Marketing Authorization Process Research Articles

Greening the Pharmaceutical Supply Chain

ABSTRACTThe pharmaceutical sector is critical from a life‐saving perspective. However, it also poses significant environmental challenges due to large consumptions of non‐renewable materials and energy, as also extensive by‐product and waste generation. Addressing these issues is paramount, though surprisingly, research on it has largely been theoretical, fragmented and incomplete. These shortcomings are sought to be addressed in this work where a comprehensive green supply chain management (GSCM) framework for the sector is first developed through a systematic literature review. It is then empirically assessed and validated for UK's pharmaceutical sector through 47 interviews and analyses of 112 corporate environmental reports that covered all key stakeholders. Innovative and Bio‐pharma players were found to be at the forefront of the greening efforts with generic players lagging behind. High levels of solvent recycling, AI‐based drug design, and emphasis on Ecopharmacovigilance were observed for the Innovative players. The key drivers for greening were found to be regulatory pressures (e.g., f‐gas, ERA, IED) and cost saving potential, with their influence being particularly greater for the Innovative players. Similarly, complex marketing authorization process, high investment requirements, lack of green culture and time pressure were revealed as the key barriers to greening. On the downstream side, lack of environment‐related regulatory guidance on prescribing and contradictory regulatory guidance on disposing unused/expired drugs were identified as factors having a significant impact on the environmental loading of drugs. Overall, the study findings can help assess the green readiness of the sector, as also develop stakeholder‐specific policy interventions and support mechanisms to increase green adoption.

Diagnostic gap due to missing patch test allergens—status quo and possible scenarios for mitigation

SummaryAccording to European Directive 2001/83/EC, test and therapeutic allergens are medicinal products in all Member States of the European Union. This applies equally to prick test and to patch test (PT) allergens (haptens). All test allergens commercially marketed in Germany are finished medicinal products requiring marketing authorization (MA). Currently, 211 PT substances are authorized in Germany, and an additional 59 are in an ongoing MA process and are marketable under a transitional provision until a decision on MA is made. The regulatory guidance (CMDh/399/2019) of the Co-ordination Group for Mutual Recognition and Decentralized Procedures—Human (CMDh), published in July 2020, specifies the regulatory requirements for different allergen products. Due to differences in origin and exposure, use, mode of action, and safety risks, the guideline clearly differentiates between products with active ingredients of biological origin (allergen extracts from natural source materials) and products with active ingredients of non-biological origin (hapten-based PT substances). Currently, guideline-compliant patch testing is hampered by the lack of numerous commercial PT allergens from the standard and special test series. Background and possible scenarios for mitigation are presented here.

Shifting application dates on cereal reduces pesticide transfer via subsurface drainage based on water flow forecasts during autumn applications.

Thanks to the changes in aquatic risk assessment within the Marketing Authorization (MA) process in France, the contamination of surface water through the subsurface drainage network is better accounted for. The measure adopted by Risk Regulations is to prohibit any use of selected pesticides on drained plots. Herbicide solutions on subsurface-drained plots are becoming scarce due to a limited number of innovations combined with the re-approvals process. Autumn weed management then becomes a major issue for winter cropping systems on drained plots. Unlike runoff prevention, few risk management measures are available to prevent the risks associated with drained plots. We analyzed data from La Jaillière, an ARVALIS experimental site (9 plots, 1993 to 2017), representative of scenario D5 from EU FOCUS Group, for four herbicides (isoproturon, aclonifen, diflufenican, flufenacet). Our study first demonstrates the relevance of the time application management measure by showing the decreasing trend in the transfer of pesticides in drained plots. The second result is to validate, still on the La Jaillière site, the hypothesis of a management measure based on an indicator of soil profile saturation before drainage flow (Soil Wetness Index). A conservative measure consisting in restricting pesticide applications during autumn, when the SWI is < 85% of saturation, reduces the risk by a factor of 4-12 for quantification above the predicted no-effect concentration (PNEC) and values of maximum or flow weight average concentrations (Cmax and CMP) by 70- and 27-fold, ratio of exported pesticide (Rexp) by 20-fold, and total flux by 32. This measure based on SWI threshold appears to be more efficient than those using other restriction factors. SWI could be easily calculated considering local weather data and soil properties for any drained field. This article is protected by copyright. All rights reserved.

The role of drug regulatory authorities and health technology assessment agencies in shaping incentives for antibiotic R&D: a qualitative study

BackgroundFew antibiotics have entered the market in recent years despite the need for new treatment options. Some of the challenges of bringing new antibiotics to market are linked to the marketing authorization and health technology assessment (HTA) processes. Research shows great variation in geographic availability of new antibiotics, suggesting that market introduction of new antibiotics is unpredictable. We aimed to investigate regulatory authorities’ and HTA agencies’ role in developing non-financial incentives to stimulate antibiotic research and development (R&D).MethodsWe conducted individual, semi-structured, stakeholder interviews. Participants were recruited from regulatory authorities (EMA and FDA) and HTA agencies in Europe. Participants had to be experienced with assessment of antibiotics. The data were analyzed using a deductive and inductive approach to develop codes and identify key themes. Data were analyzed using thematic analysis including the constant comparison method to define concepts, and rival thinking to identify alternative explanations.ResultsWe found that (1) interpretation of key concepts guiding the understanding of what type of antibiotics are needed vary (2) lack of a shared approach on how to deal with limited clinical data in the marketing authorization and HTA processes is causing barriers to getting new antibiotics to market (3) necessary adaptations to the marketing authorization process causes uncertainties that transmit to other key stakeholders involved in delivering antibiotics to patients.ConclusionsA shared understanding of limited clinical data and how to deal with this issue is needed amongst stakeholders involved in antibiotic R&D, marketing authorization, and market introduction to ensure antibiotics reach the market before resistance levels are out of control. Regulatory authorities and HTA agencies could play an active role in aligning the view of what constitutes an unmet medical need, and direct new economic models towards stimulating greater diversity in the antibiotic armamentarium.

Review on: Dossier submission in the European countries by using mutual recognition procedure and decentralized procedure

There is different procedure used to submit drug product for marketing authorization process. Mutual recognition procedure (MRP) is one of them. The European commission had published the procedure in consultation with competent authorities of member state. Using MRP, the applicant can apply for marketing authorization in one or more European Union nations. (MAH) who already holds authorization for a medical product in a EUROPEAN UNION (EU) member state can use the mutual recognition method to get authorization in additional EU member states. Directive 2004/27/EC established the decentralized procedure. Because the mutual recognition mechanism is also reliant on national authorities recognizing a first assessment done by one-member state, the distinction is that it only applies to pharmaceutical products that do not yet have a marketing authorization at the time of application.

P-225 HTA recommendations for biosimilars implementation in oncology field in MENA region

With the presence of concept of biosimilar products at last decade which defined by WHO as a biotherapeutic product which is similar in terms of quality, safety and efficacy to an already licensed reference biotherapeutic product. Implementation of practice framework for biosimilars implementation in oncology field putting the following objectives (patient’s safety, efficacy, health care resources, NOCEPO Effect and finally patient compliance and adherence) are challenges facing every health system. as model used to assess bioequivalence for generics does not apply to biosimilars. Since 2006, the EMEA has approved several biosimilars. With special nature of oncology field including (disease nature, patient profile) When WHO (World Health Organizations) developed HTA definition (the systematic evaluation of properties, effects and/or impacts of health technology. It is a multidisciplinary process to evaluate the social, economic, organizational and ethical issues of a health intervention or health technology. The main purpose of conducting an assessment is to inform policy decision-making. To solve a health problem and improve quality of life. Need was raised for developing evidence-based tools for informing and supporting for managing and overcoming previous challenges. The main objective for this study is to determine the how can HTA body support Health care decision makers The appropriate ways for establishing an evidence based frame work of biosimilars implementation in oncology field taking into consideration patient’s needs and health system needs. Integration between a systematic literature review and descriptive analysis of FDA, WHO EMA, local guidelines and local data from regulatory body for efficacy, safety, quality for biosimilars & ISPOR plus WHO guidelines for HTA plus 68 websites of HTA organizations. Of these, 50 HTA organisation websites had at least one document discussing biosimilar content. Interviews were conducted with Key stock holders for health system in Egypt, Tunisia, Jordan, and Saudi Arabia, United Arab Emirates, Spain, Turkey, Germany and industry representatives. A framework was proposed for biosimilars reimbursement decision making which included price and four non-price criteria. Pharmaceutical price (20% weight), quality module (33%), regulatory body approval for interchangeability (25%) post marketing studies (11%) clinical decision (11%). Biosimilars should not be treated as generic products. In terms of HTA there is a need to conduct a selection criteria specialized for biosimilars, pricing process should be on case by case basis due to the nature of technology of biosimilars. The need for evidence base data for switching from innovator products to biosimilars should be mandatory during marketing authorization process. An integration between regulatory body and HTA should be initiated as both bodies differ for their prospective and they need to integrate in order to minimize time consumption and unifying concepts for biosimilars. Effective assessment and evaluation for biosimilars the comparator of HTA should be different standard of care may and may be not contain the reference product or second generation of biosimilar. In the presence of validated and strong evidence comparing different generations of biosimilars should be conducted otherwise payers will facing a lot of challenging to conduct effective health policy.

Analysis of GMP for marketing authorization of ATMPs: comparison in the US, the EU, Japanand South Korea.

Aim: This study compared regulatory systems of competent authorities related to GMP for marketing authorization of advanced therapy medicinal products (ATMPs). Methods: Dossiers for GMP and regulations and guidelines for facilities and equipment were analyzed using gap analysis. The risk-based approach (RBA) and GMP inspection were evaluated with regulations and guidelines. Results: The dossier was similar for thecompetent authorities. However, whereasasite master file is required in the EU, Japan and South Korea, the US requires only a biologics license application. The regulations and guidelines of facilities and equipment emphasized preventing contamination. There are differences among the competent authorities in GMP inspection and RBAs. Conclusion: Differences among the competent authorities in the marketing authorization process related to GMP for ATMPs should be considered.

Authorization of Vaccines in the European Union

The current COVID-19 pandemic has had a vertiginous accelerating effect on the time from identification of a new virus to a vaccine being deployed. A key step in this journey, the marketing authorization process, is under intense scrutiny and time pressure. The marketing authorization is a necessary gateway that protects public health and provides healthcare professionals and the general public with reliable and relevant evidence reflected in the product information to allow the safe and effective use of these vaccines. Regulators have the expertise and the duty to evaluate vaccines’ benefits and risks and, importantly, monitor safety during clinical use. This evaluation is more important than ever during a pandemic—and must be allowed to be as thorough as ever.

Dynamics of patents, orphan drug designation, licensing, and revenues from drugs for rare diseases: The market expansion of eculizumab.

BackgroundThis study examines the dynamics of the eculizumab patenting, orphan designation, and marketing authorization process in different countries and regulatory systems and analyzes drug revenues since its first marketing authorization.MethodsA retrospective case study was conducted. Multiple information sources were used to: determine the status of eculizumab patents; examine the designation of orphan drug status by US, European, Japanese, and Brazilian regulatory authorities to determine registration status and approved clinical indications; estimate the prevalence of associated clinical conditions; investigate the history of the drug manufacturer, Alexion Pharmaceuticals, Inc., and its financialized business model; and examine global eculizumab sales revenues since its first marketing authorization.ResultsOur search yielded 32 patent families divided into 98 applications. The first patent granted was filed in 1995 by Alexion Pharmaceuticals, Inc. in the US. Eculizumab has always been as an orphan drug, except in the Brazilian regulatory agency. All clinical indications approved thus far refer to rare diseases (e.g., paroxysmal nocturnal hemoglobinuria syndrome, atypical hemolytic-uremic syndrome, refractory and generalized myasthenia gravis, and neuromyelitis optica spectrum disorder). Alexion’s revenues amounted to more than US$25 billion between 2007 and 2019, showing a growing trend. Eculizumab led sales from the beginning, being the only product in the company’s portfolio until 2015. In 2019, the drug accounted for 79.1% of all revenues.DiscussionOur findings show that a strategy focused on obtaining orphan drug designation, expanding therapeutic indications and the geographic range of marketing approvals, extending monopoly periods, and prioritizing public procurement niches has enhanced revenues and helped the company achieve leadership in a highly specific and profitable market.

Regulatory reliance to approve new medicinal products in Latin American and Caribbean countries.

ABSTRACTObjective.To describe the current status of regulatory reliance in Latin America and the Caribbean (LAC) by assessing the countries’ regulatory frameworks to approve new medicines, and to ascertain, for each country, which foreign regulators are considered as trusted regulatory authorities to rely on.Methods.Websites from LAC regulators were searched to identify the official regulations to approve new drugs. Data collection was carried out in December 2019 and completed in June 2020 for the Caribbean countries. Two independent teams collected information regarding direct recognition or abbreviated processes to approve new drugs and the reference (trusted) regulators defined as such by the corresponding national legislation.Results.Regulatory documents regarding marketing authorization were found in 20 LAC regulators’ websites, covering 34 countries. Seven countries do not accept reliance on foreign regulators. Thirteen regulatory authorities (Argentina, Colombia, Costa Rica, Dominican Republic, Ecuador, El Salvador, Guatemala, Mexico, Panama, Paraguay, Peru, Uruguay, and the unique Caribbean Regulatory System for 15 Caribbean States) explicitly accept relying on marketing authorizations issued by the European Medicines Agency, United States Food and Drug Administration, and Health Canada. Ten countries rely also on marketing authorizations from Australia, Japan, and Switzerland. Argentina, Brazil, Chile, and Mexico are reference authorities for eight LAC regulators.Conclusions.Regulatory reliance has become a common practice in the LAC region. Thirteen out of 20 regulators directly recognize or abbreviate the marketing authorization process in case of earlier approval by a regulator from another jurisdiction. The regulators most relied upon are the European Medicines Agency, United States Food and Drug Administration, and Health Canada.

Were it business opportunities or hidden risks: Observations on clinical trials and marketing authorizations of Gilead Science's remdesivir in China.

New drugs against the in COVID-19 pandemic are urgently needed. Gilead Science's remdesivir has been introduced to China through special approval procedures, and was directly conducting the Phase III clinical trial. As expected, the marketing authorization process was completed soon. The drug brought hope to patients as well as business opportunities to companies. However, we must pay attention to the patent competition, generic drug competition and other unfair competition that remdesivir may face in China. China also needs to strengthen the innovation ability and international cooperation ability of local pharmaceutical companies by taking advantages of the opportunity to introduce remdesivir.

Involvement of oxidative stress in the sensitivity of two algal species exposed to roxithromycin.

Algal species Raphidocelis subcapitata and Chlorella vulgaris are commonly used to test the chemicals with an antibacterial mode of action during marketing authorization process. However, significant differences in the sensitivity toward antibiotic exposure have been reported. The selection of an inappropriate test species would thus underestimate the environmental hazard of target chemicals and pose a potential threat to the ecosystem. Since oxidative stress is a crucial factor determining the inhibition of algal growth, an investigation on oxidative stress and antioxidant defense mechanisms in these two species was performed to explore its roles in species sensitivity. Here, roxithromycin (ROX), a macrolide antibiotic extensively used to treat respiratory, urinary and soft tissue infections, was used for testing. After 7 days exposure to ROX at the low (0.01 mg L-1) and high (0.09 mg L-1) concentrations, R. subcapitata was inhibited while the growth of C. vulgaris was stimulated. We investigated the roles of oxidative stress in algae by measuring the oxidative stress biomarkers (MDA), non-enzymatic antioxidants (GSH), and antioxidant enzymes (SOD, CAT, GP, GST). The results suggested that when the growth of algae is inhibited, MDA content as well as activities of oxidative stress enzymes would increase, and thus, activating the antioxidant system. On the contrary, it was inferred that when the growth is stimulated, MDA content and oxidative stress enzymes activities would decrease.

Evaluation of the Performance of the Turkish Regulatory Agency: Recommendations for Improved Patients' Access to Medicines.

BackgroundThis study was to evaluate the Turkish regulatory review process and timelines between 2016 and 2018 with a view to assess the changes that had taken place since the previous study, which evaluated the Turkish review processes and timelines 2013 to 2015.MethodsData related to the Turkish Medicines and Medical Devices Agency (TİTCK) organizational structure and general information were collected from publicly available sources. A standard questionnaire was then used to collect data with the aim of identifying the TİTCK’s review practices and key milestones for the marketing authorization process. Subsequently, a comparison with the previous study was conducted to identify the key changes and developments that had taken place from 2015- 2018.ResultsThe TİTCK has made considerable efforts to improve its regulatory capacity since 2016, which has contributed to the overall decrease in the agency review times. The overall median approval time for new active substances; however, increased from 529 calendar days (2016) to 663 calendar days (2018), with the review time in the agency decreasing from 408 calendar days to 326 calendar days, while the company time increased from 137 to 268 calendar days, respectively, over this period.ConclusionsFor the TİTCK to become an international reference agency, they will need to fully implement good review practices and a structured framework for benefit-risk assessment and decision making; consider implementing verification and abridged reviews based on a reliance model and expedite the PIC/S mutual recognition process as well as become a full member of the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH).

OP163 European Network for Health Technology Assessment Joint Action 3 Relative Effectiveness Pilots: Pharma Company Experience

Introduction:More than 50 HTA agencies evaluate the clinical value of medicines in Europe, resulting in duplication of work for HTA agencies and manufacturers, and lengthy and variable time to reimbursement for patients across Europe. A consistent, single European relative clinical scientific benefit assessment of medicines could become a key element in ensuring patients get equitable and timely access across Europe. The European Network for Health Technology Assessment (EUnetHTA) is responsible under Joint Action 3 (JA3, 2016–2020) to pilot more than 30 Relative Effectiveness Assessments (REAs) of medicines. The first EUnetHTA JA3 REA pilots are now being completed and Roche, with its participation in the REA pilot for alectinib, has gathered relevant experience.Methods:The goal of this analysis is to summarize and reflect upon the experience with one of the first EUnetHTA REA assessments in JA3. The authors also propose potential process improvements.Results:The experience with the alectenib REA shows that EUnetHTA processes have improved compared to JA2. The timing of the assessment has been aligned with the EU regulatory marketing authorization process by shortening the duration of the scoping phase. More EUnetHTA members than in JA2 seem to be committed to use the reports in national HTA, pricing and reimbursement processes. At the same time, the REA pilots have identified other areas that could benefit from further refinement, for example the active engagement of patient group representatives and clinical experts, rules and principles related to the handling of confidential information.Conclusions:Based on the limited number of REA pilots for medicines it is too early to draw final conclusions on the state of EU-level collaboration. But first signals indicate a positive development compared to REA pilots conducted in JA2. Interim evaluations are recommended to assess progress, and capture learnings for future pilots.

Rheumatoid Arthritis Patients’ Perspectives On The Value Of Patient Preferences In Regulatory Decision-Making During Drug Development: A Qualitative Study

To explore how Rheumatoid Arthritis (RA) patients value the use of patient preferences in regulatory decision-making during drug development. Five semi-structured individual interviews with RA patients were conducted to gather first insights into patients’ knowledge and opinions on patient preference studies, drug development and regulatory decision-making. The results of the individual interviews were used to draft and validate the topics for the interview-guide used during four focus groups. Patients were purposively sampled from RA patients who were registered at the Swedish RA patient organization and living in Stockholm or Uppsala. Each focus group consisted of 6-8 patients (n=31 in total). All interviews were audio-recorded, transcribed verbatim and analysed using content analysis Patients think their preferences should be used in the marketing authorization processes since it is helpful to understand what the end-users of the drug want. While patients think their preferences matter, they also shared some doubts. Firstly, patients feel that preferences can only be measured when patients are well-informed about the drug and its’ different aspects. Secondly, patients are quite unsure whether regulators can rely on their stated preferences since, at this moment, they feel they might not be informed enough. Thirdly, they are unsure how and where in the marketing authorization process, patient preference information is most important to be included. According to RA patients, their preferences are valuable in regulatory decision-making during drug development. However, regulators have reasons to increase awareness among patients about why their preferences are useful, inform them about how their preferences will be measured and to ensure that all patients are well-informed when they are asked for their preferences. Acknowledgement; This work has received support from the EU/EFPIA Innovative Medicines Initiative [2] Joint Undertaking PREFER grant n° 115966.

Scientific Evidence in Health Technology Assessment Reports: An In-Depth Analysis of European Assessments on High-Risk Medical Devices

BackgroundThe aim of this study was to examine the scientific evidence on clinical effectiveness and safety used in health technology assessments (HTAs) of high-risk medical devices (MDs) in Europe. MethodsWe applied a systematic approach to identify European institutions involved in HTA and to select reports assessing MDs considered high-risk according to the definition in the new German health care regulation §137h. Reports published between 2010 and 2015 were considered in our subsequent analysis. We used a structured tool based on widely accepted methodologic principles from Drummond’s framework to extract key information on the clinical evidence considered in the reports. ResultsOut of 1376 identified reports, 93 were eligible for analysis. All reports based their assessment primarily on direct evidence, in most cases (68%) identified through an independent systematic literature search. In more than half the identified studies considered in the reports, clinical evidence for demonstration of effectiveness and safety was of moderate or low quality. Even when systematic reviews and randomized controlled trials were available for assessment, most studies showed an unclear or high risk of bias. ConclusionsThis study confirms that the quality of scientific evidence used in HTA of high-risk MDs is low and therefore the use of evidence needs improvement. The European Commission recently updated the regulation on MDs but mainly focused on the safety of materials and the CE (Conformité Européene [European Conformity]) mark. Our results show that additional changes are necessary, specifically with regard to the marketing authorization process of MDs, with stricter quality requirements based on methodologically robust trials, possibly in combination with other evidence sources.

Regulating phage therapy: The biological master file concept could help to overcome regulatory challenge of personalized medicines.

In a note published in The Lancet in December 1915, Frederic Twort described the discovery of an infectious, filterable agent that causes the glassy transformation and eventual killing of bacteria, now identified as Staphylococcus hyicus [1]. Two years later, Felix d'Herelle independently described an invisible microbe antagonistic to dysentery bacilli in a note to the Comptes Rendus de l'Academie des Sciences [2]. These two reports are the first published descriptions of bacteriophages, a term coined by d'Herelle, who foresaw the therapeutic potential of these newly identified bacteriolytic agents. > The key issue is whether phage therapy medicinal products (PTMPs) require a marketing authorization or not. Yet, phage therapy, despite varying degrees of success during the 20th century, never made it into widespread clinical use owing to the discovery of antibiotics [3]. However, the increasing antibiotic resistance among major pathogens such as Staphylococcus or Mycobacterium has become a critical public health problem—in the European Union (EU) alone, around 25,000 patients die each year from an infection with drug‐resistant bacteria (http://ecdc.europa.eu/en/publications/publications/0909\_ter\_the\_bacterial\_challenge\_time\_to\_react.pdf). Although difficult to estimate, the annual global death toll attributable to antimicrobial resistance might range from the hundreds of thousands to as much as millions in the coming decades (https://amr-review.org/sites/default/files/AMR%20Review%20Paper%20-%20Tackling%20a%20crisis%20for%20the%20health%20and%20wealth%20of%20nations\_1.pdf). In light of this growing health crisis, phage therapy has attracted renewed interest as an alternative to antibiotics [3]. ### Regulatory challenges for phage therapy However, this reemergence raises regulatory concerns. There has been intense discussion on how to classify phage‐based therapeutics within the EU's regulatory framework [4], [5], [6] with some consensus among Members States' regulatory authorities and the European Medicines Agency that these would be regulated as biological medicinal products [7]. Nonetheless, positions still vary because the current medicinal product regulation is not well suited for this unorthodox therapeutic …

Guideline on allergen-specific immunotherapy in IgE-mediated allergic diseases: S2k Guideline of the German Society for Allergology and Clinical Immunology (DGAKI), the Society for Pediatric Allergy and Environmental Medicine (GPA), the Medical Association of German Allergologists (AeDA), the Austrian Society for Allergy and Immunology (ÖGAI), the Swiss Society for Allergy and Immunology (SGAI), the German Society of Dermatology (DDG), the German

The present guideline (S2k) on allergen-specific immunotherapy (AIT) was established by the German, Austrian and Swiss professional associations for allergy in consensus with the scientific specialist societies and professional associations in the fields of otolaryngology, dermatology and venereology, pediatric and adolescent medicine, pneumology as well as a German patient organization (German Allergy and Asthma Association; Deutscher Allergie- und Asthmabund, DAAB) according to the criteria of the Association of the Scientific Medical Societies in Germany (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften, AWMF).

Relations between SPC and data exclusivity

Supplementary protection certificates for medicinal products for human use (SPC) and data exclusivity are legal instruments that provide protection for pharmaceuticals. They differ, however, with respect to the rationale, requirements and scope of their protection. An SPC does not prolong the basic patent, but extends protection conferred by the basic patent, within the limits prescribed by the marketing authorization for a given medicinal product, which is usually different from the scope of protection granted by the basic patent. The aim is to provide an additional period of protection in the case where a pharmaceutical marketing authorization process was particularly long. This is to allow a pharmaceutical company that holds the basic patent to recoup the investment made in research and development of the pharmaceutical. An SPC rewards a product – a patented active ingredient or a combination of active ingredients, as opposed to the first submitted regulatory data as in the case of data exclusivity. Data exclusivity is a “quasi” – intellectual property right which prevents health authorities responsible for granting marketing authorizations from relying on the original data submitted by the first market entrant as well as preventing subsequent applicants from cross-referring to the original data. Data exclusivity should be distinguished from market exclusivity. Market exclusivity means that a subsequent market entrant may not market a particular product on which a marketing authorization has been issued, irrespective of the fact whether he refers to data submitted by the first market entrant or he has generated the data himself. Data exclusivity should neither be confused with data protection, as there are other legal instruments, such as trade secrets, which serve to protect undisclosed, confidential know-how. Complex relationships between SPCs, data exclusivity and market exclusivity may occur i.e. the scope and period of protection conferred by them may overlap or complement each other. In the latter case they enhance the overall protection for a given medicinal product. They are even more important during the period when no other type of protection is available, and there is only data exclusivity or SPC protection. Due to the interesting interrelations between SPCs and data exclusivity they are both worth a profound analysis. The paper aims to touch upon the importance of data exclusivity in the light of other legal protection instruments available, such as an SPC.

Efficacy and Quality of Antibacterial Generic Products Approved for Human Use: A Systematic Review

Concerns have recently emerged about the efficacy and the quality of antibacterial generic products approved for use in humans. We searched Medline and Embase for original research articles on antibacterial generic products published in English or French before July 2013. We selected 37 original research articles: 15 on β-lactams, 10 on glycopeptides, and 12 on other antibacterial agents. The majority of articles (73.0%) were published during 2008-2012. Study designs included analytical chemistry (n = 9), in vitro susceptibility studies (n = 14), animal experiments (n = 6, including 5 using the neutropenic mouse thigh infection model), and clinical studies in humans (n = 15). Of the 37 studies, 14 (37.8%) suggested that some generic products may be inferior to the innovator in terms of purity (n = 2), in vitro activity (n = 3), in vivo efficacy in experimental models (n = 4), clinical efficacy (n = 2), taste (n = 2), or compliance and acceptability in children (n = 1). The majority of in vitro studies (78.6%) found no significant difference between generic products and the innovator. Most (5/6) in vivo studies suggesting a difference between generic products and the innovator were performed in an animal model that is not validated for the evaluation of the efficacy of antibacterial agents. The level of evidence was constantly low in clinical studies. Published data on antibacterial generic products are limited and heterogeneous, thus precluding any attempt to generalize the study results. This systematic review suggests that additional evidence would be needed before considering a revision of the marketing authorization process for antibacterial generic products.