A facility operated by fatty acid specialist Equateq on the island of Lewis in Scotland has met with UK good manufacturing practice (GMP) standards for the production of lipid-based APIs for the drug industry.
The accreditation, which was recently issued by the Medicines and Health Regulatory Authority (MHRA), restores the facility’s previous GMP status that was allowed to lapse by its previous owner, Scotia Pharmaceuticals.
The MHRA’s inspection in late July confirmed that the plant is compliant with the European Commission’s Directive 2001/83 manufacturing requirements, enabling the Scottish firm to being the production of APIs for medical applications.
In an interview with in-PharmaTechnologist, Equateq CEO Adam Kelliher set out some of the firm’s ambitions for the plant, beginning with a discussion of its lipid technology and how it can be used by the pharmaceutical industry.
What are the some of the applications of lipid-based APIs in pharmaceutical products?
“Lipids have an extremely wide range of applications, which we are only just starting to appreciate. Because they are safely tolerated, having been an essential part of the human food chain for millions of years, they can be used as carriers for drugs.
“Under this process, we would marry an existing API with a lipid carrier, making it more efficacious at lower doses. Secondly, and we think more importantly, the parent fatty acids are typically metabolised into a myriad of derivatives that are known to have potent beneficial mechanisms within the body.
“At Equateq, we have devised methods to mimic this natural process of metabolism, and thus have been able to synthesise these potent compounds for use as APIs. Our explorations so far show that taking only small amounts of these novel compounds can be extremely effective, without any debilitating side effects.”
What specific manufacturing capabilities does the plant offer?
“We are able to do all the key processes of lipid manufacturing, such as esterification, hydrolysis, distillation, and refining. But our core expertises are in two areas that do set us apart. Firstly, we employ a method called low temperature fractionation, that allows us to get any triglyceride fatty acid and extract its most polyunsaturated fraction. The result is a non-synthetic oil, and very suited for use as an enriched all-natural food additive.
“We would then use the fractionated material as feedstock for our second key expertise: preparative HPLC. We have the capability to deliver commercial quantities of up to 99 per cent pure fatty acids by using this method. These concentrates are of great use for the pharmaceutical industry, or for researchers, who want to explore with confidence that they are using the highest-grade lipid compounds.”
In terms of manufacturing operations, what are specific aspects of Directive 2001/83 that you have met?
“The inspection found that we comply with the EU Guidelines on GMP, Medicinal Products for Human and Veterinary Use Part II - Basic Requirements for Active Substances used as Starting Materials, Section 19 -- APIs for Use in Clinical Trials.”
What is the facility’s current GMP status with respect to both the wider EMEA and the US FDA?
“The MHRA approval falls under the EMEA, and so has validity throughout the EU. You may also be aware that there both the MHRA and the FDA have embarked on a pilot programme to explore ways in which both bodies can recognise and accept the other's inspections. So certainly the MHRA approval will carry weight with our American customers.”
“Regarding future approvals, I think my staff will have a well-deserved breather after the successful MHRA certification, which is for our manufacturing processes in general, not for a specific product. I would anticipate that we will be applying to both the EMEA and the FDA as part of applications for specific APIs.”
Will Equateq produce its own lipid API-based drugs at the facility or focus on supplying them to third-parties on a contract basis?
“We intend to do both: develop in-house APIs, and do work on a contract basis for any pharma company that wants to stay at the cutting edge of the lipid space.
“The bottom line is that this all comes down to resources: pharma development can yield great rewards, but does cost a lot of money. So we have at the moment articulated five lipid compounds that we think hold great promise as breakthrough interventions for specific conditions. They are what we would categorise as low-hanging fruit, which we have the in-house resources to develop, with a reasonably abbreviated development path.
“But we also see massive potential in other areas, some of which are just too large for us to take on. So we would certainly be open to license these compounds to any pharmaceutical company with an interest in pursuing a new and remarkable method of treatment. And we could of course make commercial quantities of specific synthetic lipids on contract, if a company required that.”
What is the facility's annual production capacity?
“Capacity depends on the quality of the feedstock, but for fractionation, we can deliver in the low hundreds of tons of material per annum. For HPLC, we can deliver about 1 ton a month of ultra-pure fatty acids.
“But all our processes are scalable, and we anticipate that we will be adding capacity as demand increases. The wonderful thing about being based in the Western Isles is that we have plenty of space on site to expand into.”
What are the key factors will affect the development of the pharmaceutical lipid API market over the next 10 years?
“Sustainability is key. If all people followed their government's health advice, and took at least 1 gram of omega-3 actives per day (mostly in the form of fish oil), the oceans would soon be empty of fish life!
“There are already pressures on the key fish sources that provide omega-3 oil feedstock, be it tuna for hi-DHA or sardines for hi-EPA and 18-12. So there will be greater interest in getting long chain omega-3 -- specifically EPA and DHA -- from non-aquatic sources, such as algae and crops that are GMO.
“It is my view that the acceptability of GMO material will become more widespread. The second key factor looking forward is that these fatty acids are in themselves blunt instruments for pharmaceutical applications. We can expect in a decade that there will be conclusive work on the efficacy of specific fatty acids delivered in high purity, and at an even higher stage, on the derivatives of these fatty acids, which will allow more focused treatment with much lower doses.
“So we think that Equateq is well placed to benefit from both these projections, being able to process feedstock from any fatty acid source, and already having resolved some of the key obstacles in lipid synthesis.”
Do you have any figures on the current value of the global lipid API market?
“I do not have an overall value, but the biggest lipid pharma success is [Pronova Biopharma’s] Omacor in the EU, marketed as Lovaza in the US, particularly since its purchase by GlaxoSmithKline last December, which indicates the massive potential for lipid treatments, as both effective and side effect-free. Lipid concentrates have a greater penetration as APIs in Japan.”
“We are quite unique in being a lipid API company. There are lipid suppliers, who process oil on a much larger scale than we do, but more for the nutritional sector. And there are specialised laboratories that can synthesise esoteric lipids, but only on a microgram scale.
“So we have the capability to make lipid API under GMP ceritfication on a kg scale, using systems that are easily scalable up to ton size. So all of this makes us very bullish about the future of Equateq!”