Regulatory Open Forum

Forwarded question from Mitchell Johnson:

"...For a GMP Exempt Class I device such as an external knee brace (see FDA classification at http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpcd/classification.cfm?ID=4824 ,and eCFR for 890.3475 ) the FDA classification cites that the device is "exempted from GMP regulation, except for general requirements concerning records (820.180) and complaint files (820.198)".  21 CFR 820.180 pertains to General Requirements for Records and starts out with "All records required by this part shall be maintained...".  

As I read it, even though the classification statement for the device states it is GMP exempt, when following the logic of 820.180 I find that the manufacturer is required to maintain all records required by part 820. 

My question:  what does it really mean in this context to be exempt from GMP if one is required to maintain all the records embedded within the GMP/QSR?

Thanks,

Mitch

------------------------------
Mitchell Johnson
Intricon Corporation
Arden Hills MN
United States..."

------------------------------
Kevin Randall RAC (U.S., Canada, Europe)
Principal Consultant
ComplianceAcuity, Inc.
Golden CO
United States
------------------------------

Mitch,

For devices that are by regulation exempted from GMP, the FDA intends that the application of 820.180 be limited to the record-keeping requirements of 820.198 (rather than calling for maintenance of all records required by part 820).  If you contact DICE, FDA will confirm this interpretation.

The basis for this interpretation is made via the Agency's intended flexibility of the Quality System Regulation (see the preamble).  Specifically, 820.5 requires (and the preamble reiterates) that the manufacturer is to establish and maintain a quality system that is "appropriate" and that meets the requirements of part 820.  But by inherent definition, not all part 820 requirements apply in a GMP-exempt scenario.  Therefore the manufacturer of a GMP-exempt device needs to clearly define and justify (for example, via the Quality Manual) the scope to which it is applying part 820 to the GMP-exempt devices.  In the direct context of 820.5, FDA's small entity compliance guide (document withdrawn from FDA's website, but underlying principles still apply), FDA said that the 820.5 word "appropriate" means that the rule is a flexible regulation.  In this context, FDA also said that it is left to manufac­turers to determine the necessity for, or extent of some quality elements and to develop and implement specific procedures tailored to their particular processes and devices.  So it is on this basis that a GMP-exempt firm would limit the scope of its 820.180 record-keeping requirements to the records called for by 820.198.

Hope this helps,

------------------------------
Kevin Randall RAC (U.S., Canada, Europe)
Principal Consultant
ComplianceAcuity, Inc.
Golden CO
United States

Original Message:
Sent: 04-04-2016 14:17
From: Kevin Randall
Subject: Record-keeping for FDA "GMP-Exempt" devices

Forwarded question from Mitchell Johnson:

"...For a GMP Exempt Class I device such as an external knee brace (see FDA classification at http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpcd/classification.cfm?ID=4824 ,and eCFR for 890.3475 ) the FDA classification cites that the device is "exempted from GMP regulation, except for general requirements concerning records (820.180) and complaint files (820.198)".  21 CFR 820.180 pertains to General Requirements for Records and starts out with "All records required by this part shall be maintained...".  

As I read it, even though the classification statement for the device states it is GMP exempt, when following the logic of 820.180 I find that the manufacturer is required to maintain all records required by part 820. 

My question:  what does it really mean in this context to be exempt from GMP if one is required to maintain all the records embedded within the GMP/QSR?

Thanks,

Mitch

------------------------------
Mitchell Johnson
Intricon Corporation
Arden Hills MN
United States..."

------------------------------
Kevin Randall RAC (U.S., Canada, Europe)
Principal Consultant
ComplianceAcuity, Inc.
Golden CO
United States
------------------------------

Hi Kevin,

Thank you also for your reply.  21 CFR 820.1(a)(3) also carries a definition of "where appropriate" which brings me to the same result. 

I conclude that a manufacturer of a Class I GMP-exempt device should identify in their quality system that those devices are subject to the record-keeping requirements of 820.198, and any other clauses of the QSR which they deem appropriate for the specific device, taking into consideration the risk and with reference to 820.5 and 820.1(a)(3).  The justification for any clauses not implemented should be documented and show that not implementing a requirement is not reasonably expected to result in product that does not meet specifications or failure to carry out any necessary corrective actions.  

You and David have been very helpful.

Best regards,

Mitch

A subtle (yet critical) nuance is that FDA uses the basic terminology "appropriate" in the context of 820.5, yet FDA uses the terminology "where appropriate" in 820.1(a)(3) and elsewhere in part 820.  Since 820.180 does not utilize the "where appropriate" terminology, I would recommend that the GMP-exempt record-keeping justification be based primarily on the liberties provided by 820.5 rather than those provided by 820.1(a)(3).

Hope this helps,

Good day to you as well David!

21 CFR part 820 includes 14 requirements that are eligible for the unique liberties of 820.1(a)(3).  Those 14 requirements are:

• An outline of the structure of the documentation used in the quality system [820.20(e)]
• Device software validation and risk analysis during design validation [820.20(g)]
• Design change verification in lieu of design change validation [820.20(i)]
• Procedures for identifying with a control number the components of surgically implanted and life sustaining devices [820.65]
• Pre-implementation validation of changes to production processes [820.70(b)]
• Documentation of the major equipment validated during process validation [820.75(a)]
• Documentation of the individual(s) performing validated processes after a process has been validated [820.75(b)(2)]
• Documentation of the major equipment used after a process has been validated [820.75(b)(2)]
• Revalidation of validated processes after process changes or process deviations [820.75(c)]
• In-process acceptance procedures [820.80(c)]
• Documentation (in acceptance records) of the equipment used for acceptance activities [820.80(e)(5)]
• Device label integrity during use of the medical device [820.120(a)]
• Installation test procedures for devices requiring installation [820.170(a)]
• Procedures for statistical techniques 820.250(a)

In stark contrast, if a 21 CFR part 820 requirement is not qualified by the term "where appropriate", then it is absolutely not eligible for the unique liberties of 820.1(a)(3). Examples of requirements not eligible for the liberties of 820.1(a)(3) include document controls, CAPA, management review, and many others. In other words, requirements such as having procedures for document controls, management review, CAPA, and others are still mandatory even if a firm (erroneously) believed that it didn’t need those procedures to meet product specifications and/or carry out corrective actions. Consequently, extending the 820.1(a)(3) liberties to requirements other than the aforementioned 14 is a sure way to undermine device quality and/or trigger an objection (i.e., FDA-483) by the Agency.

Hope this helps,

Good day to you as well David!

21 CFR part 820 includes 14 requirements that are eligible for the unique liberties of 820.1(a)(3).  Those 14 requirements are:

• An outline of the structure of the documentation used in the quality system [820.20(e)]
• Device software validation and risk analysis during design validation [820.20(g)]
• Design change verification in lieu of design change validation [820.20(i)]
• Procedures for identifying with a control number the components of surgically implanted and life sustaining devices [820.65]
• Pre-implementation validation of changes to production processes [820.70(b)]
• Documentation of the major equipment validated during process validation [820.75(a)]
• Documentation of the individual(s) performing validated processes after a process has been validated [820.75(b)(2)]
• Documentation of the major equipment used after a process has been validated [820.75(b)(2)]
• Revalidation of validated processes after process changes or process deviations [820.75(c)]
• In-process acceptance procedures [820.80(c)]
• Documentation (in acceptance records) of the equipment used for acceptance activities [820.80(e)(5)]
• Device label integrity during use of the medical device [820.120(a)]
• Installation test procedures for devices requiring installation [820.170(a)]
• Procedures for statistical techniques 820.250(a)

In stark contrast, if a 21 CFR part 820 requirement is not qualified by the term "where appropriate", then it is absolutely not eligible for the unique liberties of 820.1(a)(3). Examples of requirements not eligible for the liberties of 820.1(a)(3) include document controls, CAPA, management review, and many others. In other words, requirements such as having procedures for document controls, management review, CAPA, and others are still mandatory even if a firm (erroneously) believed that it didn’t need those procedures to meet product specifications and/or carry out corrective actions. Consequently, extending the 820.1(a)(3) liberties to requirements other than the aforementioned 14 is a sure way to undermine device quality and/or trigger an objection (i.e., FDA-483) by the Agency.

Hope this helps,

Hi Kevin,

Thank you also for your reply.  21 CFR 820.1(a)(3) also carries a definition of "where appropriate" which brings me to the same result. 

I conclude that a manufacturer of a Class I GMP-exempt device should identify in their quality system that those devices are subject to the record-keeping requirements of 820.198, and any other clauses of the QSR which they deem appropriate for the specific device, taking into consideration the risk and with reference to 820.5 and 820.1(a)(3).  The justification for any clauses not implemented should be documented and show that not implementing a requirement is not reasonably expected to result in product that does not meet specifications or failure to carry out any necessary corrective actions.  

You and David have been very helpful.

Best regards,

Mitch

Mitch,

For devices that are by regulation exempted from GMP, the FDA intends that the application of 820.180 be limited to the record-keeping requirements of 820.198 (rather than calling for maintenance of all records required by part 820).  If you contact DICE, FDA will confirm this interpretation.

The basis for this interpretation is made via the Agency's intended flexibility of the Quality System Regulation (see the preamble).  Specifically, 820.5 requires (and the preamble reiterates) that the manufacturer is to establish and maintain a quality system that is "appropriate" and that meets the requirements of part 820.  But by inherent definition, not all part 820 requirements apply in a GMP-exempt scenario.  Therefore the manufacturer of a GMP-exempt device needs to clearly define and justify (for example, via the Quality Manual) the scope to which it is applying part 820 to the GMP-exempt devices.  In the direct context of 820.5, FDA's small entity compliance guide (document withdrawn from FDA's website, but underlying principles still apply), FDA said that the 820.5 word "appropriate" means that the rule is a flexible regulation.  In this context, FDA also said that it is left to manufac­turers to determine the necessity for, or extent of some quality elements and to develop and implement specific procedures tailored to their particular processes and devices.  So it is on this basis that a GMP-exempt firm would limit the scope of its 820.180 record-keeping requirements to the records called for by 820.198.

Hope this helps,

------------------------------
Kevin Randall RAC (U.S., Canada, Europe)
Principal Consultant
ComplianceAcuity, Inc.
Golden CO
United States

Original Message:
Sent: 04-04-2016 14:17
From: Kevin Randall
Subject: Record-keeping for FDA "GMP-Exempt" devices

Forwarded question from Mitchell Johnson:

"...For a GMP Exempt Class I device such as an external knee brace (see FDA classification at http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpcd/classification.cfm?ID=4824 ,and eCFR for 890.3475 ) the FDA classification cites that the device is "exempted from GMP regulation, except for general requirements concerning records (820.180) and complaint files (820.198)".  21 CFR 820.180 pertains to General Requirements for Records and starts out with "All records required by this part shall be maintained...".  

As I read it, even though the classification statement for the device states it is GMP exempt, when following the logic of 820.180 I find that the manufacturer is required to maintain all records required by part 820. 

My question:  what does it really mean in this context to be exempt from GMP if one is required to maintain all the records embedded within the GMP/QSR?

Thanks,

Mitch

------------------------------
Mitchell Johnson
Intricon Corporation
Arden Hills MN
United States..."

------------------------------
Kevin Randall RAC (U.S., Canada, Europe)
Principal Consultant
ComplianceAcuity, Inc.
Golden CO
United States
------------------------------

FORWARDED QUESTION FROM MITCHELL JOHNSON:

"...For a GMP Exempt Class I device such as an external knee brace (see FDA classification at http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpcd/classification.cfm?ID=4824 ,and eCFR for 890.3475 ) the FDA classification cites that the device is "exempted from GMP regulation, except for general requirements concerning records (820.180) and complaint files (820.198)".  21 CFR 820.180 pertains to General Requirements for Records and starts out with "All records required by this part shall be maintained...".  

As I read it, even though the classification statement for the device states it is GMP exempt, when following the logic of 820.180 I find that the manufacturer is required to maintain all records required by part 820. 

My question:  what does it really mean in this context to be exempt from GMP if one is required to maintain all the records embedded within the GMP/QSR?

Thanks,

Mitch

------------------------------
Mitchell Johnson
Intricon Corporation
Arden Hills MN
United States..."

FORWARDED BY:

------------------------------
Kevin Randall RAC (U.S., Canada, Europe)
Principal Consultant
ComplianceAcuity, Inc.
Golden CO
United States
------------------------------