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European Journal of Clinical Pharmacology

, Volume 74, Issue 6, pp 811–818 | Cite as

A comparison of new drugs approved by the FDA, the EMA, and Swissmedic: an assessment of the international harmonization of drugs

  • Minette-Joëlle ZeukengEmail author
  • Enrique Seoane-Vazquez
  • Pascal Bonnabry
Pharmacoepidemiology and Prescription

Abstract

Introduction

This study compared the characteristics of new human drugs approved by the Food and Drug Administration (FDA), the European Medicine Agency (EMA), and Swissmedic (SMC) in the period 2007 to 2016.

Methods

The list of new drugs and therapeutic biologics approved by the FDA, the EMA, and SMC in the period 2007 to 2016 was collected from websites of those agencies. The study included regulatory information, approval date, and indication for each drug. Descriptive statistical t tests and x2-tests were performed for the analysis.

Results

From 2007 to 2016, 134 new drugs were approved by all three regulatory agencies. Overall, 66.4% of the drugs were first approved by the FDA, 30.6% by the EMA, and 3.0% by SMC. The difference in approval dates between SMC and the EMA, SMC and the FDA, and the FDA and the EMA were statistically significant. The indications approved by the FDA, the EMA, and SMC for the same drugs were similar in content for 23.1% drugs and different in 76.9% of the drugs. Significant differences in indications existed between the FDA and SMC and the FDA and the EMA, but not between the EMA and SMC.

Conclusion

There were differences in the characteristics of new drugs approved by the EMA, the FDA, and SMC in the period 2007–2016. Overall, two thirds of the new drugs were first approved by the FDA. Differences in indications were found in three out of four new drugs approved by the three regulatory agencies. Despite international drug regulation harmonization efforts, significant differences in the characteristics of new drugs approved by different agencies persist.

Keywords

US Food and Drug Administration European Medicines Agency Swissmedic Drug approval Drug labeling Pharmacoepidemiology 

Introduction

Since 1990, the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) collaborates with national and regional agencies to harmonize the requirements for registration to ensure drug efficacy, safety, and high quality [1]. Despite the trend towards regulatory harmonization, differences between approval decisions of regulatory agencies still exist [2, 3, 4, 5, 6, 7, 8].

Disparities in drug approvals among drug regulatory agencies have been attributed to differences in approval procedures [2, 9, 10], evaluation of drug efficacy [2, 11, 12], approaches to decision-making [5, 13, 14, 15], and post-marketing approaches [4, 16, 17, 18, 19, 20, 21]. Additionally, regulatory schemes are evolving quickly, affecting researchers, health professionals, and patients [2, 22, 23, 24].

The Food and Drug Administration (FDA) is responsible for the approval of new drugs and biologics in the USA. The new drug and new biologic applications submitted by pharmaceutical companies provide information that the FDA uses to assess the drug efficacy, safety, and risk/benefit ratio. Furthermore, through the application, the FDA determines if the sponsor drugs proposed labeling is appropriate. In response to the need for new therapies for unmet medical needs, the US Congress has provided the FDA with four regulatory designations intended to facilitate timely drug approvals: priority review, accelerated approval, breakthrough therapy, and fast-track [25, 26, 27]. The standard review process is used for drugs that do not fall into one of those designations.

In the European Union (EU), new pharmaceutical products can be approved using the European Medicines Agency (EMA) centralized procedure or by national procedures of individual EU member countries. The EU centralized procedure is mandatory for certain classes of human drugs, including those for treatment of HIV/AIDS, oncology, diabetes, neurodegenerative disorders, and autoimmune and viral disease and those derived from biotechnology processes. The EMA through the Committee for Medicinal Products for Human Use has four procedures to review new drugs: standard assessment, accelerated assessment, conditional approval, and PRIME designation [26, 27, 28].

Swissmedic (SMC) is the agency responsible for the approval and regulation of drugs and biologics in Switzerland (CH). For a drug containing a new active substance (NAS), sponsors must apply to get the commercial authorization to distribute the medicine in the country. Requirements for NAS are contained in the Federal Ordinance on Drug Requirements (OEMéd) [29]. In addition to the standard review, SMC has processes for accelerated review, pre-announced review, orphan medicine review, and international mutual recognition [30, 31].

Previous studies compared regulatory agencies’ review time and time gaps in approval of new drugs [5, 22, 32, 33, 34], and in indications approved by the EMA and the FDA [2, 9, 35] and SMC, the EMA, and the FDA [13, 36]. To the authors’ knowledge, only one study comparing the FDA and the EMA provided a comprehensive comparative analysis of differences in the characteristics of approved drugs [5].

This study compared differences in the characteristics of new drugs and therapeutic biologics approved by the FDA, the EMA, and SMC in the period 2007 to 2017.

Material and methods

The list of all new drugs and therapeutic biologics approved by the FDA in the period 2007 to 2016 was collected from the electronic versions of the FDA-approved drug products with therapeutic equivalence evaluations (Orange Book-OB) and Drugs@FDA [25]. Drug labels were extracted from the DailyMed (DM) website maintained by the US National Library of Medicine [37]. The list of drugs approved using the EU centralized procedure was extracted from the EMA’s website [28]. The drug information was derived from the European Public Assessment Reports (EPAR) available on the EMA’s website [28]. The list of drugs authorized for marketing in CH was extracted from the SMC’s website [31], while the labeling information was collected from the Swiss medicinal product information (AIPS) website [38] and the Federal Office of Public Health [39].

The therapeutic classes were derived from the Anatomical Therapeutic Chemical (ATC) classification system published by the World Health Organization Collaborating Centre for Drug Statistics Methodology [40].

The study analyzed new human drug and therapeutic biologics approved by the FDA, the EMA, and SMC; other biologic products including blood, vaccines, phytotherapeutic medicines, anthropomorphic drugs, allergenics, tissues, and cellular and gene therapies were excluded from the analysis.

The dataset for analysis included generic name, active ingredient, ATC class, application type (New Drug Application—NDA or Biologic License Application -BLA), approval date, and submission type. The FDA, the EMA, and SMC do not provide a definition of the term “indication” [25, 28, 31]. In this study, we consider indication as the purpose of the use of a drug.

The information collected from the indication sections of the label/EPAR/AIPS included indication, restrictions of use, limitations of use, and outcomes limitations. Indication discrepancies for each drug approved by the three regulatory agencies were categorized and described. The indication information was considered similar when the differences only were in wording or organization of the information.

Labeled restrictions to a drug indication were classified in disease class or stage, maintenance treatment or symptoms, pediatric use, previous therapy failure (patients must fail one of more alternative therapies before using the drug, duration to decide that the therapy is failed, restricted diet conjunction), inappropriate alternative therapy (alternative therapies are contraindicated or not recommended), pharmacogenomics, patient therapy history (use of certain therapies prior to the use of the drug), use as monotherapy or combination, and use for prevention or treatment [5].

Limitation of drug use included any constraints in drug utilization that was mentioned in the label (i.e., not used for certain disease, diseases stage, specific function, certain gene, adjuvant treatment, in combination, other organs, drug substitution or if the patient is asymptomatic) [5].

An indication was considered to contain an outcome limitation if the label contained any description about limitation in the drug safety, limitation in data availability, or if ongoing efficacy trials were mentioned [5].

Other information included in the indication section of the approved label/EPAR/AIPS that did not define, restrict, limit, or qualify the evidence for the indication was not included in the analysis [5].

The study also compared the posology, strength, dosage form, and route of administration of the drugs approved by the three regulatory agencies.

The regulatory time lag for the drug approval was calculated as the difference in the number of months between the first approvals dates as reported by each regulatory agency. Outliers were evaluated using QQ-plots and by measuring the skewness of the different distributions.

The assessment of differences in drug characteristics was performed by two researchers, and discrepancies were resolved by consensus.

All data were extracted using Python 3 and organized in csv files. Descriptive statistics analyses were performed for all variables. Statistics Student’s tests (t tests) and Pearson’s chi-squared tests (x2-tests) were used to assess differences in averages and proportions, respectively. The significant level was set a priori to a p value of 0.05. Analyses were performed using Python 3 and Microsoft Excel 2016.

Results

The FDA, the EMA, and SMC approved 134 new drugs in common during the period 2007–2016 (Fig. 1), including 100 (74.6%) NDAs and 34 (25.4%) BLAs. The largest number of drugs approved by the three agencies was antineoplastic and immunomodulating agents (41.0%), followed by alimentary tract and metabolism drugs (14.2%) and anti-infectives for systemic use (8.2%) (Table 1).
Fig. 1

Flowchart of selection of the drugs included in the analysis. ATC anatomical therapeutic chemical, LS Liste des spécialités (list of drugs reimbursed by the compulsory Swiss insurance), G generics, ANDA abbreviated new drug application, NME new molecular entitie, BLA biologic license application. Submission class code type: 1 = new molecular entity; 2 = new active ingredient; 3 = new dosage form; 4 = new combination; 5 = new formulation or new manufacturer; 6 = new indication (no longer used); 7 = drug already marketed without approved NDA; 8 = partial Rx to OTC switch; 9 = new indication submitted as distinct BLA, consolidated. *ATC codes were not available for some drugs

Table 1

Therapeutic class of the therapeutic biologic applications (BLA) and new drug applications (NDA) approved by the by the FDA, the EMA, and SMC between 2007 and 2016

 

BLA

NDA

Total (%)

Antineoplastic and immunomodulating agents

22

33

55 (41.0%)

Alimentary tract and metabolism

4

15

19 (14.2%)

Anti-infective for systemic use

11

11 (8.2%)

Nervous system

 –

10

10 (7.5%)

Blood and blood forming organs

2

7

9 (6.7%)

Cardiovascular system

1

8

9 (6.7%)

Respiratory system

1

6

7 (5.2%)

Genito urinary system and sex hormones

5

5 (3.7%)

Various

3

3 (2.2%)

Musculoskeletal system

2

1

3 (2.2%)

Sensory organs

2

2 (2.2%)

Systemic hormonal preparations, excl. sex hormones and insulins

1

1 (0.7%)

Total

34

100

134 (100.0%

The FDA approved first 89 (66.4%) of all drugs, 67 (75.3%) of NDA, and 22 (24.7%) of BLA. The EMA approved first 41 (30.6%) of the drugs and 30 (73.2%) of the NDAs. The SMC approved first four (3.0%) of the drugs and three (75.0%) of the NDAs.

Drugs that had an approval time lag below − 45 months or above + 45 months were removed from the study, resulting in five, seven, and six outliers removed when comparing the time lags between the EMA and the FDA, SMC and the FDA, and SMC and the EMA, respectively. All distributions of time lag have skewness parameters between − 1 and + 1, and the QQ-plots showed a distribution much closer to normal after outlier removal.

New drugs are approved by the FDA and the EMA an average of 10 ± 12.4 months (median = 8.6 months) (p < 0.0001) and 7.4 ± 9.8 months (median = 5.4 months) (p < 0.0001) earlier than SMC (Fig. 2). The average time lag from FDA to EMA approval was 2.5 ± 11.6 (median = 3.6 months) (p < 0.017).
Fig. 2

Time lag for new drug and therapeutic biologic applications approved by the FDA, the EMA and SMC from 2007 to 2016

Overall, 65 (48.5%) of the drugs approved by the three agencies had at least one difference in posology, strength, dosage form, or route of administration. Differences in posology were found in 24 (17.9%) of the drugs, and for 8 (6.0%) drugs, the posology was different in the three agencies.

Differences in strength were found in 60 (44.8%) of the approved drugs. Among those, the strength of 22 (16.4%) drugs was higher for the FDA and SMC compared to the EMA, and the strength of 15 (11.2%) drugs was higher in the FDA compared to the EMA and SMC. The SMC had more available dosages than the FDA and the EMA in two (1.5%) drugs (brivaracetam and vortioxetine). No differences were found in the route of administration.

The trade name was the same for 98 (73.1%) of the drugs approved by the 3 agencies. There were 31 (23.1%) drugs that had the same trade name approved by the EMA and SMC and a different trade name approved by the FDA.

The indications approved by the FDA, the EMA, and SMC were different for 103 (76.9%) drugs. Compared to SMC, indications approved by the FDA and the EMA were different for 87 (64.9%) and 58 (43.3%) of the drugs approved, respectively. Concerning the FDA and the EMA, indications were different in 98 (73.1%) drugs.

The indications approved by SMC and the EMA were different from those approved by the FDA in 37 (27.4%) drugs, with most of these differences related to restrictions in use (24 drugs) including disease class, previous failed therapy, or inappropriate alternative therapy as well as in combination or monotherapy. SMC was more restrictive in use than the EMA and the FDA for 14 (10.4%) drugs, mostly due to restrictions in disease stage, use in combination or monotherapy, and failure of previous therapies.

There were 112 (83.6%) drugs with differences in indication restrictions, limitation of use, and outcome limitations among the 3 agencies. Differences in restrictions of use were found in 81 (60.4%) drugs.

Differences in pediatric indications were found for 25 (18.7%) approved drugs. The FDA had the largest number of drugs with approved pediatric indication (20, 14.9%), followed by the EMA (19, 14.2%) and SMC (16, 11.9%). Most differences in pediatric indication were related to age and weight (12, 9.0%).

Limitations of use were different for 38 (28.3%) drugs. The FDA included more limitations of use that the EMA and SMC for 31 (23.1%) drugs. These differences in limitations included caution use for certain patients, contraindication for certain diseases, and combination use.

Differences in outcome limitations were found in 22 (16.4%) drugs. The FDA had more outcome limitations than SMC and the EMA, including mentions to limited data availability and ongoing clinical trials or efficacy trials. Overall, differences in restrictions of use, limitations of use, and outcomes limitations varied according to ATC therapeutic class (Table 2). Antineoplastic and immunomodulating agents had the highest percentage of differences (55, 35.2%).
Table 2

Differences on indication, restrictions of use, limitations of use, outcomes limitation, and any differences by therapeutic classes for new drugs approved by FDA, the EMA, and SMC between 2007 and 2016

 

Number of new Drugs

Differences

Indication

Restrictions of use

Limitations of use

Outcomes limitation

Any differencea

Antineoplastic and immunomodulating agents

55

42 (40.8%)

33 (40.7%)

11 (28.2%)

10 (45.5%)

138 (35.2%)

Alimentary tract and metabolism

19

16 (15.5%)

12 (14.8%)

9 (23.1%)

1 (4.5%)

59 (15.1%)

Anti-infective for systemic use

11

10 (9.7%)

8 (9.9%)

5 (12.8%)

3 (13.6%)

39 (9.9%)

Nervous system

10

6 (5.8%)

6 (7.4%)

0 (0.0%)

3 (13.6%)

34 (8.7%)

Blood and blood forming organs

9

8 (7.8%)

6 (7.4%)

3 (7.7%)

1 (4.5%)

29 (7.4%)

Cardiovascular system

9

8 (7.8%)

6 (7.4%)

1 (2.6%)

4 (18.2%)

28 (7.1%)

Respiratory system

7

7 (6.8%)

6 (7.4%)

7 (17.9%)

0 (0.0%)

34 (8.7%)

Genito urinary system and sex hormones

5

1 (1.0%)

0 (0.0%)

2 (5.1%)

0 (0.0%)

9 (2.3%)

Various

3

1 (1.0%)

1 (1.2%)

0 (0.0%)

0 (0.0%)

7 (1.8%)

Musculoskeletal system

3

2 (1.9%)

2 (2.5%)

1 (2.6%)

0 (0.0%)

10 (2.6%)

Sensory organs

2

1 (1.0%)

1 (1.2%)

0 (0.0%)

0 (0.0%)

3 (0.8%)

Systemic hormonal preparations, excl. sex hormones and insulins

1

1 (1.0%)

0 (0.0%)

0 (0.0%)

0 (0.0%)

2 (0.5%)

Total

134

103 (100.0%)

81 (100.0%)

39 (100.0%)

22 (100.0%)

392 (100.0%)

aIncluding differences in posology, strength, dosage form, or route of administration

The EMA granted conditional approval to four antineoplastic and immunomodulating agents that were first approved by the FDA. The indication for daratumumab was different between the FDA and the two other agencies. The FDA approved daratumumab for use in combination as a second line of treatment of myeloma, while the EMA and SMC approved daratumumab for use in monotherapy and as a last line of therapy.

Idelalisib is not indicated for first-line treatment by the FDA and SMC, but the EMA approved that this drug as first-line treatment in the presence of a mutation in patients who are not eligible for any other therapies. The drug was approved in July 2014 by the FDA, September 2014 by the EMA and January 2015 for SMC.

Pirfenidone is indicated for the treatment of idiopathic pulmonary fibrosis (IPF) by the FDA and SMC and for mild to moderate IPF by the EMA. This drug was first approved by the EMA.

Trametinib was approved for use as a single agent or in combination by the FDA (2013) and the EMA (2014), but SMC (2016) approved this drug only for use in combination. Furthermore, the strength 1 mg only exists in the USA and not in the EU and CH markets.

Discussion

This study is the first comprehensive analysis evaluating differences in the characteristics of new drugs approved by the FDA, the EMA, and SMC using public available information. Significant differences were found in the characteristics and approval time of new drugs approved by the three regulatory agencies. These differences persist despite current drug regulation harmonization efforts [1].

The pharmaceutical sector faces scientific, technological, and regulatory challenges, and regulatory agencies need to adapt their decision-making processes and criteria to ensure adequate assessment of drug efficacy and safety. Differences in review processes, approval criteria, and approval time may affect sponsor companies’ selection of the first regulatory agency to submit new drugs for review [25, 28, 31, 41, 42, 43, 44]. This study confirms the results from prior studies comparing the FDA and the EMA [5, 32, 34] and SMC [13, 45] that also found that most new drugs were approved first by the FDA [46], particularly oncology drugs [2, 6, 11, 12, 47].

Some companies may have the perception that the review and approval process is lengthier and more restrictive (based on restrictions placed on the initial label) in SMC than in other regulatory agencies [13]. This perception may be driven by the fact, confirmed by this study, that SMC is more specific in the label description than other agencies [13].

Discrepancy on indications and other drug characteristics (administration route, dosage form, strength, and posology) reflect in part differences in regulatory policies for review and approval [35]. In addition, the results of clinical studies conducted according to common technical documents and submitted in support of new drug applications can be interpreted differently by the different agencies. Pharmaceutical companies may also submit applications with different drug information and proposed drug labels depending on the regulatory agency. Thus, the observed differences likely reflect different regulatory agency requirements and approval processes and different sponsor marketing strategies tailoring the drug characteristics to each market.

This study also confirms the results of previous research that found significant discrepancies in the characteristics of the drugs approved by different regulatory agencies. A previous study comparing EMA and FDA approvals between 2000 and 2008 found that 93.3% of the antimicrobial drugs assessed contained major and minor differences between both agencies [35]. Another study also assessing FDA and EMA oncology drug approvals between 1995 and 2008 found discrepancies in 47.4% of the drugs [12]. More recently, a study assessing priority review drugs approved by the FDA and the EMA between 1999 and 2011 found substantial discrepancies in indications and other drug characteristics between the FDA and the EMA [5].

Previous studies also found that the SMC had higher percentage of discrepancies in the characteristics for new drugs when compared with the FDA than with the EMA. A study assessing differences in 63 drugs approved by the FDA, the EMA, and SMC in the period 2006 and 2010 found differences in indication in 35% of the drugs approved by SMC and the FDA and 13% of the drugs approved by the EMA and SMC [13].

Differences in characteristics of drugs approved by different agencies may have direct consequences on clinical practice, including timely access to new drugs. Differences in drug indications, restrictions of use, limitation of use, and outcomes limitations may result in differences in clinical guidelines, clinical practice, public funding, pricing policies, drug utilization, and patient outcomes. Prescribers can also decide to use drugs off-label following the recommendations of a regulatory agency from a different jurisdiction [48]. Off-label use is prevalent in pediatric populations and certain therapeutic classes such as oncology [49]. Thus, off-label use may reduce the potential clinical consequences of the differences in drug indications and characteristics found in the study.

International drug regulation harmonization effort are important to eliminate duplication of clinical trials, reducing drug development costs, speeding the dissemination of pharmaceutical innovation, improving coordination among regulatory agencies, and strengthening the efficiency of the pharmaceutical sector [1, 46]. However, each country has its own economic, social, political, and cultural characteristics as well as healthcare insurance, financing, and provisions that explain why differences in drug regulation and outcomes remain. [7]. Although regulatory decisions are the result of complex review processes based on clinical and other scientific data included in drug applications [13, 50] they are affected by many other factors including public health needs, health and economic policies, and disease epidemiology specific for each country and region.

The study results must be considered with a few caveats. This retrospective study assessed new drugs approved from three regulatory agencies in the last 10 years. Also, unlike for the EMA and the FDA, SMC does not provide public access to the companies’ applications for the approved drugs, making it difficult to provide a comparison of drug applications based on the data presented by the sponsor companies [51].

Assessing the effect of differences in characteristics of drugs approved by different regulatory agencies on health outcomes requires evaluating the clinical value of those differences in the context of the available treatment alternatives in each healthcare system. Future studies may explore how differences in drug characteristics may affect the efficacy, safety, and quality of drugs [5].

Conclusions

There were substantial differences in the characteristics of new drugs approved in the period 2007–2016 by the FDA, the EMA, and SMC. Overall, two thirds of the new drugs were first approved by the FDA. Differences in indications were found in three out of four new drugs approved by the three regulatory agencies.

Despite international drug regulation harmonization trends, significant differences in the characteristics of new drugs approved by different agencies persist.

Notes

Acknowledgements

The authors are very grateful to Dr. Xavier Dumusque for the precious help for the SMC and the FDA labeling extraction.

Compliance with ethical standards

Conflicts of interest

The authors declare that they have no conflict of interest.

Ethics statements

This study uses secondary readily available data available on request. The study does not constitute human subjects research.

This manuscript has not been published and is not being considered for publication elsewhere. All authors meet authorship requirements and approved the manuscript.

Supplementary material

228_2018_2431_MOESM1_ESM.docx (406 kb)
ESM 1 (DOCX 405 kb)

References

  1. 1.
    ICH (2017) ICH—harmonization for better health.[24.04.2017]; Available from: http://www.ich.org/home.html
  2. 2.
    Zhang Y, Hueser HC, Hernandez I (2017) Comparing the approval and coverage decisions of new oncology drugs in the United States and other selected countries. J Manag Care Spec Pharm 23(2):247–254CrossRefPubMedGoogle Scholar
  3. 3.
    Wolfe SM (2013) When EMA and FDA decisions conflict: differences in patients or in regulation? BMJ 347:f5140CrossRefPubMedGoogle Scholar
  4. 4.
    DeMuro C, Clark M, Doward L, Evans E, Mordin M, Gnanasakthy A (2013) Assessment of PRO label claims granted by the FDA as compared to the EMA (2006-2010). Value Health 16(8):1150–1155CrossRefPubMedGoogle Scholar
  5. 5.
    Alqahtani S, Seoane-Vazquez E, Rodriguez-Monguio R, Eguale T (2015) Priority review drugs approved by the FDA and the EMA: time for international regulatory harmonization of pharmaceuticals? Pharmacoepidemiol Drug Saf 24(7):709–715CrossRefPubMedGoogle Scholar
  6. 6.
    Roberts SA, Allen JD, Sigal EV (2011) Despite criticism of the FDA review process, new cancer drugs reach patients sooner in the United States than in Europe. Health Aff (Millwood) 30(7):1375–1381CrossRefGoogle Scholar
  7. 7.
    Nieminen O, Kurki P, Nordstrom K (2005) Differences in product information of biopharmaceuticals in the EU and the USA: implications for product development. Eur J Pharm Biopharm 60(3):319–326CrossRefPubMedGoogle Scholar
  8. 8.
    Seoane-Vazquez E, Rodriguez-Monguio R, Alqahtani S (2016) Response to letter to the editor regarding Alqahtani et al. article on priority review drugs approved by the FDA and the EMA: time for international regulatory harmonization of pharmaceuticals? Pharmacoepidemiol Drug Saf 25(6):745–746CrossRefPubMedGoogle Scholar
  9. 9.
    Wiedermann, C.J. and K. Eisendle (2017) Comparison of hydroxyethyl starch regulatory summaries from the Food and Drug Administration and the European Medicines Agency. J Pharm Policy Pract, 10(1):12Google Scholar
  10. 10.
    Larochelle M, Downing NS, Ross JS, David FS (2017) Assessing the potential clinical impact of reciprocal drug approval legislation on access to novel therapeutics in the USA: a cohort study. BMJ Open 7(2):e014582CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Tafuri G, Stolk P, Trotta F, Putzeist M, Leufkens HG, Laing RO, de Allegri M (2014) How do the EMA and FDA decide which anticancer drugs make it to the market? A comparative qualitative study on decision makers’ views. Ann Oncol 25(1):265–269CrossRefPubMedGoogle Scholar
  12. 12.
    Trotta F, Leufkens HGM, Schellens JHM, Laing R, Tafuri G (2011) Evaluation of oncology drugs at the European Medicines Agency and US Food and Drug Administration: when differences have an impact on clinical practice. J Clin Oncol 29(16):2266–2272CrossRefPubMedGoogle Scholar
  13. 13.
    Dorr, P., et al. (2016) An Analysis of Regulatory Timing and Outcomes for New Drug Applications Submitted to Swissmedic: Comparison With the US Food and Drug Administration and the European Medicines Agency. Therapeutic Innovation & Regulatory Science, 50(6):734–742Google Scholar
  14. 14.
    Hirako M, McAuslane N, Salek S, Anderson C, Walker S (2007) A comparison of the drug review process at five international regulatory agencies. Drug Inf J 41:291–308CrossRefGoogle Scholar
  15. 15.
    Eichler HG, Abadie E, Raine JM, Salmonson T (2009) Safe drugs and the cost of good intentions. N Engl J Med 360(14):1378–1380CrossRefPubMedGoogle Scholar
  16. 16.
    EU Risk Management Plans. Accessed 20 April 2017 http://www.ema.europa.eu/docs/en_GB/document_library/Regulatory_and_procedural_guideline/2017/03/WC500224771.pdf Google Scholar
  17. 17.
    Pouwels KB, van Grootheest K (2012) The rosiglitazone decision process at FDA and EMA. What should we learn? Int J Risk Saf Med 24(2):73–80PubMedGoogle Scholar
  18. 18.
    Lis Y, Roberts MH, Kamble S, J Guo J, Raisch DW (2012) Comparisons of Food and Drug Administration and European medicines agency risk management implementation for recent pharmaceutical approvals: report of the International Society for Pharmacoeconomics and outcomes research risk benefit management working group. Value Health 15(8):1108–1118CrossRefPubMedGoogle Scholar
  19. 19.
    Pitts PJ, Louet HL, Moride Y, Conti RM (2016) 21st century pharmacovigilance: efforts, roles, and responsibilities. Lancet Oncol 17(11):e486–e492CrossRefPubMedGoogle Scholar
  20. 20.
    Aronson, J.K. (2017) Post-marketing drug withdrawals: Pharmacovigilance success, regulatory problems. Therapie, 72(5):555–561Google Scholar
  21. 21.
    Downing NS, Shah ND, Aminawung JA, Pease AM, Zeitoun JD, Krumholz HM, Ross JS (2017) Postmarket safety events among novel therapeutics approved by the US Food and Drug Administration between 2001 and 2010. JAMA 317(18):1854–1863CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Howie, L.J., B.R. Hirsch, and A.P. Abernethy (2013) A comparison of FDA and EMA drug approval: implications for drug development and cost of care. Oncology (Williston Park), 27(12):1195, 1198–1200, 1202 passimGoogle Scholar
  23. 23.
    Makuch RW, Shi R (2014) Comparison of drug approvals in Europe versus the United States: an analysis of discrepancies between drug products reviewed by EMA and FDA. Ther Innov Regul Sci 48(3):362–366CrossRefGoogle Scholar
  24. 24.
    Senderowicz AM, Pfaff O (2014) Similarities and differences in the oncology drug approval process between FDA and European Union with emphasis on in vitro companion diagnostics. Clin Cancer Res 20(6):1445–1452CrossRefPubMedGoogle Scholar
  25. 25.
    FDA (2017) Food and Drug Administration (FDA)—Drugs. [25.05.2017]; Available from: https://www.fda.gov/Drugs/default.htm
  26. 26.
    Nagai S, Ozawa K (2016) Regulatory approval pathways for anticancer drugs in Japan, the EU and the US. Int J Hematol 104(1):73–84CrossRefPubMedGoogle Scholar
  27. 27.
    Van Norman, G.A. (2016) Drugs and Devices. JACC: Basic to Translational Science, 1(5):399–412Google Scholar
  28. 28.
    EMA (2017) European Medicines Agency—human regulatory. [25.05.2017]; Available from: http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/landing/human_medicines_regulatory.jsp&mid=
  29. 29.
    OEMéd (2001) Ordonnance du 9 novembre 2001 de l'Institut suisse des produits thérapeutiques sur les exigences relatives à l'autorisation de mise sur le marché des médicaments. [23.04.2017]; Available from: https://www.admin.ch/opc/fr/classified-compilation/20011693/index.html
  30. 30.
    LPTh (2016) Loi fédérale du 15 décembre 2000 sur les médicaments et les dispositifs médicaux. [24.04.2017]; Available from: https://www.admin.ch/opc/fr/classified-compilation/20002716/index.html
  31. 31.
    Swissmedic (2017) Swissmedic—Institut suise des produits thérapeutiques. [25.05.2017]; Available from: https://www.swissmedic.ch/index.html?lang=fr
  32. 32.
    Downing NS, Zhang AD, Ross JS (2017) Regulatory review of new therapeutic agents—FDA versus EMA, 2011-2015. N Engl J Med 376(14):1386–1387CrossRefPubMedGoogle Scholar
  33. 33.
    Zeitoun JD, Lefèvre JH, Downing NS, Bergeron H, Ross JS (2015) Regulatory review time and post-market safety events for novel medicines approved by the EMA between 2001 and 2010: a cross-sectional study. Br J Clin Pharmacol 80(4):716–726CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Downing NS, Aminawung JA, Shah ND, Braunstein JB, Krumholz HM, Ross JS (2012) Regulatory review of novel therapeutics—comparison of three regulatory agencies. N Engl J Med 366(24):2284–2293CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Pappas G, Ierodiakonou V, Falagas ME (2009) Lost in translation: differences in antimicrobial indication approval policies between the United States and Europe. Clin Ther 31(7):1595–1603CrossRefPubMedGoogle Scholar
  36. 36.
    Dalla Torre S (2016) Comparaison entre les décisions d’autorisation SMC / EMA / FDA 2005–2014. Swissmedic, BernGoogle Scholar
  37. 37.
    NIH (2017) Daylimed [23.05.2017]; Available from: https://dailymed.nlm.nih.gov/dailymed/
  38. 38.
    Swissmedic (2017) Arzneimittelinformations-Plattform (AIPS). [23.04.2017]; Available from: http://www.swissmedicinfo.ch
  39. 39.
    OFSP. OFSP - Liste des spécialités (LS). [23.05.2017]; Available from: http://www.listedesspecialites.ch
  40. 40.
    WHOCC. ATC/DDD Index 2017. [23.04.2017]; Available from: https://www.whocc.no/atc_ddd_index/
  41. 41.
    Kesselheim AS et al (2015) Trends in utilization of FDA expedited drug development and approval programs, 1987-2014: cohort study. BMJ 351:h4633CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Shah RR, Roberts SA, Shah DR (2013) A fresh perspective on comparing the FDA and the CHMP/EMA: approval of antineoplastic tyrosine kinase inhibitors. Br J Clin Pharmacol 76(3):396–411CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Darrow JJ, Avorn J, Kesselheim AS (2014) New FDA breakthrough-drug category--implications for patients. N Engl J Med 371(1):89–90PubMedGoogle Scholar
  44. 44.
    Johnson JR, Ning YM, Farrell A, Justice R, Keegan P, Pazdur R (2011) Accelerated approval of oncology products: the food and drug administration experience. J Natl Cancer Inst 103(8):636–644CrossRefPubMedGoogle Scholar
  45. 45.
    Pfenninger A, Dalla Torre S (2016) Délais d’autorisation des médicaments à usage humain en Suisse 2015 : Etude de benchmarking commune Swissmedic / industrie. Swissmedic, Bern Available from: https://www.swissmedic.ch/swissmedic/fr/home.html
  46. 46.
    CIRS. The Centre for Innovation in Regulatory Science (CIRS). [25.05.2017]; Available from: http://www.cirsci.org
  47. 47.
    Samuel N, Verma S (2016) Cross-comparison of cancer drug approvals at three international regulatory agencies. Curr Oncol 23(5):e454–e460CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    APC (2016) Recommandations de l'Association des pharmaciens cantonaux (APC) concernant l'Off-labell use de médicaments—Interpétation technique. Accessed  17 March 2017 http://www.kantonsapotheker.ch/fileadmin/docs/public/kav/posipapiere/0007_recommandations_off-label-use.pdf
  49. 49.
    Rose K (2017) New drugs for rare diseases in children. Clin Ther 39(2):246–252CrossRefPubMedGoogle Scholar
  50. 50.
    Krumholz HM, Ross JS, Presler AH, Egilman DS (2007) What have we learnt from Vioxx? BMJ 334(7585):120–123CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    DFI (2017) Médicaments : réglementation simplifiée, exigences de sécurité maintenues. Confédération helvétique CH, Berne. Accessed 30 July 2017 https://www.admin.ch/gov/fr/accueil/documentation/communiques.msg-id-66620.html

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.School of Pharmaceutical SciencesUniversity of Geneva, University of LausanneGenevaSwitzerland
  2. 2.Biomedical and Pharmaceutical Sciences Department, School of PharmacyChapman UniversityOrangeUSA
  3. 3.PharmacyGeneva University HospitalsGenevaSwitzerland

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