As appeared in Tablets & Capsules April 2012, Copyright CSC Publishing www.tabletscapsules.com outsourcing How to help your CMO meet your lead time David Simpson P.J. Noyes This article addresses factors and challenges associated with determining a new product’s lead time and how you can help your CMO keep the project on track. A lmost every manufacturing project starts with the question, “What’s your lead time?” I can hear the snickers already. It has almost become a joke when the answer is, “Four to 6 weeks.” Frustratingly, the lead time often becomes 10 to 12 weeks, or more. When it is vital for your business to have a product delivered on time, and being on time requires relying on your CMO, it helps to know some of the factors that determine a realistic lead time and keep your project on schedule. Regulatory categories It is important to determine the regulatory category of your products from the outset. Those involved in the Rx, OTC, or dietary-supplement industries can appreciate how regulatory requirements can affect a timeline. To start the project on a good note, ask yourself: • Does the product and/or active ingredient(s) meet a specific monograph? • Is it a new dietary ingredient (NDI)? • Is USP testing desired or required? • Has stability testing been started to support label claims and expiration dating? The answers to these questions can help you determine a realistic timeline. Working with sound legal counsel to understand and navigate structure-function label claims and monographs is also recommended. Specifications for raw materials, components, and finished product Unless clearly defined from the start and communicated throughout the project, specifications can derail a lead time in a blink. Determine whether you will supply the raw materials and components or if you are looking for a turnkey solution. Often a CMO has a broader network of suppliers and better purchasing power, so it may be able to help manage your costs. Keep in mind that minimum-purchase requirements may lead to excess materials being stored. It is also not uncommon to have stored items priced as a separate line item above and beyond the unit cost of the product. Also consider what specifications the material and components must meet. Questions you should be able to answer include: • What type of package is required (HDPE, PET, pouch/film, glass, etc)? • For specified extracts, what part of the plant is used? Has alcohol been used in your product? If so, what is it denatured with? For active pharmaceutical ingredients (APIs) or vitamins, what strength is required (4to-1, versus 400-to-1)? • Is an international source acceptable or is a domestic source required? • Have you defined the type of label (paper, laminate, or shrink) and the label coating required? How about the type of adhesive and the wind direction for adhesive labels? • What is the density of your capsule ingredient(s)? Have you confirmed that your dosage will fit inside the capsule you specified? • Have shipping trials been completed to determine the type of cardboard to use? How does your preferred packaging hold up to temperature changes during transport and storage? Is there a friability issue with your tablets because there is no cotton used in the bottle? Are your labels getting scraped and scuffed because of the laminate used or because the dividers are too tight? Supply chain Supply chain issues challenge even the best CMO and branded-goods company. Lead times on components and raw materials are affected by many factors, including location, availability, transportation, production schedules for a specific component, and even the weather. Delays may arise if materials have to go through customs or aren’t available. In some cases, the wrong material or component is shipped, and by the time it comes in, you’ve already lost several weeks. The biggest challenge is maintaining control over a variety of vendors. Having a backup supplier can save considerable time and help manage costs. For example, recent shortages of turmeric or jojoba oil may have added weeks to a production schedule. It is also important to keep in mind that CMOs and brand owners also face daily challenges, ranging from equipment breakdowns to scheduling conflicts. Accounting for supply chain issues and defining what the longest lead time is for a material will help establish a production start date. Testing Testing comes with many differing opinions and practices. As the FDA continues its review of brand owners’ claims—and determines whether manufacturers are in compliance with cGMP guidelines such as 21 CFR 210, 211, and 111 specific to OTCs and dietary supplements —the importance of understanding testing’s role in establishing a production timeline is essential for avoiding delays. Recent reviews of FDA warning letters and 483s show that the following tests are often absent: • Incoming raw material testing, • Package stability/integrity, and • Finished-good testing, including stability, microbial, and assay(s) of actives. Also consider if an in-house lab or qualified thirdparty lab will be used for the tests. If your CMO is partnered with an outside lab, the lab is likely providing services to multiple accounts and may not always be able to rush a project. Also, make sure your CMO has audited and validated its lab partners. Paperwork We’ve all heard the phrase, “If it isn’t written down, it didn’t happen.” In the manufacturing industry, we can pretty much guarantee there will always be a need for a paper trail. The following are documents that you can expect to include and that can require extensive time to complete. Certificate of analysis. A certificate of analysis (CoA) is supplied by the raw material supplier and details the makeup of the material. This document is used to ensure that the material received is the correct material for use in the formula. Remember that until a supplier and three lots of its material have been qualified, as well as one lot annually thereafter, quality inspection and receiving personnel cannot rely solely on the CoA to release a raw material. Certificate of compliance. The certificate of compliance (CoC) is a CoA, but for components. The document lists specific characteristics such as color, resin or glass information, type of adhesive used on labels, dimensions, and other criteria. Finished-good specification sheets. A document usually supplied by brand owners. It provides details on how the finished product should look, be packaged, and be configured on the pallet. Inspection sheets. A quality document drafted by your CMO for inspecting all components and raw materials. Material safety data sheet. The material safety data sheet (MSDS) informs workers and emergency personnel about procedures for handling or working with that substance in a safe manner and lists information about physical data, toxicity, health effects, first aid, reactivity, storage, disposal, protective equipment, and spills. Supply agreements. This document defines the partnership between you and your CMO and the responsibilities between the brand owner and the CMO. Remember that if you’d like to have legal consultation, it can add considerable time. Quality agreements. This document sets the parameters for the quality of the product. It details who will be responsible for the testing, retained product, label claims, recalls, customer complaints, and other details. Certificate of insurance. If you’re launching a new product, a certificate of insurance (COI) may not be something you’ve thought to share with a CMO. However, in most cases, both parties will exchange a COI that provides insurance coverage for both parties. Amounts vary from company to company and depend on the product. Stability protocol. This report details the types of testing to be performed, what methods will be used, and how many samples would be needed prior to starting a stability study. Master formula or batch records. Master formula records (MFR) or master batch records (MBR) are often missing during FDA inspections. These records are essential to ensure that a product is made in a consistent manner. Process validation. Required for OTC products and strongly recommended for dietary supplements, process validation uses the MBR. It requires the same process be followed in three consecutive batches to validate process uniformity and consistency in batching and packaging of a product. Lab, pilot, and production batches Do you have a finished formula and process or one that just requires a little tweaking? The answer could mean the difference of several weeks or several months. Once you do get a production batch, often the finished-good testing has not been factored in. But it is necessary to make sure that the product is safe, effective, and meets label claims. As the popular saying goes, “You can’t hurry bugs.” Plan for at least 5 days of microbial testing, as well as assays, if there are actives listed in the drug fact or supplement panel. Equipment requirements are often a factor as well, even for existing products. It’s often thought that a “filler is a filler, a tank a tank”, but spend a few minutes talking with manufacturers, and you’ll find that moving a formula and process from one CMO to another may seem easy, but has many variables. Check with your CMO to see if its process includes a lab batch and/or a scale-up pilot batch before moving into production. If not, make sure you’ve specified in the supply agreement which company is responsible for a failed batch. Conclusion This article addresses a few of the factors that affect lead time. Remember that clear, constant communication with your CMO is key. Also, defining your timeline from the beginning and working with your account manager or project manager can help you determine whether it’s realistic. Don’t be afraid to share your thoughts and experiences from a brand owner’s perspective. Let us know how we in manufacturing can work with you to meet your lead time. T&C David Simpson is business development manager at P.J. Noyes, 89 Bridge St., Lancaster, NH 03584. Tel. 800 522 2469, fax 603 788 3873. Website: www.pjnoyes.com. P.J. Noyes is an FDAregistered, GMP-compliant, and NSF Certified-for-Sport contract manufacturer and packager for the nutraceutical and pharmaceutical industries. It is committed to working with companies of all sizes, from R&D projects to production, in tablets, capsules, and liquids.