The Medicines and Health Care products Regulatory Agency (MHRA) on Wednesday cited US-based contract manufacturing organization Pharmaceutics International, Inc. (Pii) for critical deficiencies at two of its Maryland facilities.
In the reports, outlined in two separate statements of non-compliance published to the European Medicine Agency's (EMA) 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."
Additionally, the inspectors identified three other "major" deficiencies:
- Organizational data governance failures relating to the generation and checking of analytical data obtained from electronic systems, and inadequate investigation into previous data integrity failures;
- Deficiencies in sterilization and depyrogenation processes; and
- Insufficient control of aseptic operations to provide the required level of sterility assurance.
As a result of the deficiencies, MHRA says it has withdrawn Pii's good manufacturing practice (GMP) certificate for its Hunt Valley, MD site. The agency has also recommended a recall of products made at both facilities including investigational products used in clinical trials, "where market alternatives and medical criticality permits."
For Pii's Hunt Valley, MD facility, this includes three commercial products: tablet and oral powder formulations of Swedish drugmaker Orphan Biovitrum's Ammonaps, which is used to manage urea cycle disorders, and Lutigest, a progesterone drug typically used alongside female fertility treatments.
However, going forward, batches of products from both sites will be banned from the EU, until the statements of non-compliance are removed.
Julien Hecht, vice president and general counsel at Pii, told Focus via email that his company is working to address the issues cited during the inspections: "Since the time of the MHRA inspections, Pii has been working continuously to remediate all of the agency's observations and comments. Beginning in the first week of April, 2016, after conducting an exhaustive selection process, Pii brought in and began working with a team of experts, each with specialized expertise, to address each of the agency's substantive areas of concern. These remediation efforts have the highest priority at Pii and significant resources, in terms of both dollars and personnel, have and will be expended as part of this process."