Process R&D and cGMAP Manufacturing

Process R&D and cGMAP Manufacturing

Mascot has comprehensive process R&D (PRD) and cGMP manufacturing capabilities to support the CMC campaigns of NCE programs. Our PRD capabilities comprises of process development & engineering, process analytical, hazard evaluation and risk assessment of processes from the laboratory to the plant scale.

Mascot follows a phase appropriate process development strategy to support the various stages of drug development. The team consists of experienced process chemists, engineers, process analysts and process safety professionals.

Mascot has state-of-the-art multiple cGMP capabilities to support the in pre-clinical and clinical stages of drug development. Our facilities have cGMP certification from DCGI and have been successfully audited for quality & safety by US, Japan, EU and Indian clients. Mascot’s facilities are highly versatile and flexible to accommodate variety of process needs in terms of operating parameters, size and type of process equipments.

These various services can be offered by Mascot as standalone basis or as end-to-end package.

Our PRD capabilities are detailed below.

Mascot has significant expertise in route scouting for identifying the most promising route for investigational APIs/ NCEs, advanced intermediates, key RMs and specialty molecules. This exercise is often done by a desk research followed by laboratory experiments to screen various routes, reagents and conditions.

Mascot has the expertise, facility and capability to perform state-of-the art process design and optimization studies. These studies are conducted by following statistical methodologies like software based design of experiments and other data analysis tools on a case to case basis.

The process design and optimization study is conducted to support the various stages of the drug development program and the development attributes depend on the phase of the study. In general, the objective is to come up with a safe, scalable and cost effective process to deliver the quality attributes required for the development phase considering the regulatory and environmental aspects.

Mascot has a well-established process engineering team to support the process research and development team and perform the following studies on need basis:

Software based DoE studies
Software based decomposition studies
Kinetic studies
Mass and energy balance studies
Corrosion studies
Filtration studies
Distillation studies: regular and packed columns
Crystallization studies
Scale-up/scale-down studies
Particle engineering studies

Mascot follows a tiered approach for the polymorph screening studies. We identify the various forms possible for a substance. We also identify the thermodynamically most stable form and the process to prepare the most stable form.

Mascot follows a systematic approach for the hazard identification and risk assessment of the processes prior to the scale up. This exercise is done at the development stage and the process is subjected to a process hazard assessment checklist followed by brainstorming sessions. Based on these sessions, the requirement of thermo chemical evaluation by DSC or RC1 is identified and evaluated. Up on thermo chemical evaluation, the process is modified further to make it a safer process.

The various aspects considered for the process hazard identification and risk assessment are:
Basic chemistry
MSDS of chemicals involved
Reaction/addition sequence
Thermo chemical calculations

Mascot has significant expertise in the development of flow processes as an alternate reaction methodology to alter the reaction pathway, increase the throughout or to develop an inherently safer process. The specific expertise at Mascot is the design and fabrication of laboratory scale flow equipment for development purpose. Mascot has capabilities to operate reactions in PFR and CSTR modes.

We have high-end flow processing equipments which include:
Reactor sizes ranging from 300 ml to 800 ml (holdup volumes)
Pumps for flow rates from 0.02 ml/min to 120 ml/min
High pressure, high temperature fittings
Corrosion free flow paths available through use of relevant materials
Temperature control thermostats for operation from – 20 °C to 200 °C
Throughput rates of up to 100 gm/ day product demonstrated

Mascot’s technology transfer of the first time scale up for the processes developed in the lab to the plant is done through a cross functional team. The cross functional team co-ordinates the requirements for the technology transfer and scale up with appropriate documentation.

Our cGMP offerings include:
Supply of material to support pre-clinical tox studies and clinical trials)
Process validation including hold time study and stability studies
Regulatory filing, CMC ,DMFs, CEPs, MRPs, DCPs and Dossiers
Exclusive commercial manufacturing
Chromatographic purification/separation
Manufacturing of High Potency Active Pharmaceutical Ingredients
Exclusive manufacturing of intermediates and other chemicals

Mascot has capabilities to take up HPLC purification/ separation by using Novasep systems and other systems both in normal phase as well as in reverse phase in a classified area.

Mascot provides manufacturing services of high potent compounds in oncology therapeutic area which represents one of the fastest growing segments of the pharmaceutical and biotechnology industry as well as for other therapeutic applications. This exclusive facility has capabilities to handle compounds up to an OEL limit of < 0.1µg/ m³-8h (TWA).

Mascot has exclusive capabilities for commercial manufacturing and expanding its current capacities to cater to growing demands. The first phase of expansion will have reactors up to 5000 L capacity and will be ready by mid-2013. The second phase of this expansion will have reactors of larger capacities and more numbers to maximise the benefit & efficiency of scale of operation.

Mascot has capabilities to support regulatory filing. Our regulatory team has experience in filing DMFs and dossiers to regulatory markets and ROW markets on behalf of the clients.

Mascot’s combined PRD and cGMP capabilities ensure seamless execution of CMC projects in a timely manner to advance the R & D programs into the clinical phase in a cost effective manner.