What exactly is viral clearance?
The development of drugs or biological processes involves the usage of human and animal tissues/proteins. These proteins or tissues may contain viruses that can be deadly or can threaten human life. Thus, to ensure that the biological product is safe to use, elimination of virus contamination is crucial. The process of virus removal or virus inactivation is called viral clearance.
Viral clearance is usually performed before phase I and phase II clinical trials. The total virus clearance validation is done before rolling out the Phase III clinical trials. To achieve the risk-free biological product, there are certain procedures that need to be followed which depends on the method chosen for viral safety.
It’s recommended that there should be two significant steps involved in the removal or inactivation of the virus. During the early phase, the tests must be performed on enveloped viruses such as herpes and non-enveloped virus such as parvovirus. The first step in the procedure involves inactivation/removal by a chemical method and the other step includes removal by a physical setup.
If viral contamination is not done properly, it can affect the raw materials, bioreactor contamination, and downstream processing in the biopharmaceutical industry. The rising prevalence of viruses such as HIV, hepatitis A, and Parvovirus B19, among others has surged the importance of viral safety. For instance, according to the study by the World Health Organization (WHO), the prevalence of Parvovirus B19 was witnessed to be 1 in 1,000-7,000 donors while for Hepatitis B it was 1 in 10,000 donors.
3 Viral Removal Methods/Procedures That Are Used in the Pharmaceutical Industry
This method is usually considered effective against viruses such as HAV and parvovirus B19. As compared to other methods, precipitation is difficult to model. During the process, the protein concentration, pH, and temperature are to be recorded for successful viral removal. Furthermore, the degree of contamination with supernatant should also be considered. Small and medium enterprise usually uses PEG precipitation virus kit owing to its inexpensive and time-saving nature. Some common chemical compounds that are used during precipitation are ethanol, polyethylene, and acetone.
Chromatography is used in the virus purification of protein as it can be effectively used for viruses such as parvovirus B19 and HAV. In this method, virus removal depends on the choice of buffers, proteins, and resins. Under the umbrella of the chromatography method, there are various types of methods such as ion exchange, affinity, and mixed-mode. Amongst all, the ionic exchange has been considered as an effective method. Few relevant properties that need to be recorded are flow rate and buffer volumes. Moreover, the number of cycles of resin use and resin package should be taken into consideration. In 2019, the chromatography method accounted for significant revenue in the viral clearance market.
In this virus removal method, the viruses are removed by size exclusion technique. This method is usually used for both enveloped and non-enveloped viruses such as parvovirus B19 and HAV which has a protein coating on it. In this process, the risk of downstream contamination is lower as compared to the aforementioned method. Moreover, it has a higher recovery of smaller proteins and does not denature proteins.
Nanofiltration depends on the size of the filter while during the process properties such as protein concentration, filter integrity, and flow-rate needs to be taken into consideration. According to the market trends, the nanofiltration method segment is anticipated to exhibit a higher CAGR owing to the growing demand for filtration and advancement in the technology.
3 Viral Inactivation Methods in the Biopharmaceutical Industry
In the viral clearance industry, enveloped viruses such as HAV, HBC, and HCV, among others are the most difficult ones to inactive. Solvent/detergent has turned out to be the well-established method as it uses simple equipment and has high process recovery. The solvents and detergents being used in the market are tri-(n-butyl) phosphate (TNBP) and Triton-X compounds. After the inactivation, solvents and detergents should be removed. This method is not feasible for the removal of non-enveloped viruses. During the process, reagent concentration levels should be observed for the successful viral inactivation.
One of the advantages of this method that it inactivates both enveloped and non-enveloped viruses. Along with this, it uses simple equipment which makes it feasible in the biopharma industry. Few protein stabilizers utilized during the process are sodium caprylate, caprylic acid, and acetyl tryptophan chemical compounds. During the process, temperature homogeneity and duration should be taken into consideration.
Low pH and high pH are the two type of treatment which depends on the type of virus. For instance, low pH inactivation is used for the monoclonal antibody purification process while high pH inactivation is used for certain types of enveloped and non- enveloped viruses. Currently, low pH treatment is the most common viral clearance method. In this method, the equipment used are easily available and simple. The vital parameters that need to be observed are time, pH, and temperature.
There are other methods such as irradiation, microwave heating, terminal dry heating, Ultraviolet-C (UVC) & high-temperature short time (HTST), and vapor heating, among others which are not extensively used in the market.
4 Techniques (Viral Detection Methods) Used in the Viral Clearance Market
qPCR (quantitative polymerase chain reaction):
qPCR assays are the most common method used in the assessment of viral clearance studies or detection of the virus in the biopharmaceutical industry.
Real-time PCR has been adopted for the detection of viruses such as the Zika Virus and COVID-19. It’s a successor of PCR with improved sensitivity and speed. Moreover, it has reduced the risk of carry-over contamination.
ELISA (Enzyme-linked immunosorbent assay):
ELISA is a plate-based assay technique for detecting various antibodies, hormones, and proteins. Many companies are providing ELISA kits to detect the host cell protein and other bioprocess impurities.
Western blot assays are used for the detection of bovine immunodeficiency virus and HIV antibodies. Many companies such as GE Healthcare, Thermfisher Scientific are marketing their western blot based products.
In 2019, the viral removal segment accounted for the largest market share and is expected to grow at a robust rate during the forecast period. The viral inactivation segment is anticipated to expand at a steady rate in the foreseeable future. In the two above-mentioned segments, chromatography and nanofiltration sub-segment are expected to offer innovations and technologies in the coming years. Meanwhile, the viral detection segment is expected to offer lucrative opportunities to the industry players in the coming years.
Impact of COVID-19 to the Viral Clearance Market
The coronavirus outbreak has slumped the burden of the healthcare system. Recently, various industry players grabbed the opportunity with the manufacturing of sanitizers, masks, and ventilators, among others. Today, government and private entities are releasing funds for the fast development of the vaccine. This has forced them to use efficient viral detection, removal, and inactivation methods and processes to compete in the market.
Investors are heavily investing in Contract Research Organizations (CROs) and Contract Manufacturing Organizations (CMOs) in this period owing to the lucrative opportunities in the foreseeable future. Particularly, the growth of the viral clearance market is expected to be exponential in the period of 2020-2026. The incidence of new viruses across the globe has fueled the demand for chromatography systems, filters, and high-quality chemical compounds, among others.
Various Industry players are expanding their product portfolio in the viral clearance market while new entrants and emerging players are striving to gain a stronghold in the market share with help of collaboration, partnerships, and innovation in the existing products in the market. Moreover, the companies are not only providing products but have also ventured into the services segment to expand their market share.
Top 6 Companies in the Viral Clearance Market
WuXi Biologics (Suzhou), a Chinese drug development &biosafety testing provider, offers downstream process development and has extensive infectivity and PCR virus detection assays. The company has developed over 15 qPCR assays for common model viruses utilized in viral clearance studies. In June 2020, Suzhou received an EMA GMP certificate for biosafety testing. During the year, it has completed the acquisition of drug product manufacturing in Germany and signed a lease for clinical manufacturing in the United States.
Charles River Laboratories:
Charles River Laboratories, an American company specializing in laboratory services, provides viral clearance and TSE clearance studies to its clients. This company offers in-process testing programs to detect the virus presence and ensure the absence of the virus. It uses qPCR analysis and TCID50 assay to find out the viral titer. In February 2019, the organization acquired Citoxlab, for approximately USD 510 Million. The latter company specializes in safety assessment services and non-regulated discovery services.
Avance Biosciences, Inc., a United States-based genomic service company, specializes in qPCR assay development, sample testing, and validation. The company offers Real-Time PCR/assays which is possible due to its ABI 7900 HT Sequence Detection System. Avance has been in the industry for nearly 20 years in the biopharmaceutical industry. Along with biological testing, it has expanded its portfolio in gene/cell therapy testing, and COVID-19 testing and vaccine development support.
Clean Cells, a France-based biopharmaceutical company, specializes in biosafety testing and quality control testing. In December 2018, ArchiMed, a healthcare equity firm, invested in Clean Cells to accelerate its growth in the industry. Over the years, the company has developed multiple assays to determine the purity of the product. It uses Residual Host Cell Protein (HCP) quantification, residual DNA testing, and endotoxin testing, among others to assess the purity of the biological product. In March 2019, Clean Cells acquired BE Vaccines to expand its share in virus production and cell structure.
Eurofins Scientific, a Luxembourg-based biological product testing provider, includes a wide range of viral clearance services such as validated qPCR assays, purified virus stocks, large volume assays, viral stocks with titers of 107 pfu/ml, and infectivity assays, among others. Moreover, the company has four service models of viral clearance studies which range from issuing down-scale procedures to validating the down-scale procedure and performing all clearance steps for the company. Eurofins has been developing and launching assay for SARS-CoV-2 pathogen detection. In the year 2018, the company acquired TestAmerica and Environex to expand its testing capabilities.
Merck Millipore, a prominent name in the biopharma industry, provides services for the detection and removal of the viral contaminants for monoclonal antibodies (mAbs). The company uses molecular testing technologies such as Next Generation Sequencing (NGS) and PCR. It provides services such as detection of emerging viruses, raw material testing, cell line characterization, and rapid detection methods, among others.
Additionally, it offers viral removal methods using downstream purification methods such as chromatography, filtration, and chemical treatment. Merck’s Viresolve® solution provides a complete solution for the viral clearance of mAbs and recombinant proteins.
The other industry players are Vironova, BSL Bioservice, Sigma-Aldrich Corporation, and Wuxi Pharmtech (Cayman), among others. Industry players are ensuring that their services are fully GMP compliant and client’s studies comply with FDA, EU, and ICH for Viral Safety Evaluation. They are focusing on product development to stronghold their market position.
4 Viral Clearance Industry Trends 2020
As per the detailed report, the global viral clearance market size was around 319.6 Million in 2019 and is expected to surpass USD 970 Million in valuation by the year 2026, expanding at a CAGR of at least 20.5% during the forecast period 2020-2026.
Large scale production of Recombinant Proteins:
Recombinant proteins are usually used for drug deliveries, tissue treatment, antibodies, and pharmaceutical products, among others. According to the research, this market segment is expected to expand at a CAGR of 8% during the forecast period. The growing demand for recombinant proteins in a wide range of applications has increased the demand for viral clearance of these proteins. Moreover, its expansion in the recombinant therapeutic use has propelled the applications for recombinant proteins.
Growing demand for mAbs:
mAbs are used in the treatment for various diseases such as cancer, cardiovascular disease, and arthritis, among others. The increasing number of government and private organizations supporting the R&D of mAbs is expected to positively influence the growth of this segment. Moreover, the innovative methods for the cost-effective production of mAbs are augmenting market growth.
Development of Vaccines:
The pandemic has encouraged various healthcare organizations to penetrate the vaccine development market. Currently, more than 20 companies are working on the coronavirus treatments which has increased the demand for viral clearance or viral safety assurance services. Moreover, the incidence of biosimilars in emerging economies such as India and China is expected to propel the demand for these services.
Stem-cell therapy is expected to offer lucrative opportunities to the healthcare industry players. Various companies are extensively investing in the development of stem-cell therapy which is eventually which is increasing the market share of the viral clearance market. Stem-cell therapy usually touted as the next chapter of organ transplantation and tissue engineering is expected to change the dynamics of the market by end of the year 2026. This market segment is expected to expand at a CAGR of at least 21% during the forecast period.
Regional Analysis of the Market
North American and European Region:
In 2019, North America accounted for the largest market share and is expected to grow at a steady rate during the forecast period. The presence of a large number of industry players contributed to the maximum revenue in this market region. Various government state bodies are supporting the development of biotechnology and also investing heavily which is fueling the market growth. Moreover, the growing investment in stem cell therapy and gene therapy products has propelled the growth of this market region. Followed by this geographical region, Europe accounted for significant market share owing to the development of various clearance methods in the biopharmaceutical and pharmaceutical industry. Furthermore, the growing production of recombinant proteins and monoclonal antibodies is spurring the growth of this market region.
Asia Pacific, Middle East & Africa, and Latin American Region:
As per the research, the Asia Pacific region is anticipated to expand at a CAGR of at least 21% during the forecast period. The biopharmaceutical CRO and CMO market in the Asia Pacific is expected to register spectacular CAGR owing to the outsourcing of drug development and related to activities to emerging economies. This in turn is due to the low labor cost and manufacturing costs as compared to other regions. The adoption of the latest technology in the healthcare sector is one of the reasons for the growth of this market region. Moreover, the increasing number of biosimilars is expected to drive the market growth.
Countries such as India and China is expected to offer lucrative opportunities owing to the government support to the local players. Talking about the Middle East & Africa, the market in this region is expected to grow at a considerable rate owing to the growing pharma sector. Meanwhile, the market in Latin America is anticipated to grow at a moderate rate during the forecast period.
Give-Away for Viral Clearance Market
The increasing number of CROs and CMOs are expected to fuel the demand for viral clearance market. However, the small and medium cell banks, cell structure laboratories, research institutions, and toxicology laboratories, among others is anticipated to help the industry players to gain a stronghold in the market.