Guest Column | August 10, 2023

Balanced Sourcing Of Custom Media/Buffer Formulations: The Case For Outsourcing

By Kara Quinn and Ewelina Flamm


Big Pharma manufacturing strategies in the 1990s could be described as “from soup to nuts,” figuratively, of course, as in a “complete or exhaustive process from beginning to end.”1 Back in the day, massive manufacturing campuses were run much like self-contained cities, producing their own potable water, staffing their own emergency fire and medical services, and employing vertical manufacturing strategies.2 Multiple stages of material production and supply were managed in-house, eliminating reliance on third-party supply chains. Big Pharma was a veritable one-stop shop in the 1990s, not for an auspicious meal of “soup to nuts” but for the exhaustive manufacturing of biopharmaceuticals, from primary cell lines hatched in-house by an isolated chicken flock to plastic pill bottles custom molded hot off the press for packaging solid oral dosage pills.

Much like other 21st century industries, the biopharmaceutical industry’s metaphorical “soup to nuts” is now largely outsourced and globalized. Today’s biopharmaceutical manufacturing assembly line is global, and not just for the highly specialized processes (i.e., gamma irradiation or NMR-testing) that are not economical to maintain in-house. Even the simplest of manufacturing support activities like formulation of culture media or a salt buffer (i.e., measure water, add salt, mix) have evolved into a supply chain that is intricately interconnected. Manufacturing has evolved extensively to outsourced single-use technology and flexible modular designs. State of the art technology and advances continue to abound, and in the number of decades that can be counted on one hand, the contrast between vertically integrated sourcing strategies of the 1990s and the incrementally dispersed global supply chains of today is striking. The pendulum has swung, but has it swung too far?

Global interconnectedness means that events halfway across the world now have the potential to influence your standard operations. When the COVID-19 pandemic began, supply chain disruptions were so pervasive it wouldn’t have mattered whether we were still vertically integrated or outsourced to a certain extent, but it was hard not to remember a time when all equipment was reusable. Give it a validated wash and sterilization, add homemade water and ingredients (if we could get them), and we’d be back in business. In some ways it almost felt as if prior decisions to outsource had now further handicapped us. We were at the mercy of our global suppliers.

Nothing is risk-free; all sourcing options have pros and cons that need to be assessed to find the best fit. For those of us who have dedicated significant portions of our careers in support of biopharmaceutical material sourcing decisions, we have always deliberated essential considerations before making recommendations on outsourcing of custom media/buffer formulations. Now more than ever, though, a critical eye on the balance of supply chain interconnectedness and independence — a “happy medium” — is warranted for the sake of a reliable supply of critical medicines. After all, in John C. Maxwell’s words, “Change is inevitable. Growth is optional.” We opt for growth, and we are sharing our experiences with custom media/buffer qualification and supply decisions of varying complexity that are relevant in both pandemic-era supply crises and business-as-usual operations. In our first of a two-part series, we share key factors to examine if you’re considering outsourcing.

3 Logical Reasons To Outsource (With Key Considerations)

To outsource or not to outsource? That is the question. It is not a stretch to understand why you might want to outsource the formulation of custom media and buffers. Some of these solutions contain up to 100 individual ingredients; that’s quite a pot of soup to stir. Also, why manage the purchase and release of hundreds of individual incoming raw materials when you could receive one that’s ready to go? If the question is who is most capable of producing the required material at the desired quality level, with the accuracy in technical specifications, at the lowest cost per unit, and with a transparency commensurate with regulated products in a reliable and consistent manner, the answer quite often is a third party who specializes in the custom formulation of sterile media and buffers on a daily basis.

Eliminating waste is the name of the game and if your core business model does not focus on the efficient formulation of custom media and buffers all day, every day to the delight of multiple paying clients, then economies of scale suggest that your investment in supplying yourself might be less cost-effective than you thought. Waste comes in many forms, and there are plenty of clear and compelling reasons to outsource:

1. You Don’t Have The Facility Capacity/Design And/Or Your Capital Is Depreciating

Before the onslaught of single-use manufacturing systems, stainless steel reigned supreme. Upstream culture media and buffers were formulated in large, fixed stainless-steel tanks combining thousands of liters of homemade purified water with custom quantities of compendial grade ingredients. The infrastructure alone to support these tanks requires a large facility footprint in addition to the essential utility support systems (i.e., CIP/SIP, a WFI/purified water system, etc.), which themselves are costly to install and maintain. So, it shouldn’t be surprising that as the capital investments of the ‘90s depreciate toward the end of a typical lifespan, manufacturers would need to weigh the costs of continued vertical integration versus outsourcing. Aging facilities, space constraints, line capacity, staffing, and repurposing of equipment are just some of the considerations that trigger or determine whether a depreciated media/buffer formulation line receives reinvestment or last rites.

A compelling argument for proactively developing strategies to decipher “the happy medium” of supply chain interconnectedness and independence is the ever-popular debate on the “facility of the future.” Invariably, it seems that the future doubles down on the notion of manufacturing processes solely conducted using disposable and single-use technologies. Facilities are being built today that do not offer the footprint, fixed equipment, or utilities to even consider formulating media/buffers in-house. As an industry dedicated to invention and progress, the risk is that we continue to repeat a narrowly focused version of the future and allow the pendulum to swing too far in the opposite direction. Ideally, the decision to outsource is made because it is the best option, not the only option.

2. It Worked Like a Charm on Your Last Project

Project timing and scale significantly influence supply chain options. Working with third-party suppliers on custom media/buffer formulations requires a certain amount of technical transfer. Ideally, experienced suppliers have agile enterprise management systems that enable them to build new products, order new materials, and publish certificates of analysis commensurate with your project’s timing and quality level. The following is a list of topics that will need to be addressed with potential suppliers as early in the project as possible:

  1. Lead times: What is the current amount of time it takes the supplier to establish a new custom product for manufacturing, testing, and delivery? What is the likelihood that disruptions in third-party manufacturing schedules could result in supply delays? Are there penalties or incentives that can be built into the contract?
  2. Expertise: Is the third party capable of meeting both in-process and release specifications? Is the third party capable of producing, packaging, and shipping sterile growth medium in a container closure validated manner? Does the supplier offer services for the shelf-life stability analysis of custom formulations to establish meaningfully expiry data?
  3. Capacity: Third-party suppliers charge a premium to manufacture formulations on behalf of their customers because allocating their line time and resources detracts from the supply capabilities of their own products. Will the capacity available at the third party be sufficient to meet all of your supply needs? Does the third party have additional capacity to scale up if required?
  4. Cost: As discussed in c., custom formulations will cost more than off-the-shelf items; therefore, if your budget is tight and in-house facilities can accommodate media/buffer formulation, vertical integration might be a way to save out-of-pocket expenses. Consider again that economies of scale suggest that the higher the volumes you contract with the third-party formulator, the lower your price per unit is likely to be.
  5. Quality management systems: As a key supplier to your process and product, ensure that the third party is amenable to on-site audits; has a supplier surveillance program of their own; and has a robust change notification system that promptly informs you of the potential need to make changes to formulation process with right of refusal per the custom contract.

3. Your Company Doesn’t Have The Resources And Focus To Produce In-House

For smaller companies without as many fungible resources, the routine production of in-house media and buffers may require an entire dedicated operation separate from the biotechnology product. Multifunctional resources are required to support that operation (i.e., process technical, maintenance, engineering, quality control, quality laboratories, etc.), which may detract from core competencies. Further, technical issues that arise in the processing of growth media containing potentially hundreds of unique ingredients, each with their own chemical/physical/biological properties to consider, may require a different set of skills or a dedicated staff than might be readily available.

Ultimately, if the best decision for your project, product, and process is to outsource, be certain to cultivate a positive, productive relationship with your supplier contacts. When reliant on a third party, your decision or need to pivot during project execution does not automatically constitute instant accommodation from your supplier at no additional cost. In fact, the timing for when to outsource should be fairly close to process finalization if the benefits of cost efficiency are to be realized.

Stay tuned for part two of our two-part series, where we’ll discuss various outsourcing scenarios that might lead you to conclude “Just because you can…doesn’t mean you should.” And, of course, we will finish the series with our favorite subject of them all, the happy medium (a strategic approach to striking the right balance in the sourcing of custom media/buffer formulations).


  1. Tréguer, P.
  2. Amadeo, K. What is Vertical Integration

About The Authors:

Kara Stockett Quinn, M.S. in regulatory science, is self-employed as an independent consultant. She has worked in the biopharmaceutical industry for 29 years developing subject matter expertise in end-to-end product development (nonclinical and clinical), technology transfer and validation, commercialization and pre-approval, licensure, and supply manufacturing. She has held positions in functional roles, including quality systems and process technology, with extensive experience in direct health authority facilitation and communications. In recent years, Quinn’s work as a thought leader in raw material qualification and supply chain management topics served to facilitate alignment in raw material risk assessment best practices, qualification standards, and novel excipient characterization.

Ewelina Flamm is an associate director at Merck and is a subject matter expert in Merck's Incoming Material Center of Excellence Group supporting large molecules. With 16 years of experience, she advances incoming material knowledge with key interests in clinical and commercial technical risk assessments (fit for function alignment), origin of materials, raw material lifecycle management strategy, and improving access to electronic supplier data.