Technology transfer in the pharmaceutical sector is among the most significant and intricate stages of the product life cycle. It connects drug development with commercialized manufacturing by helping to ensure that all knowledge, process parameters and quality standards from R&D are replicated with precision and consistency at manufacturing scale.
The successful completion of a technology transfer will allow the new manufacturing site to produce the drug efficiently, safely and in compliance with all current Good Manufacturing Practice (cGMP) and other applicable local regulations. On the other hand, if a technology transfer isn't executed properly it can create major delays, produce quality problems or lead to a product recall.
The purpose of this article is to identify the components, phases and best practices involved in a successful technology transfer within the pharmaceutical sector.
Additionally, there are other considerations when transferring;
Ultimately, the outcome of the process should be reproducible; that is, that the receiving organisation is capable of consistently producing products that meet all applicable Quality, Safety and Efficacy requirements.
1. Commercial Readiness: Preparedness for production increases while maintaining product quality.
2. Regulatory Compliance: Evidence of an organization’s understanding of and control over its processes, as required by the FDA, EMA, WHO etc.
3. Operational Efficiency: Loss of key field data between the research and production teams is minimized.
4. Cost Savings: Production ‘batch’ failures, deviations and rework are minimized during production expansion.
5. Business Continuity: When transferring production from one site/company to another or from one contract manufacturer to another, the production can proceed without interruption during the transfer process.
A successful technology transfer is more than just transferring materials; rather it is a joint partnership process based on data and documentation and scientific rationale.
The Technology Transfer Plan will be prepared and approved, resulting in a written agreement between the sending and receiving organisations defining how and when the transfer will occur.
The sending unit is expected to deliver complete organized and structured knowledge packages which must include:
The steps for this stage/phase may consist of, but are not limited to:
The data generated as a result of these runs is to be used as the basis for subsequent process validation, along with any regulatory submissions.
Analytical Method Transfer typically consists of the following steps:
1) Familiarity with and verification of the method
2) Comparative testing between the sending and receiving laboratories
3) Validation of the analytical methods using the five parameters of accuracy, precision, linearity, robustness and usefulness.
Regulatory agencies expect that Analytical Method Transfers are conducted in accordance with ICH Q2(R2) to ensure that the data is reliable.
The results of process validation supports regulatory submission of the product's New Drug Application (NDA), Abbreviated New Drug Application (ANDA) and variations post-approval and inclusion of the new site or process within the product license.
Joint oversight bodies (Governance Team or Transfer Committee) should be created by both parties to track progress, problem resolution and ensure that both parties are aligned.
Standardized documentation for all technology transfer activities should be utilized across both parties. The following standard templates are recommended:
This verification includes:
Properly developed training programs will provide a thorough understanding of:
1) Review and approve all changes
2) Document and investigate any deviations or non-conformance from the established standard
3) Verify that CAPAs have been enacted and are operational.
1. Lack of documentation leading to an incomplete transfer of knowledge.
2. Equipment differences or difference in scale causing the need for optimization again.
3. Potential variability among raw materials/excipients from different supply sources.
4. Gaps in communication between R&D and manufacturing.
5. Delays from waiting on necessary validation data prior to obtaining acceptance from regulators.
2. Use of consistent templates and/or checklists.
3. Open communication and utilize real-time collaboration tools.
4. Involve the regulatory team early in the transfer process.
QbD establishes an understanding of:
1. Identifying Critical Quality Attributes (CQA’s) as early as possible.
2. Defining Design Space and Control Strategy.
3. Using Design of Experiments (DoE) to optimize all relevant inputs in order to improve output quality.
Thus, providing more reproducibility as well as confidence from a regulatory perspective by transferring not only the process to replicate an optimum product but also the scientific rationale behind how the process is developed.
This includes ongoing development of the technology transfer process through:
The transfer of technology in the pharmaceutical industry is a vital connection between developing new drugs/therapeutics through research and providing patients with those products. To do this successfully, you need a careful plan, work with a lot of different people and disciplines and have a high level of scientific diligence.
Success in technology transfer means guaranteeing that the new site can manufacture the intended product with the same quality as intended and the same process performance; all while being safe, with efficiency and with compliance.
By concentrating on having clear and concise documentation, risk management activities, equipment readiness checks and sharing knowledge, companies are able to turn technology transfer from simply a regulatory requirement into an opportunity for a competitive edge.
In today's pharmaceutical industry where both time to market and product quality are the most important factors, perfecting the ability to transfer technology will yield not only regulatory approval but also excellence in operations and continual success!
The purpose of this article is to identify the components, phases and best practices involved in a successful technology transfer within the pharmaceutical sector.
What Is Technology Transfer?
Technology transfer is a methodical procedure for passing along product or process technology from one point in a product lifecycle to another (usually from R&D sending to manufacturing receiving).Additionally, there are other considerations when transferring;
- Moving from one location or company to another (e.g. Co-Manufacturing Organizations).
- Changing sizes (pilot production to commercial production).
- Moving analytical methods/formulations/packaging/testing method.
Ultimately, the outcome of the process should be reproducible; that is, that the receiving organisation is capable of consistently producing products that meet all applicable Quality, Safety and Efficacy requirements.
Significance of Technology Transfer
Through a planned transfer of technology, several crucial end results can be accomplished, including:1. Commercial Readiness: Preparedness for production increases while maintaining product quality.
2. Regulatory Compliance: Evidence of an organization’s understanding of and control over its processes, as required by the FDA, EMA, WHO etc.
3. Operational Efficiency: Loss of key field data between the research and production teams is minimized.
4. Cost Savings: Production ‘batch’ failures, deviations and rework are minimized during production expansion.
5. Business Continuity: When transferring production from one site/company to another or from one contract manufacturer to another, the production can proceed without interruption during the transfer process.
A successful technology transfer is more than just transferring materials; rather it is a joint partnership process based on data and documentation and scientific rationale.
Significant Steps in Transferring Technologies
A methodical, systematic approach is key to providing a structured transfer with nothing left to chance throughout the transfer operation. The overall process may be divided into five principal stages:A. Planning & Assessment (the first stage in the technology transfer operation)
Objectives- Define the limits and the strategy of the transfer.
- Identify the stakeholders in R&D, manufacturing, quality and regulatory groups.
- Develop the time frame and responsibilities for the transfer and create a list of the criteria necessary for determining transfer success.
- Conduct feasibility studies that can be used to assess the abilities of the receiving site location (e.g. equipment, facilities and utilities).
- Assess the differences between the development environment and the production environment by conducting a gap assessment.
- Create a written Technology Transfer Plan (TTP) which will include a detailed description of the deliverables, an assessment of the risks and the milestones.
The Technology Transfer Plan will be prepared and approved, resulting in a written agreement between the sending and receiving organisations defining how and when the transfer will occur.
B. Knowledge Transfer and Documentation
For any successful effort related to technology transfer, comprehensive documentation is critical.The sending unit is expected to deliver complete organized and structured knowledge packages which must include:
- Description of analytical test methods used; all validation data associated with these analytical test methods.
- Specifications for raw materials, intermediates and finished product.
- Listing of all necessary equipment and calibration procedures and cleaning procedures for that equipment.
- Listing of all requirements for environment, health and safety.
C. Transfer of Process and Scale Up
This stage or phase consists of replicating the processes physically at the receiving unit using the knowledge that has been transferred.The steps for this stage/phase may consist of, but are not limited to:
- Mapping and qualification of equipment.
- Pilot or engineering batches to be run to identify any challenges associated with scaling.
- Adjusting any process parameter(s) as necessary to account for differences in equipment and/or differences in site.
- Optimizing raw materials to remain in compliance with required Product Quality Attributes (CQAs).
The data generated as a result of these runs is to be used as the basis for subsequent process validation, along with any regulatory submissions.
D. Analytical Method Transfer
Analytical Method Transfer (AMT) is the transfer and validation of analytical methods from one laboratory to another. In order to verify test results are reliable, it is necessary for laboratories that are receiving an analytical method to continue to validate that method in accordance with ICH Q2(R2).Analytical Method Transfer typically consists of the following steps:
1) Familiarity with and verification of the method
2) Comparative testing between the sending and receiving laboratories
3) Validation of the analytical methods using the five parameters of accuracy, precision, linearity, robustness and usefulness.
Regulatory agencies expect that Analytical Method Transfers are conducted in accordance with ICH Q2(R2) to ensure that the data is reliable.
E. Process Validation and Regulatory Submission
Process validation is quality assurance for process performance and compliance after completing analytical method transfer through the analytical method validation process and is used to verify this by the successful manufacture of three consecutive validation batches under normal operating conditions. In addition, the receiving laboratory must demonstrate that it meets established specifications and quality targets for the product; and all documentation supporting the process validation criteria must be kept for review and audit purposes.The results of process validation supports regulatory submission of the product's New Drug Application (NDA), Abbreviated New Drug Application (ANDA) and variations post-approval and inclusion of the new site or process within the product license.
Fundamental Factors Leading to Success in Technology Transfers
Technology transfer success or failure is heavily influenced by multiple Critical Success Factors (CSFs).A. Open Communication and Cooperation
Open channels of communication and frequent interaction between both transfer partners throughout the project is necessary to facilitate successful completion. Frequent meetings, sharing the status of activities and an established platform for content exchange will help to eliminate communication errors.Joint oversight bodies (Governance Team or Transfer Committee) should be created by both parties to track progress, problem resolution and ensure that both parties are aligned.
B. Comprehensive Documentation
All documentation associated with transferring technology must be compiled accurately, systematically and in accordance with ALCOA principles to ensure its integrity. Lack of documentation and/or incomplete documentation accounts for the majority of delays and deviations.Standardized documentation for all technology transfer activities should be utilized across both parties. The following standard templates are recommended:
- Technology Transfer Protocols (TTP).
- Batch Records.
- Equipment Qualification Report (EQR).
- Analytical Method Transfer Report (AMTR).
C. Comprehensive Risk Management Plan
Proactive risk management enables proactive problem resolution. Proactive risk management includes identifying all potential failure points in the transfer process (prior to occurrences) using various tools to assess risks based on probability and/or consequences. Tools used for risk assessment include:- FMEA - Failure Mode and Effects Analysis
- Ishikawa (Fishbone) Diagram
- Risk Matrix
D. Readiness of Equipment and Facilities
The recipient organisation will verify that the equipment and facilities being delivered are capable of supporting all operations of the previously supporting entity with respect to both the equipment and facilities required to support equipment operation.This verification includes:
- Checking capacity and identifying all equipment on site at the service provider's facility.
- Validating the qualification of all required equipment (IQ/OQ/PQ).
- Verifying utility services (heating/cooling, Pure Water; Compressed Air).
E. Development of Training and Competency
Staff at the new site should be provided with appropriate training on the new processes and analytical methodologies being implemented.Properly developed training programs will provide a thorough understanding of:
- Process Controls and Critical Process Indicators
- Requirement for GMP Documentation
- Requirements for Safety and Environmental Procedures
F. Management of change and quality monitoring
All changes made during the transition, for example modification of equipment or processes, should to be managed by a formally established Change Control System. QA should:1) Review and approve all changes
2) Document and investigate any deviations or non-conformance from the established standard
3) Verify that CAPAs have been enacted and are operational.
G. Effective Project Management
The overall timeline of the transfer process should be monitored by a specific individual who is responsible for project management (this may be an individual or cross-functional team), responsible for coordinating project activities and ensuring that the project is delivered on-time. Notable responsibilities for the project management include:- Monitoring important timelines/milestones and deliverables.
- Management of all necessary resources and budgets.
- Maintain readiness of all regulatory documentation.
Common Challenges for Technology Transfer
Even with meticulous preparation, there are potential challenges around the technology transfer process:1. Lack of documentation leading to an incomplete transfer of knowledge.
2. Equipment differences or difference in scale causing the need for optimization again.
3. Potential variability among raw materials/excipients from different supply sources.
4. Gaps in communication between R&D and manufacturing.
5. Delays from waiting on necessary validation data prior to obtaining acceptance from regulators.
Possible solutions
1. Running pilot lots to find and address potential scale-up difficulties early.2. Use of consistent templates and/or checklists.
3. Open communication and utilize real-time collaboration tools.
4. Involve the regulatory team early in the transfer process.
The role of Quality by Design (QbD) in Technology Transfer
By applying QbD principles early in the technology transfer process, QbD provides an increase in the strength of the overall transfer process since it provides scientific understanding (or rationale) behind decisions made during the transfer process. This sounds simplistic, but it is indeed profound.QbD establishes an understanding of:
1. Identifying Critical Quality Attributes (CQA’s) as early as possible.
2. Defining Design Space and Control Strategy.
3. Using Design of Experiments (DoE) to optimize all relevant inputs in order to improve output quality.
Thus, providing more reproducibility as well as confidence from a regulatory perspective by transferring not only the process to replicate an optimum product but also the scientific rationale behind how the process is developed.
Continuous Review and Improvement of the Technology Transfer
Once the first batch of the product has been manufactured to market, technological transfers will still require evaluation and enhancement. Ongoing evaluations will ensure that the processes will maintain strength and reliability over the life of the product.This includes ongoing development of the technology transfer process through:
- Reviewing historical and current production data to assess trends.
- Reviewing any instances of deviation, number of complaints registered or out-of-specification results.
- Conducting periodic facility audits of the location where product is manufactured.
- If applicable, updating standard operating procedures and validation documents.
The transfer of technology in the pharmaceutical industry is a vital connection between developing new drugs/therapeutics through research and providing patients with those products. To do this successfully, you need a careful plan, work with a lot of different people and disciplines and have a high level of scientific diligence.
Success in technology transfer means guaranteeing that the new site can manufacture the intended product with the same quality as intended and the same process performance; all while being safe, with efficiency and with compliance.
By concentrating on having clear and concise documentation, risk management activities, equipment readiness checks and sharing knowledge, companies are able to turn technology transfer from simply a regulatory requirement into an opportunity for a competitive edge.
In today's pharmaceutical industry where both time to market and product quality are the most important factors, perfecting the ability to transfer technology will yield not only regulatory approval but also excellence in operations and continual success!
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