Biosimilars: Current regulatory perspective and challenges
Notice bibliographique
Résumé
Sir, Biosimilars—the generic version of biologicals is the new buzz word in pharmaceutical industry. With annual growth rate of 7%, the sector is expected to grow to $172 billion by 2015.[1] Biosimilars are highly similar to licensed reference product notwithstanding minor differences in clinically inactive components; also there are no clinically meaningful differences between the biologicals and the reference product in terms of safety, purity, and potency. Beginning with human insulin, human growth hormone, and erythropoietin (1982, 1985, and 1989) >200 biosimilars have hit market. The market for erythropoietin was worth $13 billion in 2011, ahead of Lipitor which had market of $12.4 billion in 2008 ($12.4 billion in 2011).[2] Biologicals differ from conventional generics in size, structure, stability, in-built heterogeneity, and analytical characterization. Their unique multidimensional structure and complicated mode of action are never fully reproducible. Even with same molecular weight and production by same type of cells, they possess different properties, e.g., European Medicines Agency (EMEA) rejected the biosimilar Alpheon (interferon-oL) due to a higher number of AEs and more frequent recurrence of disease in patients treated with Alpheon than reference–Roferon-A. For immunoglobulins, small differences in core fucosylation led to big changes in receptor binding and consequently impacted immune functions like cellular cytotoxicity.[2] The classical paradigm of bioequivalence cannot be applied to protein drugs as evident from case of Retacrit. EMEA/Committee for Medicinal Products for Human Use (CHMP) burgeoned the concept of biosimilarity. Biosimilars’ approval should consider exactly same high standards and stringent requirements for quality, efficacy, or safety. First recommendation for the approval of biogenerics came in 2004 by the European Parliament. By 2011, 14 marketing authorizations were made by EMEA. EMEA lays that biosimilars be fully characterized for physicochemical and biophysical attributes.[3] Guidelines are laid for human soluble insulin, somatropin, granulocyte colony stimulating factor (G-CSF), and epoetins. With France as only exception, there are no regulations in other countries of EU. Australia adopted the EMEA guidelines, whereas Japan and Singapore issued guidelines in 2009, followed by Health Canada in 2010. WHO and some national guidance documents recommend EMEA approaches. FDA recommends two approaches: (1) biosimilar approach and (2) stand-alone approach. The guidelines are under construction and vary case to case. Sandoz's somatropin product, Omnitrope, was approved by FDA, but this pathway cannot be used for other products.[4] Till recently in India, marketing authorizations were in line with US approach. In July 2012, “Guidelines on Similar Biologics: Regulatory Requirements for Marketing Authorization in India” was introduced. It draws cues from EMEA/ICH guidelines.[5] The main points to consider about biosimilars are their safety, automatic substitution, naming, and labeling/prescription. The safety profile of biosimilars is not identical to reference as seen for biosimilar growth hormone, Valtropin, which had different precautions and warnings from reference, Humatrope. The immunogenicity of biosimilars cannot be fully predicted using preclinical/clinical studies. Robust pharmacovigilance still remains critical consideration. The story of epoetin therapy is instructive and called for subtle changes in manufacturing. Biosimilars cannot have the same international non-proprietary name as innovator. “Quality by design” approach provides assurance of quality of the reference product but requires critical understanding of variability ofevery product attribute. A manufacturer may well establish the design space for his product but cannot use this concept to ensure similarity with the reference. Every biological is different and healthcare professionals should interchange biologicals after careful analysis of supporting data.[2]
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».