Regulatory Open Forum

This message was posted by a user wishing to remain anonymous

Hi all,

My company is working with a design and manufacturing subcontractors. We are a startup in the early phases of implementing our QMS. However, we would like to start getting Quality Agreements in place with our subcontractors. 

Who is typically responsible for these? In my previous experience, the Quality team had owned the Quality Agreements with subcontractors but a consultant mentioned that this is usually the Legal team.  

Does anyone have further insight?

The very first question is to determine why you want a quality agreement – does it add value?

The only regulatory requirement I know of is ISO 13485:2016, 4.1.5 which requires a quality agreement for outsourced processes. The ISO 13485:2016 Handbook explains that the quality agreement does not have to be a separate document. It could the contract, the T&Cs, etc. The point is that when you outsource a process the supplier needs to know what counts as "good".

So, rather that writing a quality agreement because "you always did it that way", ask what would be in it that is not already covered in other documents, e.g., what is not in other documents.

Also, ask what your intention for its legal status. If it is an agreement between quality managers, then failure to comply is not enforceable in court, should it come to that. If you want it enforceable, then it must have legal standing which means it must be reviewed by legal.

My recommendation is that you don't write a separate quality agreement. Instead put everything in the existing contractual documents.

If it is an agreement only between quality managers, then Quality owns it.

If it is an enforceable part of the contract, then Purchasing owns it. Purchasing Agents are the legal agents for the company. However many documents are in this category. A Statement of Work. SOW, may come from Engineering with review by Quality. A separate Quality Agreement may come from Quality with review by Legal. As long as they are part of the order, then Purchasing owns them.

My recommendation is to avoid separate Quality Agreements. Put everything in the SOW, T&Cs, etc. as part of the PO or contract. Do not add more documents than necessary.

------------------------------
Dan O'Leary CQA, CQE
Swanzey NH
United States
------------------------------

Original Message:
Sent: 13-Mar-2023 05:08
From: Anonymous Member
Subject: Quality Agreements - Who is responsible?

This message was posted by a user wishing to remain anonymous

Hi all,

My company is working with a design and manufacturing subcontractors. We are a startup in the early phases of implementing our QMS. However, we would like to start getting Quality Agreements in place with our subcontractors. 

Who is typically responsible for these? In my previous experience, the Quality team had owned the Quality Agreements with subcontractors but a consultant mentioned that this is usually the Legal team.  

Does anyone have further insight?

The Quality and/or Regulatory departments need to be the primary authors of the Quality Agreement.  Yet the Quality Agreement nonetheless still needs to be corporately/legally executed between the parties.  Thus, the signatories should be executive officers in order to assure the Agreement has the necessary weight.  

It's fabulous that you are working on your Quality Agreements.  Those are international, including U.S. FDA, staples of proper supplier control.  While it may be tempting to conclude that Quality Agreements are just a figment of ex-U.S. ISO 13485 scenarios, U.S. FDA investigators will in fact (I've had it happen) ask to see your "Quality Agreements" also.  Not only is FDA already using that language in practice, the agency is only 12-24 months (my estimate) from formally putting it into its revised Quality Management System Regulation; so don't get caught off guard or pick a semantical fight that you won't win with FDA.  Indeed, while FDA's current QS Regulation doesn't actually use the words "Quality Agreement" (instead using "quality requirements", "purchasing data", and "purchasing documents"), the fundamental intent and requirements are generally the same.  Remember that FDA's current QS Regulation's supplier control requirements were fashioned after ISO's "subCONTRACTor" requirements.  And FDA and other international agencies can be preferential to the GHTF's (Global Harmonization Task Force's) and NBOG approach, which also push this into contractual terms.  So we are in fact talking about quality contracts ("Agreements") here.

Specifically, Quality Agreements need to cover a number of key things such as, but not necessarily limited to:

• Corrective action and preventive action
• Process Validation
• Acceptance and verification activities
• Complaint investigational support
• Supplier training/competence
• Design process
• Change control
• Handling of non-conformities
• Access for audits
• and others.

I would recommend against getting too creative or cute when achieving the parties' contractual agreement on these topics, especially since the world has already adopted, with FDA soon to officially follow, the "Quality Agreement" vernacular.

------------------------------
Kevin Randall, ASQ CQA, RAC (U.S., Europe, Canada)
Principal Consultant
Ridgway, CO
United States
© Copyright 2023 by ComplianceAcuity, Inc. All rights reserved.
------------------------------

Original Message:
Sent: 13-Mar-2023 05:08
From: Anonymous Member
Subject: Quality Agreements - Who is responsible?

This message was posted by a user wishing to remain anonymous

Hi all,

My company is working with a design and manufacturing subcontractors. We are a startup in the early phases of implementing our QMS. However, we would like to start getting Quality Agreements in place with our subcontractors. 

Who is typically responsible for these? In my previous experience, the Quality team had owned the Quality Agreements with subcontractors but a consultant mentioned that this is usually the Legal team.  

Does anyone have further insight?

It's unclear if you are referring to Quality Agreements for drugs or devices (perhaps devices as you mention "design").  It seems the advice provided so far refers to devices.  For drugs, the situation may be different.  First FDA, the responsibility for oversight of contracted (GMP) activities and ultimate responsibility lies with the application (NDA, ANDA, BLA, NADA) holder.  Activities can be delegated to a contract organization (CMO/CDMO), but the responsibility cannot be delegated.  Drug GMPs Parts 210/211 contain a number of requirements that must be assured by the application holder, which if contracted out, must be monitored and overseen.  In 2016, FDA (CDER, CBER and CVM) issued a Guidance for Industry: "Contract Manufacturing Arrangements for Drugs: Quality Agreements" which outlines FDA expectations for Quality Agreements, also referencing drugs, including APIs. and biologics. The EU in Eurdalex Volume 4 devotes an entire chapter (7) to Outsourced Activities as does ICH Q7, Chapter 16. 

As for what part of the company should be responsible for Quality Agreements, it should be the "Quality" organization as it is a "Quality Agreement".  The Quality Agreement should clearly outline the responsibilities for each party, including shared responsibilities.  Quality Agreements should be separate from "supply" agreements, which are legal agreements.  Creation of Quality Agreements should avoid "the lawyers" as much as possible since most company legal groups have very little knowledge of GMP and quality requirements.   Either party (contract giver or contract receiver) can initiate a Quality Agreement, especially if one has an existing format as a starting point which then can be tailored to meet the situation.
 

------------------------------
Peter Smith
Principal
Smith GMP Consulting
Narragansett, Rhode Island
USA
------------------------------

Original Message:
Sent: 13-Mar-2023 05:08
From: Anonymous Member
Subject: Quality Agreements - Who is responsible?

This message was posted by a user wishing to remain anonymous

Hi all,

My company is working with a design and manufacturing subcontractors. We are a startup in the early phases of implementing our QMS. However, we would like to start getting Quality Agreements in place with our subcontractors. 

Who is typically responsible for these? In my previous experience, the Quality team had owned the Quality Agreements with subcontractors but a consultant mentioned that this is usually the Legal team.  

Does anyone have further insight?

I agree with Peter. Quality agreement should be the responsibility of quality department. If no quality function exists in a startup company, it could be either manufacturing or regulatory's responsibility. If these don't exist I suggest the startup company needs to get these functions in place then talk about quality agreement.

------------------------------
Gene Zhu
Principal Consultant
Pasadena, CA
USA
------------------------------

Original Message:
Sent: 14-Mar-2023 07:55
From: Peter Smith
Subject: Quality Agreements - Who is responsible?

It's unclear if you are referring to Quality Agreements for drugs or devices (perhaps devices as you mention "design").  It seems the advice provided so far refers to devices.  For drugs, the situation may be different.  First FDA, the responsibility for oversight of contracted (GMP) activities and ultimate responsibility lies with the application (NDA, ANDA, BLA, NADA) holder.  Activities can be delegated to a contract organization (CMO/CDMO), but the responsibility cannot be delegated.  Drug GMPs Parts 210/211 contain a number of requirements that must be assured by the application holder, which if contracted out, must be monitored and overseen.  In 2016, FDA (CDER, CBER and CVM) issued a Guidance for Industry: "Contract Manufacturing Arrangements for Drugs: Quality Agreements" which outlines FDA expectations for Quality Agreements, also referencing drugs, including APIs. and biologics. The EU in Eurdalex Volume 4 devotes an entire chapter (7) to Outsourced Activities as does ICH Q7, Chapter 16. 

As for what part of the company should be responsible for Quality Agreements, it should be the "Quality" organization as it is a "Quality Agreement".  The Quality Agreement should clearly outline the responsibilities for each party, including shared responsibilities.  Quality Agreements should be separate from "supply" agreements, which are legal agreements.  Creation of Quality Agreements should avoid "the lawyers" as much as possible since most company legal groups have very little knowledge of GMP and quality requirements.   Either party (contract giver or contract receiver) can initiate a Quality Agreement, especially if one has an existing format as a starting point which then can be tailored to meet the situation.
 

------------------------------
Peter Smith
Principal
Smith GMP Consulting
Narragansett, Rhode Island
USA

Original Message:
Sent: 13-Mar-2023 05:08
From: Anonymous Member
Subject: Quality Agreements - Who is responsible?

This message was posted by a user wishing to remain anonymous

Hi all,

My company is working with a design and manufacturing subcontractors. We are a startup in the early phases of implementing our QMS. However, we would like to start getting Quality Agreements in place with our subcontractors. 

Who is typically responsible for these? In my previous experience, the Quality team had owned the Quality Agreements with subcontractors but a consultant mentioned that this is usually the Legal team.  

Does anyone have further insight?

Quality agreements are required by FDA for drugs and biologics in a contract manufacturing situation. However, FDA does, in its device Quality System Regulation, lay out numerous requirements that a quality agreement must cover. So even though the FDA doesn't explicitly require a quality agreement, creating one may still help you meet other requirements.

Some important points to remember about Quality Agreements:

• All things financial belong in the MSA, all things quality belong in the Quality Agreement 
• Make sure the Definitions section is crystal clear. One person's critical defect is another person's minor defect.
• Make sure the term "days" is clarified for calendar days or business days.
• Make sure time windows for review of documents, etc. are specified and reasonable ("timely manner" is not a time window).
• I find it helpful to go through the regulations and generate each section of the Quality Agreement based on each section of the regs. Helps avoid missing anything important.
• Do not try to make the document text only – that makes it very difficult to find/interpret who is responsible for what when you need to know. Use a responsibilities matrix such as this one:

Section	Item	Contractor	Sponsor
5.1	Pest control measures will be implemented and monitored at all times in appropriate areas of the building	X
7.2	Proposed Specifications will be reviewed and returned with comments within 10 business days	X	X
9.6	Critical Deviations from the approved manufacturing process will be reported to the Sponsor within 24 hours	X
12.8	Notify the other Party of any changes to the regulatory filing regarding the Product within 10 business days		X

Also make sure there is a clause that the Contractor will provide all needed documentation in support of regulatory filings.

While it is important that Executive management sign this agreement, it must also be reviewed and signed off by QA. Since most start-up companies bring on a QA function as an afterthought, early Quality Agreements seldom get a QA review. I have seen far too many start-up CEOs sign off on a Quality Agreement with no understanding of the quality/regulatory requirements, leaving the company unprotected and holding the bag for many of the Contractor's responsibilities.

------------------------------
Arvilla Trag RAC
Principal Consultant
CMC Compliance Services
Iron River MI
United States
------------------------------

Original Message:
Sent: 13-Mar-2023 05:08
From: Anonymous Member
Subject: Quality Agreements - Who is responsible?

This message was posted by a user wishing to remain anonymous

Hi all,

My company is working with a design and manufacturing subcontractors. We are a startup in the early phases of implementing our QMS. However, we would like to start getting Quality Agreements in place with our subcontractors. 

Who is typically responsible for these? In my previous experience, the Quality team had owned the Quality Agreements with subcontractors but a consultant mentioned that this is usually the Legal team.  

Does anyone have further insight?

This may be helpful for drugs.

This guidance describes FDA's current thinking on defining, establishing, and documenting manufacturing activities of the parties involved in contract drug manufacturing subject to current good manufacturing practice (CGMP) requirements. In particular, we describe how parties involved in contract drug manufacturing can use quality agreements to delineate their manufacturing activities to ensure compliance with CGMP.

https://www.fda.gov/media/86193/download

------------------------------
David Manalan
Principal, INQC Consulting
Acton MA
United States
------------------------------

Original Message:
Sent: 14-Mar-2023 08:41
From: Arvilla Trag
Subject: Quality Agreements - Who is responsible?

Quality agreements are required by FDA for drugs and biologics in a contract manufacturing situation. However, FDA does, in its device Quality System Regulation, lay out numerous requirements that a quality agreement must cover. So even though the FDA doesn't explicitly require a quality agreement, creating one may still help you meet other requirements.

Some important points to remember about Quality Agreements:

• All things financial belong in the MSA, all things quality belong in the Quality Agreement 
• Make sure the Definitions section is crystal clear. One person's critical defect is another person's minor defect.
• Make sure the term "days" is clarified for calendar days or business days.
• Make sure time windows for review of documents, etc. are specified and reasonable ("timely manner" is not a time window).
• I find it helpful to go through the regulations and generate each section of the Quality Agreement based on each section of the regs. Helps avoid missing anything important.
• Do not try to make the document text only – that makes it very difficult to find/interpret who is responsible for what when you need to know. Use a responsibilities matrix such as this one:

Section	Item	Contractor	Sponsor
5.1	Pest control measures will be implemented and monitored at all times in appropriate areas of the building	X
7.2	Proposed Specifications will be reviewed and returned with comments within 10 business days	X	X
9.6	Critical Deviations from the approved manufacturing process will be reported to the Sponsor within 24 hours	X
12.8	Notify the other Party of any changes to the regulatory filing regarding the Product within 10 business days		X

Also make sure there is a clause that the Contractor will provide all needed documentation in support of regulatory filings.

While it is important that Executive management sign this agreement, it must also be reviewed and signed off by QA. Since most start-up companies bring on a QA function as an afterthought, early Quality Agreements seldom get a QA review. I have seen far too many start-up CEOs sign off on a Quality Agreement with no understanding of the quality/regulatory requirements, leaving the company unprotected and holding the bag for many of the Contractor's responsibilities.

------------------------------
Arvilla Trag RAC
Principal Consultant
CMC Compliance Services
Iron River MI
United States

Original Message:
Sent: 13-Mar-2023 05:08
From: Anonymous Member
Subject: Quality Agreements - Who is responsible?

This message was posted by a user wishing to remain anonymous

Hi all,

My company is working with a design and manufacturing subcontractors. We are a startup in the early phases of implementing our QMS. However, we would like to start getting Quality Agreements in place with our subcontractors. 

Who is typically responsible for these? In my previous experience, the Quality team had owned the Quality Agreements with subcontractors but a consultant mentioned that this is usually the Legal team.  

Does anyone have further insight?

Hi,

I concor with your thought. Industry practice is that responsibility lies with Quality Supplier team (and a good idea to have the legal team as a stakeholder, along with manufacturing department, QC department, R&D and others)

------------------------------
Noopur Gupta
Brønshøj
Denmark
------------------------------

Original Message:
Sent: 13-Mar-2023 05:08
From: Anonymous Member
Subject: Quality Agreements - Who is responsible?

This message was posted by a user wishing to remain anonymous

Hi all,

My company is working with a design and manufacturing subcontractors. We are a startup in the early phases of implementing our QMS. However, we would like to start getting Quality Agreements in place with our subcontractors. 

Who is typically responsible for these? In my previous experience, the Quality team had owned the Quality Agreements with subcontractors but a consultant mentioned that this is usually the Legal team.  

Does anyone have further insight?