The Document Nobody Reads Until Something Goes Wrong
Quality agreements are one of those documents that get negotiated carefully, signed by the right people, filed away, and never looked at again. Until something goes wrong.
When a GMP deviation occurs, when a batch fails, when a regulatory inspection raises a question about oversight, the quality agreement is the document that defines who was responsible for what. If it is vague, incomplete, or has not been reviewed since the programme started, the consequences are predictable.
A good quality agreement is not just a legal formality. It is a genuine operational tool that prevents disputes, clarifies accountability, and ensures that GMP responsibilities are distributed logically between the sponsor and the CDMO.
The Regulatory Requirement
EU GMP Chapter 7 on outsourced activities and the FDA’s guidance on contract manufacturing both require written quality agreements between sponsors and their contract manufacturers. The agreement must define the GMP responsibilities of each party clearly and must be reviewed and approved by the quality units of both organisations. It is not sufficient for a general commercial contract to contain quality provisions; a standalone technical or quality agreement is the regulatory expectation.
What a Strong Quality Agreement Covers
| Section | What It Should Define | Common Weakness |
| Scope of work | Exactly which activities are covered; what is in scope and out of scope for the agreement | Scope defined too broadly; changes in the programme not captured by agreement updates |
| GMP responsibilities | Which party is responsible for each GMP activity: batch record review, release, deviation investigation, CAPA | Joint responsibilities listed without specifying the primary responsible party |
| Change control | Which changes require sponsor notification; which require sponsor approval before implementation | CDMO retains right to make process changes without sponsor approval; sponsor not notified in time |
| Deviations and OOS | Timelines for notification; who investigates; who approves the investigation report | Notification timelines too loose; sponsor does not receive deviation reports until batch review |
| Regulatory inspections | What each party does when the other is inspected; how the agreement is referenced in submissions | No provision for inspection support; sponsor not informed of CDMO inspection findings |
| Stability | Who owns the stability programme; who has responsibility for out-of-trend results | Stability ownership split between parties without clear escalation path |
| Batch release | Authorised person responsibilities; what happens when the sponsor and CDMO disagree on release | Release responsibility assumed but not explicitly assigned; AP not named |
| Annual product review | Which party leads the APR; what data the CDMO provides; timelines | APR responsibility not assigned; CDMO data not available when sponsor needs it |
The Change Control Problem
Change control is the section of quality agreements that generates the most disputes in practice. The question is simple: when the CDMO wants to change something about the manufacturing process, the equipment, the supplier, or the facility, what does it need to tell the sponsor, and when?
From the CDMO’s perspective, the ability to make routine operational improvements without seeking sponsor approval for every change is a reasonable operational requirement. From the sponsor’s perspective, any change to the process that manufactured their clinical batches is a potential CMC filing issue that could trigger a regulatory amendment.
The resolution is a tiered change control classification. Minor changes are notified; significant changes require sponsor review; major changes require sponsor approval before implementation. What counts as minor, significant, or major should be defined explicitly in the agreement, not left to interpretation.
Reviewing and Updating the Agreement
Quality agreements should be reviewed at least annually and updated whenever the scope of work changes materially. A quality agreement written at the start of a Phase I programme will not adequately cover the same programme at Phase III. New manufacturing sites, new dosage forms, and new regulatory filings all need to be reflected in the document.
In practice, quality agreements often lag behind the programme. Amendments are negotiated slowly, and in the meantime the teams operate under informal understandings that have no contractual force. Building a formal review cycle into the programme management plan, with responsibility assigned to a named individual on each side, is the most reliable way to prevent this.
How Ardena Approaches Quality Agreements
Ardena’s quality team produces quality agreements that are specific to each programme rather than generic templates with blanks filled in. The change control classifications, notification timelines, and responsibility assignments in an Ardena quality agreement reflect the actual work being done and the regulatory context of the programme.
