The first two products we are producing at PrIME Biologics are Albumin and IVIG. We can produce a wide range of other plasma products including FVIII and FIX. Please contact us for more information.
Disposability ensures the elimination of possible batch to batch contamination. This allows PrIME Biologics to process underutilised plasma. Further, the PrIME Technology provides an additional level of pathogen safety over and above the normal viral/bacterial processes used by existing fractionators. It should be noted only plasma that has been tested in accordance with EMA and HSA guidelines will be processed to ensure the therapeutic products produced using the PrIME Technology are as safe as possible.
For more information on the PrIME Technology clink this link.
Plasma Market Overview
This section is designed to provide some background information on the Therapeutic Plasma market. Some of this information has been drawn from third party sources, which are referenced should you be interested in viewing the original source documents.
Blood plasma products represent a US$11.7B global market of which Marketing Research Bureau (MRB) estimated US$1.7B is sold in Asia including China and India. This market is dominated by 5 major manufacturers who have undergone considerable consolidation and reorganization in the recent past. Plasma fractionation is a capital intensive, inflexible, high cost production process similar to the old steel mills. According MRB US sales of human derived plasma products have grown at a compound rate of 10% over the past 18 years to sales of $4.0 billion in 2008, which represented an 11.5% increase over 2007.
The fractionators are focused on the European and US markets. The Asian market is largely untapped. As a result supply in Asia is variable and pricing high. There are no South East Asian plasma fractionators. In part this is due to the small size of many Asian countries making it uneconomically to set up a fractionation facility.
 Worldwide Supply and Demand of Plasma and Plasma Derived Medicines Patrick Robert Marketing Research Bureau article on Iranian Journal of Blood and Cancer Volume 3 Number 3 2011. http://www.ijbc.ir/browse.php?a_id=205&slc_lang=en&sid=1
 Worldwide Plasma Fractions Market 2008, Marketing Research Bureau April 2010
The Plasma fractionation process was originally developed by Dr Edwin Cohn to deliver Albumin for the Allies in World War II. This process was developed further after the war to produce a number of therapeutic products including Factor VIII and IVIG. The major change to this process occurred in the late 1980’s with the realization that viruses could be transmitted via plasma products. As a result a number of virus removal steps were added to the original Cohn process creating a multi step low yield process.
 See Wikipedia Edwin Joseph Cohn, http://en.wikipedia.org/wiki/Edwin_J._Cohn
Today the Therapeutic Plasma Fractionation processes only recover about 50% of the total protein from a litre of plasma. In other words, approximately 50% of the Albumin and IVIG is destroyed in the current fractionation process. For example the Plasma Proteins Manufacturing Association has produced the following table of manufacturing yields:
By comparison the average person has between 35 and 55g of Albumin and 10g of IVIG per litre of plasma.
The PrIME process consistently yields over 85% of the Therapeutic Plasma products from a litre of plasma. This high yield is achieved by eliminating steps and time it take to purify each of the Therapeutic Plasma products.
In the 1980’s it became apparent that virus such as AIDS were infecting people who had received blood transfusions. There were also a few rare cases of people who were also being infected after receiving plasma products, particularly Hemophiliacs. This lead to a complete reorganization of the blood collection and fractionation industries. Since this time there have been very few cases of people contracting diseases from blood transfusion and no known cases of disease transmission following Therapeutic Plasma products.
In order to achieve this significant increase in safety the fractionators have added a number of steps to the manufacturing process which either inactivate the viruses or partition them from the Therapeutic Plasma product. The industry talks about log reductions that each step offers. Each log reduction reduces the number of pathogens by a factor of 10. Generally the current fractionation processes reduce the pathogen level by 8 to 12 logs. You can never completely say that all of the pathogens have been removed, but at this level any remaining pathogens are considered to be harmless.
As the PrIME system generally purifies the desired Therapeutic Protein by moving it across a membrane it also achieves a simultaneous removal of undesirable pathogens. This pathogen removal is different to any other pathogen removal system as the driver of the separation is electrical and not pressure. As a result the PrIME can potentially remove pathogens that existing systems can’t. Below is a graphic that shows how the PrIME removes viruses:
A significant amount of work has been undertaken showing the pathogen removing capacity of the PrIME process. This body of data shows the PrIME process consistently removes more than 4 logs of viruses and greater than 2 logs of prions from contaminated plasma. By incorporating the PrIME into an existing plasma fractionation process we increase the overall safety of the finished Therapeutic Products. Below is a table comparing the PrIME Biologics product to existing products.
|Purity||> 99 %||> 99 %|
|Pathogen removal||> 12 log||> 8 log|
|Endotoxin removal||>99 %||>99 %|
|Prion removal BLD*||Yes||?|
To put the Asian market into perspective, the Australian Government spent A$400m in 2009-10 on Therapeutic Plasma products with a population of 21 m people. On this basis the potential Therapeutic Plasma market of the following Asian countries is:
|Country||Population||Potential Market Size|
The above table indicates the size of the potential for a novel technology like the PrIME to address the significant shortage of Therapeutic Plasma products in Asia. None of these countries are self sufficient and all are looking to increase the supply of Therapeutic Plasma products to meet their local needs.
Currently the European market which represents 11% of the world’s population accounts for 36% of the world’s Therapeutic Plasma consumption. By comparison the Asia & Pacific markets account for 58% of the world’s population but only represent 15% of the world’s consumption of Therapeutic Plasma products.
 See National Blood Authority of Australia 2009-10 Annual Report page 34
 Worldwide Supply and Demand of Plasma Derived Medicines Patrick Robert Marketing Research Bureau article on Iranian Journal of Blood and Cancer Volume 3 Number 3 2011, page 115.
The regulators will not allow the fractionators to process plasma from certain countries for safety reasons. This wasted or ‘currently underutilised Plasma’ accounts for approximately 50% of all the plasma collected in most Asian countries.
As a result most Asian countries are forced to buy from the fractionators and discard the plasma they collect.
There is an opportunity to supply the Asian plasma market for a technology that:
- Can process small volumes (less than 10,000L batches); and
- Is based on a disposable manufacturing system so that it can fractionate Currently Underutilised Plasma.
- Make countries in Asia self-sufficient in their plasma product requirements in line with 2010 WHO mandate.
This is the unique niche that the PrIME process addresses. The existing fractionators cannot address the Currently Underutilised Plasma market as their manufacturing processes are continuous leaving them open to batch to batch contamination. This is why the regulators, will not allow fractionators in their countries to import Currently Underutilised Plasma.
 World Health Organisation – 63 World Health Assembly 10-12 May 2010, Resolution 63.12 – Availability, Safety & Quality of Blood Products
The use and manufacture of plasma products was originally set up as a World War II effort to reduce the front line troop deaths. As a result manufacturing processes were developed in a rapid fashion without consideration for cost or efficiency. This process was so successful that after the war it was handed over to the civil sector in order to help save lives in the general community medicine.
The manufacturing process has changed little since this time. There have been two major changes to the general manufacturing process since this time. The first was in the mid 80s with the realization that HIV could be transmitted via plasma products which led to a number of additional viral removal/inactivation steps being added to the then existing manufacturing processes. The second change came in the late 90s/early 2000s when the US FDA closed a number of the fractionators for failing to meet GMP requirements. This led to an increase of process control, but not a change of actual manufacturing process. As a result the plasma fractionation industry is highly regulated and stuck using a manufacturing process dated back to the 1940’s.
Below is a diagram produced by Bayer (now Grifols) that compares a number of different fractionation technologies. As can be seen the existing Cohn process (Fraction Precipitation) is not an ideal system. According to Bayer the best alternative is the PrIME technology. The problem that all the fractionators face is the cost of taking this or any other technology through the regulatory process. Currently they have regulatory approval to manufacture their products in a cascade process. Thus a change to one product would require validation of all of their products. In their view this would be prohibitively expensive.
The fractionators have dabbled with Affinity and Ion exchange chromatography over the years. These technologies were developed in the 70s and have been added into the fractionation process by a number of the fractionators to remove various contaminants. They are not considered viable alternatives to Cohen as they are very expensive and introduce their own contaminants.
GE are offering to build a 150,000L affinity chromatography fractionation plant for US$100m. Chromatography is expensive to set up and the resin beads (media) need to be replaced at regular intervals. By way of example the BAC BV affinity media for purification of IVIG is estimated to cost about US$2m to process 12,000L pa and would need to be replaced at least every 2 years. To undertake the 80,000L Singapore production using affinity would increase the budgeted COGS by 50% before adding any CIP costs.
The PrIME process is the only disposable plasma fractionation system available. This allows for the complete removal of CIP costs. These costs represent at least 20% of the general COGS for the existing fractionators. It is also the main area of concern for the regulators, as any failure in CIP can lead to virus etc passing from one production batch to the next. By using the PrIME process the Singapore Company will be able to process plasma from all of ASEAN/China/India. Much of this plasma is Currently Unprocessable Plasma referred to above and is thrown away as the regulators in the countries in which the fractionators operate will not allow plasma from these countries to be processed in their plants. The regulators fear that the CIP will not remove some contaminates from the Currently Unprocessable Plasma leading to contamination of their home Therapeutic Plasma products. Again this is not an issue when using the PrIME process.