合同QP能为制药厂商带来什么：eXmoor Pharma顾问谈批次认证之外的GMP职责

Drew Hope, PhD, BSc (Hons), MRSB, GMP compliance consultant and UK qualified person at eXmoor Pharma, looks at what manufacturers should expect from a contract QP.

If the first time a QP sees a problem is at the point of batch certification, then the issue has usually started much earlier. During my QP training, a lecturer explained to a class of eager delegates that a contract QP cannot expect, or be expected, to show up at a site solely to certify batches. Although the legal batch certification duties of a QP are the key deliverable in a contract, their wider responsibilities as a custodian of GMP at a manufacturing site are frequently more demanding. In my sector, where Cell and Gene Therapy (CGT) manufacturing is complex, sterile and often aseptic, I know that the QP’s effectiveness depends on how well they understand the wider operation. In this article we will consider how contract QPs avoid those first-sight-at-certification problems, and what contract-giving manufacturers should expect from a QP.

A contract QP embedded onto a site must ensure they have sufficient understanding to take reasoned decisions and discharge their responsibilities properly. They should complete, as a minimum, a checklist of knowledge assimilation. This must cover, for example: the manufacturing authorisations held; the quality system procedures; the equipped facility and its maintenance and qualification; the products and associated indications and any patient safety highlights; how products are made and tested; responsibilities clarified in agreements with critical suppliers of materials or outsourced activities, and supply chain complexities; and management oversight to monitor control. In doing so, a contract QP must build relationships with key personnel in all functions of the contract giver’s organisation. During this process, with fresh eyes, compliance gaps or inefficiencies may become apparent; these should be noted for future action. Only when this checklist is complete should they be comfortable with being named on the manufacturing authorisation.

However, onboarding to a site is only the beginning of the contract. A QP operating entirely remotely may struggle to fulfil some of the wider responsibilities expected under Annex 16 and the QP codes of practice; instead, they must be involved.

As a contract QP, I want to avoid handling difficult decisions at batch disposition. A QP should be involved deeply enough to prevent avoidable surprises, and work together with the site in solving problems. The site’s people, information, documentation, premises, and procedures must not only be made readily accessible by the contract giver but also frequently accessed by the contract QP.

Manufacturing and quality teams should benefit from a contract QP’s experienced judgement, particularly in issues affecting product safety, regulatory compliance or batch release. For this to work, the QP should be involved in deviations, particularly

investigations and impact assessments. They should ensure that conclusions are clear and supported with rationale. Good contract QPs can help embed consistent processes for reasoning based on rules, policy and principles, or through analogy. Such an approach engenders a quality system that is consistent and justifiable to support safe, effective medicines.

The site teams and the QP must engage together in change controls and CAPAs, to ensure that they effectively achieve their quality objectives and drive continuous improvement. Inevitably, some change actions and CAPAs are delayed; a contract QP must have full knowledge of these to assess the impact on the site’s compliance and batch disposition decisions.

During batch certification, a contract QP’s confidence in the control of risks in the overall manufacturing process will be based on their deep understanding of how the strategy is supported. While working at sites making sterile products, particularly aseptically made ATMPs, I have learned that Quality Assurance elements are not isolated compliance exercises; they are linked to product, process and release risks. On such sites, a contract QP’s involvement with the entire Contamination Control Strategy is vital.

For example, QPs should disseminate expertise in quality risk management and be involved in all stages of risk identification, assessment and control. They can help prevent bias and subjectivity, ensuring assessments and controls are based on evidence. This should enable better strategies for environmental and product monitoring and trending, and in-process and finished product sampling and testing. It will also reassure them that contamination risks are adequately represented in Aseptic Process Simulation and that the Self-Inspection programme focuses on the most critical activities and areas. And a QP’s risk management input is useful during the design, review and implementation of any significant change.

All contract QPs should be present during regulatory inspections and involved in inspectorate communications. They should bring a calm, authoritative perspective during difficult findings, exemplifying a collaborative peer-to-peer professional relationship with the inspectors. Similarly, for a CDMO, they should contribute to client audits, both to explain their role and support the review and finding-related CAPAs.

Often, small companies with few trained and experienced auditors appoint contractors. In these scenarios, QPs should participate in audits of a site’s suppliers and providers of outsourced services. This is particularly important when such audits are associated with statements of compliance to be made by the contract QP that form part of regulatory filings for clinical trials and product licensing applications. Also, QPs should be closely associated with audits for assessing controls for quality and safety of excipients, starting and critical raw materials. And assistance from experienced QPs in

helping define responsibilities between the site and these external parties in agreements can be extremely helpful, ensuring specifications are clear and ambiguities are eliminated.

A contract QP’s role is not solely directed at things: batches, facilities, controls etc. All QPs are quality leaders. Experienced contract support delivers for people, leaving the client’s team stronger, less dependent on external input. Successful QP leaders mentor the site senior team and key personnel, constructively challenging their thinking and decisions, and bringing them together in difficult times. This approach supports a strong quality culture, where the value of compliance is regarded as more prominent than the cost.

Furthermore, a contract QP can benefit the site’s other QPs. Sometimes, recruiting a full-time employed QP with relevant experience can be a challenge; an alternative strategy is to support the transition of a QP from a different pharmaceutical sector with the aid of an experienced contractor. And, importantly in the UK, they can sponsor a trainee QP through their application process. This was my route to becoming a QP, and I have since successfully supported client trainees’ applications by doing the same for them.

Manufacturers appointing a contract QP to support their operations must look beyond the batch disposition legal duties and see the opportunity to bring wider value to their site. Eligibility, availability and affordability matter, but experience and judgement should carry greater weight. When assessing a contract QP, manufacturers should look for:

• relevant experience with their product dosage forms and modalities
• a proven track record of working within site quality systems
• good judgement under pressure
• clear communication with site leadership
• a willingness to support internal capability development

Avoid those desiring only batch certification responsibilities.

For both the manufacturer and the contract QP, medicinal product disposition and certification remain critical responsibilities. But judging contracted support only by batch release capacity misses much of the role. The strongest appointments bring oversight, judgement, leadership and practical GMP experience. This is especially important in sectors where risks and complexities are higher, like aseptic, sterile and ATMP manufacturing environments. When this is done well, the relationship is rewarding for both the manufacturer and the contract QP.