A growing list of companies have chosen Pharma 4.0 as the digital transformation roadmap of choice. It was conceived by the International Society for Pharmaceutical Engineering (ISPE) to adapt Industry 4.0 principles to the pharmaceutical industry, with a focus on adopting advanced digital elements and practices into current pharmaceutical quality systems, such as ICH Q10 and ICH Q12.
One of the central requirements underlying this modernization push is the digitalization of technology transfer. Chemistry, manufacturing and controls (CMC) processes produce complex digital data meant to be leveraged cross functionally across many enterprise processes and systems.
In today’s global, extended value chains, complete visibility of information, collaboration and orchestration of both structured and unstructured data across the chain is vital for efficient technology transfer, quick scale-up and speed to market.
Challenges of data complexity and scale
In a conservative and highly regulated industry with famously long product development cycles, pharma manufacturers face mounting tech transfer challenges as the size and complexity of the data, and globalization of the value chain continues to grow. Even in cases where well-defined data standards exist, these standards are not always translated into technology solutions to facilitate efficient internal or external knowledge collaboration and propagation.
Many organizations wrestle with multiple data management systems — such as electronic lab notebooks, laboratory information management systems and product life cycle management systems — that are siloed and don’t talk to one another. These silos of structured, semi-structured and unstructured data impede efficient knowledge transfer and data re-use, breaking what could otherwise be a continuous and leverageable data flow across the organization.
Additional hurdles include manual processes for technology transfer that are time consuming and break down at scale; and insufficient digitalization of information from paper-on-glass artifacts that fail to make critical data elements extractable and reusable. All the while, diverse and multiple digital artifacts must be effectively managed and shared in a secure fashion.
Pharma companies often face difficulty replicating ideal conditions across facilities to maintain product and process consistency. This makes it difficult to meet complex and market specific compliance mandates on product quality, safety and efficacy. A large global product fulfillment environment may have dozens or hundreds of processes and recipe ‘flavors’ to address regional variations in line and equipment configurations, labeling, dose, instructions for use, packaging and more.
To complicate matters further, non-linear scaling typically means certain key process parameters developed in laboratory and pilot production areas will need to be adjusted at scale to maintain consistent critical quality attributes (CQAs) that ensure quality, safety and efficacy. Throughout, embracing Pharma 4.0 requires increased levels of security due to the increased vulnerability of interconnected automated systems that may include an extended network of internal and external partner organizations.
Not surprisingly, the required technology transfer can become quite complex, with constant adjustments in the product and process life cycle across labs and pilot plants that present a huge burden on the extended value chain. Poorly designed technology transfer makes the ramp to production more time-consuming, adds avoidable latencies and is resource-intensive. It’s also more expensive and inefficient, as data assets are siloed and not harvested, aggregated and structured effectively.
Product and process life cycle management is particularly difficult without efficient digital technology transfer. Typical stumbling blocks include manual data identification, collection and aggregation – with paper based and labor-intensive calculations of KPIs; no real time aggregation of materials, process and quality information; and ultimately, no single source of truth across all data management systems.
In response, pharma manufacturers are realizing that streamlining and integrating the flow of data across internal and external architectures and systems is critically important. Processes can be optimized only to the extent organizations can unlock the flow of harvested, shared and reusable data. As they achieve this, companies are increasingly realizing that a more digitalized technology transfer approach can be the foundation for continuous ‘digital thread’ capabilities.
Unlocking the power of digital thread
Digital thread is a seamless flow of data that connects business processes across IT and OT to enable a data-driven record of the performance of your entire value chain – information assets, physical machines, automation and control, manufacturing processes, automation code, maintenance procedures, and more.
These information sources collectively provide visibility into past, present and future states for assets and operations, in essence enabling the creation of digital twin techniques to plan and optimize systems and performance. Supported with robust technology transfer, digital thread brings greater connectivity and transparency; enables faster decision-making; and uncovers more opportunities for process improvements throughout the pharmaceutical product life cycle.
This advanced leverage and reuse of digital data connects your business processes across the organization — from product and process design to operations — all with real-time insights to accelerate innovation and increase quality and efficiency. It facilitates real-time collaboration, drastically reducing the need to email files across the organization and reconcile the inevitable version control issues that go along with that.
Fully optimized digital thread capabilities provide pinpoint control over operations and quality. Such capabilities are especially useful in the critical areas of data integrity, risk mitigation and top line growth. Operational excellence is created by bringing new levels of agility and flexibility to manufacturing that increase workforce productivity and value chain resiliency. This agility with data and technology transfer translates into improved product quality and fewer instances of both planned and unplanned downtime.
Pharmaceutical companies can mitigate risk and futureproof physical and digital investments by leveraging data for robust decision traceability throughout the value chain. This reduces campaign delays and errors in manufacturing process design or implementation. And it contributes to top-line growth by improving product and process design and the ability to respond to shifting market demand and preferences.
In the production context, advanced tech transfer information powered by the digital thread can be used for digital twin simulations to virtually pilot and test line configurations and contemplate process changes. This can decrease market lead time and time to market as organizations find themselves more adept at incorporating changes to business models and unlocking new revenue streams.
Enabling tech transfer capabilities
Enablement of the right technology transfer capabilities is only possible with the proper digital threads underpinning them. Superior technology transfer is the key to accelerating scale-up and ensuring coherent integration of changes or additions to production lines into existing manufacturing, supply chain, quality and regulatory processes. The ability to streamline and enhance data context is especially important. That’s because pharma manufacturing involves highly-regulated and dynamic production environments, where formulas and manufacturing processes evolve over time and may need to adjust with scale.
Nowhere is this more critical than in pharmaceutical and other life sciences manufacturing environments. Pharmaceutical, cell and gene therapy, biotechnology and contract development and manufacturing (CDMO) companies need to securely share knowledge and data flow through their extended value chain networks in order to accelerate product commercialization.
Digital tech transfer helps create secure collaboration with government, academia, research, development and manufacturing network partners. This is achieved using a natural language processing mechanism that understands the documents — the context of the words, the semantics, the grammatical intent — along with a machine-learning algorithm that can understand the intent of each document and convert it to an ISA 88 structured format Essentially, it takes the documents and stitches them together with digital data to come up with a reusable digital data construct your systems can readily ingest.
The right digital technology transfer solution enables robust change control from discovery, clinical and commercial development through internal or external manufacturing. This ensures seamless technology transfer and scale-up, unlocking significant timeline, cost and profitability improvements.
Implementation targets and strategy
Reliable and scalable digital technology transfer capabilities facilitate data reuse, continuous flow of information and real-time insights across the value chain. This helps shorten scale-up time by eliminating tech transfer redundancies and human error. The benefits are being realized in a constantly growing list of use cases, including:
- Network node management
- Control strategy
- Secure product, process and equipment intellectual property
- Data conversion and mapping
- General recipe and transformation for site-specific or market variations
- Process and operations management and planning
- Digital work instructions and SOPs that can provide the content for AR applications
- Product and process change management and synchronization
- Electronic batch record management, publication and analysis
- Digital certificate of analysis creation and submission
- Retrospective Continued Process Verification (CPV) analysis of EBR records
Digital tech transfer solutions should ideally include powerful change management, data governance and exchange mechanisms so that organizations can map their ISA 88 based models and data structures across the entire network. In addition, open technology architecture, standardized data models and digital data reuse will likely be required to enable a continuous digital thread across network boundaries.
Throughout, it’s important to adopt a holistic approach to technology transfer, one that views the process as a continuous improvement life cycle made up of several key phases:
- Plan & collaborate: Define process, operations, equipment classes, critical process parameters (CPP) and document data constructs.
- Map: Map datasets, security access controls and transfer events between trading partners.
- Transfer: Transfer relevant data based on defined events; apply change control on inbound data.
- Ingest: Map internal Digital Knowledge Management system and other solutions (ELN, LIMS, RIMS, etc.) to ingest inbound data.
- Integrate: Propagate data to execution systems (ERP, MES, MOM, etc.); execute changes in digital knowledge management and send instructions to the shop floor.
Chief operating officers, process development engineers and technology operations personnel all benefit from full digitalization of technology transfer and the removal of manual processes. Ideally, all data elements of knowledge assets and documents should be extractable and reusable – regardless of whether the service value chain is primarily within one company or spread across different partners. This greatly enhances efficiency and speeds time to market for process-based life sciences manufacturing companies and their outsourcing networks.
The Return on Investment (ROI) from a successful digital technology transfer implementation is revealed in a myriad of ways. Key benefits to look for include reduced overall cost of internal and external transfers to manufacturing partners; assurance of data integrity; improved closed loop quality by design; and increased labor efficiency of development, manufacturing, quality and regulatory resources.
Further operational gains include reduced latency of facility, line and equipment provisioning and start-up; improved batch quality; reduced scrap and waste; and improved traceability into batch genealogy across products and locations. Meanwhile, faster and more efficient process validation and improved speed to clinical trials and market authorizations help speed regulatory submission and approvals.
Digital tech transfer is for Pharma 4.0
Pharma 4.0 is a promising framework of technology and compliance standards that can transform pharma business models. In effect, Pharma 4.0 lays out a pathway of practical guidance and regulatory best practice to advance Industry 4.0 principles in the pharmaceutical industry. Well-implemented digital technology transfer capabilities in the pharma context enable companies to blend knowledge about materials, process, equipment, control strategy and validation across the spectrum of drug discovery, development and manufacturing.
Advanced digital thread and technology transfer capabilities can help organizations optimize their processes, integrate new manufacturing modalities, enhance digital connectivity and support smart industry systems and advanced analytics. While achieving these outcomes is easier said than done, it’s well worth the ROI as pharma manufacturers learn how better to anticipate and adapt to shifting market trends with increased organizational visibility, flexibility and agility.