I strolled into one of those mega-sized grocery stores in my town the other day to pick up some dog food for our 90-pound Golden-doodle, D'Arcy. This was a new experience for me as this chore has always been undertaken gleefully by my wife. (It's her dog, after all.) I never gave dog food much thought in the past. As I recall from my childhood, your choices were either a bag of Purina Puppy Chow or cans of Alpo; there really wasn't much beyond that. But as I turned the corner in hopes of finding the dog food "section" without too much difficulty, I stood paralyzed in utter disbelief as I came face-to-face with a 150 foot-long aisle of shelving completely lined on either side from top to bottom with an inconceivable array of dog food. I struggled to comprehend the seemingly endless varieties, brands, sizes, and dietary formulas. They were further delineated into sub-categories - cans, bags, pouches, bins and buckets - and sub-sub-categories, such as breeds, sizes, ages, healthy coats, strong bones and a host of other "special needs."
All of this of course, was driven by consumer demand (human, certainly not dog) or a marketing need - either real or perceived. I was overwhelmed. Was all of this necessary? There were simply too many choices. How do I select just the "right" one? What to do? I called in an expert: my wife. Then, it was only a matter of locating the right brand, breed, size, presentation and formula and double-checking that the label met all of her prescribed requirements. I left the store relatively confident but not totally convinced that I had made the correct choice.
In the world of pharmaceutical cold chain management, I see a similar phenomenon occurring. Only a decade ago, there was virtually no guidance for the testing of insulated packaging systems used to transport time and temperature-sensitive drug products and only limited guidance on handling of these types of products in transportation and distribution. But as the volumes and diversity of temperature-sensitive drug therapies increased, and their availability became more widespread, it caught the attention of regulatory authorities who applied greater scrutiny to the distribution supply chain. Knowledge and expertise within the temperature-sensitive drug distribution chain grew among regulators, drug manufacturers and supply chain partners. This has resulted in a greater understanding of the hazards and levels of risk. Subsequently, a plethora of regulatory requirements has sprung up from various countries around the world and a mad scramble has ensued among supply chain partners and industry associations, many of which have produced guidance to meet the ever-growing and increasing fractured regulatory expectations.
Regulatory requirements and/or guidance for the storage and transport of temperature-sensitive drugs can be as varied as the countries from which they originate. At last count, I believe I have filed away such regulations from at least 16 different countries. They range from specific and restrictive - like Argentina's Law for Regulating the Cold Chain of Medicine - to broad and interpretive - like Chapter 5 of the U.S. FDA's Food, Drug and Cosmetic Act (also known as the adulterated drug rule). Some are law (like the two mentioned above) and some are guidance - strongly recommended suggestions that bandy around unqualifiedly ambiguous words and phrases like "should" and "may," "shall" and "will," and "is, but is not necessarily limited to," all of which can differ subtly enough in their meaning as to cause confusion across cultures.
Regardless of their wording, they all serve the same purpose and carry the same expectation: drug manufacturers are ultimately responsible for maintaining the quality of their drug product from manufacture to the end user. And this, our industry has learned, is no simple task. Companies continuously wrestle with maintaining control of their product through the wildly diverse and often uncontrollable distribution environment.
The first practical and widely accepted guidance for the transport of temperature-sensitive drugs to extend beyond the confines of drug manufacturing was issued in 2005. That is when the Parenteral Drug Association (PDA) first published Technical Report No. 39 Guidance for Temperature-Controlled Medicinal Products: Maintaining the Quality of Temperature-Sensitive Medicinal Products through the Transportation Environment. It was an instant hit among drug manufacturers and regulators alike. Its purpose was twofold: to provide a high-level document of requirements and expectations agreeable by users in the industry (primarily drug manufacturers and shippers) and as an audit-leveling instrument among various regulatory authorities, beginning with the U.S. FDA and eventually other global authorities.
Within a few months of the release of Technical Report No. 39, came the United States Pharmacopeia (USP) General Chapter <1079> Good Storage and Shipping Practices, Health Canada's GUIDE-0069 Guidelines for Temperature Control of Drug Products during Storage and Transportation, and the World Health Organization's Guidelines on the International Packaging and Shipping of Vaccines. To keep pace, industry associations, trade organizations and interest groups soon got into the act by recommending methods to their members for closing the gaps and reducing the levels of risk within specific sectors the distribution environment.
The International Air Transport Association (IATA) completely revamped its perishables cargo regulations creating a separate chapter for air transport logistics for time and temperature-sensitive healthcare products. The International Safe Transit Association (ISTA) updated its test procedures 5B Focused Simulation Guide for Thermal Performance Testing of Temperature controlled Transport Packaging, and 7D Thermal Controlled Transport Packaging for Parcel Delivery System Shipments. Meantime, the European Cool Chain Association (CCA), European Pharma Logistics Forum (PLF), and Canadian Association of Pharmacy and Distribution Management (CAPDM) all drafted and published their own regulations and guidance. Late in 2009 the Healthcare Distribution Management Association (HDMA) in the U.S. released its guidance Managing Cold Chain & Temperature Sensitive Products, and the entire industry went from "0 to 60" in a very short period of time. As new regulations emerged and compliance expectations evolved, the industry responded.
Technical Report No. 39 underwent considerable revision in 2007 and is scheduled to be revised again in 2011 to include, among other things, medical devices. The PDA earlier this year released Technical Report No. 46 Last Mile: Guidance for Good Distribution Practices for Pharmaceutical Products to the End User, but not without some controversy over the accuracy and applicability of its content. The interest group within the PDA responsible for forming the work groups and drafting such guidance is the Pharmaceutical Cold Chain Interest Group. That group is in the final stages and is expected to soon release new guidance on Recommended Best Practices for Manufacturers of Temperature Sensitive Products to Comply with TSA Cargo Screening Requirements, and another on required stability studies for drug products in distribution. The latter will enable manufacturers to use supporting data to ship or allow during shipment, excursions of product temperatures beyond their label claim - a concept not embraced by regulatory agencies in certain countries. Also nearing publication is a PDA guidance on excursion management, and several guidances related to packaging.
The USP has yet to release its major overhaul of General Chapter <1079> and Health Canada has had GUIDE-0069 in rewrite mode for over a year. The World Health Organization's Harmonized guidance for the storage and transport of time and temperature–sensitive pharmaceutical products is awaiting final release and IATA has recommended the use of a new handling label for time and temperature-sensitive healthcare products that has yet to be adopted. ISTA is rescinding the heavily relied upon Test Procedure 7D and is replacing it with a substantially more complex 7E. Additionally, since there are no regulations defining cold chain packaging standards for construction or performance, ISTA is proposing the purchase of one through its association, along with requirements for insulated package certification, laboratory certification and a program to certify cold chain laboratory personnel. This has been done largely without industry input or a peer-review process.
To many within the industry involved in cold chain packaging, storage and distribution, all of this is beginning to take on a look similar to the dog food aisle at the grocery store - there are simply too many choices. While the industry has come a long way in its knowledge and understanding of the distribution environment, there has never been one overarching, all-encompassing cold chain management document intended to meet all supply chain segments, market needs and regulatory requirements. And it is likely there never will be, because there is no global consensus on such requirements. Drug manufacturers and shippers on the whole, are trying to comply by staying abreast with current best practices but face increased complexity and diverse requirements in a global market. Even the most diligent feel a bit vulnerable; they may be confident but not totally convinced that they have made the correct choice.
Kevin O'Donnell is director and chief technical advisor to industry at Tegrant Corp., ThermoSafe Brands. He can be reached at email@example.com. His blog, Where Cooler Heads Prevail, can be found at http://www.coolerheadsblog.com/blog/