Steven J. Lynn is executive vice-president, Pharmaceuticals for Regulatory Compliance Associates, Inc.

Steven J. Lynn 

Experts Steven J. Lynn, executive vice-president, Pharmaceuticals for Regulatory Compliance Associates, Inc., and Susan J. Schniepp, distinguished fellow for Regulatory Compliance Associates, Inc., provide simple answers to frequently asked questions regarding regulatory inspections, although many of the concepts can be applied to internal and supplier audits as well.

Q. What documentation should I have ready to present to the inspectors?

A. There are a number of documents and supporting evidence that can be staged prior to an inspection whether it is in-person or is being handled remotely. The objective is to make the inspection process go smoothly for both parties. At a minimum, there should be a list of all current standard operating procedures (SOPs) provided to the auditor so they can choose the specific ones they are interested in reviewing, a listing of customer complaints for the past two years, a list of current closed and open deviations and corrective and preventive actions (CAPAs) for the past two years and the site’s quality manual, the current organizational charts, a copy of the employee training program, and a map of the facility. In addition, it is advisable to have a short introductory presentation (5–10 minutes) that describes the facility, the products produced, and the operating hours of the facility. This information can be provided up front for the inspectors.

Q.How long should an inspection/audit take?

A. There is really no specific time frame defined for an audit. Typically, supplier and internal audits should take between one to two days and a regulatory inspection typically takes three to four days. Any inspection/audit can be extended depending on what the auditors/inspectors observe during the inspection. If things go well, the inspection will be completed quickly. If problems arise, the auditors may wish to extend the inspection and pursue the issue. This time frame is consistent whether the audit is done in-person or remotely.

Q. Do I need to make copies of everything the inspectors request?

A. In organizing for an inspection, it is advisable to track all documentation provided to the inspector. This is an important activity whether the inspection is performed in-person or remotely. The inspection tends to run more smoothly when both parties are looking at and discussing the same documents. Whatever documentation is provided and kept by the inspector, it is advisable that the hosting site keep a record of the documentation being provided so they can refer to the specific document when responding to any observations associated with that documentation. Basically, the hosting site needs to have an accurate log, so they are able to recreate the audit activities after the inspector leaves. This is especially important when responding to the audit observation because it eliminates any questions about which document/information was discussed. Audits are fast paced, and anything that helps people remember what was discussed benefits the ability to understand and respond to any observations associated with the documentation that was reviewed.

Q. How much time do I have to answer a question after the inspector asks it?

A. There really isn’t a defined time frame to answer the questions. Questions that can be answered immediately should be answered immediately. Questions that need a little more investigation or clarification before answering should be responded to in a timely manner.

Let’s look at an example. If the inspector is reviewing a technical document, they may ask to see a previous version of the document. If this document is stored off site, then it may take a day or two to retrieve it. This is acceptable as long as you inform the inspector why there is a delay in providing the requested information. Bottom line, all questions and documentation should be answered as soon as possible, and if there is a delay, it is important to be transparent with the inspector and explain the reason for the delay.

Q. If an inspector makes an observation, do I need to have a corrective action in place before the inspection ends?

A. No, there is no reason to have a corrective action in place before the inspection ends. In some cases, the observation may be easily corrected, so it might be possible to have the corrective action in place before the conclusion of the inspection, and if the correction is acceptable to the inspector, it may actually help remove that observation from the final inspection report. Having said that, the best advice is to wait until the inspection is completed before you implement any corrective action so you can be sure the action is appropriate for the observation and you have had time to make sure related documentation and activities have also been updated in relation to the observation. 

Steven J. Lynn is executive vice-president, Pharmaceuticals for Regulatory Compliance Associates, Inc., and Susan J. Schniepp is distinguished fellow for Regulatory Compliance Associates, Inc.

When referring to this article, please cite it as S. J. Lynn and S.J. Schniepp, “Frequently Asked Questions on Regulatory Inspections,” 

Articles

Frequently Asked Questions on Regulatory Inspections

The audit function of a pharmaceutical company is one cornerstone of an effective and efficient quality management system. There are several types of audits that comprise a robust auditing program, including supplier audits, internal audits, and regulatory audits. Each of these specific audits requires preparation to make sure the audit is productive and accomplishes its intended purpose, which, in the manufacturing world, is to ensure facilities are manufacturing fit-for-use products in full adherence (hopefully more) to current good manufacturing practice (CGMP) requirements.

Supplier audits are performed to confirm that the suppliers of raw materials, packaging, and labeling components, etc., are able to provide a continuous, uninterrupted supply of the materials that are compliant with CGMPs. Regulatory authorities perform inspections to determine if the manufacturing company is providing materials that comply to CGMPs. Internal audits are performed by the company as a self-assessment for the purpose of identifying areas/issues that might affect their compliance status. Internal audits are solely under the purview of the company, while regulatory/supplier audits involve two distinct entities. Supplier audits are conducted using personnel from the supplier company and the client, and regulatory audits are conducted using personnel from the regulatory authority and the company being inspected.

Pre-pandemic, preparing for a supplier or regulatory audit typically consisted of the regulatory inspector or the auditor for supplier/internal audits providing the facility being audited with an agenda listing the areas to be toured (e.g., incoming raw material area, quality control [QC] chemistry and microbiology laboratories, manufacturing, etc.) and a list of documents to review (e.g., quality manual, list of standard operating procedures, open deviations, and corrective and preventive actions [CAPAs]) and any additional supporting evidence the auditor chooses to review. This information helps auditing authorities assess and decide the compliance status of the facility.

Performing external audits during a pandemic

The documentation that would have been reviewed on-site pre-pandemic is the same documentation that is needed for review during and post the COVID-19 pandemic. The documentation and supporting evidence review conducted pre-pandemic would most likely have occurred at the facility. However, audits conducted during the pandemic require the documents and supporting evidence to be shared electronically to the auditor using secure electronic systems. This electronic exchange helps make time more efficient for both the auditor and the facility being audited. The documentation can be reviewed by the auditor, and questions can be communicated to the audit manager via email or conference/video calls. While this may not be ideal, because it eliminates the in-person interaction, it is still an effective way to conduct an audit when there are conditions prohibiting face-to-face interaction.

Touring the facility is challenging when the audit is conducted during a pandemic, but the challenges are not insurmountable. Live video feed could be streamed to the auditor, while the company’s audit manager and/or subject matter experts are available to answer questions that might arise during the live feed. Additionally, operations could be recorded, and that recording could be provided to the auditor, again with the understanding that the audit manager would be available to answer any questions posed by the auditor upon the review of the video. While the recorded version of the tour is probably not the most ideal, because the auditor needs to see things in as real time as possible, it does allow for the auditor to pause and go back to review a specific operation in more detail if warranted.

Preparing for a supplier audit requires the same discipline as preparing for internal and regulatory audits. During the COVID-19 pandemic, many companies reduced the number of employees allowed at the site, and many of the quality personnel that conduct audits are allowed to work remotely.

Conducting a supplier audit is different from the other audit types, whether it is pre-, during, or post-pandemic. If designed and implemented appropriately, the value of the supplier audit is that it allows both the supplier and client company to find vulnerabilities in their existing supply chain and remediate them before they are discovered by an external auditor. Supplier audits should not be looked at as punitive from the supplier perspective. The best supply audits are ones where the client auditors are looked upon as partners in the overall continual improvement efforts of the supplier company.

Supplier audits can provide valuable information that can be used to prevent issues at the supply company before they become compliance concerns that may disrupt the supply chain. Issues that can be discovered during a regulatory inspection may be identified during a supplier audit. If these issues can’t be completely remediated before a regulatory audit, a plan to correct them can be established and action taken to mitigate them. Having corrective actions in place before others identify the issue may lessen the impact of the observation and instill confidence that the quality system is under control and there is a process in place for continuous improvement. In addition, the results from the supplier audit can be used for training staff and communicating valuable information to the organization.

The objective of a client when conducting a supplier audit is not to pretend to be the regulatory authority and show up unannounced, but rather to work in cooperation with your supplier to identify and solve potential issues. An effective program establishes a partnership between the client and the supplier so they can work together to solve issues before they affect the ability of either partner to supply material/product that complies to current standards. The ideal tone for a supplier audit should be a collaborative team-oriented activity that is instructive, informative, open, honest, and inclusive.

There are several factors that help contribute to establishing this tone, even during a pandemic. One way to set the proper tone is to publish the audit schedule/agenda in advance and make sure the functional areas personnel are informed of the schedule. During a pandemic, the agenda takes on another level of importance because it ensures that the site can have the proper documents ready to go and upload them either before or during the audit. Prior planning precludes poor performance in this area. Also, the audit itself should be forward thinking and unlimited in scope, even during the pandemic.

The auditor’s behavior is also important to obtaining valuable information. Auditors should be direct and avoid asking questions designed to intentionally stump people. Another important behavior is the ability of the auditor to listen to the answers personnel give and refrain from judging. The exact same behavior defined for the auditor should also be the exact same behavior displayed by the auditees. Auditees should be direct and avoid deflecting or obfuscating answers and take the time to explain why they do things the way they do them. They need to listen to the auditor’s concerns and not overreact to questions being asked. They should be proactive and point out things of concern and seek advice on how to remediate them. Both parties need to remember they are not enemies, rather they are the partners in improving their organization together.

The pandemic has allowed the industry to creatively utilize technology-based applications to communicate and perform an effective audit. The documentation and supporting evidence review can be conducted remotely, and confidentiality can be maintained. After reviewing the documentation and supporting evidence, the auditor can request interviews with various personnel, which can then be scheduled via video conferencing to accommodate both the auditor and the facility personnel.

The outcome is that, with appropriate planning and the proper use of technology, remote auditing can be as effective and informative as in-person auditing, as well as being more time and cost effective for companies who typically allocate a great deal of budgetary resources to an audit program. The post-pandemic sweet spot will likely be balancing remote and in-person audits.

Steven J. Lynn is executive vice-president, pharmaceuticals for Regulatory Compliance Associates, Inc., and Susan J. Schniepp is distinguished fellow for Regulatory Compliance Associates, Inc.


Supplement: Partnering for Bio/Pharma Success
February 2021
Pages: s24–s25

When referring to this article, please cite it as author, “Conducting Effective Audits During and Post Pandemic,” Partnering for Bio/Pharma Success Supplement (February 2021).

With appropriate planning and the proper use of technology, remote auditing can be as effective and informative as in-person auditing.