Clinical Trial-Enabling Activities
Because the QPS is actively involved in establishing the release specification, stability strategy, reference material, and
QC testing and control during manufacturing, they author the relevant sections of an investigational new drug (IND), IND amendments,
and regulatory filings for other countries. The QPS is also responsible for addressing quality-related questions from various
regulatory agencies. Clinical development is a dynamic environment. Regulatory and quality requirements are quite different
from those of commercial products. In addition, different countries may have different expectations regarding these requirements
for clinical trials conducted in their countries. The QPS is expected to be familiar with these different requirements during
clinical development and ensure their product meets them.
For clinical trials conducted in Europe, the product specification file is required by a qualified person (QP) for releasing
the investigational drug. This document generally includes and refers to such information as specification and analytical
methods for starting materials, intermediates, bulk and finished products, and packaging materials; the manufacturing process
and in-process testing methods; stability data, storage, and shipment conditions; and relevant clinical trial protocols. The
information in the product specification file forms the basis of the assessment of the suitability for certification and release
of a particular batch by the QP. Thus, the product specification file contains comprehensive information about the manufacturing
process and controls. Because of their comprehensive role in quality, the QPS authors this document. In this capacity, the
QPS collaborates with various process-development functions and quality groups. This document is valuable not only for QP
release but also for many internal customers because it contains key manufacturing and control information in a single source.
The QPS is accountable for the GMP stability program of the clinical product. The GMP stability study is a critical element
of the overall control strategy during clinical development. The data from the study are used to support the expiration dates
of drug substance and drug product used in clinical trials; a product quality evaluation in the event of a temperature excursion
during shipment and storage; and acceptable ranges that are established for critical quality attributes at the time of the
commercial regulatory filing. The QPS is accountable for drafting the study protocol, reviewing and approving the time point
data, trending the stability data, and managing the out-of-trend or out-of specification (OOS) investigations. In addition,
the QPS participates in the review committee for setting the overall stability strategy throughout the product lifecycle.
The QPS proposes the product's shelf life based on updated GMP and supportive R&D data (generated by pharmaceutical development)
and generates the appropriate documents to justify the proposed shelf life. The shelf life of a clinical product is critical
to ensure the successful completion of clinical trials. As stability studies are continuous, the QPS is responsible for updating
the shelf life of the drug substance and drug product. In this role, the QPS collaborates with QC testing and pharmaceutical
development to evaluate stability data to determine if a product meets its quality requirements. Certain non-US countries
require either notification or a formal approval process for updating shelf life. The QPS ensures that, before labeling the
product with the newly proposed shelf life, it is approved in those countries where the clinical trial is conducted. In this
regard, regulatory affairs is responsible for notifying and filing with the relevant countries to obtain approval.
Ensuring uninterrupted clinical supply is critical to achieve a successful clinical trial. In this regard, the QPS also plays
key roles. During shipping to and storage of clinical materials at clinical sites, temperature is usually controlled to a
certain range to ensure product quality. However, temperature excursions often happen because of various reasons. This is
especially true if it is a global trial involving multiple countries on different continents. When such an event occurs, the
QPS is responsible for assessing if the materials impacted can still be used for the intended clinical trial. The QPS uses
available stability data obtained from stability-indicating assays to determine whether the temperature and duration the material
was exposed results in potential degradation that warrants quarantine of the material, or is not significant as to impact
the product quality. During the evaluation process, the QPS interacts with a formulation scientist for technical discussion
and QA for capturing the event in a QA discrepancy system. In addition, the QPS is accountable for timely communication to
clinical operations on the quality decision made at a quality review board meeting to reduce impact on the clinical material
supply. Under this scenario, once a discrepancy is discovered and under investigation it may affect the timely shipment of
clinical materials. The QPS will work with the clinical operation group closely so that they are informed of the material's
suitability for use.
Interactions with External Partners and CMOs
As Genentech's clinical pipeline became more diverse, we had an increased need for collaboration with CMOs or partners to
use their specialized technologies for process development and clinical manufacturing. To effectively manage the development
activities with the CMOs or partner, the project team needs a single point of contact identified from each of the key functional
areas (e.g., project management, process development, quality (QC and QA), etc.) to be responsible for the interactions with
the CMOs or partners. In this situation, Genentech's external QA serves as the point of contact for the quality assurance
function and ensures that the product is compliant, reputable, and reliable for patients, while the QPS serves as the point
of contact for quality control function and manages the QC activities from method transfer to various QC testing and QC investigations.
In many cases, multiple QC laboratories and sites are involved in the QC activities for a project. This requires the QPS not
only to have the ability to manage multiple issues at the same time, but also to have the broad knowledge and technical skills
to dive deep into issues when guidance is required. This eliminates the need to have all of the QC groups involved in interactions
and ensures quick responses to QC issues.
The QPS is also involved in the due diligence evaluation for selection of the CMOs. This allows the QPS to identify the gaps
and risks from a QC perspective and address them in advance of a contract.