Elements of a Thorough Investigation

Nonconformances are an inevitable part of any process. Whether it is in a manufacturing, production or laboratory environment, at some point, you will encounter an observation or result that is contrary to its pre-determined requirements or specifications. In such instances, some type of an investigation will be required. The subject of this week’s blog is to outline some of the elements of a thorough investigation that supports compliance to the regulations and provide some brief examples.

A comprehensive quality system or GMP investigation must be substantiated by documented evidence. Documentation provides the necessary objective evidence to support any claims or findings of the investigation. Documentation is what provides an investigator or auditor, the assurance that the claims that you are making in support of the root cause(s), or corrective action(s) are valid.

Documentation also serves as proof of what element or process or idea that has been eliminated as potential root causes. And in the eyes of an investigator, “if it is not documented, it’s a rumor”. Your investigation packet can contain all of the elements to show how the product was manufactured, packaged, or tested in a laboratory setting; but unless you can show via documented evidence the actions taken and relate those actions back to your investigation, then you do not have the necessary evidence required to support your claim.

What does documentation consist of and what sorts of actions require documentation? Well, Documentation consists of written records that guide activities and prove what has occurred. Documentation in support of an investigation must clearly demonstrate the actions that were taken, when they taken, who executed such actions, as well as the qualifications of such individual. If you recall, personnel qualifications is mandated by both the GMP and QS regulations. 21 CFR 211.25 states the following in regards to personnel qualification:

(a) "Each person engaged in the manufacture, processing, packing, or holding of a drug product shall have education, training, and experience, or any combination thereof, to enable that person to perform the assigned functions. Training shall be in the particular operations that the employee performs and in current good manufacturing practice (including the current good manufacturing practice regulations in this chapter and written procedures required by these regulations) as they relate to the employee's functions. Training in current good manufacturing practice shall be conducted by qualified individuals on a continuing basis and with sufficient frequency to assure that employees remain familiar with CGMP requirements applicable to them."

Next, the documentation to support your investigation must clearly show the sequence of events and conclude whether they confirm or eliminate a root cause. This can be easily accomplish by a heading or a brief footer that describes what this data support. It should not be left to the auditor to “guess” at what the data support. They may arrive at a different conclusion than you intended. Be upfront and clear at all times.

Finally, documentation of your corrective actions must not only comply with the points above but must also support your root cause. That is, the documentation that you are including as part of your investigation packet to support the validity of your corrective actions must clearly tie back to your root cause(s). If it does not, the investigation leaves the door open to potential causes that remain unexamined and the possibility that the given nonconformance may reoccur.