prabhu R, Pillai R. Production and in vitro characterization of solid dosage form incorporating drug nanoparticles. Drug Dev Ind Pharm. 2008;34(11):1209-18.
25. Nekkanti V, Karatgi P, Joshi M, Pillai R. Developing nanoparticle formulations of poorly soluble drugs. Pharm Tech Europe. 2008 Nov;20(11):24.
26. Nekkanti V, Pillai R, Venkateswarlu V, Harisudhan T. Development and characterization of solid oral dosage form incorporating candesartan nanoparticles. Pharm Dev Technol. 2009;14(3):290-8.
27. Singare DS, Marella S, Gowthamrajan K, Kulkarani GT, Vooturi R, Srinivasa P, Rao PS. Optimization of formulation and process variable of nanosuspension: an industrial perspective. Int J Pharm. 2010;402(1-2):213-20.
28. Nekkanti V, Venkateswarlu V, Ansari KA, Pillai R. Development and pharmacological evaluation of a PEG based nanoparticulate camptothecin analog for oral administration. Curr Drug Deliv. 2011 Nov;8(6):661-6.
29. Nekkanti V, Muniyappan T, Karatgi P, Hari MS, Marella S, Pillai R. Spray-drying process optimization for manufacture of drug-cyclodextrin complex powder using design of experiments. Drug Dev Ind Pharm. 2009; 35(10):1219-29.
30. Nekkanti V, Karatgi P, Paruchuri S, Pillai R. Drug product development and pharmacological evaluation of a sparingly soluble camptothecin analog for peroral administration. Drug Deliv. 2011 May;18(4):294-303.
31. Kronish IM, Woodward M, Sergie Z, Ogedegbe G, Falzon L, Mann DM. Meta-analysis: impact of drug class on adherence to antihypertensives. Circulation. 2011;123(15):1611-21.
32. Stegemann et al. Improved therapeutic entities derived from known generics as an unexplored source of innovative drug products. Eur J Pharm Sci. 2011;44:447-54.
33. Cuba develops its first industrial-scale nanopharmaceutical. Latin American Herald Tribune. 2013 Feb 12. Available from: http://www.laht.com/article.asp?ArticleId=587208&CategoryId=14510
34. Pareek A. Leveraging innovation in generics: a business imperative for pharmaceutical companies. First conference on Supergeneric innovation 2010; Mumbai, India.
35. Ross MS. Innovation strategies for generic drug companies: moving into supergenerics. IDrugs. 2010 Apr;13(4):243-7.
36. Gassmann O, Reepmeyer G, Zedtwitz M. Leading pharmaceutical innovation. 2nd ed. Berlin: Springer Verlag; 2004. Chapter 2: Pharmaceutical innovation: the case of Switzerland, p. 23-52, chapter 3: The science and technology challenges, how to find new drugs? P. 53-77.
37. Kale D. Learning to innovate: the Indian pharmaceutical industry response to emerging TRIPs regime. DRUID Academy Winter 2005 PhD Conference; 2005: Aalborg, Denmark.
38. Simoens S, De Coster S. Sustaining generic medicines markets in Europe. Journal of Generic Medicines. 2006;3(4):257-68.
39. Le Pen C. Consommation pharmaceutique et indicateurs de santé publique. Leem. 2009.
40. Ring in generics in 2012 and beyond. Zacks Equity Research – 2011 Dec 29 [cited 2013 Feb 4]. Available from: http://www.zacks.com/stock/news/67042/Ring+in+Generics+in+2012+and+Beyond
41. Dingermann T. Innovator companies should focus on innovations. Generics and Biosimilars Initiative Journal (GaBI Journal). 2012;1(1):6. doi:10.5639/gabij.2012.0101.003
42. Class JN, Langis l. A patient-centred paradigm for the biosimilar market? Generics and Biosimilars Initiative Journal (GaBI Journal). 2012;1(1):17-21. doi:10.5639/gabij.2012.0101.006
43. Van Lerberghe W. The world health report 2008. Primary health care [homepage on the Internet]. 2013 [cited 2013 Feb 4]. Available from: http://www.who.int/whr/2008/en
44. Shaw B. The role of the interaction between the user and the manufacturer in medical equipment innovation. R & D Management. 1985;15(4):283-92.
45. Terziovski M. Building innovation capability in organizations: an international cross-case perspective. Imperial College Press, London; 2007. p. 157-75.
46. Cheng CJ, Shiu E. Re-innovation: the construct, measurement, and validation. Technovation. 2008;28(10):658-66.
47. Miele E, Spinelli GP, Miele E, Tomao F, Tomao S. Albuminbound formulation of paclitaxel (Abraxane ABI-007) in the treatment of cancer. Int J Nanomedicine. 2009;4:99-105.
aNanotechnology is the science of manipulating materials on a scale so small that they cannot be seen with a regular microscope. The technology could have a broad range of applications, such as increasing the effectiveness of a particular drug, improving the packaging of food, or altering the look and feel of a cosmetic. Nanotechnology could also be used in medicines designed for the detection, treatment, and prevention of disease; food production and preservation; water decontamination and purification; environmental remediation; lighter and stronger materials for construction and transportation; and energy resources such as solar cells and fuel-efficiency additives, just to name a few. Paul C Howard, PhD, Director of the Office of Scientific Coordination and Director of the Nanotechnology Core Facility at FDA’s National Center for Toxicological Research, FDA website, 2011.
bSkyepharma and Elan have developed technologies that have been used to reposition well-known drugs (fenofibrate, megestrol and sirolimus).
|
Author for correspondence: Fereshteh Barei, PhD, LEGOS – Laboratory of Economics and Management of Health Organizations, Paris Dauphine University, Place du Maréchal de Lattre de Tassigny, FR-75775 Paris Cedex 16, France |
Disclosure of Conflict of Interest Statement is available upon request.
Copyright © 2013 Pro Pharma Communications International
Permission granted to reproduce for personal and non-commercial use only. All other reproduction, copy or reprinting of all or part of any ‘Content’ found on this website is strictly prohibited without the prior consent of the publisher. Contact the publisher to obtain permission before redistributing.
Source URL: https://gabi-journal.net/the-generic-pharmaceutical-industry-moving-beyond-incremental-innovation-towards-re-innovation.html
Copyright ©2024 GaBI Journal unless otherwise noted.
