By Gerald Finken, R.Ph., M.S.
The clinical issues the industry is faced with today are the same issues that have been around for years, but exacerbated by the current economic and political climate. These issues, including timelines, costs, resources, and limited drug product, all plague a sponsor at one time or another.
Clinical trial studies are constantly changing, with each change affecting timelines, resources, and drug requirements. Looking at the current clinical supplies process, the focus is primarily on commercial GMP practices, which have few products, few strengths, and large batches with operations that are automated and limit change. Over the years, it has become clear that with clinical supplies, the focus needs to be on a GMP process that allows for many products, many strengths, and small batches with operations that are manual and constantly changing.
In 2008, the FDA issued a guidance document that addressed IDP (investigational drug product) for certain Phase 1 studies, stating: “Because certain requirements in part 211, which implement 501(a)(2)(B) of the FD&C Act, were directed at the commercial manufacture of products typically characterized by large, repetitive, commercial batch production, they may not be appropriate to the manufacture of most investigational drugs used for Phase 1 clinical trials.” (quoted from Guidance for Industry cGMP for Phase 1 Investigational Drugs)
As the FDA and the European Medicines Agency (EMEA) clearly realized, the adoption of regulations meant for commercial manufacturing does not necessarily mean that the commercial practices and operations management systems will work well for IDP manufacturing, packaging, and labeling.
The Next Generation Of Packaging And Labeling
Given the unique manufacturing, packaging, and labeling needs of clinical trials, the industry has looked for innovative ways to manage clinical trial material (CTM) while still adhering to GMP processes. Many commercial manufacturing methods have been adopted, including just in time (JIT) and lean manufacturing. However, clinical trial flexibility and the need for change is a constant concern with these methods.
Recently, many companies have begun to utilize a packaging and labeling method that mimics pharmacy dispensing: preparing CTM after the receipt of a shipment request, versus waiting to prepare the material in bulk. The purpose is to produce only what is requested, when it is requested, and most importantly, be able to ship the requested supplies the next day (or within the industry standard of one to three days). Because supplies are prepared only as needed, study changes affecting clinical supplies may be implemented almost immediately with minimal waste, delay, or rework.
Where this method has really benefited companies is when IDP is in short supply, expensive, or has a short retest date or short period of use upon “activation.” When IDP is prepared, it is labeled with the most current retest date and is sent to the site(s). With this, there is no risk of preparing too much, only to have it expire on the shelf due to study enrollment or other issues. For example, when produced in bulk, kits sit at study sites waiting for patients to be ready. As a study progresses, there is always potential for patients to drop out, which means time-sensitive kits end up going to waste. Also, with supplies that require activation, clients usually prefer that the sites are not responsible for activating or dealing with this part of the drug preparation.
This method has also helped in adaptive randomizations when the dosages of drugs change or the study starts with multiple dosage strengths, and then based on the patient’s response, the dosage range is altered. Because you prepare only what is requested, doses can change easily without the need to package and label all options, not knowing which option will be the one chosen as the study progresses.
As mergers, downsizing, and cost cutting continue, the industry must look for ways to significantly decrease timelines and allow for change while maintaining flexibility. As new operational methods continue to emerge, they will allow us to focus on delivering protocol-specific drug supplies as requested, when needed, all while being cost-effective.
Gerald Finken has almost 30 years of clinical supplies experience in the biotechnology and pharmaceutical industries. He is the founder and CEO of Clinical Supplies Management, Inc., in Fargo, ND.