Tech Transfer,Process Scale Up and Trouble-shooting

PROCESS DEVELOPMENT

Pharmatech has developed a reliable methodology which integrates compliance, technical, operational and CMC considerations to design and implement processes which can support routine manufacturing and provide a defensible control strategy. Integrating engineering, product design, facility design, sampling and testing considerations together, we have the expertise and framework to establish processes which are well-characterized, and predictable. Our experts have a strong foundation in experimental design and quality-by-design. The results are processes which are reproducible, compliant and capable of supporting the new Stage 1 and Stage 2 requirements of Process validation.

PROCESS SCALE UP AND TECH TRANSFER

Pharmatech has developed proven frameworks for characterizing processes for scale-up and technology transfer. Our methodologies leverage existing operation, compliance and quality management systems to understand the key parameters which drive process validation for legacy products. For new product programs we identify the mechanistic drivers between product design, process variability and ultimately product performance. Using a structured and nimble methodology our technical experts are able to rapidly identify critical parameters and identify product critical quality attributes. With our international experience we have developed and successfully transferred products to Asia intended to be manufactured for the US and European markets. This expertise and experience has provided us the insight necessary to anticipate technical and regulatory issues before they happen, driving down your program risk.

PROCESS TROUBLESHOOTING

Pharmatech’s approach to troubleshooting and optimization is based upon a strong foundation in science coupled with a mechanistic approach to diagnosing non-conformances or process excursions. This approach has the advantage of quickly eliminating potential root causes which have little or no likelihood of causing the excursion. Due to Pharmatech’s deep understanding of your product’s ecosystem, we are able to provide smaller and more focused technical teams that can anticipate and collaborate with your key stakeholders in quality, regulatory, operations and management. We have developed a global reputation for excellence in diagnosing and remediating process issues earning us the moniker as “the Cadillac of process troubleshooting consultants” by our clients.

FACILITY DESIGN

The largest capital investment a life science company is likely to make is in a new facility or campus. Pharmatech has decades of experience in evaluating proposed facility designs against the sometimes contradictory requirements of different regulatory environments. It is this experience that allows us to determine the best possible trade-off decisions to achieve maximum program success. Pharmatech’s design ecosystem is unique, and takes a potential new facility through every component of the drug development lifecycle, touching upon compliance, regulatory, operational, organizational and financial tradeoff analyses.

PROCESS TROUBLESHOOT: A GENERIC SOLID ORAL DOSAGE FORM

OBJECTIVES

Identify root cause and implement process changes within regulatory constraints

Pharmatech will analyze mechanistic drivers of lot failures and design experiments (DOE) to identify root cause of lot failures. Relevant analytical methods will be assessed by Pharmatech for suitability by Measurement System Analysis (MSA). Pharmatech will propose solutions within the constraints of the regulatory environment (CBE 30 or better). Pharmatech will demonstrate the process changes are robust and reproducible.

EXECUTION

Application of process variation analysis, DOE, and MSA

Pharmatech personnel integrated directly with the client’s engineering team. Twice weekly updates were provided by the team to maintain communication with the client’s senior management due to the criticality of the project. Pharmatech identified potential mechanisms for dissolution failures as due to a) coating thickness, b) coating surface area or c) permeability of the coating. Pharmatech implemented improved particle size measurement systems (static image analysis and cross-sectional SEM) to evaluate coating thickness and surface area mechanisms. Pharmatech designed experiments to explore factors, which could impact coating permeability. Process changes were implemented and multiple lots were produced under protocol to show that the process remained robust and reproducible.

RESULTS

Identified raw material and process water impact as root cause

Pharmatech implemented a new particle size measurement system to replace sieve analysis. The root cause as lot variation of coating polymer and process water content leading to variability of the coating permeability. Per Pharmatech recommendations, new coating polymer evaluation procedures were implemented by the client to screen out unsuitable lots. Quantitative Karl Fisher moisture analysis was introduced to replace qualitative method used to determine moisture content of solvents. Pharmatech recommended further process changes to reduce overall variation of dissolution results. Process remains robust and reproducible as further client work continues to improve raw material specifications and performance screening methods for the coating polymer.