What are quality agreements, why do we need them, who should be involved with writing them, and what should they contain?
In May, the Food and Drug Administration (FDA) published new draft guidance for industry entitled "Contract Manufacturing
Arrangements for Drugs: Quality Agreements" (1). I just love the way the title rolls off the tongue, don't you? You may wonder
what this has to do with spectroscopy or indeed an analytical laboratory, which is a fair question. The answer comes on page
one of the document where it defines the term "manufacturing" to include processing, packing, holding, labeling, testing,
and operations of the "Quality Unit." Ah, has the light bulb been turned on yet? Testing and operations of the quality unit
— could these terms mean that a laboratory is involved? Yes, indeed.
Paddling across to the other side of the Atlantic Ocean, the European Union (EU) issued a new version of Chapter 7 of the
good manufacturing practices (GMP) regulations that became effective on January 31, 2013 (2). The document was updated because
of the need for revised guidance on the outsourcing of GMP regulated activities in light of the International Conference on
Harmonization (ICH) Q10 on pharmaceutical quality systems (3). The chapter title has been changed from "Contract Manufacture
and Analysis" to "Outsourced Activities" to give a wider scope to the regulation, especially given the globalization of the
pharmaceutical industry these days. You may also remember from an earlier "Focus on Quality" column (4) dealing with EU GMP
Annex 11 on computerized systems (5) that agreements were needed with suppliers, consultants, and contractors for services.
These agreements needed the scope of the service to be clearly stated and that the responsibilities of all parties be defined.
At the end of clause 3.1 it was also stated that IT departments are analogous (5) — oh dear!
Also, ICH Q7, which is the application of GMP to active pharmaceutical ingredients (APIs), has section 16 entitled "Contract
Manufacturing (Including Laboratories)." This document was issued as "Guidance for Industry" by the FDA (6) and is Part 2
of EU GMP (7). Section 16 states that "There should be a written and approved contract or formal agreement between a company
and its contractors that defines in detail the GMP responsibilities, including the quality measures, of each party." As noted
in the title of the chapter, the scope includes any contract laboratories, which means that there needs to be a contract or
formal agreement for services performed for the API manufacturer or any third-party laboratory performing analyses on their
Therefore, what we discuss in this gripping installment of "Focus on Quality" is quality agreements, why they are important
for laboratories, and what they should contain for contract analysis. The principles covered here should also be applicable
to laboratories accredited to International Organization for Standardization (ISO) 17025 and also to third-party providers
of services to regulated and quality laboratories.
What Are Quality Agreements?
According to the FDA, a quality agreement is a comprehensive written agreement that defines and establishes the obligations and responsibilities of the quality units
of each of the parties involved in the contract manufacturing of drugs subject to GMP (1). The FDA makes the point that a
quality agreement is not a business agreement covering the commercial terms and conditions of a contract, but is prepared
by quality personnel and focuses only on the quality of the laboratory service being provided.
Note that a quality agreement does not absolve the contractor (typically a pharmaceutical company) from the responsibility
and accountability of the work carried out. A contract laboratory should be viewed as an extension of the company's own facilities.
Why Do We Need Quality Agreements?
Put at its simplest, the purpose of a quality agreement is to manage the expectations of the two parties involved from the
perspective of the quality of the work and the compliance with applicable regulations. Under the FDA there is no explicit
regulation in 21 CFR 211 (8), but it is a regulatory expectation as discussed in the guidance (1).
In contrast, in Europe the requirement is not guidance but the law that defines what parties have to do when outsourcing
activities as (2):
Any activity covered by the GMP Guide that is outsourced should be appropriately defined, agreed and controlled in order to
avoid misunderstandings which could result in a product or operation of unsatisfactory quality. There must be a written Contract
between the Contract Giver and the Contract Acceptor which clearly establishes the duties of each party. The Quality Management
System of the Contract Giver must clearly state the way that the Qualified Person certifying each batch of product for release
exercises his full responsibility.
Who Is Involved in a Quality Agreement? (Part I)
Typically, there will just be two parties to a quality agreement; these are defined as the contract giver (that is, the pharmaceutical
company or sponsor) and the contract acceptor (contract laboratory) according to EU GMP (2). Alternatively, the FDA refers
to "The Owner" and the "Contracted Facility" (1). Regardless of the names used, there are typically two parties involved in
making a quality agreement unless, of course, you happen to be the Marx Brothers (the party of the first part, the party of
the second part … the party of the 10th part, and so forth) (9).
If the contact acceptor is going to subcontract part of their work to a third party, then this must be included in the agreement
— with the option of veto by the sponsor and the right of audit by the owner or the contracted facility.
Figure 1 shows condensed requirements of EU GMP Chapter 7 regarding the contract giver or owner and the contract acceptor
or contracted facility to carry out the work. Responsibilities of the owner are outlined on the left-hand side of the figure
and those of the contracted facility are outlined on the right-hand side of the diagram. The content of the contract or quality
agreement is presented in the lower portion of the figure. These points will be discussed as we go through the remainder of
Figure 1: Summary of EU GMP Chapter 7 requirements for outsourced activities.