Outsourcing pharmaceutical manufacturing gives companies access to specialist expertise and manufacturing capacity, but it also creates responsibilities that must be clearly defined and effectively controlled. When a GMP quality agreement does not accurately describe the responsibilities of the parties involved, quality decisions can be delayed, investigations can remain unresolved, and manufacturing changes may be implemented without an adequate assessment of their quality or regulatory impact. The result can be avoidable delays and uncertainty at the point of batch certification.

The risks increase when production, testing, packaging and Qualified Person (QP) certification are performed by different organisations or at different sites. Information must be exchanged accurately and promptly, and the responsibilities of each party must be clearly established, yet a general commercial contract rarely describes the quality decisions in sufficient detail. EU GMP Chapter 7, Outsourced Activities, requires outsourced activities to be appropriately defined, agreed and controlled through a written contract. An agreement should therefore reflect the real supply chain and the way quality work is performed, rather than simply reproduce a standard template.

An effective GMP quality agreement gives both parties a common operational reference: responsibilities are clear, quality concerns can be escalated and the information needed for oversight is available. Billev Pharma East supports pharmaceutical companies facing these challenges with specialist GMP support, quality-system expertise, audit support and EU QP services. The earlier potential gaps are identified, the easier it is to build a manufacturing relationship that can withstand day-to-day pressures and regulatory scrutiny. In practice, problems tend to emerge at the handover points: a batch record reaches the certification site without a completed investigation, or a change is implemented before its regulatory impact has been assessed.

Our GMP consulting approach is designed to help companies recognise these risks before they become recurring quality problems.

What should pharmaceutical companies do before signing a GMP quality agreement?

Before signing a GMP quality agreement, a pharmaceutical company should establish precisely which activities are being outsourced and whether the proposed manufacturer is legally authorised, suitable and competent to perform them. In accordance with EU GMP Chapter 7, this assessment should consider the contract acceptor’s facilities, equipment, personnel, knowledge, experience and ability to perform the agreed activities in compliance with GMP. The assessment should also address relevant quality systems, including deviation management, change control, documentation and data integrity. The extent of assessment should be proportionate to the activities and associated risks. A GMP certificate alone does not replace the need to assess the contract acceptor’s suitability for the specific activities.

Next, the parties should work through the manufacturing process from material receipt to the transfer of batch documentation. They need to identify who performs each operation, who reviews the results, who approves critical decisions and when another party must be informed. Particular attention is needed for out-of-specification results, changes with potential marketing authorisation impact, subcontracted testing and information required by the certifying Qualified Person. Written responsibilities should match operational procedures and the actual parties involved.

Companies should also agree on practical communication routes, escalation contacts, document accessibility and review arrangements. In a more complex supply chain, the contract structure itself deserves scrutiny: the MAH, manufacturing authorisation holder and sites undertaking manufacturing or testing may be different legal entities. An appropriately tailored GMP quality agreement helps keep those arrangements coherent and reduces the chance of discovering a responsibility gap during a deviation, inspection or batch release. An early discussion should also cover what happens when a decision cannot be reached immediately.

A well-defined GMP vendor qualification process should therefore inform the quality agreement rather than remain a separate exercise.

How can Billev Pharma East help with GMP quality agreements?

Quality agreements often appear straightforward until the parties start negotiating real responsibilities. Who is allowed to approve a manufacturing change? What must the contract manufacturer provide before a batch can be certified? How should an urgent quality defect be escalated across different organisations? Billev Pharma East helps pharmaceutical companies address these questions with a practical GMP perspective, rather than relying on broad contractual language.

Our GMP consulting expertise can support the preparation and review of a GMP quality agreement, a targeted review of existing quality arrangements and the identification of gaps between contractual language and everyday quality-system practice. We can help clients examine responsibilities for deviation investigations, CAPA, change control, documentation, subcontracting and oversight, with attention to the manufacturing setup and applicable EU GMP expectations.

Billev Pharma East also offers GMP audits, quality management system consulting and EU QP support. These services are valuable when an agreement must function across several sites or when batch documentation and certification processes depend on reliable information exchange. The objective is not merely a document that can be signed, but an arrangement that personnel can actually use.

Whether you are starting a new manufacturing partnership or finding weaknesses in an established one, our specialists can help you approach the review systematically and prioritise issues that may affect compliance or supply continuity. Working with Billev Pharma East gives your internal team access to focused GMP expertise when decisions matter most.

We approach these projects by examining the way quality decisions are actually made.

For an existing partnership, a gap assessment in pharma can expose missing responsibilities before the agreement is revised.

What should be included in a GMP quality agreement with a contract manufacturer?

A GMP quality agreement should describe the products, sites and activities covered by the outsourcing relationship, then assign the quality responsibilities associated with each activity. It should be clear who controls incoming materials, manufacturing and packaging operations, sampling and analytical testing, validation-related work and the creation and review of GMP records, including data integrity in pharma. The level of detail should fit the scope of the outsourced work: a full manufacturing arrangement will need different provisions from an agreement covering only a specific laboratory test.

The agreement should also explain how the parties handle deviations, out-of-specification results, complaints, quality defects, recalls and CAPA. For change control, it should establish which types of changes require prior assessment, notification or approval and who determines whether a regulatory submission is necessary. It should cover subcontracting, audits, inspection support and relevant information exchange, with defined contacts and communication timelines where these are important.

For batch certification, the parties must address documentation access, responsibility for record review and the arrangements that allow the certifying QP to fulfil applicable obligations. Record retention, traceability, data integrity and access to electronic systems also deserve attention. EU GMP Chapter 7 expects the contract to specify responsibilities and communication processes, and Annex 16 is relevant where batch certification forms part of the supply chain.

A useful GMP quality agreement is specific enough to prevent ambiguity without duplicating every underlying SOP. It should direct the parties to controlled procedures where appropriate and remain consistent with the marketing authorisation and applicable GMP requirements. The level of detail should match the risk and complexity of the work.

Clear arrangements for data integrity in pharma are especially important when records are generated or stored by different organisations.

How should quality responsibilities be divided between the parties?

An effective GMP quality agreement should show not only who carries out a task but also who reviews, approves and receives the outcome. The pharmaceutical company acting as contract giver needs suitable processes for overseeing outsourced operations and assessing the contract acceptor. The manufacturer, in turn, must be able to perform the agreed work with adequate facilities, personnel, equipment and procedures. Outsourcing an operation does not eliminate the contract giver’s oversight obligations.

Consider a deviation detected during manufacturing. The contract manufacturer may investigate the event and document the initial impact assessment, but the agreement should clarify when the pharmaceutical company is notified, who approves conclusions and what happens when the issue could affect multiple batches or markets. The same distinction matters for analytical results, manufacturing changes, complaints and quality defect investigations. Unclear quality assurance roles and responsibilities, including ambiguous approval language, can be as problematic as an entirely missing responsibility.

The allocation becomes more complex where the marketing authorisation holder (MAH), the manufacturing authorisation holder (MIA holder) responsible for QP certification and other manufacturers are separate entities. EMA guidance addresses the written contracts expected between these parties and the circumstances in which alternative contract chains may be acceptable. The GMP quality agreement and related contractual arrangements must therefore be assessed against the actual supply chain, rather than treating every outsourcing model as identical. This is why quality assurance roles and responsibilities should be explicit even where several teams collaborate on the same activity.

Billev Pharma East can help clients examine responsibility assignments and communication routes, helping make the written arrangement more useful in real manufacturing and release decisions.

How should deviations, CAPA and change control be addressed?

Deviations, investigations and changes are part of pharmaceutical manufacturing. What matters is how quickly the parties recognise their significance and how consistently they decide what happens next. A GMP quality agreement should state which party initiates and investigates a deviation, determines root cause, evaluates batch or product impact, proposes CAPA and verifies whether actions have been effective. It should also define when the other party must be notified, which findings require urgent escalation, and how decisions affecting batch disposition or certification are communicated.

Change control should be addressed with similar precision. A change to raw materials, equipment, process parameters, analytical methods, premises or subcontractors may affect product quality or the marketing authorisation. The agreement should specify which changes need prior notification or agreement, who assesses quality and regulatory impact and how the outcome is recorded before implementation, including any required CAPA plan. A general statement that the manufacturer will “inform the customer of changes” is rarely sufficient for high-impact situations.

Billev Pharma East can support a focused review of these arrangements, helping companies spot vague provisions and align the GMP quality agreement with the quality processes needed to manage issues before they disrupt batch certification or supply.

The parties should agree how open investigations will be reflected in batch decisions, what constitutes an acceptable interim measure and which documents demonstrate CAPA effectiveness. A workable CAPA plan depends on clear ownership of actions, approvals and effectiveness checks across organisational boundaries.

When should a GMP quality agreement be reviewed and updated?

A GMP quality agreement should remain aligned with the actual manufacturing and supply-chain arrangements throughout the contractual relationship. Changes to manufacturing sites, outsourced activities, products, responsibilities, subcontractors or contractual structures should prompt an assessment of whether the agreement needs revision. An agreement that once described the relationship accurately can gradually become disconnected from how work is actually performed. This is especially risky when outdated contacts, approval routes or documentation requirements remain in circulation.

Companies should set a justified, risk-based review approach and define the events that trigger an earlier review. Significant changes to outsourced activities, manufacturing sites, responsibilities or supply-chain structure should prompt an assessment. Repeated deviations, audit findings, delayed investigations or communication failures may also indicate that responsibilities or procedures require clarification. EU GMP Chapter 7 expects the contract giver to monitor and review the contract acceptor’s performance, although it does not prescribe one universal quality-agreement review interval.

During the review, the parties should check whether the scope and listed sites remain correct, whether technical responsibilities match current procedures and whether previous audit findings have been addressed and whether QP-related documentation and communication arrangements still function. Any revisions should pass through controlled review and approval, with affected teams informed of changes.

Billev Pharma East helps pharmaceutical companies approach these reviews with a compliance-focused perspective. An expert assessment of an existing GMP quality agreement can identify outdated or incomplete provisions before they contribute to quality problems, inspection observations or avoidable manufacturing delays. Repeated audit findings can be a useful signal that contractual expectations and actual practice no longer match.

Strengthen your GMP quality agreement with Billev Pharma East

A reliable GMP quality agreement provides more than contractual certainty. It helps pharmaceutical companies maintain oversight of outsourced manufacturing, make timely quality decisions and ensure that essential responsibilities are understood across the supply chain. Reviewing its content before problems arise is often more effective than correcting gaps under the pressure of a deviation, inspection or delayed batch release.

Billev Pharma East supports pharmaceutical companies with GMP expertise, audits, quality management system expertise and EU QP services. Whether you need to establish a new GMP quality agreement or assess an existing arrangement, our specialists can help you identify practical compliance gaps and strengthen the quality framework supporting your manufacturing partnership. Contact Billev Pharma East to discuss the GMP support your organisation needs.

Our GMP consulting services provide a practical route to reviewing contractual quality arrangements with experienced specialist input.

Frequently asked questions about GMP quality agreements

Sources: 1 – European Commission. EudraLex Volume 4 – EU Guidelines for Good Manufacturing Practice, Chapter 7: Outsourced Activities, 2 – European Commission. EudraLex Volume 4 – EU Guidelines for Good Manufacturing Practice, Annex 16: Certification by a Qualified Person and Batch Release, 3 – European Medicines Agency (EMA). Good Manufacturing Practice (GMP) and Good Distribution Practice (GDP) Questions and Answers.