Resource Planning

Resource planning is a critical part of every project and organization. At Genentech, the process development functions have been successfully using standardized resource planning tools to forecast resource needs during product development. By collaborating with various quality-related functional groups, we developed a standardized quality–resource-requirements model based on the type and development stage of the product. With this information, the QPS is able to communicate to the project team early on to ensure that resources in quality are in alignment with the overall product timeline and goals. This standardized approach also ensures consistency and eliminates the need for requesting information from various groups every time milestones move or change.

GMP Manufacturing Control System

Collaborating with key CMC stakeholders, especially analytical chemistry, the QPS proposes an overall control strategy for GMP drug substance and drug product. The control strategy covers in-process, release, stability testing, and their respective acceptance criteria (i.e., limits). The proposal is usually presented to an upper management analytical review committee, which consists of key CMC functional directors, and is implemented only after the committee's endorsement. After this endorsement, the QPS is responsible for drafting and approval of the formal drug substance and drug product specifications documents in the QA documentation system. In this capacity, the QPS works with our regulatory affairs and analytical chemistry groups to ensure the overall quality control strategy meets the standards of the relevant regulatory agencies (FDA, EMA, etc.). This task requires that the QPS be familiar with relevant ICH, FDA, and EMA guidelines and take into consideration the quality requirements that are appropriate for the development stage of a clinical product.

Analytics

Although the QPS is not directly involved in analytical characterization and method development, they are expected to be familiar with all of the methods used in the control system (including in-process, release, and stability testing). The scope of these methods covers analytical, physical, microbial, and viral testing methods. With this knowledge, the QPS understands why and how these methods are used for monitoring and controlling the quality attributes at each manufacturing process step.

In collaboration with various QC testing and analytical chemistry groups, the QPS is responsible for proposing the overall method qualification/validation strategy appropriate with the phase of development and internal quality standards. At the conclusion of method qualification/validation studies, the QPS also drafts a final report that summarizes all of the method validation/qualification studies. This report is a useful reference during regulatory agency inspections. It also serves as a valuable source for the lifecycle management of analytical method development.

Another key responsibility of the QPS is managing the reference materials. During biopharmaceutical development, a product-specific reference material often needs to be generated because there is no international standard available. The reference material serves as the standard for the product and the control for many QC methods. In this capacity, the QPS is responsible for authoring and approving the qualification protocol and coordinating the reference material manufacturing, testing, and release. Afterwards, the QPS continues to maintain the reference material and summarizes the reference material data from QC testing groups to evaluate its stability. These responsibilities can go to outside companies in special cases such as when a contract manufacturing organization (CMO) is used to manufacture and maintain the corresponding reference material. In this case, the QPS will interact with the CMO to ensure the relevant activities are completed from the quality perspective.

Building the Product Knowledge History

Valuable product knowledge can be acquired during development by strategically managing discrepancies, investigations, and change controls. Because the QPS is involved in quality aspects of their product, they are in the position to take full advantage of these experiences. The QPS is responsible for identifying major quality-impacting discrepancies that occur during GMP manufacturing and testing. Quality-related investigations involve the identification of a possible cause, determination of the impact (or not) on quality, and corrective-action implementation. The QPS leads the effort in presenting a conclusion to and seeking endorsement from the appropriate clinical quality review committee (i.e, quality review board, QRB) and seeking the support of senior quality management to bring the investigation to a successful conclusion. They begin with discussions with the QRB chair to determine if the issue is serious enough for a formal QRB meeting. If needed, they coordinate with various stakeholders to present to the QRB, participate in the QRB meeting discussion and decision-making, facilitate the QRB for endorsement and recommendation, and execute the QRB recommendation. The QPS can also be involved in discrepancies or investigations by performing a quality assessment and providing relevant history and recommendations to the QRB committee to facilitate an effective and efficient outcome.

Ultimately, the quality-related discrepancy investigation history is valuable when building the design space in support of Quality by Design. By formally evaluating and documenting these deviations and their conclusions, they can be used as unplanned design of experiments, and they may sometimes represent possible manufacturing variations.

Change control is a quality system that documents changes that impact GMP activities. Its goal is to ensure that the proper assessment is conducted to systematically evaluate potential impact before implementing a change. In this process, the QPS sometimes initiates a change-control record and also participates in the assessment related to the QPS activities stated above. Because the QPS is the quality single point of contact on the project team and knows the product quality history, many proposed changes are often evaluated by the QPS to see if their potential impact on quality has been thoroughly assessed. For various tasks, we have developed a corresponding business process to maintain consistency. As drug candidates advance through development, the manufacturing process usually experiences many changes. The change control system becomes a very valuable source of development history. By capturing and analyzing the development history using discrepancy management and change control, the QPS builds a robust history database that includes all quality aspects of the product.