Complex Double Blinded Packaging Study Demands Operational Excellence to Meet Looming FPI Date
Our client, one of the top major pharmaceutical companies, approached us with a challenging study – a double blinded study with the added complexity of a light sensitive drug in extremely fragile ampoules, also requiring distribution to investigator sites in remote locations across China. The Sponsor, who had worked with Fisher Clinical Services in the past, initially approached the project management team to discuss the complexity of this new trial with a view to evaluating possible solutions to the hurdles it was facing.
Foreseen challenges included:
- The IMP was a light sensitive drug in an ampoule which was very fragile. An ampoule is a small sealed vial which is used to contain and preserve a sample, usually a solid or liquid, in this case the light sensitive IMP. Extra care would need to be taken during the packaging and labelling processes as each fragile ampoule had to be protected from light at all times. The appearance of the active drug (IMP) and the placebo drug had to be identical.
- Consideration had to be given to the best way to distribute these supplies to remote locations throughout China. Would standard cartons be of sufficient quality to hold the ampoules in place during transit?
- Time was of the essence as the packaging volume was large with the FPI (First Patient In) date close.
- The placebo drug would not be ready until a date very close to the expected FPI date.
With expectations set that Fisher Clinical Services Beijing would have the expertise to address these challenges, the Sponsor made the decision to request a one-stop service from Fisher Clinical Services Beijing for comparator sourcing, label and tamper seal printing, carton design, labelling and packaging, distribution, returns and destruction.
Fisher Clinical Services Beijing nominated team members to work together to facilitate the smooth execution of this complex trial. In an effort to shorten the project timeline this team set up a weekly meeting with the Sponsor to discuss the study requirements with particular focus on what action could be taken to speed up the project deliverables. As Fisher Clinical Services has been exclusively focused on clinical trials for over 25 years, with an established network of GMP facilities across the globe, the team in Beijing was able to call on the expertise of subject matter experts worldwide to discuss their packaging, labelling and distribution challenges.
It was known from the outset that the timelines for receipt of the placebo were close to the FPI date. Quick action had to be taken to secure adequate supplies of placebo within the given timeframe, i.e. before the FPI date, as the placebo had to be labelled and packaged in advance of distribution. The Fisher Clinical Services Beijing Sourcing Team did not delay in securing adequate supplies of placebo.
Advance preparation for labelling and packaging
The packaging volume was large with an impending FPI date looming and an anticipated delay in getting placebo supplies. In anticipation of this tight timeline a proactive approach was taken to prepare all label and carton packaging materials in advance of receipt of the placebo supplies. Fisher Clinical Services asked the Sponsor to provide a briefing so that a sample label and carton could be produced by Fisher Clinical Services at the early stages of this project. This sample was immediately reviewed and approved by the Sponsor so that Fisher Clinical Services could prepare all labels and packaging materials in advance of receiving the placebo supplies at Fisher Clinical Services Beijing.
Adapting procedures to address complexity
A batch record (BR) is a document gathering all process data on a particular process step. Batch records are produced in cGMP biomanufacturing. Usually batch records are created once all of the required materials and products are received and recorded in the GPMS system at the facility. However, due to the complexity of this study, Fisher Clinical Services Beijing took the decision to create the master batch record for this study in advance of the materials and products arriving at the facility. This helped to accelerate the approval process at the Sponsor level and at project management and quality assurance level. Having pre- approval of the Master Batch Record ensured a quick start of the packaging and labelling process once all materials were received for this particular study.
Double blinding capability
For this double blinded study the appearance of the active drug (IMP) and the placebo drug would have to look identical. Labels were designed especially for this one trial to meet specific measurements of the ampoule vials. Intense training was given to the technicians as this label was difficult to apply. Samples of the blinded label and the ampoules were provided to the technicians so that they could practice in advance of the project. By the time the project was ready to start the Fisher Clinical Services technicians were ready to apply the label correctly and with speed. It was decided to use the same team of technicians to package both the IMP and the placebo thereby maintaining consistency across all supplies.
Staffing levels, roles and responsibilities
Initial review of the requirements of this complex packaging project suggested an allocation of 3 technicians for each kit. However, Fisher Clinical Services decided to allocate 4 technicians to each kit which resulted in considerable time savings, optimizing the packaging process and saving ~35% total physical packaging lead time. Furthermore, additional measures were taken to address the light sensitive nature of the IMP. Each kit was assembled within a defined time allocation and with minimal exposure to light.
Due to the complexities of this packaging project, in addition to the standard reconciliation that is carried out for all studies at the completion of each project, Fisher Clinical Services conducted additional quality reconciliation measures for this project alone. Reconciliation was carried out for each kit completion and a daily reconciliation was also recorded.
Our packaging design teams were conscious of the fragility of the ampoules. The Fisher Clinical Services technicians were advised to handle the ampoules with extra care due to their fragility. Additional precautions were taken at all stages of the packaging process. All ampoules were put on a plastic box during the packaging process so as to avoid damage.
Distribution with care
Why take all that care when packaging and labelling without considering the distribution aspect of these supplies? Fisher Clinical Services Beijing has expertise in sourcing local packaging solutions and in designing new carton packaging to accommodate all types of clinical supplies. It was decided that customised packaging would need to be developed to hold the ampoules in place in the cartons – two layers of insert with 44 holes to hold the ampoules in place during transit and additional sponge padding at the bottom and also at the top of the carton. To this end all ampoules stood steadily and independently in each carton, ready for distribution to remote sites across China’s vast landscape.
This complex packaging and labelling project presented many challenges for the Sponsor and for Fisher Clinical Services Beijing from the outset. However, careful planning, attention to detail and teamwork combined with unparalleled global expertise, flexibility and operational excellence resulted in the smooth execution of this trial and FPI dates being met.