SubscribeIntroduction and definitions: This group of medicines was created in Spain under Law 13/1996 for Fiscal, Administrative and Social Measures from December 30th 1996 which, in its chapter III, modifies certain points in the Law of Medicaments.
We could define GPS as the specialities with the same pharmaceutical form and equal qualitative and quantitative composition in medicinal substances as another reference speciality, whose performance in terms of efficacy and safety are sufficiently established by its continued clinical use.
The generic pharmaceutical speciality must prove its therapeutic equivalence with the reference speciality by means of the corresponding bioequivalent studies. The different oral pharmaceutical forms of immediate release will be considered as the same pharmaceutical form as long as they have proven their bioequivalence.
In this manner, GPS are defined by the addition of section 6 bis to article 8 of the law. According to this, not only must they comply with certain requirements, but the actual reference specialities must also do so.
In brief, so that a pharmaceutical speciality may be considered as a GPS:
- Coincidence with reference speciality in pharmaceutical form and qualitative and quantitative composition in medicinal substances.
- It must prove a therapeutic equivalence with respect to the reference speciality by the corresponding bioequivalence studies.
Reference specialities must also fulfil some conditions: its efficacy and safety performance must be sufficiently established by continued clinical use.
Finally, there are certain special conditions: different oral therapeutic forms of immediate release may be considered as the same pharmaceutical form as long as they have proven their bioequivalence.
There isn't an express obligation to use the sameadditives in the GPS as in the reference speciality. However, it is convenient to bear this in mind, as the presence of an additive may condition in certain cases the medicament's kinetics, and also include a degree of variability as far as definite therapeutic equivalence of the medicine is concerned. It is also necessary to confirm that intolerances and/or allergies do not exist.
To guarantee the therapeutic effect of a GPS it must be proved beyond doubt that it has the identical equivalence performance as the reference product. Pharmacokinetically they have similar Cmax, Tmax and AUC as the original medicine, this guarantees the same pharmacologic and toxicological properties.
Clinical studies undertaken in respect ofbioequivalence must clearly prove that the generic specialities are equivalent to the original ones, so a generic medicine will have the same therapeutic efficacy as the original medicine. The demonstration of therapeutic equivalence to the original is based on the bioavailability that indicates that at equal quantity and speed of absorption of the same active principle, the same pharmacological effects are obtained. So, by measuring successively in time the plasma concentration after the administration of both formulations to a certain number of individuals, the bioequivalence between both specialities can be established.
The terms bioequivalence and bioavailability cannot be thus used indiscriminately.
Advantages of generic medicines
The main advantage lies in an inferior pricethan the medicine of a known make. Independently from the delays and vacancies produced by the time lapse in classification of the laws on patents, the notable differences that exist between the price of medicinal substances from a product that supports the important costs of R&D, and the market prices once the patent right has outdated (20 years), is the reason that will allow that a generic medicine be commercialized fully guaranteed at a price sensibly lower than that of the reference medicine.
Also, the competence between laboratories takes its toll when reducing fabrication costs and on the offering of more competitive prices. On the other hand, there is no clinical or preclinical research. There is only pharmaceutical development. There are no costs derived from proving safety and efficacy (they are the same as those of the reference product). The administrative process of legal registrationis simpler and faster, and notably less costly.
Market for GPS in Spain
The pharmaceutical market in Spain is characterised by the predominance of makes and growth rates superior to 10%, as new measures, not very effective, are started each year to contain costs. One of the latest measures introduced to rationalise the market have been the generic pharmaceutical specialities (GPS), who together with the reference prices try to redirect this situation.
The total market of generic medicines in Spain is at a standstill. In the period between April 2002 and March 2003, the medium market quote in economic values, represented a 3.75% (one of the lowest in Europe), one decimal point more than in all 2002. In December 2002 it represented a 4.1% of the total pharmaceutical market, whilst in March 2003 it was 4% (going down .1%). Between June 2003 and May 2004, the medium market quote in economic values with respect to the pharmaceutical prescription market was 4.3%, which represents a null growth with respect to the mean for all 2003.
The evolution of the market in sold GPS units, also show the low penetration with respect to the total pharmaceutical market. Between April 2002 and March 2003 the mean of those months was 4.8% (three decimal points more than in all 2002). In March 2003 it was 5.5% and finally in May 2004 it reached 7.1%.
In Spain generic specialities are a long way from the European mean, which varies around 15%, and very far from countries such as Germany (34%) or the United Kingdom (33%).
Volume (in %) in penetration of generic specialities in 2002
On the other hand, generic medicines give considerable saving to the pharmaceutical invoice, effectively reducing the cost of medicines around 25-50%.
The real market for generic medicines in Spain is of 48.305.856 units, which represents 12.9% of the potential market. In economic values, the real market of these products is of 249.853.351€, which is 12.7% of the potential market.
The market numbers in units of GPS sold prove their small penetration with respect to the total pharmaceutical market: the median quote for the last 12 months was 6.1%, which represents a 0.3% increment with respect to the median value for all 2003.
The total pharmaceutical prescription market in Spain, groups together all the medicines that need a prescription, is of 945.045.600 units. From that quantity the potential market for the active principles with GPS is actually the equivalent of 39.6% of the total market.
In terms of economic value, the prescription pharmaceutical market is worth 6.621.622.000€. The potential market of the active principles with GPS is the equivalent of 29.7% of the total market.
Finally, we reach the conclusion that until the market quote for GPS' doesn't get above the prescription market growth (11.7%), it won't be possible to control pharmaceutical costs.
In November 2004 the market for generic medicines is composed by 105 active principles. At the end of October 2004 the number of GPS' approved by the Spanish Medicament Agency was 1988, of which 1302 can be found on the market. Also, in Spain there are 125 laboratories with GPS.
Requirements for GPS in Spain
So that a certain medicine may obtain the GPS denomination it must fulfil a series of sanitary, technical and legal conditions.
- Sanitary requirements: The Ministry of Health published a circular 3/97 through the Director General of Pharmacists and Sanitary Products on the procedure for evaluation, authorization and register application for generic pharmaceutical specialities that explained certain aspects of the law and eased the application procedures. In this circular a few requirements were detailed, such as:
- To have the same qualitative and quantitative composition in active principles and the same pharmaceutical form as the original medicine.
- To be safe and effective.
- It must not possess a slim therapeutic margin no special biodisponibility features that make it unrecommendable for its approval as a GPS.
- It must be able to prove its quality.
- It must be essentially similar to the authorized reference pharmaceutical speciality.
- It must be correctly identified.
- On its labelling the letters "GPS" must appear.
- Legal requirements: After the previous details, one must add that for the commercialization and production of a certain medicament that contains a molecule initially created by another laboratory it is necessary for at least 10 years to have gone by since the authorization of the commercialization in Spain of the original medicine, or that it be authorized as a generic pharmaceutical speciality in another country of the European Union.
For this we start at de Patent Law of 1986. The problem of patents in Spain is that up until 1992 only procedure patents existed, and since then a new Patent Law was applied for pharmaceutical products, but until 2012 this law has no retroactive effects so until then it is possible to find copy medicines of others with procedure patent rights, but obtained by different procedures; or what is the same, copy medicines that contain active principles with procedure patents still in force. - Technical requirements needed by an GPS for its authorization:
1. Detailed report on its characteristics.
2. All information relative to the synthesis and fabrication of the active principle that must be kept in a confidential document called Drug Master File, that is at the disposal of the Health Authorities and that represents the guarantee of the material in question's quality, independently of its country of origin. It guarantees the quality of the initial material used for the fabrication of a generic speciality.
Procedure to register a GPS in Spain
Generic specialities are registered by the same legal mechanisms as the rest of pharmaceutical specialities, trough a centralized system (EMEA) or, more frequently by national register procedures of mutual recognition.
- National procedure: A certain original product may be commercialized en different countries under different commercial makes or fantasy names. In this case, the GPS of each country will have to prove their equivalence to the original medicine following the corresponding laws in each case. The period is of 120 days and the authorization is given out by the evaluating agency in each country.
- Mutual recognition procedures: In this case the same pharmaceutical speciality may be legitimized and commercialized in various countries of the EU, under different conditions, that appear in the "Summaries of product characteristics" or technical description. The procedure is started by applying its authorization for commercialization in a country member of the EU, the called Reference State, so that the technical description is identical to that of the new product in said country. Once its commercialization is approved in the Reference State the register my mutual recognition procedures will start in other countries belonging to the EU. Each country has a time period of 90 days in which it must decide its authorization. The authorization is given by the country's Evaluating Agency. The problem is that the characteristics on the technical description of the approved GPS in the Reference State, don't always coincide with the one authorized for the new products in the different participating countries in the normal register procedure of GPS, and so they opt for the national procedure.
- A third procedure exists, the centralized procedure where the medicament's evaluation is done by the EMEA and results in only one commercialization authorization for all the countries members of the EU, with the same commercial name and the same information about the product. The pre authorization process lasts 120 days. The authorization is given out by the EMEA. This system isn't used by generic specialities.
All is legislated under the Royal Decree 767/1993 from May 21st whereby the evaluation, authorization, register and dispensing conditions of pharmaceutical specialities and other human use medicines industrially produced are regulated, and has been updated under Order SCO/3461/2003. On the other hand, the European Parliament approved at the beginning of 2004 a new legislation that allows the registry of generic specialities after eight years.
