Global Trends in Clinical Trial Logistics: 2020 perspective
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
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 Pharma, 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 costs.
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 expenses.
Conclusion: the growth of clinical logistics market will significantly exceed the overall growth of clinical trials market
Clinical Trials Move to New GeographiesPharmaceutical 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 America. 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-sensitive, which means that they require refrigeration during transportation and storage. The report entitled, "Cold Chain Biopharma Logistics Sourcebook 2015" 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 MHRA. 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 that. According to industry estimates, in emerging markets vaccines will grow on average by 8% per annum through the next five years.
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 products.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 . 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 SupplyNew 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 .
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 BoomComparator 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 . 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 .
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 market.
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 . 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 Pharma, 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||
WW Product Sales ($m)
Humira (Abbvie + Eisai)
Anti-tumour necrosis factor alpha Mab
insulin glargine recombinant
Enbrel (Amgen + Takeda + Pfizer)
Tumour necrosis factor alpha inhibitor
Remicade (JNJ + Merck & Co + Mitsubishi)
Anti-tumour necrosis factor alpha MAb
|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)||
||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
|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)||
||Androgen receptor antagonist||545||5 353|
|Soliris (Alexion Pharmaceuticals)||
||Anti-complement factor C5 MAb||1 551||5 202|
|Imbruvica (Pharmacyclics + JNJ)||
||Bruton's tyrosine kinase inhibitor||14||5 123|
||Anti-HER2 (ErbB-2) MAb||6 562||5 054|
|Kadcyla (Roche + Chugai)||ado-trastuzumab emtansine||
Anti-HER2 MAb-DM1 maytansinoid conjugate
|Stribild (Gilead Sciences)||
cobicistat; elvitegravir; emtricitabine;
tenofovir disoproxil fumarate
Nucleoside reverse transcriptase inhibitor,
HIV integrase inhibitor & CYP3A inhibitor
|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|
Cyclin-dependent kinase (CDK) 4 &
|Humalog (Eli Lilly)||insulin lispro recombinant||Insulin||2 611||2 902|
|Kalydeco (Vertex Pharmaceuticals)||
Cystic fibrosis transmembrane
conductance regulator potentiator
fluticasone propionate; salmeterol xinafoate
||Beta 2 adrenoreceptor agonist & corticosteroid||8 251||2 849|
|Gilenya (Novartis + Mitsubishi Tanabe)||
||Sphingosine-1-phosphate receptor modulator||1 953||2 845|
|Ledipasvir/Sofosbuvir (Gilead Sciences)||
Hepatitis C nucleoside NS5A & NS5B
|Symbicort Turbuhaler (AstraZeneca)||
budesonide; formoterol fumarate dihydrate
||Beta 2 adrenoreceptor agonist & corticosteroid||3 483||2 781|
|Levemir (Novo Nordisk)||
||Insulin||2 057||2 780|
|Anoro Ellipta (GlaxoSmithKline)||umeclidinium bromide; vilanterol trifenatate||
Long-acting beta 2 adrenoreceptor agonist
& long-acting muscarinic antagonist
|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||
||1 413||2 573|
|Invokana (JNJ + Mitsubishi Tanabe)||canagliflozin||
Sodium-glucose cotransporter-2 inhibitor
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
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
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/)