Single-use or disposable biomanufacturing replaces stainless steel tanks, bioreactors, and plumbing with plastic, to provide flexibility, agility, and speed to the production of therapeutic proteins. A recent market study estimates demand for for Single Use Upstream Processing to grow at up to 15% per year through 2021, when demand will reach $3.7 billion..

As disposable processing worked its way from less critical steps (e.g. media and buffer storage) to more critical unit operations (cell culture, filtration), extractables and leachables (E&L) became a cause of concern. Leachables are chemicals that migrate from the single-use container into the process solution during normal use. Extractables, a subset of leachables, are found when single-use equipment undergoes heating or contact with solvents.

Just as consumers are concerned about chemicals from plastic packaging entering their food, biomanufacturers worry about the effects of E&L on patient health. E&Ls may interact unfavorably with, or even neutralize, biopharmaceuticals, thus rendering medicines ineffective. Moreover, the toxicology of plasticizers, slip agents, surface enhancers, monomers, and initiators normally found in plastics opens up a closet of unknown, potential health effects.

E&Ls affect the health of cultured cells as well. A study by Amgen scientists confirming that a common anti-oxidant additive to plastics inhibits cell growth is just one of many such investigations. For a fanatically risk-averse industry like biotech cell toxicity, the potential for human toxicology, and the prospect of falling out of compliance suffice to warrant action.

As the the senior expert on E&L at Nelson Laboratories, Matthew Jorgenson, Ph.D., oversees the design of E&L studies in a dynamic regulatory and competitive environment. Nelson Labs also educates manufacturers and interacts with regulators on the science and regulation of E&Ls.

Nelson explains that over the last several years E&L testing has become significantly more complex and sophisticated. “Five years ago, an extractables study involving measurement of dried residuals by FTIR only was considered acceptable. Today, methods once common only to pharmaceutical work have been streamlined and applied more universally to medical devices and single-use biomanufacturing devices.” Today, extractables studies involve the use of multiple solvents plus analysis for metals, volatile organics, semi-volatile organics, and non-volatile organics using chromatography and mass-spectroscopy.

“The application of chemistry, vs. biological, data to make determinations regarding the use of devices and patient safety is relatively new. In vivo and in vitro biological tests, for example modified Eagles medium (MEM) elution for cytotoxicity, and chromosomal aberration for genotoxicity, have traditionally dominated the evaluation.”

Manufacturers and regulators now accept that chemistry tests provide more detailed and better-predictive data for systemic toxicological effects of E&Ls than biological testing. The evolution of these tests has been rapid as the adoption of single-use bioprocessing continues.

Single-use bioprocessing equipment uses biocompatible plastics as materials of construction. , which have a history of safe use and regulatory acceptance via the medical device industry. Adapting these materials to single-use bioprocessing has proved to be more problematic than anticipated, and plastics manufacturers are unlikely to invent new materials specifically for bioprocessing any time soon.

“Biocompatible plastics represent a tiny sliver of the overall plastics market, diminishing the motivation for raw material suppliers to accommodate the stricter standards of end material with reduced E&Ls,” Jorgenson says. Instead, suppliers have focused on reducing E&Ls by employing higher-purity homopolymers (plastics consisting of a single subunit). “Part of the shift to low E&L-releasing plastics has been the increased use of chemistry testing in material evaluation and the upcoming enforcement of regulations requiring the use of CMR-freematerials.”

In this climate, where E&Ls will remain an accepted risk in single-use bioprocessing for the forseeable future, the object is to characterize, understand, and control the implications of E&Ls rather than to eliminate them. Major stakeholders are therefore focusing efforts there, and on developing appropriate regulatory standards.

At the same time the regulatory landscape is changing rapidly. The recently released ISO 10993-1standard, for example, shifts the focus towards evaluation of single-use plastics using a risk-based approach to evaluating biocompatibility. “And the ISO 10993-18 standard, on ‘chemical characterization of materials,’ which is in the final revision stages, will dramatically update the current acceptable approaches to E&L,” Jorgenson says. “There has been a lot of movement and feedback from the FDA regarding what they expect from these studies. Just within the last six months, our perception of what regulators expect in terms of E&L has changed quite significantly.”

 

Special thanks to Angelo DePalma, PhD for his contributions to this article.

1.5 Billion Yet-Unclaimed Revenue in The LATAM IVD Market: Report

There is IVD sold almost everywhere in the world but revenue growth is not found everywhere. For most of the top IVD companies, adding scores of millions in growth would be helpful to business plans. That’s why growth regions such as Latin America offer promise beyond their market size. The maturation of IVD markets in developed countries (growth rate 1%-2%) has IVD companies casting their nets in developing countries where rising incomes and standards of living are anticipated to spark a new health consciousness population with growing demands for quality medical care.

A New Report From Kalorama Information Projects $1.5 Billion in as-yet-unclaimed market dollars in the Latin American in vitro diagnostics market in the next five years.

Latin America (LATAM) is a key target for IVD manufacturers.  Kalorama’s report, IVD in Latin America, focuses on the market for reagents and instruments in the most important countries of the continent. Argentina, Brazil, Chile, Colombia, Mexico, and Peru are singled out for a deeper level of analysis; the countries of Bolivia, Costa Rica, Cuba, Dominican Republic, Ecuador, El Salvador, Guatemala, Guyana, Haiti, Honduras, Nicaragua, Panama, Paraguay, and Uruguay are also considered to provide a complete overview of the region. Combined, these countries represent a population of 626.5 million; a large potential IVD market audience. Brazil and Mexico represent the two largest countries in terms of population, accounting for more than half of LATAM total population. For this reason, these two countries have been the focus for many IVD suppliers in recent years.

However, as economic conditions strengthen in other countries and demand increases for quality health services, there are additional opportunities in countries such as Argentina and Chile.

The estimated GDP for the countries studied in this research is an average of 0.1% annual growth for the year 2017 but consists of a declining GDP for Venezuela; excluding Venezuela, the region records 2.2%. GDP per capita is reported at $16,635 on average for the region.

Inequalities and social deprivation are always present in Latin America, where poverty is not declining; in fact, it sometimes increases. Although not all the countries in Latin America present similar circumstances or have the same players, there is a permanent and historical social inequality present in all countries of the region. Throughout the region there are highly educated citizens with high economic income; while there are also citizens without or with low education with financial struggles.

Over the last years, the countries in the Atlantic zone grew more rapidly than those in the Pacific zone, basically because of the rise in the price in commodities, currently slowing and declining. Venezuelan, Argentinian and Brazilian currencies have experiences wide currency fluctuations, mostly declining in value. Additionally, both Argentina and Venezuela are going through a high inflation rate process.

The total revenues calculating the IVD market in LATAM are generated by the sales of reagents, consumables, controls, calibrators and solutions categorized in well-defined segments. The market for IVD in Latin America is estimated at $2.4 billion in 2018 and will grow at 8.4%. That’s nearly one billion and a half dollars of extra market value that companies will compete for. Population growth, government insurance, newly insured patients and updated healthcare facilities will drive growth.

Brazil is the largest in vitro diagnostics market within Latin America and represents 45% of the market. Mexico ranks second with an estimated 19%.  Brazil, Chile and Colombia are among the highest growers.

Key IVD Market Competitors in Latin America

Abbott

Abbott Laboratories is a global, diversified healthcare company active in pharmaceuticals, nutritionals, devices and diagnostics. Abbott’s diagnostic product strength is its sheer presence worldwide. In LATAM, the company dominates in immunoassay-based microbiology and molecular microbiology, and is competitive in all countries in immunoassays.

Market Share for IVD Players in Latin America with rankings can be found in Kalorama Information’s New Research Report on Latin American IVD

Danaher

Beckman Coulter, Inc., a subsidiary of Danaher Corporation (DHR), has developed, manufactured, and marketed IVD tests for more than 75 years. The company reports that more than 275,000 Beckman Coulter systems operate in both diagnostics and life sciences laboratories on six continents.   Beckman Coulter’s strength is in chemistries, immunoassays, flow cytometry and hematology.   Danaher also operates the blood analyzer leader, Radiometer, and histology leader Leica Biosystems.

Becton Dickinson

Becton Dickinson (BD) is a leading global medical technology company that develops, manufactures and sells medical devices, instrument systems and reagents. Founded in 1897 and headquartered in Franklin Lakes, New Jersey, BD employs nearly 30,000 associates in more than 50 countries throughout the world. The company serves healthcare institutions, life science researchers, clinical laboratories, the pharmaceutical industry, and the general public.  BD has operated in China since 1994 and in India since 1996. In LATAM, the company specializes in microbiology, flow cytometry, and molecular solutions.

bioMérieux

bioMérieux is present in more than 150 countries through 39 subsidiaries and a large network of distributors. bioMérieux is best known for its microbiology business that includes immunoassays, traditional microbiology, and chromogenic media; however, the company is moving to capitalize on its acquisition of Organon Technika’s molecular technology, BOOM, and NASBA technologies.

Roche

Roche Diagnostics dominates clinical chemistry, urinalysis, POC, and hematology and is competitive in molecular and immunoassays. Roche is the world’s largest supplier of clinical diagnostics products; Roche’s global product sales are still almost twice its nearest competitor. Roche is also the world leader in in vitro diagnostics and tissue-based cancer diagnostics, and a frontrunner in diabetes management. Roche’s personalized healthcare strategy aims at providing medicines and diagnostic tools for patient disease management. Roche’s Ventana Medical Systems business also contributes to their market strength.

Siemens Healthineers

The Siemens Healthineers business is one of the world’s largest suppliers to the healthcare industry and a major player in medical imaging, laboratory diagnostics, medical information technology, and hearing aids. The diagnostics division includes products for clinical chemistry, drug testing, hematology, coagulation, immunoassay, infectious diseases, microbiology, molecular diagnostics, plasma proteins, point of care testing, blood gases/electrolytes, and urinalysis. In addition, Siemens operates a clinical laboratory and offers laboratory informatics and automation.