Forming Key Partnerships in the Production of Combination Products

The pharmaceutical industry is in the midst of unprecedented change. Scientific knowledge is expanding at such a rapid rate, that it is difficult for pharmaceutical developers to keep up with all of the opportunities for commercialization. There are several specific areas that are fuelling this trend, but discovery in the field of genomics is by far having the greatest influence. Furthermore, genomic research is resulting in a paradigm shift in how healthcare professionals treat medical conditions moving from a reactive approach to a preventative one that includes highly personalized care thanks to our greater understanding of the role human genetic make-up plays in the tendency to certain diseases and illnesses.

Another area of innovation that is having a great impact on the marketplace is the proliferation of combination products where a drug or biological is combined with a delivery device such as pre-filled syringes, implantable devices, or transdermal patches. This opens up an entirely new area of competition for pharmaceutical marketers where the developer with the most effective delivery device can potentially win a huge share of the pharmaceutical market. 

However, all of this innovation and rapid change creates a very complex environment in which a drug developer must operate. Tom Hayes, a veteran in the field of pharmaceutical manufacturing and currently the General Manager of ATS Compliant Solutions, explains: “There are huge opportunities for the commercialization of new products, but the size of the opportunity is matched only by the size of the risk. While in the process of developing new products, a pharmaceutical manufacturer must also keep abreast of rapid change, reduce time to market, control financial risk, all the while meeting the requirements of regulatory bodies – sometimes in several geographic regions.”

The challenge presented by the ever-changing landscape is evident in the FDA’s approach to the proliferation of combination products. At this time, U.S. manufacturers of combination products have only the document entitled Guidance for Industry and FDA Current Good Manufacturing Practice for Combination Products for reference. The document states that “the primary mode of action (PMOA) of the combination product” is what dictates under which department’s jurisdiction a new product falls. For example, “if the PMOA of a device-biological combination product is attributable to the biological product, the Agency component responsible for pre-market review of that biological product would have primary jurisdiction for the combination product. The lead center generally has responsibility for oversight of the regulation of the combination product, including the evaluation of current good manufacturing practice”. However, after describing several combination product scenarios, the document adds that the “FDA recommends that manufacturers of combination products discuss with the Agency how current good manufacturing practice regulations apply to their products”. In effect, the drug developer must deal with the department responsible for the active pharmaceutical ingredient or biological for the device component as well.

In order to succeed in this complex new environment, many drug developers and manufacturers are moving away from the customer/supplier model of bringing a new product to market, to a partnership model. Hayes, whose group provides consulting expertise for drug marketers requiring automated manufacturing systems, explains that “in the past, the developer of a new product containing Active Pharmaceutical Ingredients (API) would ask a manufacturing equipment provider, ‘Have you done this before?’ With innovative new products and processes, the relationship between developer, automation consultant, equipment provider, and contract manufacturer must be approached as a partnership, and the question to ask is ‘How can you help me?’”

It all comes down to core competencies and return on investment. How are your time and resources best spent in order to get the greatest rate of return? If the answer to that question is drug development and clinical trials, you may consider forming partnerships with organizations who possess the necessary expertise in pilot line development; validation of the manufacturing process; or manufacturing for the mass market so you can move on to your next breakthrough pharmaceutical.

A successful partnership is one that is based on good communication and mutual respect for the skills and experience each party brings to the table. You will get the most out of a partner who is brought into the process early to provide input on critical decisions. You will not get the most out of a partner who is brought in for crisis management when the project is already behind schedule and over budget – or even worse, has taken a technological wrong turn. If you have made the determination that you would benefit from forming partnerships to look after the tasks outside of your core competency, the next thing you need to know is what to look for in those partners.

ATS Compliant Solutions is primarily concerned with the pre-build phase of automated assembly systems offering consulting services for everything from operational efficiency improvement; process support; automation engineering; product development and design for automation; to project engineering; project management; validation and certification. When a situation demands it, Compliant Solutions can also extend its range of services through its relationship with ATS Automation Tooling Systems for aspects such as pilot line development, proof of principle studies of critical components, as well as full turnkey automated assembly systems. Hayes asserts that in addition to possessing the expertise required in whichever area a consultant has been enlisted to help, a consulting partner must have proven ability in two key areas:

1. Realizing optimal overall equipment efficiency (OEE)
2. Achieving timely regulatory approval

Additional strengths to look for in an automation consultant are:

1. An understanding of production processes and automated manufacturing systems
2. Specialized analysis and simulation tools
3. First-hand experience working with regulatory bodies
4. Access to the methods of diverse industries
5. Ability to apply a flexible approach

A basic expectation for any automation consultant participating in a new pharmaceutical product launch is a solid understanding of current Good Manufacturing Practices (cGMP) and related regulatory requirements. The best consulting partner will also have experience working within a manufacturing environment, and a broad appreciation for the best practices in manufacturing technology and automation. Too often, these skill-sets are distinctly separate, and not common in the same company. However, a thorough understanding of the practical aspects of design, build and qualification of the specified systems combined with the principles of GMP can help to avoid cost overruns, delayed production schedules, and missed opportunities for dramatic OEE improvements.

It takes more than equipment and labour costs to fully assess, plan and prove how a production system or process will help you lower costs and raise productivity. To determine which solution will deliver the highest OEE, an automation consultancy should offer expertise applying advanced analytical tools such as 3-D visualization, dynamic simulation, and Total Cost of Ownership (TCO) analysis. Visualization and simulation programs allow you to run comparative tests and analysis on proposed automation concepts in a virtual factory environment. In addition, the use of TCO analysis provides you with the confidence that the solution being proposed will lower your overall production costs and get you the most value from your investment.

An effective automation consultant must also have in-depth knowledge of the requirements of regulatory bodies such as the FDA and be diligent in keeping up-to-date with the changes to the regulations. Ideally, a consulting partner should have first-hand experience with the FDA audit process and understand what an auditor expects. Most importantly, a consultant should be mindful of the primary concerns of such regulatory bodies which are consumer safety and documentation accuracy. With these guiding principles, a consultant can navigate you through all phases of a new product launch from conception to qualification with the end result being a safe, high-quality product and a manufacturing process that complies with all regulatory requirements.

It is also beneficial for an automation consultant to be familiar with the best practices and technological developments taking place in multiple industries in order to help you capitalize on new opportunities and innovation. Each industry has its own set of pressures that influence the pace of development and the need for new ways of thinking on a variety of fronts. Examples of innovations from other industries a consultant can apply to pharmaceutical manufacturing projects include miniaturization from the electronics industry and lean manufacturing methodologies from the automotive industry. With cross-industry know-how, the right automation consultant can help you get an advantage over the competition.

Some consultants will immediately attempt to lock you into expensive, long-term commitments and then proceed to apply rigid templates and unyielding methods that they have used for years. However, on one hand, in the rapidly changing environment of the drug development industry, you need a partner who is a creative problem solver; possesses an innovative spirit; and one who is as flexible as your needs are varied. On the other hand, because of the risk involved, you need a partner who has financial strength and stability and will be with you for the long term. Signs that an automation consultant has a flexible approach are a consideration for your needs before deciding on the best methods to apply; and a willingness to offer financial arrangements that are in line with your needs.

Equipped with this knowledge, the next time you seek the services of an automated manufacturing consultant, you will be able to ask the right questions to get the expertise you need at a competitive cost, and with the least amount of risk.