EH & S Evaluation:
The product should be evaluated with respect to environmental health and safety, such as handling instructions, personal protective equipment’s and deactivating agents should be determined and made available to every personnel who are making contact with the product. Depending on nature of product, the studies are performed to validate the deactivating agents and procedures. Although it poses additional cost and timing to technology transfer, but it is the first line risk assessment for technology transfer with intending of protecting those who will be producing the product. However during technology transfer the EHS system should be maintain standards across the company.
The EH&S standards to be maintained for the technology transfer are as follows:
Management Systems Standards
These Standards provide the framework for EHS risk management, incorporating many key elements to successful EHS management such as regulatory compliance, risk assessment, communication, self-audit, and senior leadership engagement.
Risk topic standards
This group of documents sets expectations for management and control of many important EHS programs including workplace safety, occupational hygiene, fire and life safety, and environmental impact reduction.
These standards address the key program areas , such as office safety, contractor safety, EHS risks from suppliers of material and services
Raw material specifications:
The raw material may seem like basic element in the manufacturing process but it can often provide most difficulty and unforeseen delays during technology transfer. Within the pharmaceutical industry there is a great emphasis on designing quality into a product by monitoring and controlling what is delivered for manufacture of the product meets the requirements for what is needed for manufacture of the product. However the material standards should meet according to their relevant regulatory bodies, but not to be excessive because this leads to the cost and potentially cause delays for technology transfer while waiting for superfluous testing results.
Analytical Method Transfers
Transfer of analytical methods should accommodate all the analytical testing required to demonstrate compliance of the product to be transferred with the registered specification
Analytical methods used to test pharmaceutical products, starting materials, packaging components and cleaning (residue) samples, if applicable, should be implemented at the testing laboratory before testing of samples for process validation studies is performed
A protocol defining the steps should be prepared for transfer of analytical methods. The analytical methods transfer protocol should include a description of the objective, scope and responsibilities of the specification of materials and methods; the experimental design and acceptance criteria; documentation (including information to be supplied with the results, and report forms to be used, if any); procedure for the handling of deviations; references; signed approval; and details of reference samples (starting materials, intermediates and finished products)
Avoid pit balls during Analytical method transfer:
The exchange of the relevant method information and subsequent compilation of the transfer protocol avoid a lot of foreseeable problems during method transfers. Nevertheless potential mistakes should be reviewed. These include
1) The calculation of the results.
- Calibration standards and correction factors
- Integration parameters(eg: minimum area, threshold, noise)
- Reporting imits, summation or averaging procedures
2) Availability of reagents, samples, and standard material.
3) correct shipment and storage.
4) Equivalent equipment
- Qualification, procedure and acceptance criteria
- Materials and carry over properties
- Temperature ranges
Equipment’s are a critical part of the transfer process. For technology transfer, technical information of products as well as those of manufacturing equipments are important. To establish equipments conforming to GMP, it is essential to obtain and understand information from R&D process so that quality assurance of subject drugs can be secured and the equipments can comply with required conditions for manufacturing. For that purpose, the following technical information should be transferred.
- The R&D department should clarify considerations of GMP compliance specific to subject drugs and manufacturing methods (manufacturing processes), and present them to a facility and equipment department.
- The facility and equipment department should establish facilities and equipments reflecting the above considerations, clearly details of the establishment and operational considerations of those facilities and equipments, and present them to a drug manufacturing department.
- The drug manufacturing department should fully understand the above information, implement validations, perform appropriate operations and controls in conformity to the established facilities and equipments, and records results of operations and controls.
All systems need to be ready before validation batches can be produced. Systems checklist, agreement on acceptance criteria and commercialization, stability plan, agreement on annual revalidation and approval of the transfer report must be complete to move to the Process Validation.
A systems checklist with quality assurance approval provides necessary documentation that was gathered in the transfer. This should include vendor audits, cleaning validation (residual solvents), Melamine requirements addressed, equipment qualification completed with operational ranges. BSE/TSE addressed, specifications and SOP’s approved. Once raw materials and packaging components are released, the transfer final report is approved. With batch records approved, risk analysis complete, and stability protocol approved, Trackwise systems are set up. Documented evidence of all required systems is placed in a file. This file is then reviewed by QA prior to signature of the Validation protocol.
The decision to commercialize validation batches is made by senior leadership based on a modified risk assessment. Included in the commercialization risk assessment are a review of the product trending report, a review of the process gap assessment and discussions with regulatory. The commercialization strategy also needs to meet the January 2011 FDA guidance for product commercialization.
The stability protocol includes stability requirements for each of the countries the product will be marketed. This may require rental of stability chambers or space in stability chambers for years as the diverse stability requirements are reviewed. The stability protocol may also include expectations for product stability results in relation to commercialization. Looking ahead, planning needs to include agreement on annual revalidation and filing activities.
Execution of the validation plan needs to follow the agreed plan. Typically a daily update meeting will be held to provide updates from the previous day’s activities and ensure all systems are a go for the daily activities. The validation team needs to act accordingly when issues occur. All deviations from the plan must be clearly identified and tracked for root cause analysis. System controls are intended to cover normal operations, external events need to be handled with facility policies and be included in the validation final report.
Hundreds of GMPdocuments are required for process transfers. The Code of Federal Regulations provides a listing of expected documentation including:
- raw material and component documentation
- batch records
- laboratory records
- distribution records
A complete list can be developed utilizing the process maps (see Gate 4) and standard documentation sets.Once the list is made, divide the documents into groups.Remember raw materials documents will probably be required first, but finished product testing protocols often require finished goods test procedures to be validated prior to accepting the product. The project schedule should provide insight into when documents will be required.
The quickest way to complete the transfer is to reformat records from the sending site, but this practice often leads to non-conformances and issues because there is a lack of understanding content and history. Each document needs to be built with the foundation process map identified in Gate 4 and utilizing Subject Matter Experts (SME) identified as part ofGate 2.The control of the critical process parameters (CPP) must be understood and the control strategy needs to be included in the documentation to ensure product attributes are achieved.
Agreement on terminology and format with quality and regulatory units helps ensure standardized documentation, which allows employees to follow repeatable processes.Each document should have a dry run with personnel who have not been exposed to the process, the related SME and a documentation author (if necessary).Pictures often help, but authors need to be mindful of what is in the background. For example, I once had a formulation tank CIPprocedure written with pictures taken in the tank manufacturer’s parking lot. Finally a document review team is formed with appropriate representation to ensure content is consistent with expectations.Often document reviewers lack the process understanding to assess technical details but can provide oversight for other requirements.The documentation tracking sheet should monitor status and escalation needs to occur if a maximum of two revision cycles is not achieved.
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