Guide To Inspections Of Medical Device Manufacturers
December 1997 - Update of 06/08/2010
TABLE OF CONTENTS
INTRODUCTION 1
GENERAL 2
PRE-INSPECTIONAL ACTIVITY 2
GMP INSPECTIONAL STRATEGY 3
Preannouncements, 483 Annotations, Post Inspectional Correspondence 3
DIRECTED DEVICE INSPECTION 3
Complaint Handling System 4
Complaint Handling Procedures 5
Determining Whether An Investigation Is Necessary 5
MDR Regulations - 21 CFR 803 6
Servicing 6
MDR-Reportable Service Reports 6
Corrective and Preventive Actions 6
Analyzing Quality Problem Information 7
Analyzing Service Records 7
Control of Nonconforming Product 8
Nonconformity Review and Disposition 8
Change Control 8
Process Validation 9
Components 11
Quality Audits 11
Design Controls 12
PMA Devices 13
Medical Device Tracking 13
COMPREHENSIVE DEVICE INSPECTION 13
General Provisions 13
Quality System Requirements 14
Personnel 15
Document Controls 15
Purchasing Controls 15
Identification and Traceability 16
Production and Process Controls 17
Production and Process Specifications 17
Reworking 17
Buildings 17
Environmental Control 17
Contamination Control 18
Personnel 18
Equipment 18
Inspection, measuring, and test equipment 19
Acceptance Activities 19
Labeling and Packaging Control 20
Handling, Storage, Distribution, and Installation 20
Records 21
Device master record 21
Device history record 21
Quality System Record 22
PRE-APPROVAL DEVICE INSPECTION 22
STERILE DEVICES 22
THE SMALL MANUFACTURER 23
WRITTEN PROCEDURES - "ESTABLISH" 23
ATTACHMENTS
A - Medical Device Industry Initiative 25
B - Temporary Enforcement Moratorium 29
C - FOI and Design Controls 31
__________________________________________________________________________________
Note: this document is reference materials for investigators and other FDA personnel. This Document does not bind FDA, and does not confer any rights, privileges, benifits, or immunities for or on any personnel.
__________________________________________________________________________________
INTRODUCTION
The "Guide to Inspections of Medical Device Manufacturers" is a consolidation of information previously provided in the May 4, 1995 Compliance Program (CP), Inspections of Medical Device Manufacturers, CP 7382.830, Attachments A. B and E only. This guide was prepared by the Food and Drug Administration (FDA), Office of Regulatory Affairs (ORA) and the Center for Devices and Radiological Health (CDRH).
The new Quality System Regulation (F.R. vol. 61, No. 195, October 7, 1996) became effective on June 1, 1997. To implement the revised regulation CP 7382.830 has been rewritten and information relative to how to inspect a medical device manufacturer has been removed. The Compliance Program still contains information on when to do a directed inspection, the definitions of comprehensive and directed inspections, and other device specific policy requirements.
This reference is intended to be used in conjunction with the:
This reference is intended to be used in conjunction with the:
Compliance Program Guidance Manuals for Medical Device Manufacturers (CP 7382.830 (GMP) and 7382.830A (Sterilization)),
Investigations Operations Manual (IOM),
Code of Federal Regulations, Title 21 (21 CFR) Part 820 Quality System Regulation,
Compliance Policy Guides (CPG) for devices (beginning with the numbers 7124 and 7133), and
Guideline on General Principles of Process Validation, FDA, May 1987.
Other references include:
the Safe Medical Devices Act (SMDA) of 1990 and the Medical Device Amendments of 1992,
Medical Device Quality Systems Manual: A Small Entity Compliance Guide,
The FDA Worldwide Quality System Requirements Guidebook for Medical Devices, and;
other device specific guidance documents prepared by CDRH for the medical device industry.
These additional guidances are posted to the CDRH Internet World Wide Web Home Page at https://www.fda.gov/cdrh
__________________________________________________________________________________
GENERAL
The medical device Quality System/GMP Regulation (QS/GMP) is an umbrella GMP intended to cover all medical devices from dental resins to magnetic resonance imaging devices to In Vitro Diagnostics (IVDs) to some engineered tissues. The Quality System Regulation specifies general objectives (e.g. calibrated equipment, training, management responsibility, process and design controls) rather than methods, since one method would not be applicable to all manufacturers. In most cases, it is left to the manufacturer to determine the best method to attain these objectives.
Manufacturers should be able to defend their methods, procedures, etc. as being appropriate and adequate. Not all sections of the QS/GMP will apply to each manufacturer. Manufacturers must determine what sections of the QS/GMP apply to their specific products and operations. When a manufacturer decides that a section of the QS/GMP qualified by the term "where appropriate" does not apply, they are required to document their justification.
Investigators should use good judgement when conducting a medical device QS/GMP inspection. They need to:
a. assess whether the manufacturer has the required written procedures,
b. is following those procedures and,
c. has documented evidence that those procedures, methods, etc. are adequate given:
1. the size of the firm,
2. the complexity of the device(s) being produced and,
3. the relative risk to users if the device does not meet its finished product specifications or the manufacturing facility is not operating in a state of control.
PRE-INSPECTIONAL ACTIVITY
Prior to the start of any medical device inspection, the factory jacket or establishment history of the firm should be reviewed. Special notice should be made of the previous inspectional findings and subsequent correspondence between the firm and FDA; of any MDR or consumer complaints where it was determined that follow-up would occur at the next inspection; and of any notifications of recalls since the last inspection.
The following on-line databases should be queried:
a. CDRH Information Retrieval System(CIRS) - for Medical Device Reporting (MDR) data (MAUDE), Registration and Listing data and 510(k) and PMA summary data (OSCAR);
b. MDRAPSY for MDR data prior to October 1996.
These databases are accessible to users with individual accounts. Accounts can be requested through the district or regional CIRS liaisons or from DEIO/Denise Dion (301) 827-5645 for MDRAPSY.
MDR data that is most useful in preparing for an inspection of a medical device manufacturer includes specific MDRs for that manufacturer (i.e. query by firm's short name) for the time frame since the last inspection; or MDRs relative to the generic devices manufactured by that firm (i.e. query by product code) for some reasonable time frame. This data assists the investigator in determining possible problem areas in the manufacture, or design, of the device, or lot or batch specific issues. This data should be used to focus the inspection.
The firm's reported registration and listing data should be verified during any GMP inspection to assure there have been no changes and the registration and listing data was accurately reported. Changes or inaccuracies should be immediately reported to the district medical device registration and listing monitor. See also Field Management Directive (FMD) 92.
510(k) and PMA data assists the Investigator in determining what devices the firm is manufacturing and whether any new devices have been designed or changed since the last inspection. This data is useful in focusing the inspection on new or changed devices as well as devices that are higher risk devices, i.e. class II or III versus class I.
_________________________________________________________________
GMP INSPECTIONAL STRATEGY
CP 7382.830 describes the inspectional strategy to be used. This Guide discusses how to perform a directed inspection, or a comprehensive inspection. It also discusses inspections of small manufacturers. In brief, all inspections of medical device manufacturers are to be directed inspections, with the exception of OAI follow-up inspections, which are to be comprehensive inspections.
Preannouncements, 483 Annotations, Post Inspectional Correspondence: ORA conducted a pilot program, Medical Device Industry Initiatives, in FY 96 through the first quarter of FY 97 which encompassed preannounced medical device inspections, annotated FDA 483s and post-inspectional correspondence for NAI and VAI inspections. The initiatives have been implemented on a permanent basis. The instructions for preannouncement, including the criteria to be used, 483 annotations and post-inspectional letters for NAI and VAI inspections are included as Attachment A to this guide.
One of the purposes to preannouncing is to assure that the appropriate records and personnel will be available during the inspection. Therefore, it is important you communicate to the firm the purpose of the inspection and a general idea of the records you may wish to review. If you find neither the appropriate personnel or records were available, please note this in your Establishment Inspection Report (EIR). This data may be used by the district in the future when considering whether this firm should be eligible for preannounced inspections.
DIRECTED DEVICE INSPECTION
With the finalization of the new Quality System/Good Manufacturing Practices (QS/GMP) regulation, FDA formally recognized a new systems approach to regulating medical devices. It is FDA's intention to use this same approach when conducting inspections. A systems level approach to conducting inspections means taking a broader view. A great deal of flexibility has been written into this regulation, which means Investigators need to more fully concentrate on the firm's state of compliance at the system level. How best can that be done?
It is important to focus the inspectional effort on those systems that will provide the firm with information regarding failures in their process, the actual device design, their raw materials, or their employee training. These systems include: complaints, MDRs, servicing, product acceptance, change control, process validation, design control, and internal audits. Problems or failures in these areas are most likely to result in faulty or hazardous devices being released into commercial distribution. These areas may also serve as first indicators for the firm that nonconforming product may have been distributed. Therefore, a firm's system for recognizing failures and implementing corrective and preventive actions is also a key system to assure a firm meets its own and FDA's requirements for quality medical device design and manufacturing.
Because of this, FDA uses a directed inspection approach for all surveillance and pre-approval inspections. Generally, more comprehensive inspections are done only after a firm has been found to not be in substantial compliance based on a directed inspection, i.e. a follow-up inspection of an OAI (Official Action Indicated) inspection.
The purpose of a directed inspection is to look at those areas that are of the greatest concern in assuring that a firm is not designing, manufacturing or distributing hazardous or non-conforming devices. These systems should be inspected to assure that they conform to the QS/GMP requirements. The information contained in these systems may also indicate there are problems in designing, manufacturing, servicing, training, testing, labeling, packaging, etc. They may indicate that hazardous or nonconforming devices have been manufactured and/or distributed. This type of information should be used to help focus the inspection on a particular device, lots or batches of devices, or on particular manufacturing processes.
As a general rule, the Investigator should select devices for inspectional coverage which, because of what they are made of or how they are made, have the highest potential for problems that could result in the design, manufacture and/or distribution of unsafe or unreliable devices. This rule should be applied when there is no evidence in the complaint, MDR, testing or servicing records of specific problem devices. If there are recall or MDR issues already known regarding a particular device, or a device manufactured by the firm has been the subject of prior warning of non-compliance, then these devices should be the focus of your inspection. Once a device has been selected, the inspection should focus on those significant systems that are meant to assure the manufacture of safe and reliable devices: process validation, component acceptance, change control, design control, and control of nonconforming product.
Evidence of nonconforming products should be viewed as an indicator of noncompliance with the QS/GMP. As an inspectional function, this is the best starting point to inspect the overall quality system. For example, if the firm does not have the documents and data related to our reports of non-conforming devices or of devices that caused injury or death (MDR) this would be a significant non-compliance with the QS/GMP.
Inspectional observations should focus on cause and effect to link observed problems to the potential of manufacturing nonconforming product(s). Start with the evidence that an unsafe and/or unreliable product was or may have been distributed as indicated in MDRs, complaint records, service records, incomplete corrective and preventive actions, and distribution records for release of nonconforming products. The inspection should then be focused on those QS/GMP systems that have a high probability of causing the problems indicated by the complaints, MDRs, etc.
Inspectional observations relative to those systems should be related to noncompliances of significant risk. It should also be determined whether other devices with these potential problems would result in the distribution of an unsafe or unreliable product.
Any observed nonconformance to written procedures should be documented with a copy of the written procedure and additional observations to show the nonconformance is not just a one time occurrence. If observations are related to people dependant processes, the inspection should provide sufficient documentation to show the problem to be a training issue, the use of unqualified people or process validation related problems.
Lastly, the QS/GMP places major emphasis on the role of management and management responsibility. The inspection process should show through the firm?s written documentation the role of management in the quality process to prevent the design, manufacture and distribution of nonconforming products.
_________________________________________________________________
1. Complaint Handling System - 21 CFR 820.198
This should be the beginning point of every inspection to determine whether the firm has received complaints of possible (or potentially) defective devices. The QS/GMP regulation requires all complaints be reviewed, evaluated and maintained by a formally designated unit. This unit could be one appropriately trained individual, or a department which is staffed with appropriately trained individuals. This unit must decide whether an investigation of the complaint needs to be performed.
Under the QS/GMP there continues to be no requirement that all complaints be maintained in one file. However, firms are now required to have written procedures for processing complaints. To assess the adequacy of the written complaint handling procedures, only complaints received after June 1, 1997 should be reviewed. However, the review of complaints to determine which devices the inspection should be focused on should not be limited only to those complaints received after June 1, 1997. The complaint file(s) must contain all complaints including those open or still under investigation.
Typically, manufacturers will keep complaints in a customer file, product returns/credit file, service file, warranty file, medical file, or legal file. The inspection should ascertain what files are maintained that meet the definition of a complaint (21 CFR 820.198). By placing complaints in different files, manufacturers may not have noted instances of repeated component/device failures with a common cause. Ask the firm if it trends or performs other analyses of complaints. If no trending or problem identification is done, then the inspection should begin with a trending of the complaints.
NOTE: The actual complaints may provide leads in identifying product defects. Deficiencies in complaint handling practices may result in lost complaint data essential to identifying product defects, and possibly quality system problems, which have not been adequately corrected by the firm. Possible corrective actions may include recall, and/or change in the design of the device, and/or change in the manufacturing process or quality system.
Review and analyze the complaints to identify existing and/or potential causes of nonconforming product or other quality problems by grouping similar products, failure modes, and failure site (use, location) for possible user or environmental related problems.
Potential environmental factors that could contribute to the failure of a device include the area of the country, weather, use factors, electromagnetic interference, vibration, shock, etc.
Determine if the firm has performed sufficient complaint investigation, or to the extent possible, to confirm the reported failure mode.
Determine the identity and qualifications of those who review complaints. Ascertain the basis for determining significance of complaints and how follow-up is conducted. Determine if oral or telephone complaints are documented.
Some firms file complaints under other names, such as "Trade Inquiries," "Technical Assistance," "Customer Contacts," "Service Requests" etc., while others make a distinction between physical/mechanical and medical complaints. Make sure all complaints are adequately covered and reported.
When a manufacturer claims to have received no complaints, determine if provisions have been made for the review and investigation of complaints when received. Determine who has been assigned the responsibility to evaluate them when and if they occur.
_________________________________________________________________
Establish and Maintain Complaint Handling Procedures - 21 CFR 820.198(a)
The firm must have written complaint handling procedures to process information in a uniform and timely manner. Indicators that the firm may not be in compliance would be shown in the firm's failure to pursue additional follow up to determine some or all of the following complaint information:
a. Identification of the complainant, including address and phone number and situation where reported event occurred.
b. Identification of complaint product to the extent necessary to identify the specific device history record for the manufacture of the implicated product.
This would be the lack of a model and serial number where one or both are necessary and the firm failed to try to obtain the information.
c. Information needed to determine time to failure and/or if the product has failed within its warranty period. This would be the lack of a beginning use or failure date (for IVDs - the expiration date).
d. Information to determine cycle to failure if the product's life is determined by cycle of use and not time. This would be failing to obtain how many times a mechanical device may have been used when the device has a built-in counter.
e. Information relative to contributing factors to the reported failure mode.
An example of this would be failing to obtain information about additional devices in use at the time, and the electrical environment during the reported failure that could be due to an Electromagnetic Compatibility (EMC) problem.
Determining Whether An Investigation Is Necessary - 21 CFR 820.198(b)
The firm should evaluate complaints thoroughly to determine whether an investigation is necessary. Indicators that the firm may not be in compliance would be shown by:
a. A history of one or more similar failure modes and has not investigated to confirm the reported failure mode.
b. The complaint records lack the reason for not investigating and/or the name of the individual responsible for the decision not to investigate.
If the firm states it has never received complaints and because of this it does not need a complaint handling system, it should be cited on the FDA 483 for failure to have a complaint handling system.
.
.
.
December 1997 - Update of 06/08/2010
TABLE OF CONTENTS
INTRODUCTION 1
GENERAL 2
PRE-INSPECTIONAL ACTIVITY 2
GMP INSPECTIONAL STRATEGY 3
Preannouncements, 483 Annotations, Post Inspectional Correspondence 3
DIRECTED DEVICE INSPECTION 3
Complaint Handling System 4
Complaint Handling Procedures 5
Determining Whether An Investigation Is Necessary 5
MDR Regulations - 21 CFR 803 6
Servicing 6
MDR-Reportable Service Reports 6
Corrective and Preventive Actions 6
Analyzing Quality Problem Information 7
Analyzing Service Records 7
Control of Nonconforming Product 8
Nonconformity Review and Disposition 8
Change Control 8
Process Validation 9
Components 11
Quality Audits 11
Design Controls 12
PMA Devices 13
Medical Device Tracking 13
COMPREHENSIVE DEVICE INSPECTION 13
General Provisions 13
Quality System Requirements 14
Personnel 15
Document Controls 15
Purchasing Controls 15
Identification and Traceability 16
Production and Process Controls 17
Production and Process Specifications 17
Reworking 17
Buildings 17
Environmental Control 17
Contamination Control 18
Personnel 18
Equipment 18
Inspection, measuring, and test equipment 19
Acceptance Activities 19
Labeling and Packaging Control 20
Handling, Storage, Distribution, and Installation 20
Records 21
Device master record 21
Device history record 21
Quality System Record 22
PRE-APPROVAL DEVICE INSPECTION 22
STERILE DEVICES 22
THE SMALL MANUFACTURER 23
WRITTEN PROCEDURES - "ESTABLISH" 23
ATTACHMENTS
A - Medical Device Industry Initiative 25
B - Temporary Enforcement Moratorium 29
C - FOI and Design Controls 31
__________________________________________________________________________________
Note: this document is reference materials for investigators and other FDA personnel. This Document does not bind FDA, and does not confer any rights, privileges, benifits, or immunities for or on any personnel.
__________________________________________________________________________________
INTRODUCTION
The "Guide to Inspections of Medical Device Manufacturers" is a consolidation of information previously provided in the May 4, 1995 Compliance Program (CP), Inspections of Medical Device Manufacturers, CP 7382.830, Attachments A. B and E only. This guide was prepared by the Food and Drug Administration (FDA), Office of Regulatory Affairs (ORA) and the Center for Devices and Radiological Health (CDRH).
The new Quality System Regulation (F.R. vol. 61, No. 195, October 7, 1996) became effective on June 1, 1997. To implement the revised regulation CP 7382.830 has been rewritten and information relative to how to inspect a medical device manufacturer has been removed. The Compliance Program still contains information on when to do a directed inspection, the definitions of comprehensive and directed inspections, and other device specific policy requirements.
This reference is intended to be used in conjunction with the:
This reference is intended to be used in conjunction with the:
Compliance Program Guidance Manuals for Medical Device Manufacturers (CP 7382.830 (GMP) and 7382.830A (Sterilization)),
Investigations Operations Manual (IOM),
Code of Federal Regulations, Title 21 (21 CFR) Part 820 Quality System Regulation,
Compliance Policy Guides (CPG) for devices (beginning with the numbers 7124 and 7133), and
Guideline on General Principles of Process Validation, FDA, May 1987.
Other references include:
the Safe Medical Devices Act (SMDA) of 1990 and the Medical Device Amendments of 1992,
Medical Device Quality Systems Manual: A Small Entity Compliance Guide,
The FDA Worldwide Quality System Requirements Guidebook for Medical Devices, and;
other device specific guidance documents prepared by CDRH for the medical device industry.
These additional guidances are posted to the CDRH Internet World Wide Web Home Page at https://www.fda.gov/cdrh
__________________________________________________________________________________
GENERAL
The medical device Quality System/GMP Regulation (QS/GMP) is an umbrella GMP intended to cover all medical devices from dental resins to magnetic resonance imaging devices to In Vitro Diagnostics (IVDs) to some engineered tissues. The Quality System Regulation specifies general objectives (e.g. calibrated equipment, training, management responsibility, process and design controls) rather than methods, since one method would not be applicable to all manufacturers. In most cases, it is left to the manufacturer to determine the best method to attain these objectives.
Manufacturers should be able to defend their methods, procedures, etc. as being appropriate and adequate. Not all sections of the QS/GMP will apply to each manufacturer. Manufacturers must determine what sections of the QS/GMP apply to their specific products and operations. When a manufacturer decides that a section of the QS/GMP qualified by the term "where appropriate" does not apply, they are required to document their justification.
Investigators should use good judgement when conducting a medical device QS/GMP inspection. They need to:
a. assess whether the manufacturer has the required written procedures,
b. is following those procedures and,
c. has documented evidence that those procedures, methods, etc. are adequate given:
1. the size of the firm,
2. the complexity of the device(s) being produced and,
3. the relative risk to users if the device does not meet its finished product specifications or the manufacturing facility is not operating in a state of control.
PRE-INSPECTIONAL ACTIVITY
Prior to the start of any medical device inspection, the factory jacket or establishment history of the firm should be reviewed. Special notice should be made of the previous inspectional findings and subsequent correspondence between the firm and FDA; of any MDR or consumer complaints where it was determined that follow-up would occur at the next inspection; and of any notifications of recalls since the last inspection.
The following on-line databases should be queried:
a. CDRH Information Retrieval System(CIRS) - for Medical Device Reporting (MDR) data (MAUDE), Registration and Listing data and 510(k) and PMA summary data (OSCAR);
b. MDRAPSY for MDR data prior to October 1996.
These databases are accessible to users with individual accounts. Accounts can be requested through the district or regional CIRS liaisons or from DEIO/Denise Dion (301) 827-5645 for MDRAPSY.
MDR data that is most useful in preparing for an inspection of a medical device manufacturer includes specific MDRs for that manufacturer (i.e. query by firm's short name) for the time frame since the last inspection; or MDRs relative to the generic devices manufactured by that firm (i.e. query by product code) for some reasonable time frame. This data assists the investigator in determining possible problem areas in the manufacture, or design, of the device, or lot or batch specific issues. This data should be used to focus the inspection.
The firm's reported registration and listing data should be verified during any GMP inspection to assure there have been no changes and the registration and listing data was accurately reported. Changes or inaccuracies should be immediately reported to the district medical device registration and listing monitor. See also Field Management Directive (FMD) 92.
510(k) and PMA data assists the Investigator in determining what devices the firm is manufacturing and whether any new devices have been designed or changed since the last inspection. This data is useful in focusing the inspection on new or changed devices as well as devices that are higher risk devices, i.e. class II or III versus class I.
_________________________________________________________________
GMP INSPECTIONAL STRATEGY
CP 7382.830 describes the inspectional strategy to be used. This Guide discusses how to perform a directed inspection, or a comprehensive inspection. It also discusses inspections of small manufacturers. In brief, all inspections of medical device manufacturers are to be directed inspections, with the exception of OAI follow-up inspections, which are to be comprehensive inspections.
Preannouncements, 483 Annotations, Post Inspectional Correspondence: ORA conducted a pilot program, Medical Device Industry Initiatives, in FY 96 through the first quarter of FY 97 which encompassed preannounced medical device inspections, annotated FDA 483s and post-inspectional correspondence for NAI and VAI inspections. The initiatives have been implemented on a permanent basis. The instructions for preannouncement, including the criteria to be used, 483 annotations and post-inspectional letters for NAI and VAI inspections are included as Attachment A to this guide.
One of the purposes to preannouncing is to assure that the appropriate records and personnel will be available during the inspection. Therefore, it is important you communicate to the firm the purpose of the inspection and a general idea of the records you may wish to review. If you find neither the appropriate personnel or records were available, please note this in your Establishment Inspection Report (EIR). This data may be used by the district in the future when considering whether this firm should be eligible for preannounced inspections.
DIRECTED DEVICE INSPECTION
With the finalization of the new Quality System/Good Manufacturing Practices (QS/GMP) regulation, FDA formally recognized a new systems approach to regulating medical devices. It is FDA's intention to use this same approach when conducting inspections. A systems level approach to conducting inspections means taking a broader view. A great deal of flexibility has been written into this regulation, which means Investigators need to more fully concentrate on the firm's state of compliance at the system level. How best can that be done?
It is important to focus the inspectional effort on those systems that will provide the firm with information regarding failures in their process, the actual device design, their raw materials, or their employee training. These systems include: complaints, MDRs, servicing, product acceptance, change control, process validation, design control, and internal audits. Problems or failures in these areas are most likely to result in faulty or hazardous devices being released into commercial distribution. These areas may also serve as first indicators for the firm that nonconforming product may have been distributed. Therefore, a firm's system for recognizing failures and implementing corrective and preventive actions is also a key system to assure a firm meets its own and FDA's requirements for quality medical device design and manufacturing.
Because of this, FDA uses a directed inspection approach for all surveillance and pre-approval inspections. Generally, more comprehensive inspections are done only after a firm has been found to not be in substantial compliance based on a directed inspection, i.e. a follow-up inspection of an OAI (Official Action Indicated) inspection.
The purpose of a directed inspection is to look at those areas that are of the greatest concern in assuring that a firm is not designing, manufacturing or distributing hazardous or non-conforming devices. These systems should be inspected to assure that they conform to the QS/GMP requirements. The information contained in these systems may also indicate there are problems in designing, manufacturing, servicing, training, testing, labeling, packaging, etc. They may indicate that hazardous or nonconforming devices have been manufactured and/or distributed. This type of information should be used to help focus the inspection on a particular device, lots or batches of devices, or on particular manufacturing processes.
As a general rule, the Investigator should select devices for inspectional coverage which, because of what they are made of or how they are made, have the highest potential for problems that could result in the design, manufacture and/or distribution of unsafe or unreliable devices. This rule should be applied when there is no evidence in the complaint, MDR, testing or servicing records of specific problem devices. If there are recall or MDR issues already known regarding a particular device, or a device manufactured by the firm has been the subject of prior warning of non-compliance, then these devices should be the focus of your inspection. Once a device has been selected, the inspection should focus on those significant systems that are meant to assure the manufacture of safe and reliable devices: process validation, component acceptance, change control, design control, and control of nonconforming product.
Evidence of nonconforming products should be viewed as an indicator of noncompliance with the QS/GMP. As an inspectional function, this is the best starting point to inspect the overall quality system. For example, if the firm does not have the documents and data related to our reports of non-conforming devices or of devices that caused injury or death (MDR) this would be a significant non-compliance with the QS/GMP.
Inspectional observations should focus on cause and effect to link observed problems to the potential of manufacturing nonconforming product(s). Start with the evidence that an unsafe and/or unreliable product was or may have been distributed as indicated in MDRs, complaint records, service records, incomplete corrective and preventive actions, and distribution records for release of nonconforming products. The inspection should then be focused on those QS/GMP systems that have a high probability of causing the problems indicated by the complaints, MDRs, etc.
Inspectional observations relative to those systems should be related to noncompliances of significant risk. It should also be determined whether other devices with these potential problems would result in the distribution of an unsafe or unreliable product.
Any observed nonconformance to written procedures should be documented with a copy of the written procedure and additional observations to show the nonconformance is not just a one time occurrence. If observations are related to people dependant processes, the inspection should provide sufficient documentation to show the problem to be a training issue, the use of unqualified people or process validation related problems.
Lastly, the QS/GMP places major emphasis on the role of management and management responsibility. The inspection process should show through the firm?s written documentation the role of management in the quality process to prevent the design, manufacture and distribution of nonconforming products.
_________________________________________________________________
1. Complaint Handling System - 21 CFR 820.198
This should be the beginning point of every inspection to determine whether the firm has received complaints of possible (or potentially) defective devices. The QS/GMP regulation requires all complaints be reviewed, evaluated and maintained by a formally designated unit. This unit could be one appropriately trained individual, or a department which is staffed with appropriately trained individuals. This unit must decide whether an investigation of the complaint needs to be performed.
Under the QS/GMP there continues to be no requirement that all complaints be maintained in one file. However, firms are now required to have written procedures for processing complaints. To assess the adequacy of the written complaint handling procedures, only complaints received after June 1, 1997 should be reviewed. However, the review of complaints to determine which devices the inspection should be focused on should not be limited only to those complaints received after June 1, 1997. The complaint file(s) must contain all complaints including those open or still under investigation.
Typically, manufacturers will keep complaints in a customer file, product returns/credit file, service file, warranty file, medical file, or legal file. The inspection should ascertain what files are maintained that meet the definition of a complaint (21 CFR 820.198). By placing complaints in different files, manufacturers may not have noted instances of repeated component/device failures with a common cause. Ask the firm if it trends or performs other analyses of complaints. If no trending or problem identification is done, then the inspection should begin with a trending of the complaints.
NOTE: The actual complaints may provide leads in identifying product defects. Deficiencies in complaint handling practices may result in lost complaint data essential to identifying product defects, and possibly quality system problems, which have not been adequately corrected by the firm. Possible corrective actions may include recall, and/or change in the design of the device, and/or change in the manufacturing process or quality system.
Review and analyze the complaints to identify existing and/or potential causes of nonconforming product or other quality problems by grouping similar products, failure modes, and failure site (use, location) for possible user or environmental related problems.
Potential environmental factors that could contribute to the failure of a device include the area of the country, weather, use factors, electromagnetic interference, vibration, shock, etc.
Determine if the firm has performed sufficient complaint investigation, or to the extent possible, to confirm the reported failure mode.
Determine the identity and qualifications of those who review complaints. Ascertain the basis for determining significance of complaints and how follow-up is conducted. Determine if oral or telephone complaints are documented.
Some firms file complaints under other names, such as "Trade Inquiries," "Technical Assistance," "Customer Contacts," "Service Requests" etc., while others make a distinction between physical/mechanical and medical complaints. Make sure all complaints are adequately covered and reported.
When a manufacturer claims to have received no complaints, determine if provisions have been made for the review and investigation of complaints when received. Determine who has been assigned the responsibility to evaluate them when and if they occur.
_________________________________________________________________
Establish and Maintain Complaint Handling Procedures - 21 CFR 820.198(a)
The firm must have written complaint handling procedures to process information in a uniform and timely manner. Indicators that the firm may not be in compliance would be shown in the firm's failure to pursue additional follow up to determine some or all of the following complaint information:
a. Identification of the complainant, including address and phone number and situation where reported event occurred.
b. Identification of complaint product to the extent necessary to identify the specific device history record for the manufacture of the implicated product.
This would be the lack of a model and serial number where one or both are necessary and the firm failed to try to obtain the information.
c. Information needed to determine time to failure and/or if the product has failed within its warranty period. This would be the lack of a beginning use or failure date (for IVDs - the expiration date).
d. Information to determine cycle to failure if the product's life is determined by cycle of use and not time. This would be failing to obtain how many times a mechanical device may have been used when the device has a built-in counter.
e. Information relative to contributing factors to the reported failure mode.
An example of this would be failing to obtain information about additional devices in use at the time, and the electrical environment during the reported failure that could be due to an Electromagnetic Compatibility (EMC) problem.
Determining Whether An Investigation Is Necessary - 21 CFR 820.198(b)
The firm should evaluate complaints thoroughly to determine whether an investigation is necessary. Indicators that the firm may not be in compliance would be shown by:
a. A history of one or more similar failure modes and has not investigated to confirm the reported failure mode.
b. The complaint records lack the reason for not investigating and/or the name of the individual responsible for the decision not to investigate.
If the firm states it has never received complaints and because of this it does not need a complaint handling system, it should be cited on the FDA 483 for failure to have a complaint handling system.
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