What are the different stages of a Clinical Trial?
There are four phases of clinical trials which involve new drugs. Each phase of the drug development process is managed as a separate clinical trial.
If the drug successfully passes through Phases I, II, and III, it will usually be approved by the national regulatory authority for use in the general population.
This stage of the drug development pipeline is a study to test a drug, procedure or other medicinal treatment. They involve in vitro and in vivo experiments using wide-ranging doses of the study drug to obtain preliminary efficacy, toxicity and pharmacokinetic information. The aim is to collect data in support of safety. Preclinical studies are required before clinical trials start.
Phase I studies – This is the first stage of testing in humans. Normally, a small (20-100) group of healthy volunteers will be selected. Phase I trials most often include healthy volunteers. However, there are some circumstances when real patients are used, such as patients who have terminal cancer or HIV and lack other treatment options.
Phase II trials – In these, the potential drug is tested in around 20 to 300 volunteer patients suffering from whatever condition the drug is to potentially treat. They are designed to show whether the drug is safe in the specific patient population and to look for signs that it might be effective.
Phase III trials – If Phase II trials are successful, then the potential drug will undergo Phase III trials, which are widespread multicenter trials on at least 300 to 3000 patients in clinics to test the efficiency of the product. They are usually randomised and double blind. Once Phase III trials are completed, the drug is filed with the relevant country authority for review. In the UK, this is the Medicines Control Agency (MCA); in the US, it is the Food and Drug Administration (FDA); in Australia it is Australian Quarantine Inspection Service (AQIS) and in Japan, the Ministry of Health and Welfare. Some Phase III trials will continue while the regulatory submission is pending at the appropriate regulatory agency. This allows patients to continue to receive possibly lifesaving drugs until the drug can be obtained by purchase. Because of their size and comparatively long duration, Phase III trials are the most expensive, time-consuming and difficult trials to design and run, especially in therapies for chronic medical conditions.
After the drug is launched, further Phase IV studies are carried out to monitor possible adverse reactions or other responses when large numbers of patients begin using the drug.
What are the different types of Clinical Trial?
There are several different types of Clinical Trials:
These look for better ways to prevent disease in people who have never had the disease or to prevent a disease from returning. These approaches may include medicines, vitamins, vaccines, minerals, or lifestyle changes.
These test the best way to detect certain diseases or health conditions.
These are conducted to find better tests or procedures for diagnosing a particular disease or condition.
These test experimental treatments, new combinations of drugs, or new approaches to surgery or radiation therapy.
Quality of life trials
These explore ways to improve comfort and the quality of life for individuals with a chronic illness.
Compassionate use trials
These provide partially tested, unapproved therapeutics prior to a small number of patients that have no other realistic options. Usually, this involves a disease for which no effective therapy exists, or a patient that has already attempted and failed all other standard treatments and whose health is so poor that he does not qualify for participation in randomized clinical trials. Usually, case by case approval must be granted by both the FDA and the pharmaceutical company for such exceptions.
What paperwork and licenses may be required for a Clinical Trial?
With regards to the movement of Clinical Trial material the paperwork and/or licences required depend on where the Clinical Trial is due to be conducted, what transport route is required and what type of material is involved.
What specialist services do Biocair provide for Clinical Trials?
- Clinical Trials Logistics – Includes logistical set-up assistance and liaison with clinical trial collection and delivery sites.
- Paperwork completion - All documentation that is required is provided (some additional charges may apply). This includes airwaybills, NES declarations, dangerous goods certificates. All labelling for transport is provided.
- Licence applications - Biocair identify and obtain / advise on permits to enable the safe shipment of regulated material.
- Insurance available on a per shipment or per study basis, as required.
- Online Booking and tracking.
- 24-hour Biocair contact
Which regulatory bodies might be involved in Clinical Trial?
If a Clinical Trial concerns a new regulated drug or medical device (or an existing drug for a new purpose), the appropriate regulatory agency for each country where the sponsor wishes to sell the drug or device is supposed to review all study data before allowing the drug/device to proceed to the next phase, or to be marketed. However, if the sponsor withholds negative data, or misrepresents data it has acquired from Clinical Trials, the regulatory agency may make the wrong decision.
In the U.S., the FDA can audit the files of local site investigators after they have finished participating in a study, to see if they were correctly following study procedures. This audit may be random, or for cause (because the investigator is suspected of fraudulent data). Avoiding an audit is an incentive for investigators to follow study procedures.
Different countries have different regulatory requirements and enforcement abilities. "An estimated 40 percent of all Clinical Trials now take place in Asia, Eastern Europe, central and south America.
What are the common issues with Clinical Trials?
Schedule of sample collection – Many busy investigators have trouble completing shipping forms fully and accurately, for either drug supplies or blood or tissue samples.
Late sample delivery – this is usually a result of missed collection, poor documentation giving rise to customs problems, or transport delays – especially if the samples are considered dangerous or due to the fact that dry ice was not available.
What are the difficulties in setting up a Clinical Trial in China?
China – What’s all the fuss about?
Not only does China have great market potential and is fast becoming a manufacturing powerhouse for the global Pharma industry, but it is also being recognised as the future epicentre of Research & Development. The drug discovering capabilities of China are largely more desirable when considering its already obvious advantages in cost. Conducting R&D in China can save research costs up to 60% and drug developers can expect typical savings of 30% compared to Western costs.
In 2008 it was predicted that China would be the World’s third largest prescription drug market by 2011. A report released by IMS Health (a pharmaceutical market research firm) shows that China’s pharmaceutical revenue is growing fast and the market may double by 2013. The domestic pharmaceutical industry has been a key contributor to the country’s impressive economic growth, which has made China the world's fastest growing pharmaceutical market.
Clinical Trials in Asia
With the costs of technology rising steadily and regulatory requirements tightening throughout the EU and US, drug development in these regions is starting to dwindle. It is becoming increasingly more time consuming and costly to initiate a Clinical Trial, particularly now that Pharmaceutical companies are faced with price pressures from the healthcare markets – forcing them to bring their margins in tighter and therefore limiting growth opportunities.
For this reason, China is becoming increasingly attractive to big companies looking to reduce these constraints. The global balance is shifting in China’s favour and with this, scores of western-trained scientists and pharmaceutical expertise are choosing China as their study destination.
So as you can see, Asia is fast becoming an international hub for Clinical Trials. China, India, Korea and South East Asia are all key regions for development. Most big Pharmaceutical companies have now expanded into Asia, taking advantage of the cheaper labour costs and rapidly expanding market intelligence. However, these benefits can come hand in hand with some complications; the regulations for importing and exporting out of Asia, particularly China are considerably more complex than elsewhere.
The difficulties with setting up Clinical Trials in Asia
Presently there is a significantly longer process involved for granting import/export approval for drugs in China than there is elsewhere in the world. Even within Asia, China has by far the longest processes. The Biotech industry is still very new to China and the Chinese Government. Although progressing at a rapid pace, processes are still being designed and optimised. Some applications still require ‘hand by hand’ operation and cannot be completed online.
The average time it takes to gain regulatory approval for a Clinical Trial in China is nine months.
India is roughly two years ahead of China and has made marked improvements to their processes in this time. Obtaining approval here now only takes two to two and a half months. But for Clinical Trials the process is prolonged further as approval must be obtained from the DGFT (Directorate General of Foreign Trade) which can take between one and two months. With the steady increase in Clinical Trials applications in Asia, the DCGI (Drugs Controller General of India) have become more experienced and ploughed more money into resources, thus rapidly reducing approval time.
Korea (closely followed by Singapore) is the most developed country in Asia in terms of Pharmaceuticals and regulatory processes. Here the average time for granting regulatory approval for a Clinical Trial is just 30 working days. In Singapore, it takes roughly a month for regulatory approval, but it takes a further month to obtain approval from the EC (Ethics Committee). Whereas in Hong Kong these processes can run at the same time, thus reducing approval time for both to an average of nine weeks. Then a licence to import a Clinical Trial must be granted, which usually takes two weeks.
The above goes some way to illustrate how difficult it is to set up a Clinical Trial in China. However, Clinical Trial Logistics can be tricky wherever they take place. Below is a simplified example of the steps that a Specialist Logistics Courier would take when organising a Clinical Trial movement from various European destinations and delivering them to a research laboratory in China:
Moving a Clinical Trial to and around Asia
We will start at the beginning:
Pharma Co. are conducting a Clinical Trial in clinics across Germany, Switzerland, Belgium and Poland. They need to move the various samples collected to its research laboratories in Shanghai, China.
Pharma Co. would go to a Specialist Courier like ABC123 Courier and request a quote.
Pharma Co. can quote for an individual shipment within the trial, or can quote for the movement of the entire Clinical Trial.
This will include multiple collection points and consignees across the globe.
In this instance, Pharma Co. would like ABC123 Courier to organise the movement of the entire trial.
For ABC123 Courier to provide a quote, they need to be able to classify the product(s) being shipped.
If Pharma Co. provides a detailed description, then the courier can classify the product more quickly.
If a description is not provided then ABC123 Courier must research the product on behalf of Pharma Co. in order to classify it correctly.
The time involved in this process is dependent on the complexity of the product.
Once the product is classified, ABC123 Courier will suggest and provide appropriate packaging so that the product arrives at Pharma Co.’s Research Laboratory in Shanghai, in perfect condition.
For example, some products need to be shipped in a temperature controlled environment.
ABC123 Courier must now design a route for the shipments that ensures they meet their required delivery schedule, as outlined by Pharma Co..
ABC123 Courier must now go back to Pharma Co. with the proposed routing, packaging and classification to receive authorisation on the shipments.
Pharma Co. can track the shipments with ABC123 Courier’s Track & Trace facility on their website.
Once the shipments have arrived at Shanghai Airport, it will go through Customs and providing the product(s) has been classified accurately and all permits are in place, there will be no delays.
ABC123 Courier’s Chinese transport unit will pick the shipments up and take them to their final destination.
ABC123 Courier and Pharma Co. will both receive confirmation that the shipments has arrived.
This process seems simple enough when broken down as above, but various timelines have not yet been considered.
Regulatory approval has to be obtained and we’ve already discussed how this can be a lengthy process. As explained above, gaining regulatory approval for importing samples to Asia is a longer process than most continents, but China can be particularly difficult. This can be for many reasons, including:
- The fact that the industry is still relatively new to China
- Their stringent import and export rules
- The amount of regulatory bodies to gain approval from
With so many bodies to gain approval from, there are far more opportunities for delays to occur – and this is something that Pharma companies need to be aware of and factor in when involving China in a Clinical Trial. For example, when choosing a Specialist Courier, it is wise to consider more than the price. A good Specialist Courier will have an in-depth knowledge and thorough understanding of all local Regulatory Bodies and their requirements. Thus ensuring the process is as swift and efficient as possible.
As mentioned above, this process takes varying amounts of time in different countries in Asia. For example, both Korea and Singapore have a relatively quick regulatory processes and are able to deliver Clinical Trial approval within 30 working days.
In 2008 we were predicting China’s success for 2010/11 – getting ready to jump on the back of the wave.
Well now we’re here and we need to start recognising that China IS the international hot spot for Pharmaceuticals. Get your surfboard out and get involved.