Pre Clinical Assessment

InViva provides strategic advice to clients on the activities required for the pre-clinical or non-clinical development stage. InViva helps to design and implement systems and processes to significantly enhance client product development timelines. This typically includes:

• Development and training in QA systems
• Preparation of documentation – SOPs, reports, licence sections, protocols, Master Validation Plans, etc.
• Planning and implementing technology transfer
• Process development
• Programme and project management

Technology Transfer refers to the process of transferring all, or part of a manufacturing process from one location to another, or from a technology developer of to a commercial partner. A key goal is that the performance and outputs must remain unchanged, particularly when transferring registered products between sites and locations.

Often technology transfer is a result of scaling-up or rolling out to multiple locations following mergers and acquisitions, as a part of the product’s clinical development and product commercialisation activities, or as activities are relocated within the same site.

How technology transfer takes place

For technology transfer to take place, several legal and commercial processes and documents need to be addressed, including:

• Provision of confidentiality and commercial agreements

• Material transfer agreement

• Deed of assignment

• License agreement

Succeeding in technology transfer

The success of technology transfer depends on the provision of information and data by the “sending location” to the “receiving location”. The information required is recoded and submitted in module 3 of a CTD, but at a greater level of detail and volume, including:

• Equipment specification (DQ, IQ, OQ, PQ) and operating ranges

• Manufacturing process steps/ stages / specifications (manufacturing Instructions)

• Validation Master Plans (VMP) and Validation Reports

• Raw materials suppliers, specifications, and storage / use conditions

• Analytical test methods, equipment used, and specifications

• Training materials

Meeting with the regulatory agencies is advised to discuss any specific requirements and to identify the relevant regulatory framework to be used for the registration of the technology transfer. This may include simple license variations and supplements, through to comparability and equivalence protocols. Acceptance criteria for individual parts of the technology transfer, as well as the overall success measures, should be agreed in advance.

How InViva can help with technology transfer

InViva has managed many technology transfers involving both pharmaceutical and biopharmaceutical products. InViva has also successfully presented several comparability and equivalence protocols to obtain regulatory approvals without the need for bridging clinical studies.

While each technology transfer has its own unique requirements, InViva has developed and published a robust set of criteria that can be used as a framework and template for transfer.

Validation Master Plans (VMPs) are an integral part of the documentation required for process development and validation.

Validation documents are used to systematically and accurately record the controlled operating limits of manufacturing processes. Validation can also be used to support any subsequent changes to a manufacturing process, demonstrate equivalence, track process development, and scale-up.

The library of validation documentation that pharmaceutical companies are required to complete and maintain is extensive and can include:

• Validation Master Plan and Individual Validation Plans (for methods, process, equipment, facilities, utilities, cleaning, etc.)

• Validation protocols including DQ, IQ, OQ and PQ

• Process development reports and Technical reports

A Validation Master Plan (VMP) documents the way a manufacturer will operate, who has control over various aspects of the validation activities, and how key activities such as production, quality assurance, quality control and personnel management will be directed.

A VMP provides the guidance for performing the appropriate validation process of systems, equipment and analytical methods and whilst not a mandatory document, it is generally requested (and expected), and viewed favourably during audits and inspections.

How InViva can help with Validation Master Plans (VMPs)

InViva works with clients to develop clearly defined process development and Validation Plans to deliver product development progress in line with corporate goals. InViva also provides qualified “man in the plant services” to ensure that third party contract manufacturers follow client plans fully.

Quality management systems (QMS) form the backbone of any commercial pharmaceutical or healthcare product. QMS comprises quality assurance (QA) and quality control (QC), working together to enable the testing, release, and sale of a commercial product. Regulatory agencies require a full GMP compliant system to be in place by the time phase III clinical trials are conducted.

Quality Systems are developed in phases throughout the pharmaceutical and clinical development process. During the early stages both the process and product are anticipated to rapidly change so benefit from less restrictive controls ahead of clinical studies.

Phases of clinical trials

Phase I clinical trials see fewer changes, however, the process and the product will not be completely defined, even at this stage and so only a small percentage of the overall quality system is required.

For phase II clinical trials expectations grow with the implantation of additional control measures, and for phase III a full GMP compliant quality system should be in place prior to licence submission and product approval.

 

The keys elements covered by a typical GMP QMS are depicted here:

 

The Quality Assurance (QA) department has oversight and responsibility for all control points during the manufacturing of a product throughout the pre-clinical/non-clinical, clinical, and commercial stages.

QA is responsible for overseeing the preparation of detailed procedures for all of the manufacturer’s operations, ensures compliance with regulations and internal written procedures, and is responsible for developing and tracking all documents within the quality system, including (but not limited to):

• Standard Operating Procedures (SOPs)

• Official forms, technical reports

• Validation plans, protocols and reports

• Batch Manufacturing Records (BMRs)

• OOS, deviations and discrepancies 

Qualified Person (QP)

The Qualified Person (QP) is responsible for managing and implementing a drug manufacturer’s core quality systems and ensuring compliance to cGMP and ICH standards. The QP has the “final word” on the release of raw materials, intermediates and final product.

The QP’ responsibilities consist of maintaining adherence with a range of processes and departments, including:

• Change control               Deviations and OOS investigations

• Training           Validation      Documentation               Auditing

• Clinical trials      Technology transfer   Raw materials          Product release

• Manufacturing       Customer complaints         Engineering              Marketing

Quality Control (QC)

Quality control is responsible for implementing many of the tests and measures to ensure product quality and safety throughout product development and commercialisations. This includes:

• QC testing (raw materials, in-process controls, and release testing)

• Stability testing (accelerated and real time)

• Investigative testing (following, for example, OOS and failures)

• QC activities must always be in compliance with cGMP and ICH standards

How InViva can help with Quality Systems (QS)

InViva provides QS support in several ways by supporting the development of new systems as well as evaluating existing systems in line with the stage of development and the resources available.

The team at InViva utilises its knowledge and expertise to ensure the most appropriate recommendations are made. We also help manufacturers to develop quality systems timelines which include an overall Validation Master Plan and determine the level of external support and assistance required to develop and implement a full Quality System.