Jacobs Terry - Good design practices for GMP pharmaceutical facilities

Edward J. Tannebaum, AIA

Novel drug delivery is an extremely important aspect of the development of a drug product. New methods of drug delivery have been developed to both improve the drugs entry into the body and extend the life of the drugs financial viability through extending its patent. This article describes unique developments in forms of drug delivery, and provides an overview of drug delivery resources.

A drug delivery method has multiple goals: to simplify the actual delivery by improving the ease of use, to minimize the side effects of introduction into the body, to direct the introduction of the product to its specific location of need, and to manage the dosage delivery from immediate to sustained or extended release accurately. Many drugs require unique processing to develop means of achieving the most direct method of applying the active chemical compound to its intended delivery point. At the same time, due to patent expirations, new methods of physical delivery may provide an extension of the drugs life span as a proprietary product within a drug manufacturers portfolio. The combination of improving delivery options and the financial implications of improved uniqueness has dramatic effects on both the products position in the marketplace and its long-term benefit to the patient.

The design of facilities with compliant construction and meeting regulatory requirements poses a variety of challenges. The design of facilities for these novel drug delivery products ranges from utilizing existing processes to the invention and utilization of newer processes that may have been used formerly for other industries and must be modified to work within a Good Manufacturing Practice (GMP) environment. Starting with the early stages of development, the project progresses from a careful analysis of the risk-based approach to scale-up and commercialization, meeting the intent of regulatory agency submissions and their clinical trial stages.

The development of unique molecules that are competitive to produce and approvable by the worldwide regulatory agencies is a primary objective when developing novel drug delivery methods.

As worldwide drug manufacturing has become more subject to counterfeiting, along with the abuse of drug forms, it has become necessary to reformulate existing drugs in unique ways to make the drugs more difficult to counterfeit or to reformulate finished forms into illegal forms of concentration, especially with controlled substances. New methods to produce molecules that are not reproducible have become a valuable addition to drug development. Inherent molecule processes that destroy an active chemical when the particles composition is altered dramatically reduce the possibilities for counterfeiting and limit the use of active ingredients for illicit purposes.

New, convenient methods of drug delivery that improve the security of accurate dosing, extended-release capabilities, and dermatological to transmucosal delivery are among the many delivery systems being added to product formulations. High-impact tablet formulations that resist tampering will extend the life of existing controlled substance products due to their ability to limit adulteration; these will become more prominent in the coming years. Electronic, PC-based system implants are among the newer forms of delivery that will ensure accurate, timely dispensing of drugs, for both inpatient and outpatient use.

The following forms of delivery for drug products are an example of these unique developments:

• Advanced controlled-release technologies

• Bioavailability enhancement

• Insoluble actives

• Unstable actives

• Potent and toxic actives

• Small-molecule delivery

• Taste masking (for liquid and solid presentations)

Contract development and manufacturing organizations (CDMOs) are in the forefront of the creation and development of these unique delivery platforms. Development firms concentrate their efforts on a narrow band of patentable delivery platforms focused on differing delivery needs.

Some of the primary delivery platforms are categorized below:

• Patient-friendly delivery systems (e.g., transdermal patches, transmucosal sprays, dissolvable films, and mini-tablets)

• Needle-free delivery systems (e.g., coated tablets with tiny needles that are exposed in the gastrointestinal tract, microfluidic atomization, refillable sprayers, microneedle technology, and jet injectors)

• Release delivery systems (e.g., immediate release [IR], controlled release [CR]pediatric and adult, and osmotic delivery)

• Focused site delivery systems (e.g., focused ultrasound delivery, implantable pumps, and MRI-directed microbubbles)

The following list of development organizations provides a sampling of the unique novel drug delivery companies that are currently striving to bring new solutions to the market, for either curing varied disease types or bringing improved efficacy to existing drug products. The major contributors to these novel drug delivery organizations are small, science-based companies, created and sustained by investors or major pharma funding to advance their research and clinical applications of their respective products. The scientific expertise of these companies grows as offshoots of major pharma organizations, where these novel approaches cannot be financially justified within the research and development programs focused on major drug programs for higher-volume drugs.

Edward J. Tannebaum has more than 45 years of experience as an architect, construction manager, and corporate facilities lead, primarily focused on the pharmaceutical industry. A graduate of the College of Architecture, Planning and Design at Kansas State University, Manhattan, Ed has been a lead figure in the design and construction of solid dosage facilities throughout the world. As the head of facility design and construction for Johnson & Johnson, McNeil Consumer Healthcare Division, he was responsible for the planning and execution of facilities, both domestically and abroad. His comprehension of the OSD business from the owners, designers, and constructors perspectives has provided him with a unique perspective into operational issues that are critical to address in these projects. His knowledge of domestic and international statutes and trends has become a larger and larger focus in recent years of consulting. As a senior principal of Integrated Project Services (IPS) for many years, he led design and build efforts and many conceptual design activities related to OSD and novel drug delivery facilities. For many years, he was a frequent speaker at International Society for Pharmaceutical Engineering educational programs related to design and project facilitation. His role as a principal of Strategic Planning Initiatives, LLC, provides him with a platform of expertise to continue assisting pharmaceutical management with strategic master planning to coincide with their business needs. Tannebaum was the author of the OSD chapter for the first edition of Good Design Practices and has provided input to bring the publication to its current level of information, authoring of this edition.