Why Do We Need Quality Agreements?

Sep 01, 2013
By Spectroscopy Editors
Volume 28, Issue 9

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In May, the Food and Drug Administration (FDA) published new draft guidance for industry entitled "Contract Manufacturing Arrangements for Drugs: Quality Agreements" (1).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 behalf.

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: Summary of EU GMP Chapter 7 requirements for outsourced activities.
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 this column.

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