Assessment of chemical Development
1.Assessment of existing technology w.r.t synthetic route( of yours) , manufacturing capabilities, analytical methods, in-process controls, product characterization and safety implications, process hazards and their impact on environment.
2. Identification of gaps in knowledge related to the synthesis and product characterization and the gaps need to be bridged for successful scale up and manufacturing APIs.
3. Assessment also indicates type of work needs to be done with ref. to Equipment techniques or facilities required.
Manufacturing of APIs
Process optimization is different aspect for laboratory trail programs compared with programs that are entering validation and commercial scale.
1. For an API that will be entering into lab trails, the key objective is usually to rapidly develop a process that can safely yield the required API with the necessary quality attributes. As the program advances toward validation and commercial launch, greater emphasis is placed on improving yield and gaining greater process understanding to support process validation and eventual launch.
2. We then optimize the process to reliably and safely generate API in adequate quality. This objective is achieved by building process understanding through many techniques, including impurity origin and control, identifying critical parameters, and setting appropriate limits on operating ranges.
3. During the final phase of optimization, experimentation is performed to determine if the API can consistently be manufactured with the required critical quality attributes. Statistical design of experiments is a particularly useful technique for these studies, because interdependent variables can readily be identified.
4. The successful completion of these phase-appropriate process optimization efforts enables us to deliver high-quality clinical batches and commercial supply in a timely manner, which is important for customers.
Analytical and Quality Assurance
To understand the process dynamics in continuous manufacturing,
1. How the process parameter variability will affect the critical quality attributes (CQA) of product
2. How predetermined changes in process parameters and material attributes will influence the outcome of the continuous step. “Capturing this information requires analytical technologies that can output in real-time the data of interest (either directly or via prediction). As a result, data is required by conducting experiments for determining residence time distribution, building kinetic models, or executing design of experiment approaches through QbD/PAT techniques.
3. Effective process analytical technology (PAT) for online monitoring during research, development, and commercial manufacturing is therefore essential. PAT can be used for many different objectives, including reaction/process characterization, process development, and long-term, robust installations.
4. IPC&PGTI (Potential genotoxic impurities) review. In-process controls (IPC) monitors impurity formation while reaction is in progress (QbA) whereas genotoxic impurities formation is not only during reaction but also may form while carrying out unit operations of the product in lower limits.
The current regulatory environment supports advancing regulatory science and innovation, which may include abandoning some traditional manufacturing practices in favour of cleaner, more flexible, and more efficient continuous manufacturing.
Regulatory authorities are encouraging the industry to adopt new technology as supported by ICH Q8(R2), Q9, Q10, and Q11; and the introduction of quality-by-design (QbD) concepts, emphasizing science and risk free-based approaches to assure product quality.
The regulatory expectations for assurance of reliable and predictive processing, which is technically sound, risk free-based, and relevant to product quality in a commercial setting, are the same for batch and continuous processing.
Quality Management System and Regulatory Compliance Management
A quality management system (QMS) is a collection of business processes focussed on achieving quality policy and quality objectives to meet customer requirements. It is expressed as the organisational structure, policies, procedures, processes and resources needed to implement quality management as per regulatory requirement.
1. SOP management
2. Regulatory submission management
3. eCTD management
4. CAPA management
5. Change control
6. Deviation management
7. Complaints management
8. Audit management
9. Learning management and training
Supply Chain & Manufacturing Strategic management
From 2005-2015, Indian generic market grew at the rate of 18% and exports reached to 20% of global exports by volume. By 2020, India is expected to capture 6-7% of $760 billion global generic market and now Indian market stands at $30 billion with the highest number of FDA approved plants outside of USA, which indicates that Indian companies play a pivotal role both locally and globally. The landscape has become more complex with interplay of factors even with established players. In addition to GST regime to influence the sourcing, manufacturing and distribution with particular impact in transportation and warehousing. Even though companies are looking for next phase of growth, but there is significant gap between the strategic vision and operational reality.
Products have proliferated exponentially and become more complicated due to patient’s growing therapeutic needs. Fragmentation at every stage of the value chain is a direct hit on Supply chain efficiency. Quality issues and price pressures have spiralled across the value chain, triggered by more regulatory scrutiny. Hence Pharma Supply chains now face a greater pressure to enhance their performance to prepare for future growth with competitive edge.
To assess the state of India’s end to end pharma supply chain which caters to local and global markets and to identify requirements for the future, to be addressed the following.
• Current state of India’s vs global pharma supply chain
• Supply chain challenges
• Competitive edge by using supply chain