Chemistry, Manufacturing and Controls (CMC)

Quality by Design (QbD)
Design for Manufacturability
Prior Approval Supplement (PAS)
Scale-up and post-approval changes (SUPAC)
Commitment of our resources today for your results tomorrow

“Quality cannot be tested into products; it has to be built in by design” (ICH Q8, Step 2 Document)

Most quality assessment today relies on end-product testing. However, the future of CMC review is based on Quality by Design (QbD), and the CMC Regulatory Decision is based on CMC Quality & Performance.

From the start of each development project, we integrate science of design - Design to reduce “Uncertainty”, process analytical technology and quality system – an approach to imbed a proactive quality system in the final product.

In our pre-approval CMC development, we will:
  Identify key steps required for the final regulatory submission in the overall development program from pre-formulation, formulation, analytical development, lab-scale and commercial-scale process design & validation, to commercial batch production
  Establish process parameters and critical control points using validated controls to show robust process end-points, meet regulatory specifications and set on-line controls
  Define end-points from the regulatory perspective and reduce regulatory uncertainty to demonstrate QbD & flexibility – “Preclinical to Commercial Plug & Play”

Conditions to execute batch records preset regulatory commitments and determine the future production cost. Based on our commercial production experience, we provide our clients with advices on “Design for Manufacturability” and on solutions to be cost-effective in their final products – creating efficiency, flexibility and scalability in CMC commitments and facilities.

  Derive characteristics important to desired performance from a combination of prior knowledge and experimental assessment during product development
  Provide data for clients to establish in vitro drug release and in vivo absorption correlation (IVIVC)
  Control excipients and other sources of “common cause” variability



 

NDA Prior Approval Supplement (PAS)
Shelf-life and/or bioavailability may have changed and/or a new impurity may be introduced that may not be detected with established analytical methods, and the sponsor may not adequately qualify changes. Upon request, we will conduct:
•  Prior Approval Supplement Assessment
•  Continuous improvement efforts to ensure adequate qualification of changes (i.e., beyond conformance to specifications)
•  Determine whether additional stability data need to be gathered

Throughout the term of the project development, we uphold our development responsibilities:
•  “Commitment of our resources today for your results tomorrow”
•  Leadership quality in process development and process optimization
•  Upper management support, commitment and decision-making
•  Innovative approaches for demonstrating therapeutic equivalence of generics
•  In the stand-by mode during your CMC review cycle
•  Troubleshooting support & root cause investigation in collaboration and team approach
•  Multidisciplinary communication and collaboration
•  Reduce “Time to Market” pressure on clients

SUPAC

If SUPAC becomes necessary, we will develop with our clients cost-efficient strategies to ensure the acceptability of scale-up and post-approval changes (SUPAC), and long-term stability commitment on post-change batches for new drug applications (NDAs) and abbreviated new drug applications (ANDAs), per 21 CFR 314.70 Supplements and other changes to an approved application.

We will:
Conduct a comparative study on the various types of supplemental amendments regarding SUPAC modifiers including: SUPAC-Immediate Release solid dosage forms (SUPAC-IR) and SUPAC Modified Release oral dosage forms (SUPAC-MR)
Develop strategies for some changes that need an approved supplement but may now be submitted as changes being effected or in the next annual report under the SUPAC terms.
Provide a mechanism to obtain substantial regulatory acceptance of the post approval changes
Validate the changes

If Bulk Actives Post Approval Changes (BACPAC) are involved, we will assist our clients and investigate the impact on the ANDA/IND/NDA and drug substance manufacturers who intend to make post approval changes in site of manufacture, scale of manufacture, equipment, specifications, and/or process for intermediates in the synthetic pathway leading to a drug substance.

Commitment of our resources today for your results tomorrow.
Throughout the term of the project development, we are committed to fulfilling our development responsibilities:
· Leadership quality in process development and process optimization
· Upper management support
· Always in the stand-by mode during your CMC review cycle
· Troubleshooting support & root cause investigation in team approach
· Multidisciplinary communication and collaboration
· Reduce “Time to Market” pressure on clients