1 of 3
Mark Dean-Netscher, Chief Operations Officer.
2 of 3
The entrance to Penn’s new, purpose-built contained manufacturing facility.
3 of 3
The API isolator with rapid transfer ports and flexibility to use disposable Hicoflex technology.
On 26 September, CMO Penn Pharma celebrated the official opening of its £14 million high containment facility for oral solid dosage products in Tredegar, Wales, UK. Editor Elizabeth Valero spoke to Penn Pharma’s COO Mark Dean-Netscher about the facility’s success since its operations began in March, its equipment and capabilities and the company’s long-term strategy.
Penn Pharma’s impressive 1,394 m2 purpose-built facility is dedicated entirely to the development and manufacture of tablets and capsules containing highly potent compounds, with a design for manufacture to scale from 1 kg development batches up to 120 kg commercial scale batches. It provides containment down to an OEL of 0.01 µg per m3 and all equipment is either fully cleanable in place or can be washed offline. As Mark explained: “A lot of the big pharma companies are moving away from contract manufacturers that rely on PPE (personal protection equipment).”
With over a million hours free of a reportable accident on site, Penn Pharma considers the safety of its staff to be paramount. So it comes as no surprise that safety has been central to the new facility design and equipment selection. There is no requirement for PPE during routine operations and all equipment has been independently tested to the latest ISPE guidelines using SMEPAC (Standardized Measurement of Equipment. Particulate Airborne Concentration.).
£14 million is indeed a large investment and — as Mark reeled off some of the leading pharmaceutical equipment brand names: GEA, Bosch and O’Hara — it is clear that no expense has been spared and no compromises made. “What we’ve got is GEA R&D granulation equipment that’s able to handle small-scale, high-shear mixing and fluid bed drying, and it’s also able to blend raw materials,” he said. “Then we’ve got the same but larger version of that equipment to allow us to scale up to 120 kg batch sizes. There’s also tablet compression machinery from Courtoy and two tablet coaters, one for R&D and one for commercial.”
A primary focus of the facility is of course oncology products — and there are a significant number of combination treatments in the cancer treatment market — hence the company’s decision to incorporate Bosch’s latest capsule filling machine, offering a micro dosing capability and used to produce combination therapies that accommodate powders and beads or mini tablets and powders in the same dosage. Keen to highlight the competitive edge this gives Penn Pharma, Mark said: “It’s Bosch’s first re-engineered, fully contained HiProtect commercial line in operation in the world and we are proud to have it within Penn.”
The capsule filler has a dual dosing station, so whereas with tablets, two different powders are simultaneously fed and then compressed together, one powder is fed into the capsule, followed by either another powder, micro tablet or spheronic bead, or a spheronic bead can be followed by a micro tablet or powder, or a micro tablet can be followed by a spheronic bead or powder. These combinations are all made possible using the facility’s new machinery.
It is well-known that there are a number of aging facilities with outdated equipment in the outsourcing market and, according to Mark, this is where Penn Pharma supercedes many of its competitors: “All the new technology is controlled by very accurate computer systems, which allows us to a manage the development and scale-up very closely and, in turn, helps us achieve high yields for our customers. We’ve also invested in expert design software that allows us to model what the batch sizes will look like at a larger scale. Then there’s the disposable technologies we’ve invested in for those customers concerned about costs and validation or speed and cleaning processes. Again, I think that affords us a unique position in the outsourcing market.”
Once predominantly used in the biopharmaceutical market, the disposable route is becoming increasingly popular amongst pharmaceutical manufacturers looking to reduce manufacturing times and costs. A firm advocate for incorporating disposable technologies in the manufacturing process of high potency drugs, Mark highlighted the main advantages: “Most outsource manufacturers go from one kilogramme to 10 kilos, then up to 50 kilos using rigid containers, stainless steel vessels or IBCs (intermediate bulk containers), and every time you use one of these you have to go through a rigorous cleaning cycle. If you’re a multi-API facility, you have to carry out more complicated cleaning validation. We’ve introduced disposable containers on our API isolator and, together with the integrated cleaning cycle, this makes the process much faster.
“Another clever bit of GEA technology we use is the Hicoflex bag, which is filled with the powder to be turned into the tablet or capsule, and all we need be concerned with is disposal of the bag.
“Also, because one of the risks when loading and unloading tablets from tablet coaters in a high potency facility is of course contamination, we’ve designed disposable isolators into our O’Hara coating machines, which means we can safely load and unload the machines, then conveniently dispose of the isolators.