Q11: Development and Manufacture of Drug Substances (chemical entities and biotechnological/biological entities) Draft Guideline by the Process/Product Development (PPD) Community of Practice (COP) Date: October 2011
This new guidance is proposed for Active Pharmaceutical Ingredients (APIs)
harmonizing the scientific and technical principles related to the description and
justification of the development and manufacturing process of drug substances
including both chemical entities and biotechnological/biological entities. The guideline
will not address the subjects covered by ICH Q7, Good Manufacturing Practice Guide
for Active Pharmaceutical Ingredients, such as qualification of facilities and equipment.
The deadline for comments on the Q11 draft guideline under Step 3 was September
2011. According to the Q11 Business Plan, some of the benefits expected once this
guideline will be in full operation are to fill a gap in the regulatory framework and bring
substantial cost savings.
The ICH Q11 guideline further clarifies principles and concepts which are included in
ICH guidelines on Pharmaceutical Development (ICH Q8), Quality Risk Management
(ICH Q9), and Pharmaceutical Quality System (ICH Q10) as they pertain to drug
substances. The “traditional” and the “enhanced” approach for developing a drug
substance are described in the guideline and emphasis is made that these two
approaches “are not mutually exclusive”; a company can use one or the other or a
combination of both.
The lifecycle management strategy (cited 18+ times!) is related to:
process development and validation
relationship between Critical Process Parameters (CPP) and Critical Quality
Attributes (CQA)
innovation
control strategy
manufacturing process performance
risk evaluations
contract manufacturing
change control and technology transfers
The guideline, which also includes five “Illustrative Examples,” has selected one
specifically to relate Quality Risk Management to Lifecycle Management of Process
Parameters, emphasizing the importance of lifecycle management.
The guideline also defines the minimum elements for manufacturing process
development which basically should consist of identification of the CQAs and definition
of the manufacturing process and the control strategy. The “enhanced” approach will
include also identification based on the risk evaluation of the impact of the materials
attributes and process parameters on the CQAs, the functional linking between CPP,
materials attributes and CQAs for the APIs (design space studies), and the possibility
of Real-Time Release Testing (RTRT).
Definitions and requirements for starting materials and source materials are given and
for the additional requirements for biotechnological/biological products readers are
referred to the specific ICH guidelines for subjects such as Q5A, Q5B, and Q5D.
The Control Strategy chapter compares the “traditional” and “enhanced” approaches
and the Process Evaluation chapter includes references to continuous process
verification, clearly linking to the new Process Validation guideline published by the
FDA.
The last item covered by ICH Q11 relates to the submission of the Common Technical
Document (CTD) and recognizes that the use of the “enhanced approach" for process
development does not have a location in the CTD dossier but it makes some
recommendations where to include QRM, CQAs, Design Space, and the Control
Strategy.
ICH Q11 follows the ICH Q8(R2) guideline in providing a wealth of information on the
“what” of product and process development, with a welcome addition of illustrative
examples showing acceptable approaches to some of the key concepts. ISPE’s
Product Quality Lifecycle Implementation good practice guides provide a valuable
resource in understanding and implementing both guidelines through further
elaboration of the key concepts of Criticality, Design Space, and Control Strategy
together with an extensive illustrative example which integrates all the concepts as
applied to the development of a tablet formulation and its ingoing drug substance.