Global Trends in Clinical Trial Logistics: 2020 perspective

Global Trends in Clinical Trial Logistics: 2020 perspective

Summary

Clinical trial logistics is a fast-growing industry which greatly depends on new technologies, market conditions and globalization of clinical trial infrastructure. The share of expenses for clinical trials in summary budgets of R&D projects is constantly growing and clinical trial logistics has become a major contributor. This article summarizes general development trends in the clinical trial supply chain management by way of analysis of the leading industry research from Evaluate Pharma, Biopharma Cold Chain Sourcebook, IFPMA among others.

12% Growth by 2020

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We are unaware of exact validated statistics which accurately estimate the volume of clinical trial logistics services. Thus, such volume is traditionally calculated as a percentage of the total clinical trials expenses. According to the forecast made by Evaluate Pharma1, in the next 5 years the clinical trials market will show a stable low growth of 2-2.5% per year, while being accompanied by a significant paradigm shift in the operational structure of cold-chain logistics and clinical trial supply, the costs of which (including manufacturing), by various estimates, may reach up to 20% of the total R&D costs2.

According to the same report, this trend of disproportionate growth will come from an increase in clinical trials of prescription medications where logistical expenses are traditionally higher than those of trials of generic products.
Also noteworthy is the prediction that by 2020 R&D projects of top-20 pharmaceutical companies will account for more than 60% of total clinical trial expenses3.



Conclusion: the growth of clinical logistics market will significantly exceed the overall growth of clinical trials market

Clinical Trials Move to New Geographies

2.pngPharmaceutical industry is experiencing a rather drastic redistribution of R&D activities to new geographic regions. According to the Biopharma Cold Chain 2012 Sourcebook, in 2016 up to 65% of growth in clinical research will come from studies conducted in emerging market counties: Asia Pacific, Eastern Europe and South America4. While the majority of clinical trials are initiated with the end goal of NDA approval in the US and in Western Europe, the vast majority of potential study subjects live outside of these regions. Thus, there is a clearly identifiable need to develop first-rate, cost-effective clinical trial infrastructure capabilities in Asia-Pacific region, Latin America, Eastern Europe and potentially in North and South Africa. BRICS countries have demonstrated willingness to make their patients more available to international clinical trials. For instance, Russia and China have recently taken steps towards simplifying the launch of clinical trials.

Consequently, major pharma companies are already executing on their plans to include BRICS in new drug development, with the understanding that these markets are becoming more attractive as commercialization targets. Biotech companies are lagging in this area mostly due to resource limitations, and because their goals are typically limited to North America and Western Europe. The demand for ex-US clinical trial locations is expected to grow, which should translate into the need for better clinical trial logistics infrastructure.




Conclusion: The need for faster recruitment at a lower per-patient cost has resulted in expansion of multinational clinical trials that include fast-growing countries of Latin America, Asia Pacific and of Eastern Europe. This geographical shift gives new possibilities to logistics providers. Not only will the growth of clinical trial market in the stated regions will affect the existing local depots and distribution chains, there is an expectation that both global pharma and logistics companies will continue to establish their own presence in order to control both cost and quality, and to expand its geographical coverage.

Cold-chain is Becoming Colder

Today 38% of all healthcare products are temperature-sensitive5, which means that they require refrigeration during transportation and storage. The report entitled, "Cold Chain Biopharma Logistics Sourcebook 2015"8 surveys growth rates for pharma, biotech, vaccines, blood products and clinical materials, monitors US and international regulatory bodies such as FDA, USP, PDA, IATA and MHRA7. It also includes data on packaging materials, technologies and refrigeration systems. Its recent report suggests that 8 of the top 10 global pharma products in 2020 will require cold-chain handling. According to the study conducted by Pharmaceutical Commerce, the size of temperature sensitive global biopharmaceutical market space is currently estimated at $8.7 billion and is expected to grow to $12.9 billion by 20206. While the North American market will grow by 15% over the next 5 years (or roughly 3% annually, in line with the overall clinical trial market projections), the global market is poised to show a growth rate that is double of that6. According to industry estimates, in emerging markets vaccines will grow on average by 8% per annum through the next five years9.

With biologics making up 36% of the late-stage pipeline and 45% of the late-stage oncology pipeline it is important to consider areas of particular risk in the supply chain management, such as transport routes when handling temperature-sensitive products9.The range of temperature conditions between global clinical trial locations should be factored in, and potential delays in import and export processes should be accounted for.

Conclusion: The demand for biopharma cold chain logistics services is growing, which in turn is generating the demand for new packaging and temperature monitoring technologies in a continuing effort to reduce pass-through costs. There is a constant market demand for new equipment that monitors temperature conditions throughout the investigational product life cycle. Some potential impactful technologies, such as RFID, should be entering the market around 2020 10. Future success of new technologies will greatly depend on the ability to guarantee cold-chain compliance and temperature monitoring while keeping the costs low.

“Direct-to-Patient” is the Future of Drug Supply

New ways of delivering investigational drugs and clinical trial supplies to patients are being constantly investigated. The “direct-to-patient supply” has a great potential to become the new gold standard for selected trials. The omission of medical facilities and biopharmaceutical depots, faster delivery to the patients and potentially, better accountability are the attractive attributes of this approach. However, at present most direct shipments are being performed without temperature control or any other monitoring modalities. One possible emerging solution to this problem is the advancement of secured patient shipments, a sophisticated shipment and delivery process that utilizes individual temperature-controlled containers. Today such shipments are prohibitively expensive but with ongoing technological advancements and with the increase in the number of orphan drug trials, temperature-controlled direct-to-patient shipments may become routine by 2020 11.

Conclusion: By 2020 new direct-to patient supply algorithms will emerge while ensuring the highest level of temperature-sensitive shipments and allowing for flexible and efficient patient management.

Comparator Sourcing Boom

Comparator Sourcing is a fast-growing industry in clinical trials that has doubled within the last three years. A recent report published by the Institute for Healthcare Informatics forecasts that the surge in cancer drug innovation is projected to continue over the next five years, with oncology currently already making up 25% of the global late-stage pipeline 11. As the majority of drug candidates are being studied against the existing standard of care, the need for secure and transparent sourcing of comparator drugs and non-investigational medicinal products (NIMPs) on a global scale is likely to rise significantly 12

Sourcing optimization is by and large achieved via gradual transition from centralized to local comparator suppliers. Global sourcing companies are beginning to assess local market capabilities for availability of quality certificates and actively export drugs for QP release. China, India and Russia are becoming formidable players in this market7.

At the same time Clinical Trial Supply Outlook 2015 Survey by Pharma IQ notes that timely availability of drugs is becoming a major concern for both Pharma and sourcing companies. More than one third of companies face out-of-stock problems, when the necessary comparator drugs are not available. According to the FDA there is an increase in the number of force majeure situations related to comparator drugs shortages. When compared to 2005, the number of such cases has tripled 14. This situation poses new challenges for packaging and logistics providers and span from supply chain forecasting, planning, risk mitigation and temperature monitoring to expiry management.

According to the report from Evaluate Pharma1, sourcing companies should pay close attention to the following list of top-selling product forecast for 2020, which is presented below:

Product (Manufacturer) Generic Name Pharmacological Class
WW Product Sales ($m)
2013
2020
Humira (Abbvie + Eisai)
adalimumab
Anti-tumour necrosis factor alpha Mab
11 014
12 707
insulin glargine recombinant
Insulin
7 592
10 252  
Enbrel (Amgen + Takeda + Pfizer)
etanercept
Tumour necrosis factor alpha inhibitor
8 778
8 572 
Remicade (JNJ + Merck & Co + Mitsubishi)
infliximab
Anti-tumour necrosis factor alpha MAb
8 367
8 217
Sovaldi (Gilead Sciences) sofosbuvir Hepatitis C nucleoside NS5B polymerase inhibitor 139 8 027      
Januvia/Janumet (Merck & Co + Daewoong) sitagliptin phosphate Dipeptidyl peptidase IV inhibitor 5 842 6 895 
Avastin (Roche) bevacizumab  Anti-VEGF MAb 6 751  6 613
Xarelto (Bayer + JNJ) rivaroxaban
Factor Xa inhibitor 1 948  6 414 
Nivolumab (Bristol-Myers Squibb + Ono) nivolumab Anti-programmed death-1 MAb      - 6 361
Tecfidera (Biogen Idec) dimethyl fumarate Nuclear factor erythroid 2-related factor
(Nrf2) pathway activator
876  6 310 
Revlimid (Celgene + Pharmstandard) lenalidomide Immunomodulator 4 302  6 253 
Prevnar 13 (Pfizer + Daewoong) pneumococcal vaccine Pneumococcal vaccine 3 763 6 078
Eylea (Regeneron + Bayer + Santen) aflibercept VEGFr kinase inhibitor 2 039 5 852 
Rituxan (Roche) rituximab Anti-CD20 MAb 7 503  5 627 
Xtandi (Astellas Pharma) enzalutamide
Androgen receptor antagonist  545  5 353 
Soliris (Alexion Pharmaceuticals) eculizumab
Anti-complement factor C5 MAb 1 551 5 202 
Imbruvica (Pharmacyclics + JNJ) ibrutinib
Bruton's tyrosine kinase inhibitor 14 5 123 
Herceptin (Roche) trastuzumab
Anti-HER2 (ErbB-2) MAb 6 562 5 054 
Kadcyla (Roche + Chugai) ado-trastuzumab emtansine Anti-HER2 MAb-DM1 maytansinoid conjugate
253 4 912
Stribild (Gilead Sciences) cobicistat; elvitegravir; emtricitabine;
tenofovir disoproxil fumarate
Nucleoside reverse transcriptase inhibitor,
HIV integrase inhibitor & CYP3A inhibitor
539 4 678
Victoza (Novo Nordisk) liraglutide Glucagon-like peptide 1 agonist  2 072  4 443 
Perjeta (Roche) pertuzumab Anti-HER2 (ErbB-2) MAb  352 4 440
NovoRapid (Novo Nordisk) insulin aspart Insulin  3 001 4 438 
Botox (Allergan + GSK)
onabotulinumtoxinA Botulinum toxin 2 201         4 311
Lucentis (Novartis + Roche) ranibizumab Anti-VEGF MAb  4 206 4 064
MK-3475 (Merck & Co) pembrolizumab Anti-programmed death-1 MAb   - 4 063 
Simponi (JNJ + Merck & Co) golimumab Anti-tumour necrosis factor alpha MAb 1 432 3 910 
Eliquis (Bristol-Myers Squibb) apixaban Factor Xa inhibitor 146  3 717
Gammagard Liquid (Baxter International) immune globulin (human) Immunoglobulin  2 118  3 533 
Xgeva/Prolia (Amgen) denosumab Anti-RANKL MAb 1 763 3 527 
Neulasta (Amgen + Kyowa Hakko pegfilgrastim Granulocyte colony-stimulating factor   4 392  3 455
Stelara (Johnson & Johnson) ustekinumab Anti-interleukin-12 & interleukin-23 MAb  1 504   3 390
Privigen (CSL) immune globulin (human)  Immunoglobulin  2 100 3 158 
Spiriva (Boehringer Ingelheim) tiotropium bromide monohydrate Long-acting muscarinic antagonist   4 719 3 129 
Tivicay (GlaxoSmithKline) dolutegravir HIV integrase inhibitor   30 3 044 
RG7446 (Roche + Chugai)  - Anti-programmed death-1 ligand-1 MAb 3 023 
Obeticholic acid (Intercept Pharmaceuticals) obeticholic acid Farnesoid X receptor agonist 2 992 
Palbociclib (Pfizer) palbociclib Cyclin-dependent kinase (CDK) 4 &
6 inhibitor
-  2 950
Humalog (Eli Lilly)  insulin lispro recombinant Insulin 2 611  2 902 
Kalydeco (Vertex Pharmaceuticals) ivacaftor
Cystic fibrosis transmembrane
conductance regulator potentiator 
371  2 867 
Seretide/Advair (GlaxoSmithKline) fluticasone propionate; salmeterol xinafoate
Beta 2 adrenoreceptor agonist & corticosteroid  8 251 2 849 
Gilenya (Novartis + Mitsubishi Tanabe) fingolimod hydrochloride 
Sphingosine-1-phosphate receptor modulator 1 953  2 845 
 Ledipasvir/Sofosbuvir (Gilead Sciences) ledipasvir; sofosbuvir 
Hepatitis C nucleoside NS5A & NS5B
polymerase inhibitor 
2 818 
 Symbicort Turbuhaler (AstraZeneca) budesonide; formoterol fumarate dihydrate 
 Beta 2 adrenoreceptor agonist & corticosteroid 3 483  2 781 
Levemir (Novo Nordisk) insulin detemir
 Insulin 2 057  2 780 
Anoro Ellipta (GlaxoSmithKline) umeclidinium bromide; vilanterol trifenatate Long-acting beta 2 adrenoreceptor agonist
& long-acting muscarinic antagonist 
 - 2 744 
Vyvanse (Shire + Shionogi)  lisdexamfetamine dimesylate Psychostimulant  1 228   2 721
Nexium (AstraZeneca + Daiichi Sankyo + Daewoong)  esomeprazole magnesium Proton pump inhibitor (PPI)
4 431  2 636 
Tysabri (Biogen Idec)  natalizumab Anti-VLA-4 MAb
1 413   2 573
Invokana (JNJ + Mitsubishi Tanabe)  canagliflozin Sodium-glucose cotransporter-2 inhibitor
 151 2 484 
Source: EvaluatePharma® (1 JUN 2014)

Conclusion: Despite market growth and development it is becoming more difficult to guarantee timely availability of comparator drugs. Comparator sourcing is experiencing globalization; local markets are becoming more useful for clinical trial supplies procurement. Russian, Indian and Chinese markets are especially conducive. Oncological medications are now and will remain the most sought after medical products in clinical trial comparator sourcing.

References:

1. EvaluatePharma report World Preview 2014, Outlook to 2020
2. Qualification of temperature-controlled storage areas Technical supplement to WHO Technical Report Series, No. 961, 2011.
3. Global Biopharma Cold-Chain Market 2015
4. Global Healthcare Cold Chain Logistics Market Report & Forecast (2011-2016)
5. Upgrading of Traditional Cold Chain Shipping Systems Using 2-8°C Phase Change Materials posted jan 1, 2012
6. http://pharmaceuticalcommerce.com/supply_chain_logistics?articleid=26469
7. Biopharma Cold Chain 2012 Sourcebook
8. Cold Chain Biopharma Logistics Sourcebook 2015
9. FACTS AND FIGURES 2014 - IFPMA
10. FDA, Oct 2011 & Jan 2013; Premier Healthcare Alliance, Aug 2011
11. A. M. Huss Analyzing Trends in Global Comparator Sourcing and Distribution in 2015 – A Preview-Journal of Clinical Research. April 2015
12. http://www.quintiles.com/~/media/library/white%20papers/expected-growth-of-industry-sponsored-clinic...
13. http://www.statista.com/statistics/303111/biopharma-logistics-spending-in-global-biopharma-non-cold-...
14. The Future of Clinical Trial Supply – Trends and Challenges 2015 Report (http://www.pharma-iq.com/logistics/white-papers/the-future-of-clinical-trial-supply-trends-and-cha/)