What is a generic medicine

Introduction

Generic medicines contain the same active ingredients with, and are equivalent to the “original” medicines produced by large (multinational) companies and are considered fully interchangeable. Generic medicines may only be placed on the market after the expiry of the monopolistic protection enjoyed by new “original” products from the relevant patent(s) and usually have their own brand names.

 

The importance of generic medicines

Generic medicines have always played an important role in providing affordable healthcare to an ever-increasing number of patients, and now in the economic crisis facing many countries, it is generally accepted that sustainable healthcare can only be maintained by the use of generic medicines.

When a pharmaceutical company discovers a new molecule with pharmacological activity then it will patent it and develop a new dosage form which once it has gained a marketing authorization will be sold as a medicine.  This medicine becomes the originator product or brand leader and other manufacturers are prevented from marketing a copy for 20 years from the date of filing of the patent.  Obviously, the exclusivity period from the date when the product is marketed will be less than 20 years.

The total cost of the research and development of a new (originator) pharmaceutical product ranges from 150 to at least 800 million US dollars. This amount includes the cost of the pre-clinical and clinical trials that are designed to establish the safety and therapeutic efficacy of the product. However, no matter how comprehensive these studies are it will not be possible to identify all the side-effects of the new medicine prior to marketing.  For this reason it is necessary for the pharmaceutical product to be monitored by regulatory authorities after its launch and this phase is known as post-marketing surveillance or pharmacovigilance. The administration of a medicine in large populations for an extended period may lead to the identification of rare or/and critical side effects, interactions and contra-indications which will enable the safety profile of the medicine to be confirmed.  On rare occasions it may be decided that a medicine is not safe and it may be removed from the market.

A generic pharmaceutical product is one which is intended to be interchangeable with the originator or innovator pharmaceutical product. The two products must have the same qualitative and quantitative composition in terms of the active ingredients and must have the same pharmaceutical form. Furthermore, the generic product has to be demonstrated to be bioequivalent to the originator and this is done by measuring the blood profile of both products in groups of normal volunteers.  The parameters that will be compared include the peak blood concentration (C max), the time to reach it (T max) and the area under the blood concentration against time curve (AUC).  If the values for these parameters are similar then the products are deemed to be essentially similar and can be interchanged when prescriptions for the active ingredient are being dispensed.

Bioavailability is defined as the rate and extent by which the active pharmaceutical ingredient is absorbed from a pharmaceutical dosage form (for example tablets, capsules or injections) and becomes available in the general circulation and is calculated from the AUC. For an intravenous (iv) injection the bioavailability is taken to be 100% whereas in other routes of administration this percentage will lower if the absorption is incomplete.

The therapeutic response will also be affected by the pharmacokinetic and pharmacodynamic properties of the active ingredient.  These can be simply defined as the way in which the body handles the drug and the effects that the drug produces in the body respectively.

Generic pharmaceutical products must have the same pharmacological and therapeutic effects as their originators. If this is the case, how can the impression of some patients that the originator pharmaceutical product is better than the respective generic be explained? For the most part, most patients tend to have a positive response to their therapy which includes the pharmaceutical product and the attention of the medical staff.  However, this positive response sometimes may be not related to the medication per se but to the subject’s expectation of a therapeutic effect in that they believe that the treatment will change their condition and thus better.  This is known as the placebo effect which is remarkable in that it can produce physiological and biochemical variations and clinically discernible effects, for example in the treatment of pain.

A placebo response is produced by a “medicine” which contains only a pharmacologically inert substance and should not induce a therapeutic response or medical improvement. Clinical trials (single blind, double blind or triple blind studies) control for the placebo effect by including in the study a group of subjects that receives a placebo treatment. The subjects in such trials (after having given relevant informed consent) do not know whether they have received the potentially active treatment or a placebo. In the double blinded trials the medical/paramedical staff also do not know which subjects are receiving the pharmacologically active or the placebo treatment. In the triple blinded trials, in addition to the above mentioned persons, the investigators (researchers, persons who analyze statistically the results of the trial) also do not know which participants were administered which preparation. On the other hand, an opposite effect has been described whereby the patient believing that they are receiving the active medication may report side effects which are imaginary. This phenomenon is called the nocebo effect. These side effects will be reported with either the active medicine or the placebo.  Although other factors (e.g. change in the diet or other habits of the patient) cannot be ignored in relation to the nocebo effect, it is possible that the question of the previous paragraph can be answered on the basis of the placebo/nocebo effect. Moreover, the placebo/nocebo effect can provide an explanation for the varying responses of  patients towards either the originator or generic pharmaceutical products.

The impact of the generics to the pharmacoeconomics of every country is significant. For example, in the European Union (EU), it appears that generics play a pivotal role in health economics. In 2006 the prescribing of generic pharmaceutical products in EU already accounted for 50% of the total drug administered. Bearing in mind that the price of generics is typically 20% to 90% below that of originator pharmaceuticals, it is obvious that the use of generics permits countries to save money and at the same time to have access to new, more expensive pharmaceutical treatments. In addition, because of the ageing population in EU, it is estimated that by 2050 for each elderly person there will be only two  citizens of working age instead of four, as now. The pharmaceutical treatment provided and the subsequent cost effects play a vital role in the policy of social and health insurance systems. Promotion of generic pharmaceutical products is of central importance. The prescribing practice (many physicians in EU prescribe pharmaceutical products according to the name of the product approved for marketing authorization) and the national policies affecting the registration and the price of the pharmaceutical products are directly implicated in the promotion and use of the generics.