Regulatory inspections

Preventive maintenance on vital equipment should be properly scheduled, carried out and documented. This program must be separate from the regulatory inspection. 

What are the rights and responsibilities of each party with regard to regulatory inspections ... 

Is there a statutory or regulatory inspection of the major equipment and do records indicate that tests are passed without problems ... 

Preventive maintenance on vital equipment, such as tractor units, tanks, pumps, hoses, hard arms, pipelines, and mooring facilities, should be properly scheduled, carried out and documented. This program should be separate from the regulatory inspection. Verify from records. 

In early 2007, the EMEA reported the analysis of GMP deficiencies in its document entitled Good Manufacturing Practice An Analysis of Regulatory Inspection Findings in the Centralised Procedure. It detailed the deficiencies reported in 435 inspections of manufacturers of medicinal products and starting materials in the European Union and third countries in the period 1995 to 2005. Altogether there were 9465 deficiencies, of which 193 were critical (2%), 989 major (10%), and 8283 (88%) others. The top 20 deficiencies are presented in Table 10.1. 

Source EMEA Inspections. Good Manufacturing Practice An Analysis of Regulatory Inspection Findings in the Centralized Procedure, Doc. Ref. EMEA/INS7GMP/23022/2007 [accessed August 28,2007]. 

The new European Directive (2001/20/EC) has reinforced the need for European agencies, as well as those of the United States and Japan, to conduct inspections of clinical trials. Sponsors, mindful of the implications of failed inspections, are carrying out audits by their QA units to try to ensure that standards at a particular site meet the regulatory requirements of GCP, and of any future regulatory inspection. Frequently, the inspections will occur 2 or more years after the end of the study. 

The instrument qualification and calibration records are among the most frequently requested items in regulatory inspections. It is vital for the pharmaceutical, biotechnology, environmental, food, cosmetic, and chemical laboratories to maintain a rigorous instrument qualification and performance... 

Validation reports are written at the conclusion of the equipment IQ and OQ and when process validation is completed. The reports should be stand-alone documents containing all pertinent information because they will serve as primary documentation for later FDA regulatory inspections and as reference documents when changes to the system are planned and the need for revalidation is under consideration. 

The importance of the qualification process of technical systems in the pharmaceutical industry has been steadily increasing over the last 10 years. It has been driven primarily by the requirements of regulatory bodies and not by the need to save money in this part of the industry. If the industry made use of the full scope of the GMP requirements, the qualification process would be more efficient and the cost of qualification would drop. On the other hand, pharmaceutical companies want to protect themselves from a less than perfect result during a regulatory inspection and therefore demand 120% effort from their suppliers and service companies. New methods and tools must be implemented to reach the goal of qualifying a technical system while minimizing effort. 

For GMP applications the software development must be based on a fully documented and structured design and formally reviewed to ensure that it is reliable, safe, testable, and maintainable. A modular approach to software design with annotated documentation will provide a better understanding of the system software throughout the relevant life-cycle activities and also during regulatory inspection. Use of standard software should be considered whenever possible. 

System owner The person(s) who have responsibility for the operational system, and bear the ultimate responsibility for ensuring a positive outcome of any regulatory inspection or quality audit of the system. 

The organization must have a well-documented audit trail to raw data that will facilitate the retrieval of any supporting data that may be required during a regulatory inspection. In case of any off-site inspection, it may be prudent to include a copy of all notebook pages and all raw data. 

All registrations stability studies, both accelerated and long-term, must of course be carried out in full compliance with cGMPs. Example 5 presents stability areas often cited as deficient during regulatory inspections. 

All regulatory inspections must be analyzed by the compliance department to determine the main areas for GMP enhancement. An action plan or GMP enhancement master plan should then be designed to correct all deficiencies—and not only those cited in an FD-483. (For a detailed discussion of this subject, refer to Chap. 16, The Compliance Upgrade Master Plan) Subsequent internal quality assessments should initially focus on areas identified during the regulatory inspection and use the FD-483 as a platform from which to launch a comprehensive compliance and quality upgrade master plan. 

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