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In December 2002, FDA notified DMV International that its pharmaceutical lactose manufacturing facility in The Netherlands had passed inspection. It was only 3 years earlier that DMV had started an ambitious programme to implement cGMP for API production conforming with ICH Q7A guidelines.
During 1999, DMV International (Veghel, The Netherlands) began an ambitious programme to implement current good manufacturing practice (cGMP) for the production of active pharmaceutical ingredients (APIs) conforming with International Conference on Harmonization (ICH) Q7A guidelines. Three years later, DMV received official notification from the US Food and Drug Administration (FDA) that its Veghel facility, which manufactures pharmaceutical lactose, had passed inspection.
As a global supplier of pharmaceutical excipients, DMV has been aware of the increasing demands of the pharmaceutical industry during recent years. Although no regulations exist with respect to GMP for excipients, DMV had already implemented a quality system based on the US Guidance on Good Manufacturing Practice for Bulk Pharmaceutical Excipients, (United States Pharmacopeia <1078>).
However, moving into the 21st century, it became obvious that this level of quality would no longer fulfil the needs of customers. Pharmaceutical companies began requiring increased quality levels from raw material suppliers. This was highlighted during audits that focussed increasingly on areas such as process validation, cleaning and computer systems, and more detailed documentation, reflecting the expectations of US and European companies.
In addition to pharmaceutical lactose for wet granulation, DMV's strategy focussed on developing and marketing lactose for direct compression and dry powder inhalation. Specifically, given its application, the latter is treated as though it were an API. Consequently, in 2000, DMV decided to upgrade its existing quality system to API standard in compliance with ICH Q7A guidelines.
To realize this ambitious plan, DMV implemented Pharma 2000 - a project backed by the company's board, which assembled a multidisciplinary team of 40 people. Based on an analysis of current standards versus ICH standards, a detailed action plan was drawn up that would allow stepwise improvements to attain the required quality level. Major areas of attention included the quality assurance/quality control (QA/QC) structure; training; documentation system; procedures and working instructions; and the validation programme. Project progress was continually monitored by internal audits and the company's customers were actively involved in the process, providing useful advice and information.
After 2 years of hard work, an external consultant was asked to conduct a mock FDA audit of the facility to API standards. The report concluded that the GMP system had been successfully installed and that DMV could move to the next phase of further implementation and increasing understanding within the company. In June 2002, the consultant returned to the facility and reported that DMV had sufficiently implemented cGMP and increased awareness to a level that would pass an FDA inspection.
Only 2 months later, DMV was officially informed that FDA planned to inspect the Veghel manufacturing plant. The inspection was triggered by a DMV customer who registered an inhalation product in the US that used pharmaceutical lactose as the carrier. The inspection was scheduled for October 2002 and was to be conducted by an investigator and a microbiologist.
Full preparations were made with the management of the operations and QA divisions heading the process, including training of all personnel involved. The company's commitment, previous experience and appreciation that there is only one chance to succeed meant that DMV was fully prepared for the inspection.
The inspection took place in October. Originally meant as a preapproval inspection in relation to the inhalation product mentioned previously, the investigator extended the audit to a general cGMP systems audit, covering the complete range of pharmaceutical lactose and using the ICH Q7A for APIs as a reference. During the exit meeting, DMV was complimented for its solid quality system and implementation. A Form 483 was issued with only one minor observation. The efforts of all involved DMV employees had paid off, leading to this major success.