首頁 > 市場調查報告書 > 醫療設備

生技設備生物工藝

市場調查報告書

商品編碼

1140701

全球一次性生物加工市場-2022-2029

Global Single-Use Bioprocessing Market - 2022-2029

出版日期: 2022年10月20日 | 出版商:

DataM Intelligence | 英文 180 Pages | 商品交期: 約2個工作天內

價格

※ 本網頁內容可能與最新版本有所差異。詳細情況請與我們聯繫。

簡介目錄

市場概況

一次性生物加工市場規模預計將在 2021 年達到 76.2 億美元，在 2029 年達到 254 億美元，在預測期間（2022-2029 年）以 18.93% 的複合年增長率增長。

一次性生物處理系統是使用一次然後丟棄的生物處理設備。一次性生物處理系統由塑料部件組成，可以使用伽馬射線進行滅菌和密封。一次性生物處理系統用於生物藥物的混合、過濾、純化、上游表達、儲存和分離。該市場主要由多種一次性生物處理系統的可用性主導，例如生物反應器和發酵罐、混合器、袋子、生物處理容器和過濾。

市場動態

由於生物製藥的日益普及，市場對一次性生物處理系統的需求不斷增長。一次性生物處理系統具有高能效、低用水量、佔地面積要求以及產品交叉污染風險極低或無風險等優點。一次性生物處理系統可以快速部署。

對生物製藥的不斷增長的需求推動了一次性生物加工市場的增長

根據聯合國人口老齡化要聞，預計到 2020 年，世界人口中將有 7.27 億人年齡在 65 歲以上，到 2050 年這一數字有望翻一番，達到 15 億。隨著老年人口在主要市場的增長，對生物製藥的需求預計將增加，因為老年人更容易患慢性病和疾病。為了滿足對生物製藥日益增長的需求，越來越多的公司正在採用一次性生物工藝系統。這是為了提高工藝效率並降低與鋼基生物反應器系統的清潔、滅菌和維護等複雜步驟相關的成本。過濾、混合、純化、上游表達、儲存和分離都是使用一次性生物處理技術的生物製藥應用。

2019 年 1 月，Sartorius Stedim Biotech 推出了“Biostat RM TX with Flexsafe RM TX”，用於生產質量穩定的細胞產品。Biostat RM TX 是一種一次性生物反應器，是一種新的波浪混合系統，專門為封閉式、自動擴展質量一致的細胞產品（如離體細胞免疫療法）而開發。它將一次性 flexsafe 袋技術與我們在生物製藥自動化方面的專業知識相結合。Biostat RM TX 專為細胞（包括患者特異性 T 細胞）的橫向擴展而設計，是一個封閉系統，由一個自動控制單元和最多兩個搖擺平台組成，可輕輕攪動一次性 Flexsafe RM TX 袋。 .

與廢物處理相關的問題可能會阻礙一次性生物加工市場的增長

由於與一次性生物加工產品相關的眾多好處，例如降低成本、加快工藝開發時間和降低資本支出，生物製藥公司越來越多地採用一次性生物加工產品。然而，對於這種替代技術產生的固體廢物的處理，仍然存在嚴重的擔憂。回收被排除在此類產品的一種選擇之外，因為將成分分離成同質部分需要付出很多努力。因此，大多數一次性系統及其組件不適合回收利用。這些因素阻礙了預測期內的市場增長。

行業分析

全球一次性生物加工市場基於波特五力、監管分析、供應鏈分析和定價分析等各種行業因素對市場進行了深入分析。

細分分析

一次性/一次性生物反應器部分預計將佔全球一次性生物加工市場的最大市場份額

一次性生物加工市場根據產品細分為培養基袋和容器、過濾組件、一次性/一次性生物反應器、一次性混合器等。一次性/一次性生物反應器細分市場在 2019 年佔有相當大的市場份額。一次性/一次性生物反應器由一次性袋子而不是培養容器組成。用於哺乳動物細胞培養的最佳一次性/一次性生物反應器依賴於高細胞密度或基於微載體的工藝。一次性生物反應器減少了清潔和滅菌的需要。這些生物反應器可有效提高生物安全性和工藝安全性。這個市場主要由幾個一次性/一次性生物反應器的可用性主導。例如，Sartorius 一次性生物反應器（Ambr15 至 BiostatSTR 2,000 L）的開發是為了便於放大和縮小。即使在大規模放大時，它也具有前所未有的高性能。這些生物反應器非常適合從工藝開發到商業生產的所有當前和未來需求。幾家公司正在通過一次性/一次性生物反應器擴大其製造設施。例如，Millipore Sigma 擴大了其一次性 cGMP 設施，增加了 Mobius 2,000 L 一次性生物反應器，並通過其提供的 Provantage 端到端服務，上游開發，我們現在能夠提供製造服務。

此外，一次性生物加工市場按最終用戶細分為生物製藥製造商、生命科學研發公司、學術研究機構、研究機構/製造商等。合同研究機構和製造商部門佔據了最高的市場份額。合同研究實驗室和製造商專注於在其製造設施中安裝一次性生物加工產品。合同研究實驗室和製造商正在部署一次性生物處理設備，包括生物反應器，用於大規模的內部生物製造。合同研究實驗室和製造商使用一次性血袋、轉移套件、T 型燒瓶和移液器進行基於細胞療法的臨床研究。

區域分析

北美佔全球一次性生物加工市場的最大市場份額。

按地區劃分，一次性生物加工市場分為北美、南美、歐洲、亞太地區、中東和非洲。在所有地區中，由於在疫苗、單克隆抗生素、細胞療法和其他療法的生產中大量採用一次性生物加工系統，北美在一次性生物加工市場中佔據主導地位。一次性生物處理系統使用高級聚合物材料和具有整體強度增強的塑料複合材料製造。一些製造商使用一次性生物處理系統，因為它們可以降低總體運營成本並提供生物製造的連續性。還有大型生物製藥生產設施。市場正在見證技術進步，例如生物過程中的自動化、大數據和機器學習 (ML) 解決方案。這些技術進步對於在醫療程序中預測錯誤和提高準確性很有用。

歐洲一次性生物加工市場在全球市場中佔據僅次於北美的第二位，市場份額突出。由於研發計劃的增加和巨大的生產能力，歐洲的一次性生物加工市場是潛在市場增長的關鍵因素。在歐洲，英國主導市場，預計在預測期內將穩步增長。預計德國和法國將在預測期內見證一次性生物加工市場的顯著增長。

預計亞太地區在預測期內將表現出積極的市場增長。一次性生物處理系統使藥物製造過程更快、更簡單、更便宜，並且一次性生物處理系統的使用正在增長。一次性生物處理系統的使用提高了產品的生產效率。有幾家公司正在開發一次性生物加工系統。一些公共和私營公司正在增加對開發一次性生物處理系統的投資。

競爭格局

一次性生物加工市場與眾多國際和國內參與者競爭激烈。產品多樣化、技術進步、收入獲取和機會正在使市場更具競爭力。3M 公司、Applikon Biotechnology、Cesco Bioengineering Co.、Danaher Corporation、General Electric Company、Merck KGaA、PBS Biotech Inc. 和 Thermo Fisher Scientific Inc. 是擁有重要市場份額的主要參與者。

公司利用新產品發布、產能利用、技術進步、新產品開發和市場擴張戰略來維持其市場地位。例如，2021 年 7 月，Sartorius收購了德國公司 Xell，並將其納入賽多利斯 Stedim Biotech 子集團。這將擴大細胞培養基和飼料補充劑的業務。Xell 還將擴展其 Sartorius 分析產品和服務，用於介質及其組件的表徵和量化，以及介質成分的優化。

2019年1月，Boehringer-Ingelheim擴大了其在中國的商業生物製劑生產基地。此次擴建是為了整合一個具有所有必要基礎設施和公用設施的生物反應器，以支持 2x 2.000 L 一次性生物反應器生產線的 GMP 操作。

例如，2019 年 3 月，生物製藥行業的領先供應商 Sartorius Stedim Biotech (SSB) 與 Novasep 在色譜和一次性生物加工領域展開合作。Novasep基於生命科學行業的專業技術提供各種產品和服務。Novasep 已建立的 BioSC 平台和 SSB 的一次性技術將成為開發創新色譜系統的基礎。

2019 年 2 月，Pall Biotech與一次性組件和流體管理技術專家 Artesyn Biosolutions 建立了合作夥伴關係。該協議包括一個聯合開發合作夥伴關係，為一次性自動化生物處理系統提供完整的臨床到商業規模的解決方案。這些系統可以通過用於生物技術和生物產品的 cGMP 製造的完全工業化標準平台加快產品開發和上市時間。此次合作將 Pall Biotech 的 Allegro 一次性解決方案從上游延伸到下游，再到最終灌裝。該合作夥伴關係將提供具有強大流體管理功能的工業和模塊化一次性生物工藝解決方案。

值得關注的重點公司

Thermo Fisher Scientific Inc

概述 Thermo Fisher 是一家美國公司，提供範圍廣泛的科學分析儀器、實驗室試劑和耗材以及科學軟件服務。成立於 1956 年，總部位於美國馬薩諸塞州沃爾瑟姆。

產品介紹

Thermo Scientific HyPerforma DynaDrive 一次性生物反應器。一次性使用的生物反應器，具有出色的性能和大容量的可擴展性。適用於灌注和分批補料工藝。

重大發展。2021 年 10 月，Thermo Fisher Scientific宣布將承擔其位於瑞士 Lengnau 的最先進生物製劑製造工廠的運營責任。它將擁有高度靈活的生物製造技術，例如一次性生物反應器和不銹鋼生物反應器。

這份研究報告提供了對全球一次性生物加工市場大約 45 多個市場數據表、40 多個數字和 180 頁的訪問權限。

Market Overview

Single-use Bioprocessing Market size was valued US$ 7.62 billion in 2021 and is estimated to reach US$ 25.40 billion by 2029, growing at a CAGR of 18.93% during the forecast period (2022-2029).

Single-use bioprocessing systems are bioprocessing equipment that is used once and disposed of. Single-use bioprocessing systems are made up of plastic components that can be sterilized and sealed by using gamma irradiation. Single-use bioprocessing systems are used for mixing, filtration, purification, upstream expression, storage, and separation of biopharmaceutical products. The market is dominated by the availability of several single-use bioprocessing systems such as bioreactors & fermenters, mixers, bags, bioprocess containers, and filtration.

Market Dynamics

The market is driven by the increasing demand for single-use bioprocessing systems with the growing penetration of biopharmaceuticals. Single-use bioprocessing systems have several advantages, such as high energy efficiency, low water usage, less floor space requirement, and very low or no risk of product cross-contamination. Single-use bioprocessing systems are faster to implement.

Growing demand for biopharmaceuticals drives the growth of single-use bioprocessing market

According to the UN Ageing Population Highlights, an estimated 727 million people in the global population will be 65 and older in 2020, by 2050, this figure is expected to double to 1.5 billion. The elderly population is more prone to chronic conditions and diseases, so demand for biopharmaceuticals is expected to rise as the senior population grows in major markets. Companies increasingly prefer single-use bioprocessing systems to meet the growing demand for biopharmaceuticals because they increase process efficiency and reduce costs associated with complicated steps such as cleaning, sterilization, and maintenance of steel-based bioreactor systems. Filtration, mixing, purification, upstream expression, storage, and separation are all biopharmaceutical applications that use single-use bioprocessing technology.

In January 2019, Sartorius Stedim Biotech launched the Biostat RM TX with Flexsafe RM TX for producing consistent quality cellular products. Biostat RM TX is a single-use bioreactor, a new wave hybrid system developed specifically for closed, automated expansion of consistent quality cell products such as ex vivo cellular immunotherapies. It combines single-use Flexsafe bag technology with the company's expertise in biopharmaceutical automation. Biostat RM TX is designed for scale-out expansion of cells, including patient-specific T cells, and is a closed system comprising an automated control unit and up to two rocking platforms to gently agitate single-use Flexsafe RM TX bags.

The problem associated with waste disposal is likely to hamper the growth of the single-use bioprocessing market

Biopharmaceutical firms are increasingly adopting single-use bioprocessing Products due to the numerous benefits associated with them, including cost savings, faster process development time, and lower capital investments. However, there are still serious concerns about the disposal of solid waste materials generated by this alternative technology. Recycling is not an option for such products because separating the components into homogeneous parts requires significant effort. As a result, most single-use systems and their parts are unsuitable for recycling. These factors are hampering the growth of the market in the forecast period.

Industry Analysis

The global single-use bioprocessing market provides in-depth analysis of the market based on various industry factors such as porter's five forces, regulatory analysis, supply chain analysis and pricing analysis.

Segment Analysis

Disposable/ single-use bioreactor segment is expected to hold the largest market share in global single-use bioprocessing market

The single-use bioprocessing market is segmented based on product as media bags and containers, filtration assemblies, disposable/single-use bioreactors, disposable mixers, and others. The disposable/single-use bioreactors segment accounts for a significant market share in 2019. The disposable/single-use bioreactors comprised of the disposable bag instead of a culture vessel. Disposable/single-use bioreactors that are ideal for mammalian cell culture depend on high cell density or microcarrier-based processes. Single-use bioreactors reduce the cleaning and sterilization demands. These bioreactors are effective for enhancing biological and process safety. The market is dominated by the availability of several disposable/single-use bioreactors. For instance, Sartorius's single-use bioreactors i.e., Ambr15 to BiostatSTR 2,000 L have been developed to ensure easy scale-up and scale-down. It is combined with unprecedented high performance even at a large scale. These bioreactors make the products perfectly suitable to serve all the current and future needs from process development to commercial production phases. Several companies are expanding their manufacturing facilities with the use of disposable/single-use bioreactors. For instance, MilliporeSigma had expanded its single-use cGMP facility with the addition of the Mobius 2,000 L single-use bioreactor, enabling the company to provide upstream development and manufacturing services using its equipment through its Provantage End-to-End Services offering

Further, the single-use bioprocessing market is also classified based on the end-users as biopharmaceutical manufacturers, life science R&D companies, academic research institutes, contract research organizations & manufacturers, and others. The contract research organizations & manufacturers segment accounts for the highest market share. Contract research organizations & manufacturers are focusing on installing single-use bioprocessing products at their manufacturing facilities. Contract research organizations & manufacturers are installing single-use bioprocessing equipment including bioreactors at a large scale for in-house biomanufacturing. Contract research organizations & manufacturers are using single-use blood bags, transfer sets, T-flasks, and pipettes for cell therapy-based clinical research.

Geographical Analysis

North America region holds the largest market share in the global single-use bioprocessing market

By region, the single-use bioprocessing market is segmented into North America, South America, Europe, Asia-Pacific, Middle-East, and Africa. Among all of the regions, North America dominated the single-use bioprocessing market due to the higher adoption of single-use bioprocessing systems for the production of vaccines, monoclonal antibiotics, cell therapies, and other therapies. The single-use bioprocessing systems are manufactured by using high-grade polymer materials and plastic composites that provide enhanced integral strength. Several manufacturers are using single-use bioprocessing systems as the use of these systems reduced the overall operational costs and provides continuity in biomanufacturing. There is a presence of large-scale biopharmaceutical manufacturing facilities. The market is witnessing technological advancement including automation, big data, and machine learning (ML) solutions in bioprocessing. These technological advancements are useful for predicting errors and improving accuracy during medical procedures.

Europe single-use bioprocessing market acquired the second position followed by North America in the global market with a prominent share of the market. Significant factors are probable the growth of the market owing to rising R&D initiatives, and huge production capabilities. In the Europe region, the United Kingdom is majorly controlling the market and estimated constant growth over the forecast period. Germany and France are projected to develop prominent growth in the Single-use Bioprocessing Market over the forecast period.

The Asia-Pacific is expected to witness positive market growth over the forecasted period. There is growing usage of single-use bioprocessing systems as these bioprocessing systems have made the drug manufacturing process faster, simpler, and cheaper. The use of single-use bioprocessing systems increases the productivity of the manufacturing of the products. There is a presence of several companies developing single-use bioprocessing systems. Several public and private players are raising their investment in the development of single-use bioprocessing systems.

Competitive Landscape

The single-use bioprocessing market is highly competitive with the presence of several international and local market players. Product diversification, technological advancement, revenue generation, and opportunities intensify the market competition. 3M Company, Applikon Biotechnology, Cesco Bioengineering Co., Danaher Corporation, General Electric Company, Merck KGaA, PBS Biotech Inc., and Thermo Fisher Scientific Inc. are the leading Market players with significant market share.

Companies are using novel product launches, capacity utilization, technology advancement, new product development, and market expansion strategies for holding their position in the market. For instance, in Jul 2021, Sartorius acquired German firm Xell, including it to subgroup Sartorius Stedim Biotech. This will lead to expanding its business of media and feed supplement for cell cultures. Xell also extends Sartorius analytical products and services for characterizing and quantifying media and its components and for optimizing the composition of media.

In Jan 2019, Boehringer Ingelheim expanded its commercial biologics manufacturing site in China. The expansion covered the incorporation of a bioreactor with all required infrastructure and utility to support the GMP operations of 2x 2.000 L single-use bioreactor manufacturing lines.

For instance, in Mar 2019, Sartorius Stedim Biotech (SSB), a leading supplier in the biopharmaceutical industry entered into a collaboration with Novasep in the area of chromatography and single-use bioprocessing. Novasep provides various products and services to the life science industry, based on specialized technologies. Novasep's established BioSC platform and SSB's single-use technology would form the basis for the development of innovative chromatography systems.

In Feb 2019, Pall Biotech entered into a collaboration with Artesyn Biosolutions, a company specializing in single-use components and fluid management technologies. The agreement would encompass a co-development partnership, delivering complete solutions from clinical to commercial-scale for single-use automated bioprocessing systems. These systems would accelerate product development and time to market through a fully industrialized and standard platform for cGMP manufacturing of biotech and biological products. This collaboration expands Pall Biotech's Allegro single-use solution portfolio from upstream through downstream, and to final filling. This collaboration would provide industrial and modular single-use bioprocess solutions, resulting in robust fluid management.

Key Companies to Watch

Thermo Fisher Scientific Inc.:

Overview: Thermo Fisher is an American company that supplies variety of scientific or analytical instruments, lab reagents & consumables, and some scientific software services. It was founded in 1956 and headquartered in Waltham, Massachusetts, U.S.

Product Portfolio:

Thermo Scientific HyPerforma DynaDrive Single-Use Bioreactor: It is a single-use bioreactor that is better in performance and scalability for larger volumes. It is suitable for perfusion and fed batch processes.

Key Developments: In Oct 2021, Thermo Fisher Scientific announced about assuming operational responsibility for Lengnau, Switzerland their latest site for biologics manufacturing. It will have a flexible bioproduction technology including single use bioreactor and stainless steel bioreactors.

The global single-use bioprocessing market report would provide an access to an approx. 45+market data table, 40+figures and 180pages.

1. Methodology and Scope

1.1. Research Methodology
1.2. Research Objective and Scope of the Report

2. Market Definition and Overview

3. Executive Summary

4. Market Dynamics

4.1. Market Impacting Factors
- 4.1.1. Drivers:
  - 4.1.1.1. Growing demand for biopharmaceuticals
  - 4.1.1.2. Growing technological advancements
- 4.1.2. Restraints:
  - 4.1.2.1. Problem associated with waste disposal
- 4.1.3. Opportunity
- 4.1.4. Impact Analysis

5. Industry Analysis

5.1 Porter's Five Forces Analysis
5.2 Regulatory Analysis
5.3 Supply Chain Analysis
5.4 Pricing Analysis

6. By Product

6.1. Introduction
- 6.1.1. Market Size Analysis, and Y-o-Y Growth Analysis (%), By Product Segment
- 6.1.2. Market Attractiveness Index, By Product Segment
6.2. Media Bags and Containers
- 6.2.1. Introduction
- 6.2.2. Market Size Analysis, US$ Million, 2020-2029 and Y-o-Y Growth Analysis (%), 2021-2029
6.3. Filtration Assemblies
6.4. Disposable/Single-Use Bioreactors
6.5. Disposable Mixers
6.6. Other

7. By Application

7.1. Introduction
- 7.1.1. Market Size Analysis, and Y-o-Y Growth Analysis (%), By Application
- 7.1.2. Market Attractiveness Index, By Application
7.2. Filtration
- 7.2.1. Introduction
- 7.2.2. Market Size Analysis, US$ Mn, 2020-2029 and Y-o-Y Growth Analysis (%), 2021-2029
- 7.2.3. Storage
- 7.2.4. Cell Culture
- 7.2.5. Mixing
- 7.2.6. Purification

8. By End User

8.1. Introduction
- 8.1.1. Market Size Analysis, and Y-o-Y Growth Analysis (%), By End User Segment
- 8.1.2. Market Attractiveness Index, By End User Segment
8.2. Biopharmaceutical Manufacturers
- 8.2.1. Introduction
- 8.2.2. Market Size Analysis, US$ Million, 2020-2029 and Y-o-Y Growth Analysis (%), 2021-2029
8.3. Life Science R&D Companies
8.4. Academic Research Institutes
8.5. Contract Research Organizations & Manufacturers
8.6. Others

9. By Region

9.1. Introduction
- 9.1.1. Market Size Analysis, and Y-o-Y Growth Analysis (%), By Region
- 9.1.2. Market Attractiveness Index, By Region
9.2. North America
- 9.2.1. Introduction
- 9.2.2. Key Region-Specific Dynamics
- 9.2.3. Market Size Analysis, and Y-o-Y Growth Analysis (%), By Product
- 9.2.4. Market Size Analysis, and Y-o-Y Growth Analysis (%), By Application
- 9.2.5. Market Size Analysis, and Y-o-Y Growth Analysis (%), By End-User
- 9.2.6. Market Size Analysis, and Y-o-Y Growth Analysis (%), By Country
  - 9.2.6.1. The U.S.
  - 9.2.6.2. Canada
  - 9.2.6.3. Mexico
9.3. Europe
- 9.3.1. Introduction
- 9.3.2. Key Region-Specific Dynamics
- 9.3.3. Market Size Analysis, and Y-o-Y Growth Analysis (%), By Product
- 9.3.4. Market Size Analysis, and Y-o-Y Growth Analysis (%), By Application
- 9.3.5. Market Size Analysis, and Y-o-Y Growth Analysis (%), By End-User
- 9.3.6. Market Size Analysis, and Y-o-Y Growth Analysis (%), By Country
  - 9.3.6.1. Germany
  - 9.3.6.2. The U.K.
  - 9.3.6.3. France
  - 9.3.6.4. Rest of Europe
9.4. South America
- 9.4.1. Introduction
- 9.4.2. Key Region-Specific Dynamics
- 9.4.3. Market Size Analysis, and Y-o-Y Growth Analysis (%), By Product
- 9.4.4. Market Size Analysis, and Y-o-Y Growth Analysis (%), By Application
- 9.4.5. Market Size Analysis, and Y-o-Y Growth Analysis (%), By End-User
- 9.4.6. Market Size Analysis, and Y-o-Y Growth Analysis (%), By Country
  - 9.4.6.1. Brazil
  - 9.4.6.2. Argentina
  - 9.4.6.3. Rest of South America
9.5. Asia Pacific
- 9.5.1. Introduction
- 9.5.2. Key Region-Specific Dynamics
- 9.5.3. Market Size Analysis, and Y-o-Y Growth Analysis (%), By Product
- 9.5.4. Market Size Analysis, and Y-o-Y Growth Analysis (%), By Application
- 9.5.5. Market Size Analysis, and Y-o-Y Growth Analysis (%), By End-User
- 9.5.6. Market Size Analysis, and Y-o-Y Growth Analysis (%), By Country
  - 9.5.6.1. China
  - 9.5.6.2. India
  - 9.5.6.3. Japan
  - 9.5.6.4. Australia
  - 9.5.6.5. Rest of Asia Pacific
9.6. The Middle East and Africa
- 9.6.1. Introduction
- 9.6.2. Key Region-Specific Dynamics
- 9.6.3. Market Size Analysis, and Y-o-Y Growth Analysis (%), By Product
- 9.6.4. Market Size Analysis, and Y-o-Y Growth Analysis (%), By Application
- 9.6.5. Market Size Analysis, and Y-o-Y Growth Analysis (%), By End-User

10. Competitive Landscape

10.1. Competitive Scenario
10.2. Market Positioning/Share Analysis
10.3. Mergers and Acquisitions Analysis

11. Company Profiles

11.1. Thermo Fisher Scientific Inc.
- 11.1.1. Company Overview
- 11.1.2. Product Portfolio and Description
- 11.1.3. Key Developments
- 11.1.4. Financial Overview
11.2. 3M Company
11.3. Applikon Biotechnology
11.4. Danaher Corporation
11.5. Merck KGaA
11.6. General Electric Company
11.7. PBS Biotech Inc.
11.8. Sartorius
11.9. Boehringer Ingelheim
11.10. NovoSep

LIST NOT EXHAUSTIVE