GXP Talk: Questions 58 & 59 | IVT

This column is one of a continuing series in which representatives of the industry and regulatory agencies have an opportunity to express their opinions on current GXP issues.

Thank you for your responses to the questions posed in the last issue of the Journal of GXP Compliance. They follow.

Question 58

How does US Food and Drug Administration define/determine appropriate training/qualification of personnel?


The current good manufacturing practices (cGMPs) define the requirements (“what to do”) but not how to meet the requirements. The “how” is left to each company. FDA is responsible for ensuring that only drug products meeting the standards for identity, safety, quality, and purity are released to the market. The GMPs require that: “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.” (1). Buried within these requirements are some keys to the FDA’s expectation of what training or qualifications personnel should have. First, the personnel must be trained in the procedures applicable to their job function. To determine whether someone is qualified for their job function, a company must define the training requirements for each. For example, an operator running an aseptic filling line would need to be trained in the procedures for operating the filling machine and aseptic techniques. 

The second training requirement is to ensure that personnel are trained in the cGMPs applicable to their job function. For example, a laboratory analyst should be trained in the cGMP requirements for lab testing and documentation. Again, the company needs to define this qualification requirement for the job. Additionally, the person should have education, knowledge, or experience in the job function. It may be necessary for some personnel to have specific college degrees or experience. For example, just because a laboratory analyst has read all applicable standard operating procedures (SOPs) and GMPs on performing an high-powered liquid chromatography (HPLC) assay does not necessarily mean that they are qualified to perform HPLC assays. 

Personnel must also be trained in their job function. Again, the minimum training requirements for a job function should be defined. Often training in a job function includes on-the-job training. 

Training is not a onetime event, but it must be ongoing to ensure that personnel remain familiar with their job function requirements. For example, when SOPs are revised, personnel need to be trained in the revised SOPs. Similarly, operators should be trained in changes to batch records to ensure that they understand the changes.

Quality risk management techniques can be used to help define the appropriate qualifications for job functions. Each job function should be defined and associated risks assessed if an improperly trained person were to perform the job function. For example, if an improperly trained warehouse worker is unaware of the need to verify the label against the expected material, the wrong grade of material could be received and used. Such a risk needs to be assessed when defining the training requirements for a warehouse operator. The risk assessment used to define the training can be used to support the rationale for the job qualifications.

When questioned about whether a person is appropriately qualified, a company should be able to provide the inspector with the training requirements for a job function as well as the training records demonstrating that the personnel have met the defined requirements. The company should also be ready to defend their rationale for the job training qualifications, which can be demonstrated through the risk assessment.

Question 59

How does one handle an out-of-specification (OOS) result for temperature and humidity in a stability chamber?


This is an interesting question, and part of the response is based on terminology. The temperature and humidity results are out-of-the-defined limits for the stability process, but they do not constitute and out-of-specification result as defined in the FDA OOS Guidance (1):

And now, here are two more questions for comment.

Question 60

It has been said that people changes fall under change control. If operator A & B are qualified, how is this change control?

Question 61

How are International Conference for Harmonisation (ICH) Guidances published into law in the US?  Where are ICH Guidances published? Which takes precedence, FDA or ICH Guidances?

Let us know your opinion on these questions. Also, let us know if you have any questions to ask of the industry. Please submit your questions or responses to Jerry Lanese or Tim Fields. You may also ask your questions or respond to these, or any previous questions, via the comment section below.

For purposes of this document, the term OOS results includes all test results that fall outside the specifications or acceptance criteria established in drug applications, drug master files (DMFs), official compendia, or by the manufacturer. The term also applies to all in-process laboratory tests that are outside of established specifications. 

The identified temperature and humidity values are not the result of laboratory testing; they are deviations from a defined process, the process for maintaining conditions in a stability chamber required for stability studies. There should be a deviation investigation that is focused on the impact or risk to the stability samples maintained in the chamber. The investigation should include an assessment of the mean kinetic temperature of the samples during the out-of-limits excursion and the risk to the samples. Even if the conclusion of the investigation is that there is no impact on the stability samples, the investigation should identify the cause of the deviation and be followed by corrective and preventive action so that process will be improved.

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