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Production and Postproduction Monitoring
CHAPTER 24
Production and Postproduction Monitoring Abstract ISO 14971 requires that manufacturers collect and evaluate information about the medical device or similar devices, in the production and postproduction phases. The US CFR, title 21, part 822 has similar requirements. Patient/user safety is enhanced by active surveillance of production and postproduction information about marketed products. The manufacturer also receives significant benefit from the surveillance, namely, the opportunity to quickly identify and rectify product/process defects. This in turn leads into reduced customer complaints, reduced field corrective actions, improved reputation and customer loyalty, which means higher sales. And if that’s not enough motivation, failure to perform product surveillance could result in substantial fines, criminal prosecutions, seizure of product, and closure of the business. Keywords: Postmarket risk management; production and postproduction monitoring; surveillance; CAPA; HHA; risk management file review
Clause 9 of ISO 14971 [3,7] requires that manufacturers collect and evaluate information about the medical device or similar devices, in the production and postproduction phases. Similarly, under section 822 of CFR 21 the FDA requires the manufacturers and distributors of medical devices to perform postmarket tracking and reporting of device malfunctions, serious injuries, or deaths. The term “postmarket” is used by the FDA in the United States. ISO 14971 [3,7] uses the terms “production” and “postproduction.” These terms are roughly equivalent. Fig. 24.1 shows the contrast between these terms. In the rest of this chapter we’ll use the term “postmarket” interchangeably with “production and postproduction.” Production information is collected during the manufacturing process, and postproduction information is collected on all the phases of lifecycle after the product has been manufactured. The most significant postproduction lifecycle phase is productuse where majority of the feedback is generated.
Figure 24.1 Postmarket versus postproduction. Safety Risk Management for Medical Devices DOI: https://doi.org/10.1016/B978-0-12-813098-8.00024-6
r 2018 Elsevier Ltd. All rights reserved.
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Safety Risk Management for Medical Devices
Listening systems should be established and tuned in to various sources of information. Examples of potential sources of information are as follows: • • • • • • • • • • • • • • • •
manufacturing/production product service/repair returned product investigations customer service field service/customer visits clinical studies, e.g., postmarket clinical follow-ups customer complaints limited market releases product demonstrations databases such as MAUDE or EUDAMED legal department regulatory agencies, competent authorities (e.g., Field Safety Notices, Safety Alerts) suppliers distributors published literature on your device or similar competitive devices social media
Surveillance should include the applicable standards, such as ISO 14971. Changes to safety related standards may require revisions to your risk management procedures and risk management files. The frequency of monitoring and trending of collected information should be established and documented. It is advisable that the frequency of data monitoring be based on the risk of the device. The higher the risk, the more frequent is the monitoring. For example, data monitoring may be executed monthly, quarterly, or yearly. It is important to define the criteria for assessing the collected data. For example, you may trend the monitored data using established statistical methods and set up trigger criteria when trended data exceed predetermined thresholds. One of the most important sources of customer feedback is complaints. Monitoring of this source of information is critical to the proper tracking and management of product field performance. In addition to providing insights to potential safety risks, complaint monitoring could provide valuable information on customer experience and product performance. This information could benefit product design teams to improve product design for better performance, safety, and customer satisfaction. Some of the sources that were mentioned earlier, feed information to the manufacturer. Manufacturers passively receive the information from them and react to the information. An example is customer complaints. Other sources must be proactively searched for information, e.g., published literature or MAUDE database. Regulatory bodies increasingly look for more proactive postmarket surveillance of medical devices.
Production and Postproduction Monitoring
Risk management is applied to the entire product lifecycle, but it is very different in the preproduction versus production and postproduction. In the preproduction phase, risk management is a predictive tool. It forecasts what Hazards will manifest and what risks the medical device will present. After the product is produced and released for use, risk management is a retrospective tool, intended to protect the public from discovered risks. Production monitoring aims to detect and prevent release of nonconforming products whose safety characteristics may have been adversely affected. Process data monitoring and trending, and quality control are some of the proactive ways in which production of nonconforming products is prevented, or their release avoided. If production monitoring indicates that nonconforming products with the potential to cause safety risks have escaped, then postmarket risk management activities should be initiated (see Section 24.1 for more details). Postproduction monitoring is intended to evaluate the performance of the product in the field. A data monitoring plan should be established that stipulates sources of information and frequency of data collection and trending. Trending of data may show that a particular signal has been increasing and may have exceeded its threshold. Even though no patient Harm may have happened, this may indicate the potential for a future adverse event. Such a signal may necessitate the creation of a Corrective and Preventive Actions (CAPA) to initiate a root-cause analysis, determine preventive and corrective actions, and plan for verification of effectiveness of said actions. Sources that should be included in postproduction monitoring are: • • • • • • • • •
nonconformance reports CAPAs with potential for safety risk to patients complaint trending signals signals from returned product investigation, and service reports of new Hazards in competitor products published information postmarket clinical follow-ups surveillance registries reports of injuries and death that are attributable to the product
If postproduction monitoring indicates reported or potential Harm from released products, postmarket risk management activities should be initiated (see Section 24.1 for more details). Postmarket-detected issues that have a potential safety impact must be addressed within certain time limits (e.g., 30 days) to limit the exposure of patients. Sometimes root-cause analysis could identify a supplier of the manufacturer as the source of a Hazard. In that case, CAPA would reflect back to the supplier. The CAPA may also impact the incoming inspection procedures at the manufacturer.
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24.1 POSTMARKET RISK MANAGEMENT As stated earlier, preproduction risk management is a predictive tool, used to forecast future Hazards and risks, while postmarket risk management is a reactive endeavor, intended to contain and limit Harm from devices that have been released to the market. Production and postproduction monitoring are the means by which to detect whether a released product has harmed patients or has the potential for causing undue harm. The result of postmarket risk management may be to hold manufactured product from being released, or issue corrective actions, including product recalls. In cases of imminent potential Harm to patients, it may be necessary to issue immediate information (Customer Letter) before new Risk Controls are developed and verified. Postmarket risk management involves understanding of: the Hazard in question, the risk of potential Harm, size and magnitude of the patients’ vulnerability, and countermeasures that should be taken until the product itself is addressed for corrective measures. A common tool that is used in this vein is the Health Hazard Assessment (HHA). In the United Stated, 21 CFR part 7 requires the conduct of an evaluation of the health hazard (actual or potential) presented by a product being recalled or considered for recall. In Europe, MDD [4] Article 10 compels similar action. Elements of an HHA are: • Identify the Hazard (actual or potential). • Identify the related Harm(s), both immediate and long term. • Identify the population at risk and whether any subpopulation is at greater risk. • Describe the mechanism of occurrence of the Hazard, and exposure to the Hazard. • Is the Hazard in question happening when the product is used under labeled conditions? • Is the Hazard in question previously predicted? • Is the Hazard in question manifesting under normal or fault conditions? • Identify conditions that would exacerbate or mitigate the risk. • Identify the degree to which the Hazard is recognizable by the patient/user and the feasibility of countermeasures. • What is the likelihood of future additional risks due to the Hazard in question? • Balance the risk of corrective action versus the risk of not taking corrective action. Example: an implanted device may pose a greater risk than previously predicted. But the risk of explant surgery could be greater than the risk of leaving the device in. • Conclusion and recommended actions. Any decision for action or inaction should be approved by appropriate personnel, e.g., medical safety officer, and the decisions and approvals should be documented.
Production and Postproduction Monitoring
Postmarket risk management may determine measures to control the discovered risks. These Risk Controls may be in the form of design changes, labeling, or training. Naturally, the new Risk Controls must be verified for effectiveness. The risk management file may need to be updated. The manufacturer may also issue advisory/field safety notices. For medical devices currently installed and used in the market, the Risk Control measures may be different from those applied to devices that are currently in production. For example, for products in the field, Risk Control measures may include sending information to doctors or patients, removing product from the field and providing replacement product. For products that are in production, Risk Control measures may include identification and collection of product, and rework or discard of product. If a recall or field product update/revision is decided, speed of action will be material to the effectiveness of risk reduction activities.
24.2 FREQUENCY OF RISK MANAGEMENT FILE REVIEW As postmarket surveillance continues to bring in new information about the product field performance, the risk management file should be periodically reviewed to determine need for update. The frequency of risk management file review depends on: • • •
the risks of the device the novelty of the device the duration of time that the device has been in the market
For a new, novel, and high-risk device do more frequent reviews; perhaps as much as monthly or bimonthly. The longer the device has been on the market and the more that has been learned about it, the review frequency can be reduced, e.g., every year or every other year. For low-risk, old-technology devices, the review frequency could be even lower, e.g., every 4 5 years. Whatever frequency the manufacturer chooses should be recorded in the Risk Management Plan. Document the rationales for your decision on review frequency.
24.3 FEEDBACK TO PREPRODUCTION RISK MANAGEMENT There is a connection between the postmarket and preproduction risk management. Knowledge gained from product performance after it is manufactured and released must be fed back to preproduction risk management in a drive to add veracity to the preproduction predictions and estimations of the risks of a medical device. The types of information that postmarket risk management can provide to preproduction risk management are: • •
Is there evidence of new Hazards that were previously not foreseen? Are the P1 and P2 estimations still valid?
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• If qualitative methods are used, are the estimates of risks still valid? • Are there reports of misuse which were not foreseen in the original risk management process? • Are the Risk Controls proving to be effective in reducing/maintaining risk levels? • Is there any evidence that the actual market experience of risk acceptability for the received benefit has changed? One of the key benefits of production and postproduction monitoring is the derivation of P1 and P2 numbers from field data. P1 and P2 estimates that are based on actual field data are far more credible than expert opinion. However, the key to successful mining of field data is thoughtful, well-planned and well-executed collection, coding and cataloging of the field data. P1 is the probability of occurrence of a Hazardous Situation. P1 is prevalence. P1 has units. The units of P1 are dependent on the application and are determined by the manufacturer. For example, for an insulin pump a sensible unit could be patient-hours of operation. For sphygmomanometer (blood pressure monitor) a sensible unit could be number of uses. To measure P1, a certain time interval needs to be selected. A hypothetical example: 50,000 units of insulin pump model X have been in operation between Jan 1, 2017 and Jun 30, 2018. During this period, the average length of service for model X has been 4000 hours. In the same time period, there have been 250 reported and confirmed cases of over-infusion. P1 5 250/(50,000 3 4000) 5 1.25 3 1026 per patient-hour This information should be fed back to preproduction risk management so that if the prediction of P1 for over-infusion was different from 1.25 3 1026 it can be updated. P2 is the probability of sustaining Harm, given that the Hazardous Situation has already occurred. In the BXM method, risk is computed in five severity classes, as defined in Table 26.1. P2 is outcome-based. To derive P2 from filed data, we need to know after the Hazardous Situation happened, what was the outcome for the patient. For example, in the insulin pump example earlier, we would ask, after the over-infusion event what was the Harm and what was the outcome to the patient? A potential Harm of insulin over-infusion is hypoglycemia. Potential answers to the above question could be: • Patient died (catastrophic) • Patient became unconscious and suffered brain damage (critical) • Patient fainted and was taken to the emergency room, but has recovered now (serious) • Patient felt a little light headed but ate a piece of candy and was fine (minor) • Patient reported feeling a little strange, but it passed (negligible)
Production and Postproduction Monitoring
Each of the above answers would be counted as one instance in each of the five severity classes. Let’s imagine that in a dataset of 97 hypoglycemia events we have the following counts: • • • • •
Catastrophic: 0 Critical: 2 Serious: 20 Minor: 25 Negligible: 50
P2 is agnostic of the Hazardous Situation. That means we want to know, for all reported cases of hypoglycemia regardless of the Hazardous Situation that caused it, what were the outcomes. So, if two different Hazardous Situations could cause hypoglycemia, we aggregate all the hypoglycemia cases together. Continuing with our example, the total cases of hypoglycemia were: 97. Therefore for the Harm of hypoglycemia P2 numbers are: • • • • •
P2(Catastrophic): 0/97 5 0% P2(Critical): 2/97 5 2.1% P2(Serious): 20/97 5 20.6% P2(Minor): 25/97 5 25.8% P2(Negligible): 50/97 5 51.5%
To ensure effective feedback loops from postmarket to preproduction risk management, it is advisable that the responsibility for maintaining the risk management file be defined and assigned to specific staff.
24.4 BENEFITS OF POSTMARKET SURVEILLANCE Clearly patient/user safety is enhanced by active surveillance of production and postproduction information about marketed products. But the manufacturer also receives significant benefit from the surveillance, namely, the opportunity to quickly identify and rectify product/process defects. This in turn leads into reduced customer complaints, reduced field corrective actions, improved reputation and customer loyalty, which means higher sales. And if that’s not enough motivation, failure to perform product surveillance could result in substantial fines, criminal prosecutions, seizure of product, and closure of the business. Another benefit of postmarket surveillance is about the clinical Hazards list (CHL) (see Section 11.5). The CHL is an invaluable tool of risk management. The CHL is claimed to be complete, at any given time. The basis of that claim is that the CHL is a living document, containing the best available knowledge at any given time. And, if any new Hazards are discovered, they are added to the CHL. Without postmarket surveillance data, we cannot make the claim of completeness.
199
Production and Postproduction Monitoring Abstract ISO 14971 requires that manufacturers collect and evaluate information about the medical device or similar devices, in the production and postproduction phases. The US CFR, title 21, part 822 has similar requirements. Patient/user safety is enhanced by active surveillance of production and postproduction information about marketed products. The manufacturer also receives significant benefit from the surveillance, namely, the opportunity to quickly identify and rectify product/process defects. This in turn leads into reduced customer complaints, reduced field corrective actions, improved reputation and customer loyalty, which means higher sales. And if that’s not enough motivation, failure to perform product surveillance could result in substantial fines, criminal prosecutions, seizure of product, and closure of the business. Keywords: Postmarket risk management; production and postproduction monitoring; surveillance; CAPA; HHA; risk management file review
Clause 9 of ISO 14971 [3,7] requires that manufacturers collect and evaluate information about the medical device or similar devices, in the production and postproduction phases. Similarly, under section 822 of CFR 21 the FDA requires the manufacturers and distributors of medical devices to perform postmarket tracking and reporting of device malfunctions, serious injuries, or deaths. The term “postmarket” is used by the FDA in the United States. ISO 14971 [3,7] uses the terms “production” and “postproduction.” These terms are roughly equivalent. Fig. 24.1 shows the contrast between these terms. In the rest of this chapter we’ll use the term “postmarket” interchangeably with “production and postproduction.” Production information is collected during the manufacturing process, and postproduction information is collected on all the phases of lifecycle after the product has been manufactured. The most significant postproduction lifecycle phase is productuse where majority of the feedback is generated.
Figure 24.1 Postmarket versus postproduction. Safety Risk Management for Medical Devices DOI: https://doi.org/10.1016/B978-0-12-813098-8.00024-6
r 2018 Elsevier Ltd. All rights reserved.
193
194
Safety Risk Management for Medical Devices
Listening systems should be established and tuned in to various sources of information. Examples of potential sources of information are as follows: • • • • • • • • • • • • • • • •
manufacturing/production product service/repair returned product investigations customer service field service/customer visits clinical studies, e.g., postmarket clinical follow-ups customer complaints limited market releases product demonstrations databases such as MAUDE or EUDAMED legal department regulatory agencies, competent authorities (e.g., Field Safety Notices, Safety Alerts) suppliers distributors published literature on your device or similar competitive devices social media
Surveillance should include the applicable standards, such as ISO 14971. Changes to safety related standards may require revisions to your risk management procedures and risk management files. The frequency of monitoring and trending of collected information should be established and documented. It is advisable that the frequency of data monitoring be based on the risk of the device. The higher the risk, the more frequent is the monitoring. For example, data monitoring may be executed monthly, quarterly, or yearly. It is important to define the criteria for assessing the collected data. For example, you may trend the monitored data using established statistical methods and set up trigger criteria when trended data exceed predetermined thresholds. One of the most important sources of customer feedback is complaints. Monitoring of this source of information is critical to the proper tracking and management of product field performance. In addition to providing insights to potential safety risks, complaint monitoring could provide valuable information on customer experience and product performance. This information could benefit product design teams to improve product design for better performance, safety, and customer satisfaction. Some of the sources that were mentioned earlier, feed information to the manufacturer. Manufacturers passively receive the information from them and react to the information. An example is customer complaints. Other sources must be proactively searched for information, e.g., published literature or MAUDE database. Regulatory bodies increasingly look for more proactive postmarket surveillance of medical devices.
Production and Postproduction Monitoring
Risk management is applied to the entire product lifecycle, but it is very different in the preproduction versus production and postproduction. In the preproduction phase, risk management is a predictive tool. It forecasts what Hazards will manifest and what risks the medical device will present. After the product is produced and released for use, risk management is a retrospective tool, intended to protect the public from discovered risks. Production monitoring aims to detect and prevent release of nonconforming products whose safety characteristics may have been adversely affected. Process data monitoring and trending, and quality control are some of the proactive ways in which production of nonconforming products is prevented, or their release avoided. If production monitoring indicates that nonconforming products with the potential to cause safety risks have escaped, then postmarket risk management activities should be initiated (see Section 24.1 for more details). Postproduction monitoring is intended to evaluate the performance of the product in the field. A data monitoring plan should be established that stipulates sources of information and frequency of data collection and trending. Trending of data may show that a particular signal has been increasing and may have exceeded its threshold. Even though no patient Harm may have happened, this may indicate the potential for a future adverse event. Such a signal may necessitate the creation of a Corrective and Preventive Actions (CAPA) to initiate a root-cause analysis, determine preventive and corrective actions, and plan for verification of effectiveness of said actions. Sources that should be included in postproduction monitoring are: • • • • • • • • •
nonconformance reports CAPAs with potential for safety risk to patients complaint trending signals signals from returned product investigation, and service reports of new Hazards in competitor products published information postmarket clinical follow-ups surveillance registries reports of injuries and death that are attributable to the product
If postproduction monitoring indicates reported or potential Harm from released products, postmarket risk management activities should be initiated (see Section 24.1 for more details). Postmarket-detected issues that have a potential safety impact must be addressed within certain time limits (e.g., 30 days) to limit the exposure of patients. Sometimes root-cause analysis could identify a supplier of the manufacturer as the source of a Hazard. In that case, CAPA would reflect back to the supplier. The CAPA may also impact the incoming inspection procedures at the manufacturer.
195
196
Safety Risk Management for Medical Devices
24.1 POSTMARKET RISK MANAGEMENT As stated earlier, preproduction risk management is a predictive tool, used to forecast future Hazards and risks, while postmarket risk management is a reactive endeavor, intended to contain and limit Harm from devices that have been released to the market. Production and postproduction monitoring are the means by which to detect whether a released product has harmed patients or has the potential for causing undue harm. The result of postmarket risk management may be to hold manufactured product from being released, or issue corrective actions, including product recalls. In cases of imminent potential Harm to patients, it may be necessary to issue immediate information (Customer Letter) before new Risk Controls are developed and verified. Postmarket risk management involves understanding of: the Hazard in question, the risk of potential Harm, size and magnitude of the patients’ vulnerability, and countermeasures that should be taken until the product itself is addressed for corrective measures. A common tool that is used in this vein is the Health Hazard Assessment (HHA). In the United Stated, 21 CFR part 7 requires the conduct of an evaluation of the health hazard (actual or potential) presented by a product being recalled or considered for recall. In Europe, MDD [4] Article 10 compels similar action. Elements of an HHA are: • Identify the Hazard (actual or potential). • Identify the related Harm(s), both immediate and long term. • Identify the population at risk and whether any subpopulation is at greater risk. • Describe the mechanism of occurrence of the Hazard, and exposure to the Hazard. • Is the Hazard in question happening when the product is used under labeled conditions? • Is the Hazard in question previously predicted? • Is the Hazard in question manifesting under normal or fault conditions? • Identify conditions that would exacerbate or mitigate the risk. • Identify the degree to which the Hazard is recognizable by the patient/user and the feasibility of countermeasures. • What is the likelihood of future additional risks due to the Hazard in question? • Balance the risk of corrective action versus the risk of not taking corrective action. Example: an implanted device may pose a greater risk than previously predicted. But the risk of explant surgery could be greater than the risk of leaving the device in. • Conclusion and recommended actions. Any decision for action or inaction should be approved by appropriate personnel, e.g., medical safety officer, and the decisions and approvals should be documented.
Production and Postproduction Monitoring
Postmarket risk management may determine measures to control the discovered risks. These Risk Controls may be in the form of design changes, labeling, or training. Naturally, the new Risk Controls must be verified for effectiveness. The risk management file may need to be updated. The manufacturer may also issue advisory/field safety notices. For medical devices currently installed and used in the market, the Risk Control measures may be different from those applied to devices that are currently in production. For example, for products in the field, Risk Control measures may include sending information to doctors or patients, removing product from the field and providing replacement product. For products that are in production, Risk Control measures may include identification and collection of product, and rework or discard of product. If a recall or field product update/revision is decided, speed of action will be material to the effectiveness of risk reduction activities.
24.2 FREQUENCY OF RISK MANAGEMENT FILE REVIEW As postmarket surveillance continues to bring in new information about the product field performance, the risk management file should be periodically reviewed to determine need for update. The frequency of risk management file review depends on: • • •
the risks of the device the novelty of the device the duration of time that the device has been in the market
For a new, novel, and high-risk device do more frequent reviews; perhaps as much as monthly or bimonthly. The longer the device has been on the market and the more that has been learned about it, the review frequency can be reduced, e.g., every year or every other year. For low-risk, old-technology devices, the review frequency could be even lower, e.g., every 4 5 years. Whatever frequency the manufacturer chooses should be recorded in the Risk Management Plan. Document the rationales for your decision on review frequency.
24.3 FEEDBACK TO PREPRODUCTION RISK MANAGEMENT There is a connection between the postmarket and preproduction risk management. Knowledge gained from product performance after it is manufactured and released must be fed back to preproduction risk management in a drive to add veracity to the preproduction predictions and estimations of the risks of a medical device. The types of information that postmarket risk management can provide to preproduction risk management are: • •
Is there evidence of new Hazards that were previously not foreseen? Are the P1 and P2 estimations still valid?
197
198
Safety Risk Management for Medical Devices
• If qualitative methods are used, are the estimates of risks still valid? • Are there reports of misuse which were not foreseen in the original risk management process? • Are the Risk Controls proving to be effective in reducing/maintaining risk levels? • Is there any evidence that the actual market experience of risk acceptability for the received benefit has changed? One of the key benefits of production and postproduction monitoring is the derivation of P1 and P2 numbers from field data. P1 and P2 estimates that are based on actual field data are far more credible than expert opinion. However, the key to successful mining of field data is thoughtful, well-planned and well-executed collection, coding and cataloging of the field data. P1 is the probability of occurrence of a Hazardous Situation. P1 is prevalence. P1 has units. The units of P1 are dependent on the application and are determined by the manufacturer. For example, for an insulin pump a sensible unit could be patient-hours of operation. For sphygmomanometer (blood pressure monitor) a sensible unit could be number of uses. To measure P1, a certain time interval needs to be selected. A hypothetical example: 50,000 units of insulin pump model X have been in operation between Jan 1, 2017 and Jun 30, 2018. During this period, the average length of service for model X has been 4000 hours. In the same time period, there have been 250 reported and confirmed cases of over-infusion. P1 5 250/(50,000 3 4000) 5 1.25 3 1026 per patient-hour This information should be fed back to preproduction risk management so that if the prediction of P1 for over-infusion was different from 1.25 3 1026 it can be updated. P2 is the probability of sustaining Harm, given that the Hazardous Situation has already occurred. In the BXM method, risk is computed in five severity classes, as defined in Table 26.1. P2 is outcome-based. To derive P2 from filed data, we need to know after the Hazardous Situation happened, what was the outcome for the patient. For example, in the insulin pump example earlier, we would ask, after the over-infusion event what was the Harm and what was the outcome to the patient? A potential Harm of insulin over-infusion is hypoglycemia. Potential answers to the above question could be: • Patient died (catastrophic) • Patient became unconscious and suffered brain damage (critical) • Patient fainted and was taken to the emergency room, but has recovered now (serious) • Patient felt a little light headed but ate a piece of candy and was fine (minor) • Patient reported feeling a little strange, but it passed (negligible)
Production and Postproduction Monitoring
Each of the above answers would be counted as one instance in each of the five severity classes. Let’s imagine that in a dataset of 97 hypoglycemia events we have the following counts: • • • • •
Catastrophic: 0 Critical: 2 Serious: 20 Minor: 25 Negligible: 50
P2 is agnostic of the Hazardous Situation. That means we want to know, for all reported cases of hypoglycemia regardless of the Hazardous Situation that caused it, what were the outcomes. So, if two different Hazardous Situations could cause hypoglycemia, we aggregate all the hypoglycemia cases together. Continuing with our example, the total cases of hypoglycemia were: 97. Therefore for the Harm of hypoglycemia P2 numbers are: • • • • •
P2(Catastrophic): 0/97 5 0% P2(Critical): 2/97 5 2.1% P2(Serious): 20/97 5 20.6% P2(Minor): 25/97 5 25.8% P2(Negligible): 50/97 5 51.5%
To ensure effective feedback loops from postmarket to preproduction risk management, it is advisable that the responsibility for maintaining the risk management file be defined and assigned to specific staff.
24.4 BENEFITS OF POSTMARKET SURVEILLANCE Clearly patient/user safety is enhanced by active surveillance of production and postproduction information about marketed products. But the manufacturer also receives significant benefit from the surveillance, namely, the opportunity to quickly identify and rectify product/process defects. This in turn leads into reduced customer complaints, reduced field corrective actions, improved reputation and customer loyalty, which means higher sales. And if that’s not enough motivation, failure to perform product surveillance could result in substantial fines, criminal prosecutions, seizure of product, and closure of the business. Another benefit of postmarket surveillance is about the clinical Hazards list (CHL) (see Section 11.5). The CHL is an invaluable tool of risk management. The CHL is claimed to be complete, at any given time. The basis of that claim is that the CHL is a living document, containing the best available knowledge at any given time. And, if any new Hazards are discovered, they are added to the CHL. Without postmarket surveillance data, we cannot make the claim of completeness.
199