FAQ inspection procedure
In addition to the German Medicines Act (AMG), the Medicines Production Ordinance 2009 (AMBO 2009), which transposes European Directive 2003/94 EC into national law, forms the regulatory basis for inspections in the pharmaceutical sector. Your facility falls under the scope of the AMBO 2009 if medicinal products are manufactured, controlled or placed on the market. For details as well as exemptions, please refer to § 1 AMBO 2009 or § 62 AMG. Depending on the scope of activity, which includes the facility to be inspected, the requirements of Good Manufacturing Practice or Good Distribution Practice must be met. The annual inspection plan is drawn up on a risk assessment based on the scope of activities and the degree of compliance with the applicable regulatory requirements, and is accredited with the Federal Ministry of Health in accordance with Section 67 (1a).
The content of the inspection depends on the planned or already approved scope of activities. In order to be able to assess which regulatory requirements are applicable to your facility, please take a look at the applicable legal bases. It is also advisable to familiarize yourself with the guidelines of a Good Manufacturing Practice (GMP) or Good Distribution Practice.
When carrying out an inspection, it is not always necessary to include all areas of the regulatory requirements; in the case of initial inspections, all the main subject areas of the applicable requirements are also checked.
The time that the on-site inspection takes depends largely on the scope of the activity, the size of the facility, and the complexity of the relevant processes, and can vary from half a day to ten days. In principle, inspections are carried out by one inspector. If the order is for an inspection with complex content, or if it involves an operation that carries out manipulation steps on the open product, the inspection is carried out as a team.
Typically, the part of an inspection that is conducted on-site at the facility consists of the following essential parts:
- Welcome and opening of the inspection in the context of a meeting.
- If applicable, a walk-through of the production or laboratory premises, usually following the flow of goods. Processes, procedural instructions including compliance with the same, machine logbooks etc. are checked for compliance with the specifications.
- Coordination of the inspectors followed by a final meeting including announcement of the observations.
In principle, any documentation related to product quality may also be reviewed by the inspectors during the inspection. This includes, for example (list not exhaustive):
- Any existing authorization(s) under medicinal product law
- Organizational chart of the facility (incl. job descriptions and proof of qualification of key personnel)
- Procedural instructions (incl. a list of the same)
- Operational description / Site Master File
- Personnel & material flow
- Quality Risk Management
- Qualification & validation records
- Training system (including personnel training records)
- Hygiene program
The rectification of any identified defects can be started immediately. Normally, all defects found during the inspection are also addressed and pre-classified during the final meeting. The classification on site is a notification, the final classification is made during the acceptance of the report before it is sent to the party hearing (§ 45 Abs 3 AVG). In order to be able to classify a defect as remedied, it is necessary to provide documented evidence in the course of the response to the initial report, which proves that measures have been taken that result in remedying the defect (e.g. photo documentation, draft documents, etc.). Letters of intent do not result in the correction of a deficiency; specific corrective and preventive actions must be taken. The submission of the action plan should be collected as a statement for the hearing of the parties.
If deficiencies that have occurred in the action plan are not addressed with corrective and preventive measures or are not remedied within the agreed period, there is a threat of official measures, up to and including the withdrawal of a license followed by a report. In addition, information about the lack of compliance with the applicable regulatory requirements will be published.
The inspection interval is largely dependent on the respective scope of activities and the degree of compliance with the applicable regulatory requirements. Follow-up inspections are performed on a risk basis within the respective maximum time frame specified in the AMG.
This means an inspection interval for
- Manufacturing and control establishments: three years max.
- establishments processing, storing or distributing human blood or blood components, if intended for transfusion: max. two years
- other establishments (distributors): max. five years