Every technical (tech) transfer is different, with companies taking different paths toward reaching their goal. Each one presents a unique set of challenges, which are most often technical, but at times may also be business related. However, all donors (outsourcing partners) and recipients (contract manufacturers) have the same overall goal — to achieve a quick, efficient transfer of process and knowledge that meets all necessary quality and regulatory requirements.
Alkermes Contract Pharma Services engages with a diverse range of donor partners on contract manufacturing. From internal transfers within Alkermes’ own development pipeline, to specialty companies with one key product in their pipeline requiring transfer, to “Big Pharma” where any individual tech transfer is one of a large portfolio of diverse transfers taking place at one time. We have found that donor companies have differing approaches to tech transfer, ranging from those who wish to be involved in every step of the process, to those who take a much more hands-off approach. Our approach is to fulfil each of their specific needs and satisfy their requirements as effectively as possible.
To help drive the tech transfer of partner products, Alkermes sought to develop a risk assessment framework that involved both the donor company and our transfer team in jointly assessing the tech transfer risks, which would address not just the usual technical challenges but also, where appropriate, the business challenges.
User Requirements for a Joint Risk Assessment Framework
The user requirements in the development of this framework were defined as follows:
- The framework had to meet regulatory guidelines on process transfer and development (ICH Q8) and follow the industry direction on risk-based process development/ transfer.
- The framework had to be effective and efficient, contributing to a quick and effective transfer.
- The framework had to be easy to use, avoiding long, bureaucratic processes and facilitating easy participation for the partner.
The aim of the joint risk assessment process was to provide a framework with the following outputs:
- Provide Alkermes and the donor with a strong, combined assessment of the risks inherent in the tech transfer.
- Identify any potential gaps or unacceptable risks in the tech transfer plan and facilitate risk mitigation/elimination.
- Identify scope of engineering studies required (if any).
- Identify any risks that may remain open on moving into the upstream stages of the transfer including clinical supply, registration, process validation, and eventually, commercial supply.
- Clarify the owner of each risk, ensuring that both sides are aware of and are in agreement on the risks.
Meeting Regulatory Requirements
As covered in the ICH Q8 Pharmaceutical Development Guidelines, the core source document for the risk assessment process is the Quality Target Product Profile. In many tech transfers, this profile is communicated to the receiving site via the donor site product quality specifications. This document identifies the Critical Quality Attributes (CQA) of the process to be transferred.
All risks assessed as part of the risk assessment are examined for their impact against the product CQAs. As the success of a tech transfer is measured not only by the quality of the product produced, but also by the efficiency of the process, each risk is also assessed against Key Manufacturability Attributes (KMAs) such as process repeatability and robustness.
Making the Framework Effective
The approach taken by Alkermes is a Quality Risk Management approach based on proven standard risk assessment tools. First the risks are identified via brainstorming. The risks are then analyzed and evaluated via a risk ranking process and the use of Failure Mode, Effects and Criticality Analysis (FMECA). As part of this process, the joint team (of donor and recipient members) starts to consider the controls that should be put in place or the additional data and/or studies required to mitigate the risks identified.
Before starting to risk assess, two critical pieces of the puzzle must be in place:
- The correct team must be assembled, comprising the technical, quality, validation and, if necessary, regulatory personnel, from both the donor and recipient sites. It is vital that these are the personnel who will be responsible for the activities throughout the tech transfer and on into clinical and/or commercial supply. All team members must be present from the start of the process.
- The structure and approach of the joint risk assessment must be agreed upon with the donor in advance. This includes the agreement of all definitions, e.g., assumptions, boundaries, high-risk ranking, critical severity, remote possibility, etc. Clear, unambiguous definition of these terms at the outset will greatly aid the efficiency of the process throughout.
Making the Framework Easy to Use
To enhance the ease of use of the joint risk assessment framework, some sub-processes were added on to classic Quality Risk Management tools.
Initially brainstorming and risk-ranking processes are performed with only the recipient team present. All risks that are suggested are included in the listing process and progressed for ranking. The risk-ranking process assesses whether the risk identified can directly impact a CQA or KMA.
By completing this portion with the recipient team first, the donor team is not required to sit through the initial debates on ranking. The provisionally ranked listing is then presented to the donor, and the donor’s input is managed by exception, i.e., the joint team only debates any rankings with which the donor does not agree. Using this approach, we typically find that the joint risk-ranking process can be completed within one working day, even for complex multi-unit operations. Our experience also indicates that this meeting should, where possible, be conducted face-to-face and attended by the full team on both sides. At this early stage, full participation is invaluable to building an understanding of each other’s systems and approaches.