The harvested porcine dermis is horizontally sectioned to the required thickness. The resultant strong, thin sections undergo a number of organic extraction stages to remove the fat content of the dermis. Once the fat has been removed, the sections undergo a number of enzymatic extractions to remove all cellular material. The temperature and environment of these operations is very tightly controlled to maintain the original three-dimensional structure of the dermal collagen matrix, whilst removing the fat and cellular material. The resulting sections retain their natural strength but are rendered safe to implant and are non-allergenic. The three-dimensional collagen matrix then undergoes a cross-linking stage where the matrix is stabilised by cross-linking. The cross-linked matrix is resistant to breakdown by naturally occurring collagenases. Finally, the implants are cut to size, packed under vacuum and gamma sterilised. The dose of gamma radiation is very tightly controlled to assure sterility of the product without damage to the collagen matrix.

This patented process with its organic and enzymatic extractions, cross-linking and sterilisation has been shown to inactivate and remove bacteria and viruses should they be present in the starting material. The resultant material is strong, safe, non-allergenic, readily colonised by host cells, and is not broken down once implanted.

All data on file at Tissue Science Laboratories plc

Starting materials

The principal material used in the manufacture of Permacol™ implant is porcine dermis. This material is harvested from pigs maintained under the appropriate EU veterinary/animal welfare schemes. Extensive veterinary checks are made to the animals on a regular basis throughout their life and both pre- and post-mortem to ensure they are healthy and suitable for use.

Harvesting of the skins takes place under controlled circumstances using sterilised instruments to ensure the lack of contamination of the dermis. All subsequent manufacturing operations take place under tightly controlled conditions and temperatures to ensure the microbiological exposure (bioburden) of the material is minimised.

Manufacturing process

The patented process (utilising organic and enzymatic extraction stages) has been demonstrated to dramatically reduce the microbiological bioburden. Each batch of material is tested at six stages throughout the process to ensure an acceptable minimal bioburden. Bioburden studies, gamma irradiation dosimetry studies and gamma sterilisation validation studies have been undertaken to assure the final product is sterile. The gamma sterilisation of the final product is very tightly controlled (by dose and temperature) to ensure sterility with minimal damage of the collagen matrix.

The manufacturing process has also been demonstrated to remove viral load from the product. The FDA/EU regulatory authorities accept a reduction of 6 logs as acceptable for surgical implants. Studies conducted to FDA Good Laboratory Practises have demonstrated that the Permacol™ implant manufacturing process exceeds this reduction in viral load. Indeed, retroviruses are reduced by more than 12 logs and porcine parvovirus is reduced by 6.7 logs.

Early experimental formulations using a similar process (but using human skin and glutaraldehyde cross-linking) showed no immune or inflammatory response to the implant in man and were colonised by host fibroblasts and blood vessels. Three years after implantation the implants showed no signs of resorption(1)

Human biopsy data on Permacol™ at six months following implantation shows cellular infiltration and blood vessel formation in the implant.

(1) British Journal of Plastic Surgery (1982) 35 519-523

All other data on file at Tissue Science Laboratories plc

The non-allergenicity of Permacol™ implant has been demonstrated in a series of animal models as described below: