La Calidad de los Medicamentos.

Un tema de crucial trascendencia para la salud y bienestar de los pacientes es el de la calidad de los medicamentos. No nos referimos √ļnicamente a los aspectos que influyen en la eficacia y seguridad de los f√°rmacos o a las buenas pr√°cticas que se aplican para su manufactura, sino tambi√©n a la calidad y confiabilidad de la informaci√≥n sobre los mismos.

El tema adquiere mayor trascendencia porque se impulsa la prescripción por genéricos o biogenéricos sin reparar en las diferencias de calidad.

En el trabajo de Heintz Redwood: Generics and You, que se publica por gentileza del autor y de, se explica el problema de la seguridad especialmente en países con insuficiente vigilancia sanitaria, así como el impulso a los biogenéricos que requieren un régimen de registro sanitario específico que, a título de ejemplo, no existe en la Argentina.

Para darnos su opinión, haga click en Blog y Comentarios, botón a la derecha de la página.


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Generics and You

Updated version [JULY 2009] of original paper for (September 2000)

When your doctor prescribes a generic drug, are you pleased, indifferent or affronted? Or are you perhaps uncertain and wondering what exactly generic means and how it will affect you?

Health authorities and insurers in many countries want to encourage physicians to prescribe generics because they are cheaper. Patients can benefit from that but also need to be assured that they are still getting the best medicine and not merely a cheaper form of second-class therapy.

What is a generic drug?

All drugs have a generic name. They can also have a brand name.

A generic name is that of the active drug substance. A brand name is the registered trademark under which the drug is being sold.

For example, Prozac is the brand of a drug whose generic name is fluoxetine. The generic name of Viagra is sildenafil. In most countries of the industrialised world, doctors may prescribe drugs either by their generic or their brand names.

As long as the active drug substance is protected by patents, only the patent holder’s own brand name or those that are licensed under agreements with the patent holder may be used. Once the patent has expired, other companies may register the drug with health authorities and sell it under their own brand names or by its generic name. In the USA and the UK, most generics are unbranded, whereas in some countries generics are commonly branded.

The doctor’s choice: brand or generic?

New drugs are normally prescribed by their brand name. If the drug is covered by a patent, the pharmacist will also dispense the brand, even if the physician has actually prescribed the drug by its generic name: patented drugs are in effect single-source brands.

After patent expiry, generics can enter the market and compete with the original brand. Generics have no medical advantage over brands. Their appeal is that they are cheaper.  For branded drugs with high sales, many generic competitors will enter the market after patent expiry. Generics will offer a price advantage by undercutting not only the brand but also one another.

At this point, the question arises whether your doctor will continue to prescribe the original brand or switch to a generic version of the same drug.

Doctors’ attitudes differ greatly from country to country. Today, most health authorities encourage doctors to prescribe generics; but some still put obstacles in the way of generic entry into the market, for example by insisting on lengthy and costly registration procedures. Some health care payers put pressure on doctors (with incentives or penalties) to prescribe generically. Others take the decision out of the doctor’s hands by allowing (or even requiring) the pharmacist to substitute a cheaper generic in place of the prescribed brand.

Generic substitution means that the pharmacist switches the physician’s prescription by dispensing a generic instead of the prescribed brand. Depending on national or state regulations, the pharmacist may do so either with or even without the physician’s prior consent. In some countries, patients may refuse a generic switch; in others, patients who insist on the prescribed brand may be asked to pay the price difference between it and an available generic.

The main reason why the authorities and health care payers support and encourage generic prescribing and dispensing is financial: generics save money.

In which countries are you most likely to receive a generic prescription?

Countries where more than one-third of all prescriptions are estimated to be generic include:

USA                          Germany

Canada                      UK

Australia                    Netherlands

New Zealand              Denmark

Turkey                      Sweden

most of East Europe   much of Latin America

Developments in the U.S. ‚Äď nationally the largest pharmaceutical market in the world by sales value -¬† demonstrate the interaction of strong patent protection for new medicines with deep market penetration by generics after patent expiry. In 2008, about 69% of all U.S. prescriptions were generic, but competitive pricing meant that generics were responsible for only 16% of all prescription costs[1]. Ten years earlier, the corresponding levels of generic market share in the U.S. were about 41% of prescriptions and 10% of sales value[2].

The massive advance of generic market penetration in the U.S. is at the expense of prescriptions for branded medicines that are no longer protected by patents. Recent years, in particular, have seen patent expiry of an exceptionally high number of ‚Äėblockbuster‚Äô medicines.

The growing but modest generic share by sales value is attributable partly to their low prices and partly to the ‚ÄėAmerican compromise‚Äô whereby patented medicines enjoy pricing freedom in order to encourage pharmaceutical innovation in which the U.S. continues to lead the world, both in chemical synthesis and in biotechnology.

Are generics ‚Äėfirst class‚Äô medicine?

That generics are a cheap form of medicine is indisputable. Whether they always represent good medicine or the best medical value is more controversial. There are four main aspects to be considered:

1 ‚Äď Are generics safe?

2 ‚Äď Is their quality as good as that of the corresponding brand?

3 ‚Äď Is your doctor or pharmacist wise in switching your usual brand to a generic?

4 ‚Äď Are generics as effective as newer, medically innovative and more costly drugs that your doctor could prescribe for the same illness?

Provided you live in a country with strict regulatory control of medicines, the answer to the first two questions is ‚ÄúYES‚ÄĚ: generics are safe and their quality is not inferior. Unregulated Internet trading of prescription drugs from sources that are outside the grasp of national regulatory control could cast doubt on their safety and quality. However, that applies not only to generics but also to counterfeit brands. That said, generics from respectable suppliers are safe and of good quality.

The answer to Question 3 is less clear-cut. Doctors are sometimes reluctant to switch your prescription from a branded drug that ‚Äėworks‚Äô and has never given you any trouble, to an equivalent generic, even though that generic is chemically and pharmacologically identical with the brand. The doctor may be quite happy to prescribe the generic to a new patient, but may be reluctant to switch existing patients on the principle ‚Äúif it ain‚Äôt broke‚Ķ‚Ķ‚ÄĚ - Why take a chance that you will come back and say ‚ÄúDoctor, I used to have the green tablet: this one is white, and I don‚Äôt think it works quite as well‚Ķ.?‚Ä̬† The doctor will want you to stop worrying, even though you may just be imagining a problem. On the other hand, the doctor will also be under pressure not to exceed his budget for prescription drugs, or the pharmacist to substitute a generic for the brand. Finally, if you are a new in-patient in hospital, you will probably never be aware of the fact that, in many countries, hospital pharmacists regularly switch brands to generics according to hospital rules and budgets, because you will not actually have seen your prescription.

Undoubtedly, the trend in most countries is to increase generic prescribing and dispensing whenever possible, certainly for new patients but also increasingly by switching.  Most patients will accept that this is a reasonable economy measure and that it will not harm them.

There are exceptional situations for some drugs where it is difficult or impossible to produce a generic that is in every respect identical with the original brand in terms of its availability within the body. That can lead to serious adverse reactions in some patients. Three old-established drugs where brands and generics are not regarded as automatically ‚Äėswitchable‚Äô are digoxin, phenytoin and theophylline[3].

Biosimilars [‚ÄėFollow-on Biologics‚Äô]

The question of doubts about a generic version being identical and clinically interchangeable with the original brand has become scientifically and politically prominent with the recent onset of patent expiry of major recombinant biotech medicines that were first launched in the 1980s and were recognised as highly  innovative: for example, epoetin alfa (for treatment of anaemia in kidney failure, or after chemotherapy); filgrastim (for treatment of neutropenia in various types of cancer therapy); and interferon beta (for multiple sclerosis).

The traditional approach to generic prescribing and brand substitution  after patent expiry is now widely recognised as unrealistic for biologics. In recombinant biotechnology, complex therapeutic protein molecules are not as accurately reproducible as small-molecule drugs obtained by chemical synthesis. Tiny variations in biotech processing may or may not produce changes in clinical  performance which may be beneficial, insignificant, or adverse.

In other words, the answer to the first three questions about generics (their safety, quality and interchangeability) cannot be a simple, affirmative ‚ÄėYes‚Äô for biosimilars. It has to be proven. That is why the original description of such medicines as ‚Äėbiogenerics‚Äô has been largely replaced by the expressions ‚Äėbiosimilars‚Äô or (in the U.S.) ‚Äėfollow-on biologics‚Äô.

Recognition of ‚Äėbio-similarity‚Äô has created the need to devise new legislation for the pathway to regulatory control of safety, efficacy and quality, before such products can be introduced after patent expiry[4].

In the European Union, an official guideline for regulatory control of biosimilars was issued by the CHMP [Committee for Medicinal Products for Human Use] in¬† 2006.¬† In¬† essence, it requires¬† manufacturers to demonstrate that the active substance of their biosimilar product ‚Äúis representative of the active substance present in the reference medicinal product‚ÄĚ (normally the original brand which must have been authorised for marketing in the EU)[5].

Unlike the procedures for traditional small-molecule generics which can obtain marketing approval by ‚Äėreferring‚Äô to the clinical data originally submitted by the former patent holder, biosimilar applicants in the EU may have to carry out some clinical work of their own in order to demonstrate safety, efficacy and quality comparable with the reference product.¬† The additional costs involved in such regulatory requirements imply that biosimilars have much less scope for deep price cuts below those of the reference brands than is customary for small-molecule generics.¬† This, together with initial hesitation by doctors to prescribe, explains why biosimilars in Europe ‚Äúare not penetrating the market as quickly as generic firms had hoped‚ÄĚ[6].

The U.S. is lagging behind Europe in adopting a regulatory pathway for biosimilars, but the Obama administration is intent upon doing so.

The main area of political contention in the U.S. is the length of ‚Äėdata protection‚Äô. This refers to clinical and other research and development data submitted to the regulatory authorities by the applicant for the original biotech brand.¬† The production of such data involves high levels of expenditure. ‚ÄėData exclusivity‚Äô represents the number of years (usually from the date of market introduction) during which the information remains the exclusive property of the originator and cannot therefore be used by biosimilar applicants as reference material for their own purposes without the consent of the owner.

Although all interested parties in the U.S. now agree that a ‚Äėpathway‚Äô to biosimilar registration should be created and various proposals are being made to Congress, the length of data exclusivity is being hotly disputed:

Congress bill (Waxman et al) 2009[7] 5  years

White House view[8] 7  years

Congress bill (Eshoo et al) 2008 & 2009[9] 12 years

BIO [Biotech industry association][10] 14 years

Assuming that a compromise is eventually reached and the pathway is set up, biosimilars will be marketed in the U.S. without first having to go through a complete programme of clinical trials.¬† But by comparison with ‚Äėsmall molecule‚Äô generics, biosimilars will involve much higher development cost and their capacity for price cutting will be correspondingly lower, at least initially.¬† Health care payers (including YOU ‚Äď the patient) will nevertheless welcome any reductions in the high cost of biotech medicines as long as their safety, efficacy and quality is guaranteed.

The fourth question about generics

This is much the most difficult and the most important for you as a patient:

Are generics as effective as the newer, medically innovative and more costly drugs

that your doctor could prescribe for the same illness?

This is where the conflict between the best medicine and saving money is sharp. New, innovative medicines have transformed drug therapy during the last seventy years and saved the lives of millions from bacterial infections (like pneumonia, meningitis, and after surgery) and viral attack (like HIV/AIDS). They have also enormously helped patients (especially elderly patients) to live  more comfortably with chronic conditions like heart disease, arthritis, ulcers and depression.

Such innovative drugs are not cheap and should not be expected to be cheap in the industrialised world. They are the result of costly research and development with high risks of product failure before a new drug can be proven safe and effective and introduced as a prescription product in hospitals and/or for outpatients. Pharmaceutical patents were first introduced in the 19th Century in order to encourage this type of research and development by rewarding inventors for a limited period of exclusivity, and with the express objective to stop the piracy of intellectual property.

Today’s and tomorrow’s problems can be stated very simply: Who is to pay for all this?

The state? the insurer? the employer? the employee? or you ‚Äď the patient ‚Äď when you hand your prescription to the pharmacist?

The health care systems of various countries have tried to find different answers to the question ‚ÄėWho Pays?‚Äô, but there is general agreement that the health benefits that innovative drugs bring to medicine and patients need to be weighed against their cost and how that cost is to be shared.

That is where the conflict between prescribing cheap generics or costly innovative drugs comes to a head. The budget of health care payers will obviously benefit if old generics are prescribed and new medicines reserved only for exceptional cases. But will you, the patient, benefit? Will your health be maintained or improved as effectively with a generic that has been prescribed for the past 30 years as with the latest drug? That is not a conflict between brand and generic (as in Questions 1, 2 and 3, above) but between traditional and innovative remedies.

In the past, your problem as a patient was that you were not really in a position to judge whether your physician‚Äôs prescribing choice was the best for you. The majority of older patients were brought up to accept the doctor‚Äôs decision without question. They were not even told what drug was being prescribed, but handed a bottle labelled ‚ÄúThe Medicine‚ÄĚ ‚Äď and that was that.

That was the past. Today, the situation has changed radically. There are self-help groups and patients’ advocacy groups for most diseases in the USA,  in Europe, and increasingly in the emerging economies. There is the Internet. You can, if you wish, become fairly expert in the range of drugs that are available for the treatment of your illness. Above all, you can seek independent advice from advocacy groups whose pharmaceutical knowledge may be more up-to-date than that of physicians who have not taken refresher courses on Recent Advances in Pharmacology.

The idea is not that we should all become our own doctors or second-guess the professionals. It is simply that we have a right to understand whether we are being fobbed off with cheap, obsolete, second-class medicine or whether cheap happens also to be best ‚Äď which in many cases it may well be.

You and generics

Generics are here to stay. Increasingly, your physician will prescribe them in place of the original brand, either willingly or under budgetary pressure from health authorities. How should patients react?

According to a Harris Poll in the U.S. in December 2008, nearly half of those who are willing to purchase a generic would be willing to pay up to US$10 for 30-days supply, and a further third would be willing to pay between $10 and $25 out-of-pocket.¬† Harris Poll also asked: ‚ÄúIf you had a choice between getting a brand name prescription drug or a generic drug, how often would you choose one over the other?‚ÄĚ The answer was that 81% would choose a generic drug more often compared with only 19% favouring brands more often. Indeed, 40% of respondents would always choose a generic while only 4% would always prefer a brand[11].

There is a clear indication here that, in a country where the patient pays or contributes out-of-pocket to the cost of drug therapy, generics have been accepted and, being much cheaper, are widely preferred to identical branded originals. That would not have been the case twenty years ago when brand loyalty was strong and generics were still under suspicion of being ‚Äėinferior‚Äô.

Your attitude?  Common sense suggests that it will be determined on the one hand by your circumstances, and on the other by your alertness. Circumstances will influence the policy of health care payers and how much you (as distinct from your insurer) will be expected to pay out of pocket if you opt for the brand instead of the generic.

Common sense will also help to convince you that, for the majority of older drugs in countries with strong regulatory control, generics will be as safe and as effective as brands. Moreover, common sense will scare you away from ‚Äėcowboy‚Äô generics obtainable from suspect sources (which may include unknown Internet suppliers in other countries).

Alertness is your greatest asset in making sure that cheap generics are not being prescribed in preference to better, costlier innovative drugs that would be more effective in maintaining or improving your health.¬† There is no substitute for being vigilant and becoming more knowledgeable, or getting to know independent advisers who know about the ‚Äėlatest and best‚Äô in a health care system that naturally gravitates towards the cheapest. Be alert!

[1] IMS statistics,¬† Generic Pharmaceutical Association, Arlington/VA, ‚ÄúEconomic Analysis: Generic Pharmaceuticals 1999-2008‚ÄĚ, May¬† 2009

[2] IMS America, as reported in Pharma Pricing & Reimbursement 4(5), 111, May 1999

[3] Carlen, ‚ÄúKosten sparen mit Generika?‚ÄĚ, Schriftenreihe No. 47, Schweizerische Gesellschaft f√ľr Gesundheitspolitik, Muri, Switzerland 1995

[4] Biosimilars are widely available in countries where the earlier biotech medicines were not protected by basic patents, for example in India, China and South Korea (World Health Organisation, ‚ÄúInformal Consultation on regulatory evaluation of therapeutic biological and medical products‚ÄĚ, Geneva 19-20th April 2007).

[5] European Medicines Agency, CHMP, ‚ÄúGuideline on similar biological medicinal products containing biotechnology-derived proteins as active substance: Quality Issues‚ÄĚ, London 22nd February 2006

[6] Scrip, ‚ÄúBiosimilars up ‚Äď but not yet running‚ÄĚ, 8th May 2009 (page 22)

[7]D.S.Levine, The Burrill Report, ‚ÄúBIO simmering over Biosimilars‚ÄĚ, online 13th March 2009

[8] Pharma Times, ‚ÄúSeven years protection sufficient for brand biologics, says White House‚ÄĚ, online 26th June 2009

[9] as Ref.7

[10] as Ref.7

[11] Harris Poll, ‚ÄúSubstantial increase in public preference for generic over brand name drugs‚ÄĚ, Harris Interactive, online 26th January 2009


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Comité Argentino de Educación para la Salud de la Población