Bioequivalence: What’s the hype about it?

What is Bioequivalence?
Bioequivalence (BE) studies are in vivo (in human) methods designed to compare the bioavailability (amount absorbed into the body blood circulation) of a medicinal product to an innovator or appropriate reference product when studied under similar experimental conditions.
Bioequivalence studies are additional tests performed on a particular medicine besides its routine in vitro (laboratory) tests.
In Malaysia, bioequivalence studies are required only for certain groups of medicine. The list is reviewed periodically to include more compounds. Regulatory authorities from other ASEAN countries will like to follow Malaysia in this requirement. After receiving advice from WHO, the regulators are working towards harmonization.

Why is Bioequivalence important?
Looking back at a black moment in history, the case of digoxin – a cardiac glycoside used in the treatment of heart failures. Digoxin, a modern medicine derived from the plant Digitalis purpura, has been introduced a century ago. Patients who switched between brands of digoxin had sudden episodes of uncontrolled heart failure while others experienced toxic side effects. Phenytoin, a medicine used in the treatment of epilepsy, is another example. While some had sudden uncontrolled episodes of epilepsy, others experienced toxic effects. These incidences sparked the US FDA to introduce tighter controls over the pharmaceutical manufacturing process, leading to the introduction of bioequivalence tests. A direct demonstration of the efficacy of a generic medicine would require a full-scale clinical trial in which their efficacy
could be compared. These clinical trials are very expensive and are normally undertaken by the innovator. In bioequivalence trials, one attempts to circumvent this direct approach by conducting a blood-level trial in which it is demonstrated that the generics give rise to essentially equivalent blood-level profiles in human volunteers. The principle underlying this concept is
important, namely that a generic medicine that results in essentially equivalent (compared with the innovator) blood-level profiles over time should elicit equivalent efficacy and safety.
“I normally buy medicine recommended by my friends”
“I have always obtained my medication from my family doctor / pharmacist”

How are Bioequivalence studies relevant to me?
Imagine a scenario whereby you are traveling to another town or country and you run out of your regular medicine. A simple solution would be to stop by a pharmacy or a local clinic to get your medication. However what happens when the pharmacy or clinic does not have the same brand of medicine you were taking? Of course, you can always opt for another brand –
maybe a generic. But let’s be reminded by the cases of digoxin and phenytoin. Ideally, the generic substitute must have exactly the same effect and safety profile as the brand you have been taking!
Take for example a medicine for treating high blood pressure (Tenormin® from AstraZeneca which contains atenolol). When you swallow the tablet, it reaches your stomach where it mixes with your stomach juices. The tablet will start to disintegrate (break) and dissolve. The mixture then slowly moves into your small intestine where it is absorbed into your blood stream.
Your blood vessels work as a network to distribute the medicine to the target location, e.g. your heart, where it will act to reduce blood pressure. After that, the medicine may first be converted into another form through a process called metabolism. Finally, the medicine is removed or eliminated from your body either through urine or faeces.
A bioequivalent generic substitute will have that the same amount atenolol absorbed at the same rate and extent when compared with Tenormin® at an acceptable range clinically. This will ensure proper blood pressure control. However, for a bio-inequivalent generic substitute, a different amount of atenolol is bioavailable and this may cause your blood pressure to be out-of-control!
A bioequivalent generic allows the Pharmacist or Doctor to switch brands confidently without any doubt of the efficacy and safety of that generic. Whether bioequivalence is just hype – it’s really up to you to decide. It’s worthwhile to know that in developed countries, healthcare professionals never dream of buying a product that is not bioequivalent!