Dr Reddy’s Laboratories launched a new manufacturing facility at its Cuernavaca site in Mexico on 17 March 2010. The facility will manufacture methyl ether polyethylene glycol (mPEG) alcohols of pharmaceutical grade at a commercial scale. Earlier, Dr Reddy’s sourced mPEG alcohol from Dowpharma, a contract manufacturer of pharmaceutical services.
The fully-equipped facility will operate at a multi-ton annual capacity. The facility has been launched by Custom Pharmaceutical Services (CPS), a strategic business unit of Dr Reddy’s. The unit offers a range of services, including analytical development, process R&D and scale-up, the production of advanced intermediaries and APIs, dosage development and contract manufacturing dosage.
mPEG alcohol manufacturing facility
The fully c-GMP-compliant mPEG alcohol manufacturing facility has been integrated completely with the operation and quality processes of the Cuernavaca site.
The Cuernavaca site is FDA inspected and includes seven manufacturing bays. Located approximately 75km south of the Mexico City, the site was acquired by Dr Reddy’s from Roche in 2005. Two of its manufacturing bays have been devoted to steroid manufacturing capabilities. Besides conducting synthesis of steroids, the site develops multiple active pharmaceutical ingredients (APIs), including naproxen and naproxen sodium and a range of intermediaries. The facility runs at an annual capacity of 3,350mt.
The site operates with approximately 400 people. There are seven reactor bays with volumes ranging between 100l and 20kl. The facility also accommodates 1,000l and 3,000l cryogenic reactors that are capable of operating at -110 °C.
mPEG alcohol production
The mPEG alcohol manufacturing facility will develop mPEGs in a broad range of molecular weights, generally between five kilodaltons (kDa) to 60kDa. mPEG alcohols are a vital raw material in the production of activated mPEG. Activated mPEG alcohols are widely used for pegylation with biologic drugs and largely for peptides and small molecule drugs.
The activated mPEG production in Mexico will be delivered to Dr Reddy’s c-GMP manufacturing facility in Mirfield, UK, which undertakes commercial scale activation. The UK facility houses two API manufacturing facilities, a GMP pilot plant and a kilo lab, and is suited for the production of commercial scale intermediates.
Part of the mPEG production will be put to captive usage for Dr Reddy’s PEGtech range of activated mPEGs while part of it will be sold to customers.
Dr Reddy’s has officially branded its broad range of activated mPEGs as PEGtech. Besides highlighting the company’s experience in product development and GMP production of activated mPEGs, PEGtech branding will put together a large product portfolio, consisting of several activating groups and molecular weights, including 5K, 10K, 20K, 30K, 40K and 60K.
mPEG alcohol manufacturing facility process technology
The facility will produce mPEG alcohol through living polymerisation of ethylene oxide. Living polymerisation is a kind of addition polymerisation technique wherein unsaturated monomer molecules are added one at a time to an expanding polymer chain. Chain termination is absent in living polymerisation. The growth rate of the chain is much more constant than that in traditional chain polymerisation techniques.
The process of living polymerisation in the facility will be conducted in the presence of a base and an initiator. Dr Reddy’s holds a US patent for this process.
Several activated mPEGs will be tested to establish the optimum mPEG. The activated mPEGs of a low diol content will be produced using a mPEG-OH analytical method that removes impurities in the diol by functionality. This will ensure that there is no interference with molecular weight.
The demand for mPEG and similar materials used in the process of pegylation is on the rise. Companies are increasingly adopting the pegylation of biologics, peptides and small molecules.
The clinical value of pegylation has been established as it has been found to be the optimum alternative in improving the pharmacokinetics of treatments by extending their half-lives.