Dutch biotech company Pharming announced it complied with the standards of Good Manufacturing Practices (GMP) following inspections by the European Medicines Evaluation Agency (EMEA) of five facilities used in the manufacturing of Rhucin, a therapeutic protein produced in transgenic rabbits.
The GMP approval, the first in the world for a transgenic rabbit facility, marks a positive step towards the anticipated European launch of the drug later this year, which would make it the second transgenic animal-derived drug on the market since last year's approval of GTC Biotherapeutic's goat-derived ATryn.
Pharming chief commercial officer Rein Strijker told in-PharmaTechnologist.com the GMP success indicated a change in thinking and showed there was a move towards greater acceptance of transgenic animal-derived drugs.
"Many people in the past have questioned whether we can use animals to make drugs and often said we could not get to the stage where authorities would approve to GMP standards.
This is proof that the authorities are satisfied with our production using animals.
This is quite an achievement."
Rhucin, a recombinant human C1 esterase inhibitor, is a human protein to treat acute attacks of Hereditary Angioedema (HAE), a rare disease characterised by painful swelling of soft tissue.
The protein has been developed through Pharming's proprietary technology which involves producing and collecting the therapeutic protein from the milk of rabbits, which have been engineered to carry and express the gene of interest in the mammary glands.
A new area in the drug world, transgenic drug-producing animals have been wrought with controversy and ethical debate, but according to Strijker the technology was more cost effective than conventional protein-producing mechanisms and had a lot of potential in the biopharmaceutical industry.
"Milk is very rich in proteins.
Mammary glands are good at producing high amounts in a high quality."
The transgenic rabbits were able to produce between 10 and 12 grams of protein per litre of milk, he said.
This is compared to highly optimised cell cultures that can typically generate 0.2 to 1 grams of protein per litre of culture medium The high protein levels were achieved by including an extra bovine milk-specific promoter sequence (alpha-S1 casein) functionally linked to the gene encoding human C1 inhibitor.
Rabbits can produce up to 10 litres of milk a year.
While scaling up was an easy process.
"Our scale up is really to breed a few more animals.
The scale up is very simple.
[And] the breeding is very quick and quite flexible."
The five Netherland-based facilities that were approved by the EMEA included Pharming's facilities for transgenic rabbits, the external facilities where milk and product are stored and processed, and the research and development facility.
The raw milk, which is collected by a milking machine, is analyzed for compliance with internal criteria, prior to release for down stream processing.
The facility for the transgenic rabbits can house 300 rabbits, though it is not up to full capacity yet, while a second housing facility is currently being considered.
Pharming chief operations officer Dr Bruno Giannetti said in a statement : "Obtaining the GMP status for our facilities and processes is a major achievement for our company.
It is a critical step in the review and approval process of Rhucin and it is difficult to overestimate the importance of achieving this milestone.
It is testimony to the hard and excellent work that our team has put in to convert a research idea of 'turning milk into medicine' into a well developed and GMP-approved manufacturing process."
While Pharming awaits EMEA marketing authorisation of Rhucin in Europe, expected later this year, the company is still to apply for US Food and Drug Administration approval.
An additional trial is required for the US application, which is currently ongoing but expected to be finished within the next few months, with the application to be submitted later this year.
The company is also developing human lactoferrin as a food supplement, recombinant human fibrinogen for blood clotting using the protein production technology, which also includes transgenic cattle.
In June last year the EMEA gave the very first European approval of a transgenically produced protein product.
ATryn, produced by US firm GTC Biotherapeutics, is produced in the milk of goats that have a transgene for human antithrombin, and is used as an anticoagulant to treat a rare congenital disease.
Initially, European regulators had rejected the drug on the grounds that not enough surgical cases were brought before them and that results from patients treated in a compassionate use programme and at childbirth could not be accepted.
However, on appeal, a reconsideration of the evidence led to an EMEA back flip.
Other firms active in the transgenic arena include US firm Hematech, owned by Japan's Kirin Brewery, which is focusing on human antibody-producing cows that will be used for the development of large quantities of polyclonal antibodies, while US-based Avigenics is pursuing avian transgenesis for treatments in oncology, infectious disease and autoimmune disease.