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
GMP Manufacturing Control System
For each new or changed drug substance and drug product GMP campaign, the QPS authors a product-specific sampling and testing
plan. This document defines QC testing requirements at each manufacturing step. It contains sampling quantity, test codes
and names, and the corresponding control limits for all of the key intermediates and release steps. Sampling instructions
(e.g., aseptically or not) are also included in this document. It is used as the primary source information by manufacturing,
QC testing and sample management, and LIMS, ensuring the appropriate samples are pulled, verified, submitted, logged into
the sample tracking system, and tested.
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.
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
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.