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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The Committee for Medicinal Products for Human Use &#40;CHMP&#41; of the European Medicines Agency in June 2013 issued a positive opinion for the approval of Remsima<span class="elsevierStyleSup">&#174;</span> and Inflectra<span class="elsevierStyleSup">&#174;</span>&#44; 2 biosimilar Remicade analogs<span class="elsevierStyleSup">&#174;</span>&#46; Numerous opinions&#44; news and articles in scientific journals and in what is called the trade press have been published over the last year&#46; However&#44; that same month of June&#44; the Spanish Agency for Medicines and Health Products authorized 107 generics with hardly any notice&#46; By the time the positive CHMP opinion on Remsima<span class="elsevierStyleSup">&#174;</span> and Inflectra<span class="elsevierStyleSup">&#174;</span> was issued&#44; there were 13 more biosimilar medicines approved by the European Commission&#46; None of these generated as much excitement as the release of the 2 biosimilars&#46; What has motivated&#44; in this past year&#44; the increased news and meetings on biosimilar medicines&#63;</p><p id="par0010" class="elsevierStylePara elsevierViewall">In 2008&#44; 3 of the 10 top-selling drugs in Europe were biologics&#46; Five years later&#44; 8 of the 10 top-selling drugs in Europe are biologics&#46; At the top of them&#44; we find the monoclonal antibodies used in rheumatology&#44; dermatology&#44; inflammatory bowel disease and various cancers&#46; Virtually all of them will lose exclusivity by 2020&#46; A market that&#44; overall&#44; is in the ballpark of 73 billion U&#46;S&#46; dollars &#40;55<span class="elsevierStyleHsp" style=""></span>000<span class="elsevierStyleHsp" style=""></span>million euros&#41; according to IMS&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> This has generated a growing interest in the availability of biosimilars and&#44; in fact&#44; there are 39 biosimilar drugs in various stages of development at this time&#46; But also&#44; as expected&#44; some interest in delaying such availability&#46; This debate often mixes arguments and scientific uncertainties&#44; regulatory positions that necessarily evolve in the light of knowledge&#44; budgetary items&#44; points of interest and disinterested views&#44; ultimately&#44; myths and realities on which we will try to shed some light&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">All medications to be approved by drug agencies need to demonstrate quality&#44; safety and efficacy&#46; When the drug is new&#44; this demonstration requires a full development &#40;clinical trials phase <span class="elsevierStyleSmallCaps">i&#44;</span> phase <span class="elsevierStyleSmallCaps">ii</span> and phase <span class="elsevierStyleSmallCaps">iii&#41;&#46;</span>When the drug is known&#44; after the expiry of the periods of patent and data protection to which they are entitled&#44; the development of new drugs with the same active ingredient can rely on the known data from the innovator&#46; For the active ingredients of chemical synthesis&#44; these drugs are called generics and clinical development is sufficient to demonstrate&#44; through bioequivalence studies&#44; that they reach the same plasma concentrations as their innovative counterparts and assume that its efficacy and safety is the same&#46; It is this abbreviated development&#44; and not the application of suboptimal quality standards&#44; which allows them to be marketed at a cheaper price&#46; Although initially they were also the focus of similar scrutiny&#44; no one responsibly disputes today the existence of generic medications&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">For biological medicinal products&#44; the comparability exercise is different&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> A biological medicinal product is a drug that contains one or more active principles produced or derived from a biological source&#46; The active principles of biological medicines are larger and more complex than those of non-biological drugs&#46; It is said that in this case &#8220;the process &#40;manufacturing&#41; is the product&#8221;&#44; trying to indicate that it is the complete combination of data quality&#44; preclinical and clinical results that constitute an individual product&#46; That is why both their complexity and the way they are manufactured may result in some degree of variability in the molecules of the same active ingredient&#44; especially in different batches of the same drug&#46; To get an idea&#44; an innovative drug that has introduced variations in the manufacturing process is required to demonstrate comparability to itself over time to maintain its permits&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">A biosimilar are biological drugs that are developed to be similar to other biological drugs that are already authorized and&#44; therefore&#44; base part of their development on what is known as the innovator&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> A biosimilar drug is not the same as a generic drug&#44; as these drugs have simpler structures and it is easier to ensure that they are identical to that of the reference medicine&#46; However&#44; the active substance of a biosimilar and the reference product is the same biological substance&#44; although there may be minor differences due to their complex nature and mechanisms of production&#46; It should be stressed that this variability exists for both innovative biologics and their biosimilars&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">In some emerging countries with laxer regulatory systems than Europe&#44; there has been a proliferation of innovative biological medicines&#44; which has been exploited by opponents of biosimilars to attack those who have been authorized in a more stable and regulated environment&#46; We have all heard of the threat posed by the &#8220;Chinese enbrel&#8221; &#40;oncologists&#8217; Chinese trastuzumab&#8217;&#41;&#46; It is important to note that we ar4e referring here to such products&#44; but rather of those same authorized products and with those same rules that were applied at the time &#40;and are continuing&#41; to innovative medicines&#46; And manufactured and implanted in the EU by solvent laboratories&#46; Therefore&#44; for a biosimilar drug to be authorized&#44; it has to be proven that the variability inherent in any biological medicinal product and other innovative drugs has no different effects on the safety and efficacy of the product&#46; When the biosimilar product is authorized&#44; it is generally used at the same dose and to treat the same diseases as the innovative referenced&#46; If there are special precautions with respect to the innovative drug&#44; these are also applicable to the biosimilar&#46; The requirements for the approval of biosimilars are very strict<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#8211;6</span></a> and their own development has made their release much slower than that of other similar innovative medicines&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Therefore&#44; when already authorized&#44; drug agencies ensure that between the innovator and biosimilar drug there are no significant differences in quality&#44; safety or efficacy&#46; In this sense&#44; there is no advantage of one over the other&#46; Obviously&#44; with an abbreviated development&#44; biosimilars can be priced lower than the innovator&#44; and this is the main advantage&#44; to allow price competition which&#44; in most cases&#44; does not occur with drugs that undergo full development&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Once these and some other questions about biosimilars are solved&#44; the biggest stumbling blocks are interchangeability and substitution&#46; What happens to patients who are already treated with a biologic and a biosimilar appears on the market&#63; This is not exactly as a generic&#44; which reasonably assures interchangeability and replacement&#46; Biological drugs are on the list of non-substitutable drugs&#46; Does this mean that you cannot switch from one to another&#63; Not exactly&#46; In fact&#44; doctors change from one biologic to another without any detected associated problems&#46; It happens that this must be done case by case and always with regard to the patient&#46; There is no experience or data on the consequences of abrupt changes or substitutions of some other biological drugs in short periods&#46; However&#44; it is expected that a number of patients with rheumatoid arthritis change treatments over a period of 2 years&#44; ever more toward a biological treatment&#46; This may be&#44; for example&#44; an opportunity for the introduction of biosimilars&#46; At this point common sense must prevail and collaborative work between the different actors within hospitals so that together&#44; on one the hand&#44; do not lose the advantage posed by the development of biosimilars but&#44; on the other&#44; do not generate a replacement policy that may jeopardize the safety and efficacy of the drugs or calls into question the consistency of the system&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">The pharmaceuticals sector is a highly regulated industry&#46; The regulation is also as sophisticated as the type of drug produced&#46; In this sense&#44; one can only say that when agencies authorize a drug it is because they guarantee quality&#44; safety and efficacy in the conditions set on the data sheet&#46; The system also has mechanisms to detect and correct problems&#46; Repeating polemics and discussions that ensued with the appearance of generic drugs in the case of biosimilars now would be a mistake for everyone&#46; What is necessary is that patients and professionals better know and understand the rules&#46;</p></span>"
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Editorial
Biosimilar Drugs, Myths and Reality
Mitos y realidades sobre los medicamentos biosimilares
César Hernández-García
Head of Departamento de Medicamentos de Uso Humano, Agencia Española de Medicamentos y Productos Sanitarios, Madrid, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The Committee for Medicinal Products for Human Use &#40;CHMP&#41; of the European Medicines Agency in June 2013 issued a positive opinion for the approval of Remsima<span class="elsevierStyleSup">&#174;</span> and Inflectra<span class="elsevierStyleSup">&#174;</span>&#44; 2 biosimilar Remicade analogs<span class="elsevierStyleSup">&#174;</span>&#46; Numerous opinions&#44; news and articles in scientific journals and in what is called the trade press have been published over the last year&#46; However&#44; that same month of June&#44; the Spanish Agency for Medicines and Health Products authorized 107 generics with hardly any notice&#46; By the time the positive CHMP opinion on Remsima<span class="elsevierStyleSup">&#174;</span> and Inflectra<span class="elsevierStyleSup">&#174;</span> was issued&#44; there were 13 more biosimilar medicines approved by the European Commission&#46; None of these generated as much excitement as the release of the 2 biosimilars&#46; What has motivated&#44; in this past year&#44; the increased news and meetings on biosimilar medicines&#63;</p><p id="par0010" class="elsevierStylePara elsevierViewall">In 2008&#44; 3 of the 10 top-selling drugs in Europe were biologics&#46; Five years later&#44; 8 of the 10 top-selling drugs in Europe are biologics&#46; At the top of them&#44; we find the monoclonal antibodies used in rheumatology&#44; dermatology&#44; inflammatory bowel disease and various cancers&#46; Virtually all of them will lose exclusivity by 2020&#46; A market that&#44; overall&#44; is in the ballpark of 73 billion U&#46;S&#46; dollars &#40;55<span class="elsevierStyleHsp" style=""></span>000<span class="elsevierStyleHsp" style=""></span>million euros&#41; according to IMS&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> This has generated a growing interest in the availability of biosimilars and&#44; in fact&#44; there are 39 biosimilar drugs in various stages of development at this time&#46; But also&#44; as expected&#44; some interest in delaying such availability&#46; This debate often mixes arguments and scientific uncertainties&#44; regulatory positions that necessarily evolve in the light of knowledge&#44; budgetary items&#44; points of interest and disinterested views&#44; ultimately&#44; myths and realities on which we will try to shed some light&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">All medications to be approved by drug agencies need to demonstrate quality&#44; safety and efficacy&#46; When the drug is new&#44; this demonstration requires a full development &#40;clinical trials phase <span class="elsevierStyleSmallCaps">i&#44;</span> phase <span class="elsevierStyleSmallCaps">ii</span> and phase <span class="elsevierStyleSmallCaps">iii&#41;&#46;</span>When the drug is known&#44; after the expiry of the periods of patent and data protection to which they are entitled&#44; the development of new drugs with the same active ingredient can rely on the known data from the innovator&#46; For the active ingredients of chemical synthesis&#44; these drugs are called generics and clinical development is sufficient to demonstrate&#44; through bioequivalence studies&#44; that they reach the same plasma concentrations as their innovative counterparts and assume that its efficacy and safety is the same&#46; It is this abbreviated development&#44; and not the application of suboptimal quality standards&#44; which allows them to be marketed at a cheaper price&#46; Although initially they were also the focus of similar scrutiny&#44; no one responsibly disputes today the existence of generic medications&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">For biological medicinal products&#44; the comparability exercise is different&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> A biological medicinal product is a drug that contains one or more active principles produced or derived from a biological source&#46; The active principles of biological medicines are larger and more complex than those of non-biological drugs&#46; It is said that in this case &#8220;the process &#40;manufacturing&#41; is the product&#8221;&#44; trying to indicate that it is the complete combination of data quality&#44; preclinical and clinical results that constitute an individual product&#46; That is why both their complexity and the way they are manufactured may result in some degree of variability in the molecules of the same active ingredient&#44; especially in different batches of the same drug&#46; To get an idea&#44; an innovative drug that has introduced variations in the manufacturing process is required to demonstrate comparability to itself over time to maintain its permits&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">A biosimilar are biological drugs that are developed to be similar to other biological drugs that are already authorized and&#44; therefore&#44; base part of their development on what is known as the innovator&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> A biosimilar drug is not the same as a generic drug&#44; as these drugs have simpler structures and it is easier to ensure that they are identical to that of the reference medicine&#46; However&#44; the active substance of a biosimilar and the reference product is the same biological substance&#44; although there may be minor differences due to their complex nature and mechanisms of production&#46; It should be stressed that this variability exists for both innovative biologics and their biosimilars&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">In some emerging countries with laxer regulatory systems than Europe&#44; there has been a proliferation of innovative biological medicines&#44; which has been exploited by opponents of biosimilars to attack those who have been authorized in a more stable and regulated environment&#46; We have all heard of the threat posed by the &#8220;Chinese enbrel&#8221; &#40;oncologists&#8217; Chinese trastuzumab&#8217;&#41;&#46; It is important to note that we ar4e referring here to such products&#44; but rather of those same authorized products and with those same rules that were applied at the time &#40;and are continuing&#41; to innovative medicines&#46; And manufactured and implanted in the EU by solvent laboratories&#46; Therefore&#44; for a biosimilar drug to be authorized&#44; it has to be proven that the variability inherent in any biological medicinal product and other innovative drugs has no different effects on the safety and efficacy of the product&#46; When the biosimilar product is authorized&#44; it is generally used at the same dose and to treat the same diseases as the innovative referenced&#46; If there are special precautions with respect to the innovative drug&#44; these are also applicable to the biosimilar&#46; The requirements for the approval of biosimilars are very strict<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#8211;6</span></a> and their own development has made their release much slower than that of other similar innovative medicines&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Therefore&#44; when already authorized&#44; drug agencies ensure that between the innovator and biosimilar drug there are no significant differences in quality&#44; safety or efficacy&#46; In this sense&#44; there is no advantage of one over the other&#46; Obviously&#44; with an abbreviated development&#44; biosimilars can be priced lower than the innovator&#44; and this is the main advantage&#44; to allow price competition which&#44; in most cases&#44; does not occur with drugs that undergo full development&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Once these and some other questions about biosimilars are solved&#44; the biggest stumbling blocks are interchangeability and substitution&#46; What happens to patients who are already treated with a biologic and a biosimilar appears on the market&#63; This is not exactly as a generic&#44; which reasonably assures interchangeability and replacement&#46; Biological drugs are on the list of non-substitutable drugs&#46; Does this mean that you cannot switch from one to another&#63; Not exactly&#46; In fact&#44; doctors change from one biologic to another without any detected associated problems&#46; It happens that this must be done case by case and always with regard to the patient&#46; There is no experience or data on the consequences of abrupt changes or substitutions of some other biological drugs in short periods&#46; However&#44; it is expected that a number of patients with rheumatoid arthritis change treatments over a period of 2 years&#44; ever more toward a biological treatment&#46; This may be&#44; for example&#44; an opportunity for the introduction of biosimilars&#46; At this point common sense must prevail and collaborative work between the different actors within hospitals so that together&#44; on one the hand&#44; do not lose the advantage posed by the development of biosimilars but&#44; on the other&#44; do not generate a replacement policy that may jeopardize the safety and efficacy of the drugs or calls into question the consistency of the system&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">The pharmaceuticals sector is a highly regulated industry&#46; The regulation is also as sophisticated as the type of drug produced&#46; In this sense&#44; one can only say that when agencies authorize a drug it is because they guarantee quality&#44; safety and efficacy in the conditions set on the data sheet&#46; The system also has mechanisms to detect and correct problems&#46; Repeating polemics and discussions that ensued with the appearance of generic drugs in the case of biosimilars now would be a mistake for everyone&#46; What is necessary is that patients and professionals better know and understand the rules&#46;</p></span>"
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ISSN: 21735743
Original language: English
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