The most common medications used in thalassaemia treatment are the iron chelating (removing) agents. However, other drugs are also used to deal with the complications of the disease, whilst at the same time medical research brings new treatments to clinical use over time.
All these medications have not only the desired effects, but also some unwanted side effects. After going through clinical trials on volunteer patients, these effects, good or bad, are described, but some long-term effects may not be recognised immediately. Furthermore, individual patients may manifest their own specific reactions, which are known as idiosyncratic.
Drugs can be categorized according to whether they are produced by the company which originally developed them (innovative brands) or whether they are produced, legally or illegally, by other companies.
What are Innovative drugs?
Innovative drugs are also known as Originator, Reference or Brand.
- have gone through three or more phases of rigorous clinical trials over almost two decades
- are authorised by officially established regulatory agencies (EMA, FDA) to be marketed and used by healthcare professionals on humans
Innovative or originator drugs are much more expensive than generic drugs because the pharmaceutical companies that produce them make considerable investments in carrying out clinical trials, which are required in order to test the safety and efficacy of innovative/reference drugs before they enter the market and provided to humans.
*Clinical trials are studies that aim to investigate the therapeutic effect(s) of medicinal products that have not yet been authorized by regulatory bodies such as the European Medicines Agency (EMA), or the value of authorized drugs in cases other than those for which it has been authorized. In addition, clinical trials are considered those studies that seek to assign specific products to a therapeutic strategy or propose to investigate effective diagnostic or monitoring procedures.Read EU Directive 2001/20/EC
For life-threatening or very serious rare diseases, specific medications are developed which are known as orphan drugs. These drugs are called ‘orphan’ because, under normal market conditions, the pharmaceutical industry has little interest in developing and marketing products intended for only a small number of patients.
A disease or disorder is defined as rare in Europe when it affects less than 1 in 2,000 citizens.
The image below summarizes some key figures about orphan medicines in Europe over the last 20 years:
Source: Eurordis Therapeutic Report, June 2020
What are Generic Drugs?
Generic drugs are similar to Innovative/Originator/Reference drugs in the sense that they contain the same quantity of the same active substances and is administered via the same route (e.g., by mouth or by injection) and at the same dose as the innovative/reference drugs.
However, generic drugs are not required to undergo the same rigorous clinical trials as the innovative or originator drugs. They are authorised to enter the market by regulatory agencies over submitting an Abbreviated New Drug Application (ANDA). Through this route, it is mainly their active ingredients, and only some of their excipients* that are reviewed and tested for their safety and efficacy profiles before the overall generic drug receives approval to enter the market.
Usually, generic drugs only undergo what is referred to as “bio-equivalence” testing to assess whether the properties of the innovative/originator drug and the generic drugs are equally efficient for humans.
A drug can be referred to as generic only if it is manufactured as described above and only after the patency protection** and the data exclusivity of the originator drug have expired.
* excipients are the other chemical ingredients that are used to bind with the ‘active’ ingredient to complete the chemical formulation of the drug
**Patency protection: the period in which the drug is protected by a patent i.e., exclusive right granted to the pharmaceutical company for the protection of a drug that provides new ways of treating a disease/condition or offers new solution to treatment.
What are Copy Drugs?
Copy drugs are manufactured by copying the innovative/reference/originator drug, violating international patency laws. Copy drugs can be of very good quality and effective for patients, but they can also be of poor quality and ineffective, and consequently carry concerns and risks.
Copy drugs may:
- only have violated patency* rules and be of good quality, or
- not have followed Good Manufacturing Practice (GMP)** rules and quality controls that are necessary in order to ensure the efficacy of the drug. In this case, a copy drug is a substandard drug.
* Patency laws are special rights granted to the pharmaceutical company that invented the drug.
** Good Manufacturing Practice (GMP) is a system for ensuring that products are consistently produced and controlled according to quality standards. It is designed to minimize the risks involved in any pharmaceutical production that cannot be eliminated through testing the final product.Read more
What are Counterfeit Drugs?
A counterfeit or falsified drug is one that carries a deliberately and fraudulently mislabelled identity and/or source. Both branded and generic products can be counterfeit, and may include products with:
- correct or wrong ingredients
- insufficient (inadequate quantities of) active ingredient(s) or
- fake packaging
- no active ingredients
What are Substandard Drugs?
Substandard drugs are drugs which use has been authorised in a country but its manufacturing has not followed the quality and safety protocols, and recommendations of official national, regional or international drug regulatory authorities. Therefore, the safety and effectiveness of substandard drugs are greatly questioned.
A substandard drug may:
- contain too much or too little of the active ingredient
- be contaminated, poorly packaged or fail to meet quality standards in other ways
- be a generic or a copy drug that has not followed quality standards and can thus have associated risks and consequences.
What are Biological Drugs?
Biological drugs are made only from biological components i.e., substances that already exist in the human body e.g., insulin for diabetes.
Biological drugs undergo rigorous testing and multiple phases of clinical trials before they receive approval to enter the market.
What are Biosimilar Drugs?
Biosimilar drugs are manufactured on the basis of biological drugs and using the information from clinical trials that biological products have previously undergone.
After the patency protection* of the biological medications has expired, pharmaceutical companies can use the information and data from these biological products to manufacture drugs of similar clinical effect.
*Patency protection: the period in which the drug is protected by a patent i.e., exclusive right granted to the pharmaceutical company for the protection of a drug that provides new ways of treating a disease/condition or offers new solution to treatment.
All substances used to treat medical conditions may cause unexpected symptoms or other effects of bodily functions. These are usually recognised in the clinical trials which take place before the product is licenced by regulatory authorities for human use. However, this may not always be the case. Clinical trials are conducted for a limited time on a specific number of patients and some symptoms or effects may not be noticed or may occur at a period greater than the duration of the trial. For these reasons there is a 4th phase in clinical trials which is post-marketing surveillance, so that adverse effects can be reported for much longer periods.
Adverse effects and disturbing symptoms are first felt by the patient. The patient may not relate the new symptoms or feelings to the new drug (or even old one) and believe that it is part of the illness or other passing condition; one example would be headache or flu-like symptoms during winter. The same goes for abnormal lab results which the doctor may relate to another reason other than the drug. Because of this possible confusion, reporting of the symptoms is highly recommended when a new treatment is prescribed, which may not necessarily be a novel, newly discovered, drug but an old one, with a side effect not previously described or rarely encountered.
Patients vary in the way they respond to medications and some very individual reactions (idiosynchratic) are sometimes encountered. This is all very important since the occurrence of serious side effects may require the discontinuation of a treatment and its replacement with an alternative.
The well noted conclusion must be that all patients on medication, new or not, must report any new symptoms to their doctor. The doctor should report these, along with any abnormal laboratory findings, to a drug regulating authority. This process is named pharmacovigilance, a term referring to the collection, detection, assessment, monitoring, and prevention of adverse effects with pharmaceutical products.
WHO established pharmacovigilance as a programme for Drug Monitoring, gathering information internationally, in response to the thalidomide disaster detected in 1961. Together with the WHO Collaborating Centre for International Drug Monitoring in Uppsala, Finland, WHO has established a system so that each country gathers and reports adverse events to the Uppsala centre.
At the end of 2010, 134 countries were part of this programme. Its objectives are to enhance patient safety in relation to the use of medicines and to support public health programmes by providing reliable, balanced information for the effective assessment of the risk-benefit profile of medicines. Each reaction is reported as ‘certain’ or a probable drug reaction from a doctor to the national authority which then transmits the report to the Uppsala Centre.