07.07.2014 |

LOGFILE No. 31/2013 - Preparing GMP Inspections - Change in EU GDP Guideline

Preparing GMP Inspections

An Excerpt from "Preparing for the EU GMP Inspection"

Supplier audits and inspections by the authorities are, in many regards, stressful situations. There is generally a great deal hanging on the result of the inspection, whether it is an order from an important customer or approval for a new product. This means that al the staff members involved in the inspection are under intense psychological pressure, which can make it difficult to present normally self-evident processes to the inspector in a comprehensible way and to 
answer questions fully and correctly.

Common concerns include the following:

  • Will the staff be able to provide the correct answers or explanations to the questions posed in spite of general nervousness?
  • Can the company prove everything with documented evidence?
  • Can the company explain that (and how) its GMP or QA system works?
  • Is the company’s GMP status adequate?
  • Will the staff make oversights because members feel watched or because they are scared to fail?
  • Will the inspectors set “traps”?
  • Will someone be tripped up by his or her own reasoning because he or she wants to make a particularly good impression?
  • How will the staff stand internally after the inspection, for example, with regard to other departments?

Only preparation can help to relieve these uncertainties and self-inspection can play an important element of this. The advantage of a a self-inspection is that a company can play with an open hand and immediately correct any deficiencies that are found. The disadvantage is that an internal auditor is generally too familiar with the individual processes (even to the extent of wearing professional blinders) and only uses the internal terminology.

This only reflects the reality of an inspection by the authorities or a customer to a limited degree: Here, the auditee may be confronted with terms or questions that he or she had not considered in the same way.
The generality of a question is often a worry: What is the meaning of “adequate water systems”? What is the inspector driving at when he or she asks about “suitable equipment” or “qualified personnel”? Even the terms used in the GMP rules and regulations do not always correspond to the expressions used in the company and can cause uncertainty: for example, if the “test procedures” are queried, does this mean the control procedures, the testing instructions, the testing plan, the analysis procedure, the IPC instructions, the calibration procedure or the stability plan? What does “process instruction” mean in a particular instance? The manufacturing formula in accordance with EU GMP, the processing instructions in accordance with EU GMP, the manufacturing description in accordance with CFR, the master production record in accordance with CPR or even an SOP?

Suppliers, in particular, who have generally structured their quality management systems according to ISO 9000 or recently ISO 9001, use very different terms than the GMP inspector of a customer, for example. How do “quality planning”, “quality control”, “quality assurance” and “quality improvement” translate into GMP terms? Is “OOS” concerned with quality fault management or remedial actions? Can Statistical Process Control (SPC) and the concept of validation be made consistent?

For suppliers, an aggravating factor is that they are often confronted with GMP requirements that the pharmaceutical customer has been only too eager to pass on to the supplier. However, on closer inspection, many of these customer requirements cannot be traced back to legal requirements because they only relate to pharmaceutical products and not to the active pharmaceutical ingredient (API), excipient, packaging material or item of equipment.

To prepare for such general questions, appoint an external consultant to carry out a mock inspection. This allows companies to test the “real situation” and, identifies any weaknesses, which would not be obvious internally.

Alternatively, or in addition to this, it is worth using checklists to deal with the questions that a GMP inspection may typically bring up. These can be considered carefully beforehand, for example, which internal documents need to be kept at hand for certain questions – this will save some moments of panic during the inspection. Some FDA inspectors like to use checklists, such as those in the Compliance Policy Guides or Compliance Policy Manual to prepare themselves for the inspection. Auditees can also use these sorts of checklists as a useful preparatory aid.

However, when using checklists to prepare for an inspection, consider the following:

  • Simply filling in these lists can at best provide an initial overview. However, it does not replace the intensive challenge of the individual quality system in place.
  • Checklists can never be as comprehensive, exhaustive or specific enough to do justice to the situation at every (pharmaceutical, supplier, packaging, etc.) company with all the various product ranges, different equipment pools and organizational differences.
  • On the other hand, they will also include many questions that may not be applicable to a particular (pharmaceutical, supplier, packaging, etc.) company. However, it is still useful to be prepared for these questions so that staff members are not irritated during the actual inspection and can point out that a certain requirement only applies to pharmaceutical products, for example, and not to APIs, etc.
  • Specific national legal requirements may have to be considered.

A list of question can also be useful for the auditor when preparing for the inspections to ensure that it covers all the relevant aspects. Nevertheless, an inspection is not only about asking the right questions, but also assessing the corresponding answers. A checklist cannot take on this task. The checklist alone is often unsatisfactory for documenting the findings during the inspection (for example, marking yes or no). More meaningful descriptions are very important in order to classify the deficiency.

Icon LOGFILE-31-Preparing-GMP-Inspections.pdf