Iqbal Zarina, Sadaf Saima
IP and Litigation Department, PakPat World Intellectual Property Protection Services, Lahore, Pakistan.
Biopharmaceutical and Biomarkers Discovery Lab, School of Biochemistry and Biotechnology, University of the Punjab, Lahore, 54590 Pakistan.
J Pharm Innov. 2022 Jul 28:1-33. doi: 10.1007/s12247-022-09665-7.
Heparin is a subject of ever-growing interest for laboratory researchers and pharmaceutical industry. One of the driving factors is its critical life-saving drug status, which during the COVID-19 pandemic has assumed a central role in disease treatment and/or prevention. Apart, heparin is one amongst few drugs enjoying a "demand constant" status. In 2020, heparin market size was valued to US$6.5 bn., and given the ongoing stability in the COVID-19 health crisis, it is expected to reach US$11.43 bn. by 2027 with yearly growth rate momentum (CAGR) of 3.9% during the forecast period (Pepi et al., Mol Cell Proteomics 20:100,025, 2021). As patent is a limited monopoly, every year, many patents on low molecular weight heparin (LMWH; a chemically or enzymatically degraded product of unfractionated heparin) are losing market exclusivity worldwide, inviting the generic/biosimilar drug manufacturers to capture market share with cheaper drug products. By tracking patent expiration, drugs in patent litigation, regulatory setbacks for innovator companies (such as those seeking data exclusivity or patent term extension), or other unexpected events affecting market demand and competition, generics can make investment decisions in manufacturing off-patent LMWH drug products of commercial significance. However, given the US Food and Drug Administration (FDA), European Medicine Agency (EMA), Drug Regulatory Authority of Pakistan (DRAP), and other regulatory authorities scientifically rigorous standards for generic/biosimilar LMWH drug products marketing approval, the market is secured and momentous for drug makers that could demonstrate through scientific and clinical dataset that the generic/biosimilar LMWH drug product is of the same quality and purity as the innovator drug product. This study presents an overview of the patent landscape of commercially available LMWHs and advanced analytical techniques for their structural and biochemical characterization for quality control and quality assurance during manufacturing and post-marketing. The study also covers FDA, EMA, Health Canada, and DRAP's current approaches to evaluating the generic/biosimilar LMWH drug products for quality, safety including immunogenicity, and efficacy.
肝素一直是实验室研究人员和制药行业日益关注的对象。其中一个推动因素是其关键的救命药物地位，在新冠疫情期间，它在疾病治疗和/或预防中发挥了核心作用。此外，肝素是少数几种处于“需求稳定”状态的药物之一。2020年，肝素市场规模估值为65亿美元，鉴于新冠健康危机持续稳定，预计到2027年将达到114.3亿美元，在预测期内年增长率为3.9%（佩皮等人，《分子与细胞蛋白质组学》20:100,025，2021）。由于专利是一种有限的垄断，每年，许多关于低分子量肝素（LMWH；普通肝素的化学或酶降解产物）的专利在全球范围内失去市场独占权，这吸引了仿制药/生物类似药制造商用更便宜的药品抢占市场份额。通过跟踪专利到期情况、专利诉讼中的药物、创新公司的监管挫折（如那些寻求数据独占权或专利期限延长的公司）或其他影响市场需求和竞争的意外事件，仿制药公司可以做出投资决策，生产具有商业意义的专利过期的低分子量肝素药品。然而，鉴于美国食品药品监督管理局（FDA）、欧洲药品管理局（EMA）、巴基斯坦药品监管局（DRAP）以及其他监管机构对仿制药/生物类似药低分子量肝素药品上市批准的科学严格标准，对于那些能够通过科学和临床数据集证明仿制药/生物类似药低分子量肝素药品与创新药产品质量和纯度相同的制药商来说，市场是有保障且意义重大的。本研究概述了市售低分子量肝素的专利情况，以及用于其结构和生化表征的先进分析技术，以在生产和上市后进行质量控制和质量保证。该研究还涵盖了FDA、EMA、加拿大卫生部和DRAP目前评估仿制药/生物类似药低分子量肝素药品的质量、安全性（包括免疫原性）和疗效的方法。
