Custom APIs

Seqens provides active Pharmaceutical Ingredient (API) and drug substance development services. We support emerging and large pharmaceutical customers in human and animal health with their pharmaceutical and biotechnology applications for complex, niche and small molecule programs through two main R&D locations in the regions of Boston and Paris.

Early Phase development for pharmaceutical solutions

Seqens’ Development team operates state of the art facilities to handle the most complex API development challenges. With a broad range of experience and knowledge of the latest technologies in organic synthesis, our chemists establish robust and economical routes for the synthesis of API’s.

Our chemists work closely with our development analysts and production teams to ensure that controls are appropriately embedded into the process IPCs, intermediate specifications, and processing instructions.
The salt form and polymorph landscape are explored within our Solid-State Analysis teams and drive the development of the API isolation process.

Our global R&D team in Porcheville, Paris, France and Devens, MA, USA, are experienced in providing API CMC (Chemistry, Manufacturing and Controls) requirements, including IND-enabling projects, to meet your project needs, including:

• Development of new, scalable API route selection
• Route development
• Chemical process development including controlled substances
• Large scale preparative chromatography for impurity isolation
• Solid state services including polymorphism screening and salt selection
• Starting material and other raw materials sourcing and development
• Analytical development and method qualification
• Preliminary ICH stability profile
• Process Safety assessments
• API clinical supply using cGMP kilo-lab suites
• IND document preparation & review (CMC or DMF preparation)

Late phase API development

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

Supporting process development for complex API

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. 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.

Custom API manufacturing Services

With 7 cGMP, FDA inspected plants in Europe, in the United States and in Israel for commercial production, supported by  pre-GMP (ISO 9001) sites in France and in India,  our customers have access to a powerful industrial network of facilities with a high level of quality, safety and environmental compliance.

Seqens invests on an ongoing basis in its production sites to provide the pharmaceutical industry with state-of-the-art equipment combined with cutting-edge technology in organic chemistry associated with proprietary gene shuffling technology for unique biocatalytic routes.

We conduct GMP manufacturing of APIs or intermediates from kilo to multi-ton quantities. Our range of scale and seamless collaboration within our manufacturing sites allow Seqens to accommodate most projects regardless of size and complexity.

Support from A to Z for the production of your API

Our custom drug substance development services include:

• Process and analytical validation
• Kilo-scale, pilot scale and commercial multi-ton cGMP manufacturing •Production in two locations for supply chain security
• Quality control and quality assurance
• Back integration of early intermediates for  supply chain security, cost or quality control
• Process intensification  and second generation processes for cost control
• Regulatory support and filings

Our Technologies

• Cryogenic (-80°C) or very high pressure capabilities
• Special containment for highly potent APIs down to 100 ng/m3
• Hydrogenation (Up to 90 bars and 230°C)
• Multicatalysis including Biocatalysis
• Flow chemistry