The US Food and Drug Administration (FDA) has sent Merck & Co a warning letter saying it has failed to correct a number of manufacturing deficiencies at its main vaccine manufacturing plant in West Point, Pennsylvania.
The agency said Merck had filed an 'inadequate response" to a Form 483 sent to the company several weeks ago, and it now needed to see immediate corrective action.
The agency highlighted several areas in which the plant deviated from good manufacturing practices (GMP). For example, Merck is accused of not investigating why some batches of product were outside of specifications, as well as "failure to maintain production and process control," according to the FDA.
There have also been complaints of vaccines vials being over-pressurised and leaking, and rogue fibres have been found contaminating some vaccine vials. In addition, unresolved issues affecting bulk drug substance manufacture at the plant included that product was re-dispensed before filling - with no additional stability testing - while material leached out of filters used in bioprocessing into process intermediates.
That aside, Merck insists that the no contaminated vaccines have been released into the supply chain.
Merck issued a recall for two vaccine products made at the plant - the childhood combination vaccines PedvaxHIB and Comvax - at the end of last year after some lots were found to have contamination problems. It also recently had three lots of its MMR II (measles, mumps and rubella) vaccines suspended by Health Canada after serious allergic reactions were seen among some recipients.
At the time Merck was supplying around half the US supply of vaccines against Haemophilus influenzae type B (Hib), one of the main organisms responsible for bacterial meningitis and a component of both PedvaxHIB and Comvax. The other major supplier of that type of vaccine is Sanofi-Aventis, and that company has since stepped in to try to ensure continuity of supply.
Other products made at the West Point facility include Merck's much-touted new cervical cancer vaccine Gardasil, as well as established products such as Vaqta for hepatitis A and Recombivax HB for hepatitis B. However, the FDA said it did not expect supplies of these products to be interrupted as a result of the warning letter.
That said, in accordance with standard FDA procedure, Merck has 15 working days from receipt of the letter (sent on April 28) to provide a written account of measures taken to remedy the failings or face regulatory action.
News of the manufacturing problems come at a time when Merck is seeing remarkable growth in its vaccines business and has positioned the division as a key growth driver in the coming years. First quarter vaccine sales rose 9 per cent to just under $1bn, with Gardasil accounting for $390m of that total.
But newsflow from the company has been largely negative of late.
Two of its pipeline drugs MK-0524a (niacin and laropiprant) for high cholesterol and a proposed fixed-dose combination of loratadine and montelukast for allergic rhinitis - have been rejected by the FDA in the last few days.
Meanwhile the firm wass knocked back after the ENHANCE study claimed that one of the firm's most eagerly-anticipated new products, the combination cholesterol lowerer Vytorin (ezetimibe/simvastatin), works no better than the widely-available generic drug lovastatin on the progression of atherosclerosis.
Adding to Merck's woes, the US Congress has launched an investigation into why it took so long for the results to be made available after completion of the study.