Susan J. Schniepp is a fellow at Regulatory Compliance Associates, Inc. and a member of Pharmaceutical Technology's Editorial Advisory Board.

Susan J. Schniepp

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.

Conducting Effective Audits During and Post Pandemic

Q: Companies have made a lot of operational changes to accommodate working through the pandemic. What changes do you think will become permanent as a result of the pandemic?

A: There are a number of operational changes that companies have made to 

Editor's Note: This article was published in 

accommodate working through the pandemic. Many of the changes were implemented out of necessity, and some of these changes have the potential to become permanent and normal operating procedures in the future. Patients still need life-saving medicines and companies need to find ways to continue manufacturing safe, effective, and compliant products for these patients despite the challenges presented by the pandemic. Conducting virtual audits, conducting effective virtual training, and enhancing communications with suppliers to ensure an uninterrupted supply chain are among the changes implemented to maintain operations, stay compliant, and continue manufacturing medically necessary products. Each one of these changes have positive and negative aspects that need to be evaluated and debated to determine if they are as effective as the previous processes.

Moving to virtual audits was one of the first changes that was implemented by companies and regulatory authorities. The necessity for virtual audits was to allow companies and regulators to continue to evaluate the compliance stature of manufacturers while respecting stay-at-home and social distancing requirements that prevented in-person site audits.

There are many advantages of performing virtual audits and the key to making a virtual audit successful is preparation and communication. Informational (organizational charts, standard operating procedures, quality manual, etc.) requests should be made prior to the audit, and the requested documents should be reviewed before the commencement of the audit.

Companies can save time and reduce travel expenditures because people will be reviewing documents from home offices. The documentation required for in-person audits will be the same as virtual audits, but rather than making copies for the auditor, the documents can be turned into a PDF file and be sent through a secure system to the requester. Questions regarding the documentation can be addressed through a number of virtual platforms as long as the platform chosen is acceptable to both parties.

Performing a tour of the facility poses unique challenges, and possible solutions need to be vetted between the two parties to determine the most efficient and secure way to share this information. The bottom line is that virtual audits have the potential to be as effective as in-person audits and perhaps may be more time efficient and cost effective.

The same principles applied to conducting virtual audits can also be applied to training. On-line training programs have been used to train remote employees for years. There are a number of technological platforms that can be used to deliver virtual training programs to employees. These platforms allow training material to be pre-recorded and comprehension questions that must be answered correctly in order to continue with the training can be inserted. Remote training allows the employee to
complete the training as their schedule allows.

Another approach is to deliver the training as a webinar using a multiple-person meeting application. You can prepare and distribute the information you will cover in the training, schedule a meeting time, deliver the training, and take questions from the employees during the webinar. If you have multiple manufacturing shifts, you can schedule a training session during each shift to make it easier for second- and third-shift employees to receive the training.

Additionally, virtual training can be enhanced by taking advantage of online training and conference options offered by external organizations. Many external organizations have converted their conferences and training topics to virtual offerings covering a wide variety of topics. Some of these venues are free, and some require a registration fee.

Enhanced communication with suppliers to ensure an uninterrupted supply chain has also become a priority during the pandemic. Many companies are reviewing and enhancing their quality agreements. This is a positive change for the industry as a whole.

The quality agreement should be a living document that is reviewed and revised as often as needed to clarify the responsibilities of the client and the supplier and define how the two parties will communicate with each other. The agreement should clearly identify the roles and responsibilities needed for a successful partnership. Defining the quality relationship between a supplier and a client is complex and requires extensive discussion and attention to detail. The relationship should be open, and communication between the two parties should be as frequent as required to assure that the product being manufactured meets the highest quality standards for the client and for the patients. Bottom line is that quality agreements are important documents that have become front and center for ensuring the supply chain during the pandemic. This is a welcome change that should carry forward in the future.

There are many changes that have the potential to become permanent procedures/operating principles even after the pandemic is under control. Three that should become permanent in the future are the use of virtual audits, the implementation and utilizations of virtual training, and more robust quality agreements that enhance communications between the client and the supplier.

Susan J. Schniepp is distinguished fellow at Regulatory Compliance Associates.


Vol. 32, No. 12
December 2020
Pages: 50, 49

When referring to this article, please cite it as S. Schniepp, "Impact of Pandemic on Permanent Procedures," 

Virtual audits, virtual training, and more robust quality agreements may become positive impacts on the industry, says Susan J. Schniepp, distinguished fellow at Regulatory Compliance Associates.


Impact of Pandemic on Permanent Procedures

Q. I am responsible for updating my company’s standard operating procedures (SOPs). My company has been cited several times in audits for not following them, and this situation has worsened since the onset of the pandemic. What advice do you have for me to make sure the SOPs are being followed for now and in the future?

A. You are not alone. Not following SOPs or not having adequate procedures in writing continues to be one of the top observations for the industry in 2019 (1). Companies usually use their SOP to show that they have control over their processes, thereby demonstrating compliance with regulatory expectations. The problem you are having with your SOPs seems to be an ongoing issue not necessarily related to the pandemic. It would seem this situation is exacerbated by the pandemic but not caused by the pandemic. My advice to you would be to take a holistic look at how you create, implement, and modify your SOPs.

There are four simple concepts to keep in mind for having compliant SOPs: Say what you do, do what you say, prove it, improve it. The ‘say what you do’ phrase equates to the written SOP that defines the steps taken to achieve compliance to a regulatory requirement. ‘Do what you say’ equates to following the SOP. ‘Prove it’ means that you need to collect and be able to present data that indicate you have followed the instructions in your SOP and have investigated any incidents where you have deviated from those instructions. Once you have mastered these concepts, you can begin to work on the ‘improve it’ concept by revising and updating your SOPs to reflect current practice and process improvements. These concepts are simple enough to follow, so the being cited by regulators for not following SOPs is disappointing.

Previously in this column, we have discussed the elements of an SOP (2). The problem you are having seems to be related to the SOP content. To address this particular problem, you need to be aware of some of the pitfalls companies encounter when writing SOPs. Writing an SOP with the correct amount of information in it—neither too restrictive nor too ambiguous—is not an easy task. It takes time and effort to create an SOP with the right balance of information (3).

The three most common pitfalls when writing an SOP are providing too much information, providing too little information, and providing unneeded specific information.

Providing too much information in an SOP results in a restrictive process that generates deviations. An example of too much information in an SOP would be listing the serial number for a piece of equipment. Should the piece of equipment need to be changed for any reason, the result is a deviation and an SOP that can’t be followed.

When listing equipment requirements in an SOP, you should describe the piece of equipment but not necessarily to the serial number. It would be best to provide a list of the equipment needed with a general description of its function and capability.

When an SOP provides too little information, it results in an out-of-control process that generates deviations. When there is lack of clarity, it allows for interpretation by the operator. There is the potential for each individual executing the process to interpret the instructions in their own unique way resulting in deviations that need to be investigated and the potential for the regulatory citation of insufficient SOPs. An example of providing too little information might be not specifying the specific order reagents need to be added to generate a reaction. If it is critical to add the reagents in a certain order, that information needs to be specified in the SOP.

SOPs that provide unneeded specific information are also problematic. An example of unneeded specific information might be how dates are recorded in a document. A company needs to be consistent in the way the date is recorded regarding the order of the day, month, and year but can be flexible regarding whether this information is separated by hyphens or slashes. There is no difference between DD/MM/YY and DD-MM-YY. Specifying hyphens versus slashes sets you up for insignificant deviations that wastes time and resources.

Other potential pitfalls to avoid are providing ambiguous information, restricting access to SOPs, allowing access to obsolete SOPs, having unnecessary SOPs describing operations that you don’t perform, and not providing clear instructions for recording data, which could lead to data integrity issues.

Writing an effective SOP and keeping it current is not an easy task.It requires time, effort, and cooperation with the users to achieve the correct balance that allows the process to be easily followed, specifies the correct data to be recorded, reflects the current operations, and can be improved as the process improves through continual improvement. Taking a critical look at the level and detail provided in your SOPs and right sizing the information contained to accurately reflect your operations will help in eliminating an audit observation of not following SOPs or having insufficient SOPs, and these steps may help improve your compliance position.

www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/inspection-references/inspection-observations

, accessed Sept. 14, 2020.
2. S. Schniepp, 

 41 (12) 2017.
3. S. Schniepp, B. Matye, and J. Moldenhauer, 

SOPs Clear and Simple for Healthcare Manufacturers

Susan J. Schniepp is Distinguished Fellow at Regulatory Compliance Associates, LLC.


Volume 44, Number 10
October 2020
Pages: 74, 73

When referring to this article, please cite it as S. Schniepp, "Writing Effective SOPs," 

The amount of detail included in SOPs may help a company stay compliant, says Susan J. Schniepp, Distinguished Fellow at Regulatory Compliance Associates, LLC.

Writing Effective SOPs

Q. I am in charge of training activities for my company. Company policy requires all employees receive annual good manufacturing practice (GMP) training. Since many employees are working from home during the pandemic, I am struggling with how to deliver effective training, and I want to rewrite the policy to eliminate this requirement. Is annual GMP training a regulatory requirement, and can I eliminate this requirement and still be compliant with the regulations?

A. It is important to maintain training for employees even during highly challenging circumstances. In the United States, the regulatory expectation for training is defined in 21 

) 211.25, which states, “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 [CGMP] (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).

EudraLex Guidelines for Good Manufacturing Practice for Medicinal Products for Human and Veterinary Use 

has similar requirements specified in Volume 4, Part 1, Chapter 2, which states, “The manufacturer should provide training for all the personnel whose duties take them into production and storage areas or into control laboratories (including the technical, maintenance, and cleaning personnel), and for other personnel whose activities could affect the quality of the product.” The guideline also states, “Besides the basic training on the theory and practice of the quality management system and Good Manufacturing Practice, newly recruited personnel should receive training appropriate to the duties assigned to them. Continuing training should also be given, and its practical effectiveness should be periodically assessed” (2). The regulatory expectation is that companies continue to provide “a high level of assurance that manufacturers comply with CGMP and that products meet specifications,” even during exceptional times (3).

To ensure that training requirements are adhered to and your compliance posture is not jeopardized, I recommend you start by triaging your employees. Those employees in critical roles should be your first priority to receive the necessary training in a timely manner. Employees in less critical roles could receive the training at a later time or maybe receive a truncated version of the training. Remember to document your decision in a well thought out and justified rationale.

The next hurdle to overcome is to determine the most effective way to deliver the training without wasting critical resources. This can be accomplished in a variety of ways. On-line training programs have been used to train remote employees for years. These programs have the capability of allowing the instructor to tape the information and embed questions into the presentation that must be answered before that trainee can continue. This is a great way to train people and measure the effectiveness of that training. It also allows the employee to complete the training as their schedule allows. If you decide to utilize this approach, you need to be sure to set a date for completion of the training and monitor the results of responses so you can follow up on employees that may need some additional explanation or understanding of the concepts included in the training. Another approach would be to deliver the training as a webinar using a multiple person meeting app. You can prepare and distribute the information you will cover in the training, schedule a meeting time, deliver the training, and take questions from the employees during the webinar. If you have multiple manufacturing shifts, you can schedule a training session during each shift to make it easier for second- and third-shift employees to receive the training.

Another approach is to research virtual training and conference options offered by external organizations. Many trade organizations have converted their conferences and training topics to virtual offerings covering a wide variety of topics. Many of these organizations offer the option of listening in real time or to taped recordings. Some of these venues are free, and some require a registration fee. The sessions are usually 90 minutes in length, and many offer an opportunity to ask the speakers questions through a chatroom feature. If you are unable to listen to the webinar live, you may have the option to purchase a recording of it and listen to it at your convenience. The recorded option offered with these webinars can be valuable for training employees who work on the second and third shifts. The companies offering these webinars advertise them well in advance of the event and often send out multiple reminders. The advertising for the webinars highlights who will be speaking, their qualifications, what they will cover in the training, and what you will learn as a participant. In addition, they will also make recommendations on who should attend so you can determine if this is appropriate training for your employees. In some cases, the webinar may offer continuing education credits for attending. This information should be printed out and used to demonstrate the appropriateness of the training.

Finally, you might consider using some employees who are not working remotely to lead some small-group internal training during their shift, employing a train-the-trainer concept. This satellite training can be led by a qualified, trusted, and trained employee representative that has the knowledge and expertise determined by their experience and job performance as determined by you. As with all other training, these discussions should be documented in your training system as well as the rationale for the selection of the designated trainer.

The bottom line is even though people are working remotely, and in-person training may not be feasible, there are still opportunities to ensure employees receive the required training to meet your company’s training expectations. You should sign up to receive emails from companies and organizations that offer online training, review them to determine if they are applicable to your operations, determine who should attend from your company, and make sure you document their attendance for their training record.

 Title 21, Part 211.25, (Government Printing Office, Washington, DC) 145.

EudraLex, The Rules Governing Medicinal Products in the European Union, Volume 4, Good Manufacturing Practice for Medicinal Products for Human and Veterinary Use

, Chapter 4, Part 1, Chapter 2: Personnel, August 16, 2013.

Draft Guidance for Industry: Planning for the Effects of High Absenteeism to Ensure Availability of Medically Necessary Drug Products


Volume 44, Number 8
August 2020
Pages: 58, 56

When referring to this article, please cite it as S. Schniepp, "Training During a Pandemic," 

When in-person training may not be feasible, there are still opportunities to ensure employees receive the required training, says Susan J. Schniepp, distinguished fellow, Regulatory Compliance Associates.

Training During a Pandemic

Q. I am in the quality department and am responsible for investigations, and I have been working from home due to the COVID-19 pandemic. The investigation standard operating procedure (SOP) requires me to perform face-to-face interviews with people and to complete the investigation within 90 days. Working remotely to conduct the interviews is taking much longer, and I am afraid I’ll miss my deadlines. Could I eliminate the interview requirement until I am able to return to the facility?

	A. I certainly understand the challenges of trying to conduct remote face-to-face interviews and the need to try and streamline processes during times of crisis, but now is not the time to take unnecessary, undocumented shortcuts with any of your procedures. My recommendation is that you step back from your frustration with the situation. Focus on the elements you need to conduct a thorough investigation and look at finding alternative means to fulfill the SOP requirements as defined in your contingency plan. If you do not have a contingency plan in place, you should immediately develop one and include appropriate risk-based information. The European Medicines Agency has a guidance on the format for a risk management plan that might help you get started on this activity (1).

	To determine how you might make your operations more efficient during crisis times, I further suggest you review the FDA’s draft guidance titled,

 Planning for the Effects of High Absenteeism to Ensure Availability of Medically Necessary Drug Products

 (2). The guidance document states, “This guidance is intended to encourage manufacturers of medically necessary drug products (MNPs) and any components of those products to develop contingency production plans to use during emergencies that result in high absenteeism at production facilities” … “The guidance provides considerations for the development and implementation of a plan for production of MNPs during a crisis, including specific elements that should be included in the plan.” 

	The contingency plan you develop should include information regarding the company’s prevention and risk mitigation processes. The guidance states, “These preventative measures can include steps to prepare personnel such as:

		“Educating employees on topics such as, in the case of a pandemic, personal hygiene (hand washing and coughing and sneezing etiquette), social distancing, and appropriate use of sick leave

		“Encouraging employees to get immunized as appropriate by providing information on local vaccination services or by offering on-site vaccination services, if reasonable

		“Providing information for and encouraging employees to develop family emergency preparedness plans

		“Reviewing CGMP [current good manufacturing practice] regulations regarding appropriate sanitation practices and restriction of ill or sick employees from production areas (see 21 

	The guideline also recommends “that manufacturers, when evaluating activities that might be reduced in frequency, delayed, or substituted by a suitable alternative, first identify and consider activities that are intended by the CGMP regulations to provide controls not connected with the manufacturing of any specific batch. Examples include:

		“Production equipment routine maintenance

		“Utility system performance checks and maintenance (e.g., air temperature, lighting, compressed air)

		“Environmental monitoring of facilities such as cell culture, harvesting, and purification rooms during production

		“Stability testing for certain drug products and components

		“Periodic examinations of data and of reserve samples” (2).

	In addition, the guideline also recommends that, “If the demand for MNPs cannot be met by the measures described above, manufacturers can consider reducing activities that are more directly connected with batch manufacturing or a product accept/reject decision provided that they have a documented rationale or risk assessment to show that the proposed changes will not unacceptably reduce assurance of product quality. Examples include:

		“Not requiring second-person verification of activities for less critical steps (though we recommend a self-check of work)

		“Reducing the number of samples for labor-intensive laboratory testing

		“Forgoing an in-process test to assure adequacy of mix, particularly when making successive batches, where the risk is judged to be low in terms of drug safety and efficacy

		“Delaying completion of deviation investigations of minor events.

		“CDER [the Center for Drug Evaluation and Research] recommends that in taking such measures, firms plan to carefully monitor indicators of product quality to note any unfavorable trends or shifts as a result of the implementation of the Plan. CDER also recommends that firms retain samples for testing at a later date in cases where testing is reduced or omitted because of lack of resources” (2).

	While it is important to act quickly and efficiently during a crisis, the process and product must still be manufactured in accordance with appropriate regulatory requirements. Before you make any drastic changes to SOPs or eliminate process steps you need to read the FDA guidance document, prepare a proper risk assessment, and justify why the removal of the requirement from the SOP does not impact patient safety and product quality. The documentation you provide and the assessments you perform to address some of the extraordinary situations facing you and your colleagues in the effort to produce necessary medical drugs should give you confidence that you have acted appropriately and within the regulations to fulfill patient needs.

Guidance on the Format of the Risk Management Plan (RMP) in the EU–in Integrated Format, 

EMA/164014/2018 Rev.2.0.1 accompanying GVP Module V Rev.2 Human Medicines Evaluation (EMA, October 31, 2018).
	2. FDA


	Volume 44, Number 6
	June 2020
	Pages: 62, 60

	When referring to this article, please cite it as S. Schniepp, "

Products must be manufactured in accordance with appropriate regulatory requirements, even during a pandemic, says Susan J. Schniepp, executive vice-president of post-approval pharma and distinguished fellow, Regulatory Compliance Associates.