Silge Anja, Bocklitz Thomas, Becker Bjoern, Matheis Walter, Popp Juergen, Bekeredjian-Ding Isabelle
1Institute of Physical Chemistry and Abbe Center of Photonics, Friedrich-Schiller University Jena, Helmholtzweg 4, D-07743 Jena, Germany.
InfectoGnostics Research Campus Jena, Centre of Applied Research, Philosophenweg 7, D-07743 Jena, Germany.
NPJ Vaccines. 2018 Oct 4;3:50. doi: 10.1038/s41541-018-0088-y. eCollection 2018.
Vaccines are complex biomedicines. Manufacturing is time consuming and requires a high level of quality control (QC) to guarantee consistent safety and potency. An increasing global demand has led to the need to reduce time and cost of manufacturing. The evolving concepts for QC and the upcoming threat of falsification of biomedicines define a new need for methods that allow the fast and reliable identification of vaccines. Raman spectroscopy is a non-destructive technology already established in QC of classical medicines. We hypothesized that Raman spectroscopy could be used for identification and differentiation of vaccine products. Raman maps obtained from air-dried samples of combination vaccines containing antigens from tetanus, diphtheria and pertussis (DTaP vaccines) were summarized to compile product-specific Raman signatures. Sources of technical variance were emphasized to evaluate the robustness and sensitivity in downstream data analysis. The data management approach corrects for spatial inhomogeneities in the dried sample while offering a proper representation of the original samples inherent chemical signature. Reproducibility of the identification was validated by a leave-one-replicate-out cross-validation. The results highlighted the high specificity and sensitivity of Raman measurements in identifying DTaP vaccine products. The results pave the way for further exploitation of the Raman technology for identification of vaccines in batch release and cases of suspected falsification.
疫苗是复杂的生物药物。生产过程耗时且需要高水平的质量控制（QC）以确保一致的安全性和效力。全球需求的不断增加导致需要减少生产时间和成本。质量控制概念的不断演变以及生物药物造假的潜在威胁，催生了对能够快速可靠地识别疫苗的方法的新需求。拉曼光谱是一种已在传统药物质量控制中确立的无损技术。我们推测拉曼光谱可用于疫苗产品的识别和区分。对从含有破伤风、白喉和百日咳抗原的联合疫苗（DTaP疫苗）的风干样品获得的拉曼图谱进行汇总，以编制特定产品的拉曼特征。强调了技术差异的来源，以评估下游数据分析中的稳健性和灵敏度。数据管理方法校正了干燥样品中的空间不均匀性，同时恰当地呈现了原始样品固有的化学特征。通过留一重复交叉验证对识别的可重复性进行了验证。结果突出了拉曼测量在识别DTaP疫苗产品方面的高特异性和灵敏度。这些结果为进一步利用拉曼技术在批量放行和疑似造假案例中识别疫苗铺平了道路。
