Why generics?

There is much confusion and misconception about the nature and efficacy of generic medicines. The following piece seeks to dispel some common myths and fallacies.

Jayabalan Thambyappa and Mohamed Azmi Ahmad Hassali

THE cornerstone of access to medicines is affordability, but the stark reality is that life-saving medicines do not always come cheap. It has been reported by the World Health Organisation (WHO) that more than a third of the world's population has no access to essential drugs and more than half of this group of people live in the poorest regions of the developing world such as Africa and Asia. In the case of these two regions, accessibility to drugs is hampered by, amongst other factors, the exorbitant cost of essential medicines. One solution to circumvent this problem lies in the use of generics.

What are generics?

Generics are equivalent medicines with the same qualities, safety and effectiveness as the originator brands. Generic medicines contain the same active ingredients in the same pharmaceutical form as the originator product. This simply means that different brands will work in the same way to treat a particular condition, with essentially the same risks and benefits.

Myths and fallacies

A popular misconception is that generics are counterfeit drugs. This arises because generic medicines come in different colours, shapes, packaging and even taste. In addition, the inactive substances (such as lactose, gluten and permitted colourings) in the medicines may differ. These differences do not in any way affect the efficacy of the generic medicines; it must also be emphasised that trademark laws do not allow generic medicines to look exactly like the originator products. Moreover, originator products as well as generics can be counterfeited.

While on the subject of counterfeit drugs, it is important to note that developed countries have cynically used the legitimate fears of medicines of compromised quality to enhance intellectual property enforcement standards in order to exert greater control over the trade in generic medicines to poor countries. They have negotiated a new treaty, the Anti-Counterfeiting Trade Agreement (ACTA), which, among other measures, requires customs officials to treat generic medicines as if they were counterfeit goods and seize them. (See the article 'ACTA: undemocratic, dangerous and wrong' in this issue.)

In fact, even before ACTA was finalised, on more than 20 occasions between 2008 and 2010, customs authorities in the Netherlands detained consignments of Indian-manufactured generic medicines that were in transit to other developing countries.

Another common misconception is that generics are inferior to the originator brand in both quality and efficacy. However, quality is assured by good manufacturing practice (GMP) while efficacy is assured by ensuring bioequivalence. It is a false perception that generic medicines are less efficacious than the originator drugs. A generic medicine is bioequivalent to the originator product as it delivers the same amount of active ingredients into the bloodstream of the patient in the same amount of time. In short, bioequivalence ensures that the generic drug is as potent as the originator drug. Thus, quality and efficacy of generics are guaranteed through GMP and also bioequivalence.

Good manufacturing practice and pharmaceuticals

GMP is a system for ensuring that products are consistently produced and controlled according to quality standards. It is designed to minimise the risks involved in any pharmaceutical production that cannot be eliminated through testing the final product. The main risks are:

*     Unexpected contamination of products, which may cause damage to health or even death;

*     Incorrect labels on containers, which could mean that patients receive the wrong medicine;

*     Insufficient or too much active ingredient, resulting in ineffective treatment or adverse effects.

WHO has established detailed guidelines for GMP (http://whqlibdoc.who.int/trs/WHO_TRS_961_eng.pdf#page=106). Many countries have formulated their own requirements for GMP based on WHO GMP. Others have harmonised their requirements, for example in the Association of South-East Asian Nations (ASEAN), in the European Union and through the Pharmaceutical Inspection Convention. 

GMP covers all aspects of production, from the raw materials, premises and equipment to the training and personal hygiene of staff. Detailed, written procedures are essential for each process that could affect the quality of the finished product. There must be systems to provide documented proof that correct procedures are consistently followed at each step in the manufacturing process, every time a product is made.

As most countries will only allow the import and sale of medicines that have been manufactured according to internationally recognised standards, GMP ensures that products comply with these quality standards.

Bioequivalence

Bioequivalence is defined as 'the absence of a significant difference in the rate and extent to which the active ingredient or active moiety in pharmaceutical equivalents or pharmaceutical alternatives becomes available at the site of drug action when administered at the same molar dose under similar conditions in an appropriately designed study'.

Two medicinal products containing the same active substance are considered bioequivalent if they are pharmaceutically equivalent or pharmaceutical alternatives and their bioavailabilities (rate and extent) after administration in the same molar dose lie within acceptable predefined limits. These limits are set to ensure comparable in vivo performance, i.e., similarity in terms of safety and efficacy.

Generic medicine manufacturers are required to prove their formulation exhibits bioequivalence to the innovator product. The purpose of establishing bioequivalence is to demonstrate equivalence in biopharmaceutics quality between the generic product and the innovator product in order to allow bridging of pre-clinical tests and of clinical trials associated with the innovator product. In Malaysia, for instance, the Ministry of Health, through its regulatory body, the Drug Control Authority (DCA), has enforced the need for bioequivalence to ensure quality, efficacy and safety of the generic pharmaceutical products that are marketed in the country. Most other ASEAN countries too require bioequivalence studies on certain pharmaceutical products. India, which is a leading manufacturer of generic medicines, also adheres to international guidelines that call for bioequivalence of the generics that are marketed.

The US and the European Union have strict guidelines for the manufacture of generics and will not allow the import of these medicines if they do not show proof of bioequivalence and that the countries of manufacture adhere to these international standards. In applications for generic medicinal products in the EU, bioequivalence is fundamental and the approval process for generic drugs is equally as stringent as the process followed to approve branded drugs worldwide. The rigorous chemistry, manufacturing and controls phase is applicable to both new branded drugs and generic drugs. Labelling and testing requirements also are the same for both branded and generic versions. Regulatory authorities evaluate the manufacturing facilities for generics and for branded products, using the same standards, to ensure compliance with all good manufacturing practices. The only meaningful difference between the generic and brand approval processes is that human and animal clinical studies to show safety and efficacy are conducted for new branded drugs, whereas bioequivalence studies are used in place of clinical studies in approving generics.

Changing negative perceptions

Providing timely access to affordable, safe and effective medicines should be a priority on every government's health agenda but one stumbling block is prohibitive medicine costs. Not only are they an equally effective alternative in healthcare management, but generic medicines also provide an opportunity for major savings in healthcare expenditure since they may be substantially lower in price than the innovator brands. For instance, it will cost less than $80 per patient per year to treat AIDS with generics, as opposed to $15,000 per patient per year if a patented drug were used. According to the then Health Minister of Malaysia, Dr Chua Soi Lek, the monthly cost of treating a patient with HIV in Malaysia in 2004 would be reduced from RM1,200 to approximately RM200 once generic drugs from India were brought in. In fact, Chua went on to say, 'With the cheaper cost, we can treat at least 4,000 HIV patients compared to the present 1,500.' The average cost of treatment per patient was reduced by over 80%, thereby increasing access to medicines to more than twice the number of patients.

WHO has been actively promoting the greater use of generics and even developed countries, through their regulatory bodies such as the US Food and Drug Administration (FDA), have sought to educate consumers on the benefits of using generic medicines. However, on their part, developing-country governments have not actively involved themselves in educating and convincing consumers on the safety, efficacy and quality of registered generics. This is extremely unfortunate as it is the developing countries that most require access to cheaper and equally efficacious medicines. It is incumbent upon the medicine regulatory bodies in developing countries to play a bigger role in changing negative perceptions towards generic medicines.

With escalating healthcare costs, governments in many countries have to adopt cost containment measures in an effort to spend their limited financial resources efficiently so that equitable access to healthcare can be provided. In order to achieve optimal outcomes, consumers must not only receive appropriate treatment, but also have the knowledge to use it to its best effect. Governments, healthcare professionals and other relevant agencies have a vital role to play in promoting quality use of medicines through good treatment choices, good communication with consumers, and collaboration with each other. The government has yet another crucial role to play - since generic medicines represent a substantial segment of the pharmaceutical market in many developing countries, the government has to ensure the sustainability of generics production.     

Jayabalan Thambyappa, a medical doctor, is Director of the Health and Safety Advisory Centre in Penang, Malaysia. Mohamed Azmi Ahmad Hassali is the head of department for the Discipline of Social and Administrative Pharmacy at the School of Pharmaceutical Sciences at Universiti Sains Malaysia in Penang. They are co-authors, with Asrul Akmal Shafie, of What You Should Know About Generic Medicines (see advertisement on p. 7).

*Third World Resurgence No. 259, March 2012, pp 6-8