EMA’s CHMP Recommends Ban of US CMO’s Medicines

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) on Friday recommended that medicines manufactured by Maryland-based contract manufacturing organization (CMO) Pharmaceutics International (Pii) should no longer be available in the EU, except for Ammonaps (sodium phenylbutyrate), which is used to treat a rare disease and is considered critical for public health.

The recommendation follows a good manufacturing practice (GMP) review after a follow-up inspection of the site by the UK’s Medicines and Health products Regulatory Agency (MHRA) and the US Food and Drug Administration (FDA).

MHRA disclosed the critical deficiencies at two of Pii’s Maryland facilities in June.

In the reports, outlined in two separate statements of non-compliance published to the EurdraGMP database, the inspectors say they identified a "failure of organizational and technical measures to minimize the risk of cross-contamination between hazardous and non-hazardous products manufactured in the same manufacturing facilities using shared equipment [and a] failure of the quality unit to ensure the effective operation of the quality system," at both sites during inspections that ended in February.

Regarding the failure of the sites' quality systems, the inspectors said the sites displayed a "gross failure of change management," by using an "unqualified" high-performance liquid chromatography system, and an employing an "unacceptable approach to production equipment qualification."

CHMP also says the inspection found that corrective measures previously agreed to had not been appropriately implemented.

“Although there is no evidence of a defect in any of the medicines produced at the site or of harm to patients, EMA’s Committee for Medicinal Products for Human Use (CHMP) concluded, as a precaution, that supply of non-critical medicines should be stopped. In addition, CHMP requested the site to implement corrective measures to ensure compliance with GMP standards,” a notice published Friday says.

CHMP’s recommendation will have an impact on the availability of medicines from Pii, including:

• Ammonaps, a medicine for treating urea cycle disorders which is exclusively manufactured at Pii, will remain available where there are no treatment alternatives. In EU countries where treatment alternatives exist, Ammonaps will be recalled.
• SoliCol D3 (cholecalciferol), a medicine for vitamin D deficiency, which is also exclusively produced at Pii but has not yet been marketed in the EU, will not be made available in the EU. The medicine can only be marketed once evidence is provided that its manufacturing is compliant with GMP standards.
• The medicines Dutasteride Actavis (dutasteride), Lutigest/Lutinus (progesterone) and associated names are registered to be produced at Pii, but are now manufactured at alternative registered manufacturing sites. The medicines from these alternative sites will therefore remain available in the EU. For Lutigest/Lutinus, some batches produced at the US site are still available on the EU market and will be recalled.

The European Commission will decide if the recommendation should be turned into a legally binding decision valid throughout the EU.

The deficiencies come as Pii announced earlier in September a definitive agreement with a consortium of investors, led by Signet Healthcare Partners and including Athyrium Capital Management, Hildred Capital Partners and Pharmascience Inc., an investment of $93 million in exchange for an equity stake in the company and debt refinancing.

EMA: Pharmaceutics International Inc., US: supply of non-critical medicines to EU to be stopped due to manufacturing failings