Global Commercial Drug Supply for Trials: How to Achieve Long-term Success Published in Journal for Clinical Studies

Transcription

1 How to Achieve Long-term Success Published in Journal for Clinical Studies For more information about sourcing in the US and EU, call or Myoderm is a leader in the sourcing, distribution, and management of commercial pharmaceutical products and supplies for clinical trials. Our clients span the globe and include the majority of the world s top 10 pharmaceutical companies. With our deep expertise, customized solutions, and personalized service, Myoderm provides the optimal drug supply solution for global clinical studies. When I joined Myoderm 11 years ago, the firm had been supplying commercial medications to support clinical trials for almost 15 years. To my surprise, a majority of companies were rather naive regarding their options for sourcing comparator medications. Some companies (even large ones) were relying on local pharmacies, and almost all had no consistent sourcing strategy. A lot has changed since then. The EU Clinical Trial Directive, the development of many specialty suppliers for comparators, and the increasing number, size, and complexities of clinical trials have encouraged sponsor companies to adopt a more sophisticated approach to the procurement of these essential products. That being said, there are still many variables sponsor companies must consider to find the optimal solution for their sourcing requirements. That solution would combine supply availability, cost efficiency, and project management to create both clinical and financial harmony for sponsoring companies. Where to Begin Every company has different needs. In order to plan for a long-term supply, you need to define the following: Which countries/regions will you be sourcing from? Which products do you forecast needing for the next months? What quantities will be required and when? Is branded product needed or will a generic version be acceptable? What regulatory documentation will be required? Are you willing to divulge any information regarding your study in order to secure supply if requested by the manufacturer? Next step is to start defining the RFI process. Picking the Right Sourcing Partner If you do not already have a shortlist of preferred suppliers then it is worth conducting an exercise to identify and evaluate suppliers you want to work with. By working with a smaller number of suppliers on a regular basis you can develop collaborative relationships with those who will better understand your requirements and ultimately deliver best value to you. Upon embarking on an RFI, first try to identify as many companies as possible. Sources for this information include industry conferences, internet searches, and recommendations from colleagues at other companies. Gain an understanding of the needs of various departments in your organisation, such as clinical supplies/operations, strategic sourcing, finance, QA, and other areas so you can build the RFI to ensure that all the relevant questions are covered. Important Criteria to Consider Include: Pricing - This is not always as simple as per unit pricing, so look for transparent pricing to determine which part of the price is product cost versus supplier markups. Supply Chain - How much product can be purchased directly from the manufacturer? If the product needs to be purchased from suppliers other than the manufacturer, can your partner provide proof of the supply chain, such as a pedigree document? Can your vendor still source the required documentation if they do not source directly from the manufacturer? Quality - What quality systems do potential partners employ to ensure that all products are handled correctly? Do they have the correct licences and facilities to properly purchase, store, and distribute medications? Will the suppliers allow a quality audit if requested? Reputation - Can the companies under consideration provide references? What is their track record? Are there colleagues that you can talk to who can provide information about them? Once you ve received responses from your RFI, there are additional ways to cull the field of candidates. Ask your finalists to make presentations that include case studies which demonstrate their sophistication and pricing. Use their presentations as opportunities to interact on a personal level to see if they re the right fit for your company. It is up to you to ultimately determine your supplier strategy, how many partners you want, and whether you want global or regional partners. 1 of 5

2 If you use multiple partners within a specific region (US, EU, Asia, etc.), try to limit them to a maximum of three companies. Any more means diminishing returns in terms of cost benefit, given the time and resources involved in managing these companies. It could also make the manufacturer of the products you seek to purchase nervous because of too many requests, and could prompt the manufacturer to ask for sponsor/trial information or refuse to supply altogether. More than Just Facts Beyond price, facilities, and sourcing capabilities, there are other pieces that need to fit together to make an ideal partner: Experience - How long has the company been in business? Is this the company s primary business? Financial - Is this company stable? Is it growing? Are they willing to offer favourable payment terms, or do they require prepayment for many orders? Intangibles - Can the company show that they can think out of the box and come up with unique and innovative solutions while still maintaining compliance? Do they overpromise? You don t want to be told they can source a particular product and hear later that they cannot. Here s a Basic Partner Checklist: Experience - Look for partners who ve been in the business for a significant period of time. Flexibility - Every study provides its own unique sourcing challenges, and your partner(s) should be willing to listen to your needs with each trial and consider all available options to create optimal strategies. Integrity - Sometimes, unfortunately, the answer is no, and your partner should have the integrity to say so and not overpromise. Communication - Your supply partners should keep an open and honest line of communication, not hiding things from you, and not going through with anything related to your projects without your approval. Insightful - Your partner should appreciate the impact on the sponsor. This is not just about dollars and cents, but has an impact on the overall success of a trial and, in the long run, on patients as well. Specialist in the Field - You want a partner who has dedicated operations for supplying commercial drugs for trials, and who is committed to this service for the long run. Avoid companies where sourcing is not a significant part of their operations. Know in Advance Once you have sourcing partners on board, it helps to have a forecast of the products and quantities you need. The farther in advance you know what medications you need and the countries/regions you plan on supplying them to, the greater the likelihood that you will get the products on time, at the best possible price, and with the documentation that you need for regulatory submissions. As part of your planning and protocols, it is important to utilise the generic name of the product. If the product is supplied under different names in various countries, the generic name will make it easier to have product accepted across all countries, regardless of the brand name. Also, you can use a generic version of the product if necessary to improve supply availability and/or save money. Provide Enough Time When you send requests to your suppliers, it is important to provide enough time to get replies, consider the best options, proceed with ordering, and receive the product in order to meet your trial schedule. The time it takes to investigate, source, and secure the products and the documentation can easily be underestimated, particularly for the larger, more complex trials. To start, give two to three weeks for initial supplier reply, especially when there are factors besides price to consider (see below). If the manufacturer needs to specially produce drugs to meet your trial supply needs, it may take three to four months to get the product, so it is important for your suppliers to clearly indicate how long it will take to source the medications. Critical Considerations When your suppliers reply back, they should be able to provide you with a variety of important information to make sure you stay on track for successful supply, including: 2 of 5

3 Shelf-life - Not just the current expiration date, but if possible, find out what is the shelf-life from date of manufacture, so you know what the maximum possible dating is for the product. For example, if the shelf-life is 24 months, you typically will not have product with more than 21- or 22-month dating. If your trial runs for three years, you ll need to factor in making multiple purchases during the course of the study. Availability of Large Volumes - Can the amount of product you need be sourced at once or in regular campaigns? Are there any manufacturer roadblocks? If you want to supply from a country in the EU for the whole global trial it s important to know if there are potential limitations. We ran into an issue once where we wanted to source a product from the UK. The amount needed for the global trial was enough to meet the country s needs for a whole year. The manufacturer obviously wanted to know why we wanted so much and could not supply it without first fitting our order into their manufacturing schedule. History of Product Shortages - To mitigate risk, it is important to know if the manufacturer frequently has problems with production or if there is significant demand that causes back orders. Approvals - Are the products approved in the countries where you want to use them? If not, then appropriate efforts have to be taken to deal with regulatory issues. Documentation - Know up front if you can get a Certificate of Analysis (COA), BSE certificate, or other documentation to allow use of products in different countries in the trial. Finding out after the fact that you cannot get those documents could mean eliminating specific countries from the study. Storage Conditions - Knowing the storage conditions in advance allows for proper handling of the product all the way through the supply chain to the patient. In addition to basic conditions, knowing the allowable temperature excursions would be helpful from a planning and quality standpoint. When getting stability and excursion information, it is important to make sure that if a product can have an excursion, you use the medication up to the expiration date listed on the package. In some cases, a product can have a temperature excursion, but it must be used within a set period of time (28 days, three months, etc.). Obviously, this could have a dramatic effect on your trial. Generic Alternatives - Is the product available as a generic in certain regions? Can those products be used in all countries for the study? Generic products, in addition to typically costing less money, have other advantages. Manufacturers are more willing to supply them in large volumes, supply regulatory documentation, and in some cases, will provide placebos or special manufacturing batches. Potential Product Changes - Be sure to ask your supplier to check if there are any potential formulation changes, product discontinuations, or other factors that could impact trial submissions if not identified in time. Global Challenges Once you know what regions you are considering for your trial, it s important to understand the sourcing differences and challenges in different regions. Compared to other countries, the US market has the best availability for most products. Most manufacturers do not restrict the supply of products, except specialty medications. Even for larger volumes, the lead time to get single lots may only be two to three weeks. On the other hand, pricing can run 20-60% more than other countries. This is one reason why it is enticing for companies to source out of the EU and then use the product for trials in the US. Another obstacle in the US is the lack of regulatory documentation. US products are not easy to use in the EU and many other markets if COAs and other documents required for clearance are not available. The EU is a preferred market to source from for global trials because of lower pricing and ready availability of regulatory documentation. If the product is marketed by the same company, and 3 of 5

4 equivalency data can show that the product marketed in the US is identical to the EU product, then, in many cases, the sponsor company can use EU product in the US for a trial. One of main challenges, however, is supply availability. Lead times for large quantities could run from three to six months. For example, when sourcing from one market, such as the UK, the quantities needed for a global trial far exceed demand for the entire country, in which case it may take several months US SOURCING Supply Availability Supply chain is more top down, from manufacturer to ADR (Authorized Distributer of Record) to pharmacies, hospitals, and secondary wholesalers. Brand manufacturers will typically only sell directly to ADRs. ADRs require a minimum volume of business in order to establish an account and make purchases. Large volumes typically available in 2 3 weeks. Supply is tightly managed by IMAs (Inventory Management Agreements) with manufacturers. Prevents speculative buying ahead of potential price increases. Each package size and strength have individual NDC (National Drug Code) numbers. FDA requires Pedigree Documentation for all US product delivered in the US. Sample Lead Times for Large Volume Purchases Lipitor ~2 weeks Xeloda ~3 weeks Norvir ~1 week Pricing EU SOURCING Products can be more readily purchased directly from manufacturers, though supplies vary by country/manufacturer. Smaller quantities may be available on a country level, but often not enough to supply a larger trial at one time. Manufacturers may direct CT purchases to one specific country. Products will have EU and/or country-specific marketing authorization numbers. Lead times range from 2 3 weeks to 6 7 months depending on product, quantity, country, and timing. Lipitor ~13 weeks Xeloda ~30 weeks Norvir ~13 weeks Manufacturers set pricing. Pricing is transparent, as WAC is industry accepted. Price increases typically are 1 or 2 times per year, and average 2 10% per increase. Generics are an exception, with pricing sometimes 80 90% less than brands. Governments typically set pricing. Pricing typically lower than US market, but wide variances on a country by country basis. Manufacturers may price CT supplies higher than the general market. Sample Price Comparisons Lipitor ~$400 Lipitor ~$140 $170 Norvir ~$260 Norvir ~$50 $90 Manufacturer Cooperation Drug supply not usually an issue, as most manufacturers do not require information. Branded manufacturers typically do not provide documentation. Only 20 30% of branded manufacturers supply COAs, but generics are more supporting. Manufacturers typically do not refuse to supply drug, but some require EUDRACT or additional sponsor/trial information. Most manufacturers supply COA, BSE/TSE, equivalency and other documentation, such as National Release for vaccines. All product names mentioned in this publication are tradenames, trademarks, or registered trademarks of their respective owners. 4 of 5

5 to manufacture enough product to meet the trial demand. In some countries, supply may be delayed because the government gets the first shot at the supply. Manufacturers may also face severe penalties if they do not have enough product available for patients. Sometimes it is necessary to source from markets that pose their own unique challenges, for example: India - There is a high rate of counterfeiting, and also challenges in assuring temperature control along the supply chain. Suppliers do not always exercise high standards for storage and transportation of medications. Latin/South America - High tariffs between some countries limit imports and may require sourcing on a local level. There is also a higher rate of counterfeiting than in the US and EU. Japan - In order to source large quantities, manufacturers must be contacted as part of a gentlemen s agreement, which allows communication and cooperation between manufacturers. If you try to source from a supplier, you may be able to get small quantities, but you cannot get larger trial supplies or regulatory documentation. Many products are restricted from export as well. China - In addition to counterfeiting concerns, some products cannot be exported from China. Proper storage and transportation by suppliers is a challenge in some cases. Russia/Ukraine - Pricing is very expensive relative to other markets. Importing product into these countries from other regions is extremely difficult, and there are also counterfeiting concerns. Michael Cohen has been with Myoderm since Through his passion, leadership, and commitment to meeting each client s unique needs, he has enabled the company to grow into a global leader in comparator and commercial drug sourcing for clinical trials. Prior to working for Myoderm, Michael held positions in the publishing, advertising, financial, and utility industries. He holds a B.S. degree in statistics from the University of Pittsburgh, and an M.B.A. degree from the university s Katz Graduate School of Business. mikec@myoderm.com Doing it Right Sourcing commercial medications is a small but significant part of the clinical supply chain. While it may seem daunting at times, remember that with the right planning, partners, and patience, it can all come together successfully. 5 of 5