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The author reviews some of the key considerations when selecting a vendor and crucial parameters that must be defined in the tech-transfer process to ensure the greatest chance of success.
For a company looking for an outsourcing partner for pharmaceutical manufacturing, the choice is vast: from companies offering solely contract manufacturing capabilities, to those with niche technologies to assist development, or even ones with specific experience in certain dosage forms. Choosing the right partner could be based on the individual project’s requirements, be it specialist handling requirements or a bespoke technology need; or it could be because the outsourcing partner has preferred status. Whatever the reasons, a successful transfer of technology is a vital element.
The decision on how and where a new product will be manufactured needs to be made before a company files for regulatory approval. The sooner an outsourcing partner can be included into the product development team to evaluate the process and its future needs, the more time there is to prepare the partner’s own staff for the technology transfer process, and the more likely the chances of success.
Seeking a credible and suitable partner, however, stretches further than technological proficiency or available capacity. Logistical implications, for example, should be taken into account, because the change of site and scale may require seeking a new source of API or excipients as well as lead to difficulties once large-scale production is necessary. A formulation that has certain, specific properties at small scale, such as attracting an electric-static charge, could be undesirable and difficult to handle at large scale.
Sources of excipients, which are in many cases commodity materials, need to be found at larger scale, and these sources may be different than the suppliers used in development and initial scale-up phases. Validation of both suppliers and products needs to occur. Where processes are transferred overseas, security of supply and quality of product must be ensured.
Despite all efforts, it is inevitable that there will be subtle differences in equipment and techniques between partners during tech transfer. It is, therefore, crucial that all analytical methodologies are fully disclosed and validated to ensure that any difference in data can be fully investigated. All methods should be discussed openly between partners before the transfer takes place to minimize the chances of a problem occurring further along in the development process.
Stability issues with the final dosage form can arise; for this reason, the packaging of the product needs to be defined at the commercial manufacturing stage and be available for stability studies. Any issues identified in these stability studies that do not directly affect the tech transfer could still have significant consequences for the product development timetable. It is important to define as soon as possible the cause of stability failures to ensure that what may be thought to be an unstable formulation is not because of in-vitro in-vivo correlation (IVIVC) issues, or incompatibility
between an API and excipient, or a result of processing issues during a batch manufacture.
Perhaps the most overlooked cause of issues in technology transfer is differences in equipment, even ones that are seemingly minor. The major pieces of processing equipment, such as reactors, tablet presses, dosage form fillers, and packaging machinery will be clearly defined, but it may not be the case for much of the other equipment that is required. For example, the pumping system, the spraying system, the mixer and mixing tank, and the fabricator may not be defined, even though they can have a significant impact on the ultimate output of the process. The specification and purchase of a whole range of equipment must also be considered, such as filter bags or cartridges, vibratory sifting screens and mill baskets, and even the tooling for the tablet press.
Once raw-material suppliers have been sourced, equipment lists prepared and planned, analytical testing requirements confirmed, and any additional partners such as contract testing laboratories for materials identified, standard operating procedures (SOPs) need to be drafted and agreed upon, followed by validation. Potential bottlenecks and long lead-time items will have to be identified, and necessary items must be ordered in good time to prevent delays that hold up production and have a negative impact on timelines. If equipment is not already available on site, it must be sourced and purchased. Everything must be installed, calibrated, and validated. SOPs for both operation and cleaning processes must be determined.
Assays for either in-process testing or lot-release must also be transferred and, if necessary, third-party labs must be identified and audited. Documentation requirements are also extensive, ranging from the generation of process flow diagrams to the development of SOPs across the board including all relevant quality considerations.
Budgets and expectations should be set to include mitigation for delays and potential issues during the technology transfer phase of the project. An understanding of how capital investments will be shared needs to be agreed upon and a consensus reached at the outset about how any additional charges that arise during the transfer activities will be addressed.
The transfer schedule should be locked in at least 90 days in advance. A similar schedule should be set for commercial manufacturing, with allowances built in for surge capacity. Launch plans need to include a view on capacity at the plant and whether a partner can offer a capacity reservation option. For maximum efficiency in a technology transfer, all parties should also have a vested interest in the long-term success of the project.
The right contract development and manufacturing organization for any project will be able to combine its expertise of highly specialized services, dedicated infrastructure, and focused personnel to efficiently provide clients with a quality product both on time and on budget. The effective technology transfer of any dosage form to a third-party manufacturer requires honesty, openness, effective team management, and communication between all the stakeholders. Technical expertise and efficient process transfer and engineering runs are crucial, but the most important factor will be the development of a good working relationship between all the parties involved, based on mutual trust and cooperation.
Pharmaceutical Technology Outsourcing Resources Supplement
When referring to this article, please cite it as M. Valazza “Planning for Successful Technology Transfer," Pharmaceutical Technology Outsourcing Resources Supplement 2016.