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.

肝素是实验室研究人员和制药行业越来越感兴趣的主题。驱动因素之一是其关键的救命药物状态，在 COVID-19 大流行期间，它在疾病治疗和/或预防中发挥了核心作用。此外，肝素是少数享有“需求恒定”状态的药物之一。2020 年，肝素市场规模为 65 亿美元，鉴于 COVID-19 健康危机的持续稳定，预计将达到 114.3 亿美元。到 2027 年，预测期内的年增长率动量 (CAGR) 为 3.9%（Pepi 等人，Mol Cell Proteomics 20:100,025, 2021）。由于专利是一种有限的垄断，每年都有许多低分子量肝素（LMWH；普通肝素的化学或酶降解产物）专利在全球范围内失去市场独占性，邀请仿制药/生物仿制药制造商以更便宜的药品抢占市场份额。通过跟踪专利到期、专利诉讼中的药物、创新公司的监管挫折（例如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，仿制药可以在制造非专利 LMWH 药物方面做出投资决策具有商业意义的产品。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) 和其他监管机构对仿制药/生物仿制药 LMWH 药品上市审批的科学严格标准，对于可以通过科学和临床数据集证明仿制药/生物仿制药 LMWH 药物产品与创新药物产品具有相同质量和纯度的制药商而言，市场是安全且重要的。本研究概述了市售 LMWH 的专利情况和先进的分析技术，用于在制造和上市后进行质量控制和质量保证的结构和生化表征。该研究还涵盖了 FDA、EMA、加拿大卫生部和 DRAP 目前评估仿制药/生物仿制药 LMWH 药物产品的质量、安全性（包括免疫原性和有效性）的方法。本研究概述了市售 LMWH 的专利情况和先进的分析技术，用于在制造和上市后进行质量控制和质量保证的结构和生化表征。该研究还涵盖了 FDA、EMA、加拿大卫生部和 DRAP 目前评估仿制药/生物仿制药 LMWH 药物产品的质量、安全性（包括免疫原性和有效性）的方法。本研究概述了市售 LMWH 的专利情况和先进的分析技术，用于在制造和上市后进行质量控制和质量保证的结构和生化表征。该研究还涵盖了 FDA、EMA、加拿大卫生部和 DRAP 目前评估仿制药/生物仿制药 LMWH 药物产品的质量、安全性（包括免疫原性和有效性）的方法。