Late Phase development for pharmaceutical solutions

Seqens is a world leader in pharmaceutical synthesis, capable of providing full CMC (Chemistry, Manufacturing and Controls) support to prepare for phase III clinical trials and drug registration globally in total compliance with the strictest regulatory, quality and EHS standards.

Our global R&D team in Porcheville, Paris, France and Newburyport, MA, USA together with our Regulatory Affairs team in Ecully, Lyon will provide API cGMP services including:

• Quality by design methodology
• Process and crystallization optimization studies
• Fate and purge studies
• Analytical method development and ICH validation
• ICH stability studies
• Kilo-scale, pilot scale or multi-ton scale manufacturing to support phase III or launch
• Special technologies like cryogenic, very high pressure or flow Chemistry capabilities
• Special containment for highly potent APIs down to 100 ng/m3
• Quality Assurance with a network of 6 cGMP/ FDA inspected sites in Europe and the United States
• Back integration of critical intermediates or RSMs for supply security
• Regulatory Services

Regarding late phase programs, Seqens applies incremental development which include development and optimization of processes, analytical development and control. Seqens provides impurity identification and control, API characterization and technology transfer for larger scale API’s as well as Regulatory Starting Material (RSM) Sourcing Development.

Seqens has placed a significant focus on advanced analytical solutions to support and guide process development for complex API processes. Seqens analytical scientists are experienced in tackling the most challenging problems and establishing controls for the synthetic process and ensuring API quality.

cGMP, ICH compliant stability studies are also performed to support regulatory CMC programs and process development:

• ICH large storage conditions:  -20°C; 5°C; 25°C/60%RH; 30°C/65%RH; 40°C/75%RH
• ICH Photostability Testing Capability
• Stress studies accelerated and long-term stability studies

In addition, Seqens has developed in-silico simulation tools to predict degradation patterns and therefore accelerate forced degradation studies and result interpretation.

As programs head towards commercialization, the process is mapped with direction provided by CMC Gap Analysis, Risk Assessment and Design- of-Experiment methodology, leading to an understanding of the operational space and potential critical process parameters.

The impurity profile is further examined, with targeted fate & purge studies, designed to ensure clearance of impurities and knowledge of carry-over and tolerable levels.

Once the process has undergone successful validation, our Regulatory Affair will support with registration with global Regulatory Authorities.

Quality by Design approach for Drug Product development

Seqens is pursuing a Quality By Design (QbD) approach in the development of new drug products. By implementing a QbD strategy, a better scientific understanding is obtained, eliminating unnecessary testing, accelerating the development process and reducing the cost.

The QbD strategy approaches is summarized through the flowing steps:

• Quality Target Product Profile (QTPP) is defined prior to formulation development to ensure desired drug product quality, safety and efficacy
• Critical Quality Attributes (CQA) of the drug product are determined
• Risk assessment is conducted to evaluate the impact of raw material attributes and process parameters on the CQA
• Design space is established describing the relation between the input (raw material attributes and process parameters) and the end-product quality

Fate & Purge studies and services

Drug substances produced by chemical syntheses contain impurities which must be controlled to ensure the desired product quality. Generation and depletion of impurities, including Genotoxic impurities (GTI), which are formed during chemical syntheses or due to limited stability of intermediates should be investigated in a “fate and purge” study which includes:

• Identification and justification of Critical Quality Attributes
• Implementation of Control Strategy
• Determination of Carryover
• Method Development & Validation
• Technical Assessments and Consultation

Seqens has a strong experience in impurity control strategy from IND through to commercial stages, with a long track-record in the design and execution of impurity fate and purge studies.

Seqens offers rapid method development and alternative analyses such as LC/MS (TQ, QTOF), GC-MS (SQ, TQ) and NMR which are required for impurity identification and quantitation, and to scientifically support study conclusions. In addition, Seqens used in silico simulation tools to predict purge factors. Impurities can then be either synthesized using traditional chemical synthesis or isolated from process streams using preparative chromatography (column chromatography or preparative HPLC).  The impurities are then characterized and can be used as reference markers / standards.

Regulatory Services

Seqens operates in the regulated environment and has the capability to support a broad range of development stages, being committed to provide our clients with our regulatory expertise and international experience all along the product development, from early stage of API development up to commercial supplies.

Seqens provide comprehensive Regulatory services conducted in compliance with the international environment (ICH, EMA, FDA, USP/PE, …) to cover IND/IMPD and NDA/CTD enabling activities:

• Regulatory review of technical reports,
• Preparation of Active Substance Master File (ASMF/DMF),
• Preparation of compliant regulatory documents for clinical trial application (IND/IMPD) and international registration (NDA/ANDA/CTD/NTA)
• Expertise and Quality Overall Summaries
• Responses to Questions
• Life Cycle Submissions (amendments, variations…)

Discover our early phase development services !