End-to-end clinical trials supply management with SAP

By Lodestone

Stakeholders point to the clinical costs as a barrier to innovation. The FDA has confirmed in its “Critical path report” that “Streamlining Clinical Trials” is one of the key priorities. A leading factor in conducting clinical studies is the efficient management of clinical supplies. Solutions that support 1) integrated processes, 2) inventory visibility, and 3) compliance in the manufacturing and distribution of clinical trials supplies are the key to the growth of pharmaceutical and biotechnology companies. Lodestone Management Consultants finds that by developing a supply chain strategy for transforming internal processes and combining it with supply chain best practices and SAP technology integration, the clinical trials organization can deliver investigational medical products more efficiently and cost-effectively.

1. Clinical trials packaging & distribution

Within the process of bringing a new drug to market, clinical development represents the longest and most expensive activity.

A key factor in successfully conducting clinical studies is the efficient management of clinical study supplies across packaging and distribution (Figure 1).

It requires precise planning and coordination of the activities of many players, both within and outside a pharmaceutical company.

In this opinion piece, the key challenges surrounding clinical trials supply management are examined and evaluate potential solutions available to pharmaceutical and biotechnology development organizations.

Figure 1.

2. Clinical trials supply challenges

The three key challenges in clinical trials supply management: planning, manufacturing and distribution deserve a closer look.

Planning
At the outset of any clinical trials, a standard formula can be used (the number of participating patients at each site, multiplied by the number of doses administered daily, multiplied by the length of time of the trials) to calculate how much of the drug and placebo/comparator have to be made available to accommodate all patients for the length of the study.

If everything worked smoothly and as in a perfect case, that would be the end of the story as far as planning goes. But things generally are not that simple. There are a variety of influences that can throw the clinical trials planning off: supply, patient availability and recruitment, clinical trials duration, among others. Effective clinical trials depend heavily on providing study supplies to various sites so that prescribed drugs are administered at the correct times throughout the study. In case of a “supply stock-out”, patients using the drug may be disqualified and the entire clinical study could be jeopardized. The investigator relationship might be impacted.

Patient recruitment can proceed at different speeds in the different study sites, resulting in “staggered” enrollment, with a fraction of the planned participants entering the study one week, additional patients coming on board during subsequent weeks, and patients being added or the study being extended over a longer period of time. Additionally, participants often drop out before the treatment is complete. As a result, some sites may enroll significantly more participants than others. However, regulatory restrictions sometimes prohibit shifting delivered product from one test site to another. Expiration dating also has an impact on supply management. Often, clinical supplies must be manufactured prior to the availability of medium- to long-term stability data. Clinical supplies may be produced and packaged with an “earliest date” and may subsequently need to be relabeled or discarded, requiring the manufacture of replacement materials. Delays or extensions in the clinical study may also result in expired supplies – again resulting in relabeling or additional manufacturing campaigns.

Manufacturing
The production of clinical supplies in most ways mirrors the production of commercial drug products. All operations and processes must be fully compliant with current Good Manufacturing Practices (cGMPs) and are subject to audit by regulatory agencies such as the Food and Drug Administration (FDA).

Clinical supply manufacturing faces a number of additional challenges that do not impact commercial drug supply chain operations to the same degree. These challenges include:

• The lack of adequate supply of the active pharmaceutical ingredient (API).
• The necessity to manufacture numerous small lots of the drug product or bulk.
• The reduced expiration dating due to lack of long-term stability data.
• The production of numerous dosage strengths, placebos and comparator products that all need to look alike but must be controlled as unique materials throughout the supply chain in case of blinded studies.

Distribution
Compliant shipments of the drug to many sites, which are often scattered in different countries, may seem simple, but it is difficult to achieve because there is a need for:

• Good Clinical Practices (GCP) and cGMP regulations.
• Tracking the drug throughout the end-to-end value chain.
• Reliable and efficient accountability process so that unused drugs may be reconciled, returned and destroyed.
• Inventory visibility for distribution planning.
• Sharing the available material information for IVRS or IWRS partners.
• Investigator stock control in order to achieve end-to-end distribution planning

3. How SAP technology can help

SAP Technology may significantly streamline and improve the planning, manufacturing and distribution of clinical supplies.

The “Standard SAP” processes from Life Sciences commercial manufacturing can be leveraged in several process steps. At least to enforce the “Supply Chain” thinking rather than isolating the packaging from distribution or to facilitate the implementation of integrated supply chain planning.

Figure 2.

However specific SAP clinical trials supply management functionality is required as depicted in Figure 2.

The commitment of planned manufacturing must take place in time in order to meet the most recent demand placed at the distribution point. This commitment supports just-in-time (JIT) packaging and labeling of product to increase flexibility in the supply chain.

Study based demand calculation aids greatly in the initial forecasting.

Requirements planning supports the global supply chain planner for subsequent adjustments and distribution planning: they evaluate study based demand requirements, taking into account the on-hand inventory, to provide the net study requirement. The output will be planned orders for packaging, purchase requisitions for to-be-purchased items, and a distribution plan for JIT distribution of the study materials to the various distribution points.

The planning module may also be used to perform safety-stock planning to ensure reasonable availability levels. Any last-minute demand changes are updated in the planning process and resolved using interactive planning to create a new demand-supply scenario.

Rough-cut capacity planning helps establish and maintain manufacturing capacity and create supply chain exceptions to warn proactively about date and material shortfalls.

Randomization tools are necessary to create medication numbers according to state of the art statistical algorithms. A randomization manager incorporates the externally generated randomization data in the process orders.

Process order handling on the shop floor is supporting the good manufacturing practices. A labeling management module allows the design of templates that can be used for a study and participating country. The label printing needs to be integrated with process order handling. The labels need to be printed for serialized materials or for batched materials before starting packaging operations.

As a consequence of the need to serialize the study materials, warehousing activities for kits becomes more complex than in commercial Life Sciences manufacturing. Warehousing & shipping for clinical trials is leveraging on new technology used from other industries dealing with serialized materials.

Batch management functionality covers the selection of batches for packaging and shipping. Specific batch functionality is required in clinical trials due to country specific restrictions.

Shop floor data collections systems with barcode scanning devices may be effectively used to manage the execution in manufacturing, packaging, labeling and shipping activities.

Regulatory requirements like e-signatures will become more important in the future.

Figure 2 shows the need of “Automations” on top of clinical trials specific functionality.

The current SAP solution suite can enable the clinical trials supply chain in a unique way. There is no other best of breed system to enable an end-to-end supply chain.

4. SAP alone is not the solution

Systems are tools to facilitate the clinical trials operation. The underlying business processes must be analyzed and improved. As an example, if a company accurately forecasts its study requirements for a three- to five-month time horizon, but the manufacturing lead time is 12 to 18 months, no software tool is going to fix the underlying problem. By evaluating the underlying issues and redesigning the clinical supplies processes, the business can then use systems to further streamline its operations.

Excellent organizations should first:

1. Define the vision: for example in-sourcing of clinical distribution, visibility on the end to end supply chain, etc,
2. Determine the operating model and business processes required to fulfill the future vision.

SAP enabled processes must be formalized as written procedures with clear roles and responsibilities for each person and group involved in the clinical trials supply processes as well as with clear time frames and metrics to verify that the procedures are followed. Additionally, the staff must be informed and trained on the new responsibilities and procedures. Finally, performance measures must be established to keep the organization on a path of continuous improvement.

5. Conclusion

A significant opportunity to speed up clinical trials awaits Life Sciences companies.

The recommendation is to build on the foundations of a first wave clinical supply chain SAP implementation because changes are never easy and existing legacy systems can act as a drag on new solutions. New roles need also to be created including the incentives to encourage new kinds of behavior.

The companies that enjoy the most success in implementing first wave changes described in this opinion piece tend to do so as part of a broad transformational program anchored around a solid vision and/or business case.

These companies envision a comprehensive program rather than isolated fixes supported by change management and organization transformation.

6. Authors

Ralph Bäumle, Partner, Switzerland

Ralph is the Engagement Partner for a large global Pharmaceutical player. In his delivery role Ralph supports Lodestone’s clients in ERP Strategy, ERP Transformation projects and as Program Manager. Ralph has been on ERP transformation projects in the Pharmaceuticals, Chemicals and Industrials for more than 16 years (14 years SAP).

Geert Crauwels, Director, Belgium

Before Geert worked as a consultant, he gained a broad experience in the Electronics and Machine industry in supply chain functions and he was responsible for various change and performance improvement projects in an international context. Geert has 11 years consulting experience, mainly into supply chain management projects in logistics centers, manufacturing plants and distribution. Geert is focusing both on innovative Life Sciences SAP projects and on SCM transformation projects.

Walter Sporleder, Managing Consultant, Germany

Walter has 11 years of consulting experience for multinational companies. He worked for several clients in Life Sciences and Telecommunications. Walter has deep expertise in defining complex supply chain processes and implementing them in SAP. Clients well accepted both the business expertise as well as his technical SAP knowledge.