Kevin O'Donnell09.06.07
Several Canadian pharmaceutical and healthcare products manufacturers, distributors and wholesalers organizations have rallied together in an effort to meet their country's rigid guidelines: Temperature Control of Drug Products during Storage and Transportation. The regulation issued by the Health Products and Food Branch Inspectorate of Canada on November 17, 2005 came as a result of a survey the HPFB Inspectorate conducted in 2003 regarding transport and storage conditions of drug products.1 The survey indicated a need for additional guidance to ensure that the requirement of the Food and Drug Regulations pertaining to storage and transport of drug products are met.
The guidance was drafted with a strong emphasis on monitoring shipments during transport. A review of the survey reveals how the agency recognized this as a critical gap and came to its recommendation. When asked whether establishments were using tools to monitor whether appropriate product conditions were maintained during shipping, only one-third of the respondents answered "yes" and 61.5% of all manufacturers, packagers, labelers, distributors, importers and wholesalers didn't monitor storage facilities or shipments at all.
A draft document was posted for comments on the Inspectorate web site in December 2004. Those comments were reviewed by the Good Manufacturing Practices (GMP) Committee and those that were accepted were included in this new document.
The tightly written eight-page document, commonly known as Guide-0069, is arguably the most restrictive and yet the most vaguely written regulatory guidances on maintaining control for temperature-sensitive drugs during storage and distribution. Typically, the Provincial Governments in Canada write legislation in generalities, leaving it open to interpretation with more detailed road mapping found in specific regulations. In the case of Guide-0069, it gives the innovators, generics, distributors, wholesalers and others within the supply chain great flexibility, but it also gives regulators equal flexibility for interpreting and enforcing the regulations as cited in the example, "Refrigerators and freezers used to store drugs should be well maintained."2
Such ambiguity has led several stakeholders -- the Canadian Association for Pharmacy Distribution Management (CAPDM), the national Research-Based Pharmaceutical Companies (Rx&D), NDMAC (Canada's $4 billion over-the-counter self-care health products industry association,) the Pharmaceutical and Personal Care Logistics Association (PPCLA), and the Canadian Generic Products Association (CGPA) -- to organize a cross-industry contingent to comply with Health Canada's mandate.
In the summer of 2006, the unified group organized a Temperature Control Coalition. Four working groups were formed to address specific areas of concern:
Each working group prepared drafts of documents in a concerted effort to comply with current regulations. Final drafts will be distributed among the constituents of each industry organization for final comments in October of 2007. The approved documents will be provided to the respective industry members for use on a voluntary basis as a guide to meet regulatory expectations, and builds on CAPDM's Temperature Control Best Practices developed in 2006.
Additionally, the leadership of the coalition has targeted a meeting with the HPFB Inspectorate Director General in Ottawa in the fall of 2007 to show the agency that industry has provided due diligence in meeting their regulatory expectations. The coalition hopes to take this opportunity to meet with the HPFB Inspectorate to lessen the two parties' cautious shadow dance and open the lines of communication. They intend to work cooperatively with the agency on a continuous improvement basis in an effort to phase-in the regulations, focusing on products that are more critical first.
Lastly, there are a number of reasons affecting the full implementation and compliance of Guide-0069, including Provincial changes in licensing procedures and the fees associated with them among drug wholesalers and distributors.
It is the inevitable hope of the CAPDM's Temperature Control Coalition to seek a realistic timeframe to become fully compliant with the regulations and to provide the Inspect-orate with substantive and constructive realities of the drug industry to incorporate into the revised edition of Guide-0069 which the HPFB Inspectorate expects to deliver in late 2007 or early 2008.
Canada's unique chain of custody requirements puts the burden of regulation on everyone who takes ownership or transfer of the drugs in distribution -- manufacturers through to wholesalers and downstream to retailers. Inventories are large and expensive and move through the process like a medicinal hot potato. No one wants to maintain ownership any longer than they have to, forcing the drugs through the distribution process quickly.
Canada's geography, the lopsided dispersion of its population, and extreme climate, further complicate and challenge the safe transportation of temperature sensitive drug products. Canada is enormous, with a land mass of nearly 10,000,000 square kilometers (4,000,000 square miles) second only to Russia. Approximately 80% of Canada's 33.4 million inhabitants (equal to that of the State of California, which is 1/25th its size) live basically on an east-west line along a 4,000-mile stretch of its southern border, within 100 miles of the U.S.
The nation's population is concentrated in four broad urban regions: the extended Golden Horseshoe in southern Ontario; Montral and environs; British Columbia's Lower Mainland and southern Vancouver Island; and the Calgary-Edmonton corridor. These areas can be reached effectively with regional distribution. However, this only accounts for 51% of the country's population.3
It is expected and we have an obligation that all parts of all provinces will be properly serviced," said Allan Reynolds, vice president of Industry & Member Relations for the Canadian Association of Pharmacy Distribution Management (CAPDM). "That means we must provide equal access to medicines and other health-care products whether it is in Montreal or Yellowknife [in the Northwest Territories]."
Although the range of temperatures across the length and breadth of this vast country is actually much less polarized than most people realize, it is still a matter of concern to the HPFB Inspectorate. Said Mr. Reynolds, "Rigorous demands are made by government inspectors regarding packaging and shipping conditions, temperature monitoring including certificates of calibration for data loggers and thermometers, temperature monitoring during transport and storage, profiling temperatures at known periods of summer and winter extremes, and many other procedures."
In addition to Guide-0069 requirements, Mr. Reynolds also cited federal law. "Canada's Food and Drug Act defines 'unsanitary conditions' as any condition(s) that may render a drug injurious to health. We thus have to interpret this to cover any degradation of products, microbial growth or other change that may adversely affect human health by exposure. Additionally, we must take into account changes in the product that may not render it harmful but render it ineffective. In other words, with the existing regulatory and legislative language, we -- as an industry -- have to be ready for anything, any time, anywhere," he said.
Lambert, Jean, Director General, Health Canada, Health Products and Food Branch Inspectorate, Guide-0069 Guidelines for Temperature Control Drug Products during Storage and Transportation, 17 Oct., 2005, p.1 // return to article
Lambert, Jean, Director General, Health Canada, Health Products and Food Branch Inspectorate, Guide-0069 Guidelines for Temperature Control Drug Products during Storage and Transportation, 17 Oct., 2005, p. 4, Sec. 1.3 // return to article
Statistics Canada, Population and Dwelling Counts, for Census Divisions, Census Subdivisions (Municipalities) and Designated Places, 2001 and 1996 Censuses, Catalogue number 93F0050XDB01003 // return to article
The guidance was drafted with a strong emphasis on monitoring shipments during transport. A review of the survey reveals how the agency recognized this as a critical gap and came to its recommendation. When asked whether establishments were using tools to monitor whether appropriate product conditions were maintained during shipping, only one-third of the respondents answered "yes" and 61.5% of all manufacturers, packagers, labelers, distributors, importers and wholesalers didn't monitor storage facilities or shipments at all.
A draft document was posted for comments on the Inspectorate web site in December 2004. Those comments were reviewed by the Good Manufacturing Practices (GMP) Committee and those that were accepted were included in this new document.
The tightly written eight-page document, commonly known as Guide-0069, is arguably the most restrictive and yet the most vaguely written regulatory guidances on maintaining control for temperature-sensitive drugs during storage and distribution. Typically, the Provincial Governments in Canada write legislation in generalities, leaving it open to interpretation with more detailed road mapping found in specific regulations. In the case of Guide-0069, it gives the innovators, generics, distributors, wholesalers and others within the supply chain great flexibility, but it also gives regulators equal flexibility for interpreting and enforcing the regulations as cited in the example, "Refrigerators and freezers used to store drugs should be well maintained."2
Such ambiguity has led several stakeholders -- the Canadian Association for Pharmacy Distribution Management (CAPDM), the national Research-Based Pharmaceutical Companies (Rx&D), NDMAC (Canada's $4 billion over-the-counter self-care health products industry association,) the Pharmaceutical and Personal Care Logistics Association (PPCLA), and the Canadian Generic Products Association (CGPA) -- to organize a cross-industry contingent to comply with Health Canada's mandate.
In the summer of 2006, the unified group organized a Temperature Control Coalition. Four working groups were formed to address specific areas of concern:
- Contracts and Information Sharing Group was tasked with developing stakeholder specific information for cross-industry sharing; delineating types of information, responsible parties, and parameters for use for both temperature excursion information and shipping times/lanes profiles. They also were responsible for developing contract templates and confidentiality templates for use between and among stakeholders.
- Temperature Control & Classification Group took on the responsibility of defining leading practices for route profiling and temperature monitor classification in addition to providing guidance for qualified packaging.
- Stability Data Group was organized to review current stability testing standards, identify and review literature sources that provide stability data facts, weed out myths and determine gaps in existing data sources.
- Government Relations Group focused on developing an education model for Health Products and Food Branch Inspectorate (HPFB), a communication strategy for HBFB Inspectorate regional operations, and establishing an ongoing dialog with the appropriate government officials.
Each working group prepared drafts of documents in a concerted effort to comply with current regulations. Final drafts will be distributed among the constituents of each industry organization for final comments in October of 2007. The approved documents will be provided to the respective industry members for use on a voluntary basis as a guide to meet regulatory expectations, and builds on CAPDM's Temperature Control Best Practices developed in 2006.
Additionally, the leadership of the coalition has targeted a meeting with the HPFB Inspectorate Director General in Ottawa in the fall of 2007 to show the agency that industry has provided due diligence in meeting their regulatory expectations. The coalition hopes to take this opportunity to meet with the HPFB Inspectorate to lessen the two parties' cautious shadow dance and open the lines of communication. They intend to work cooperatively with the agency on a continuous improvement basis in an effort to phase-in the regulations, focusing on products that are more critical first.
Lastly, there are a number of reasons affecting the full implementation and compliance of Guide-0069, including Provincial changes in licensing procedures and the fees associated with them among drug wholesalers and distributors.
It is the inevitable hope of the CAPDM's Temperature Control Coalition to seek a realistic timeframe to become fully compliant with the regulations and to provide the Inspect-orate with substantive and constructive realities of the drug industry to incorporate into the revised edition of Guide-0069 which the HPFB Inspectorate expects to deliver in late 2007 or early 2008.
Market Reality
Canada's unique chain of custody requirements puts the burden of regulation on everyone who takes ownership or transfer of the drugs in distribution -- manufacturers through to wholesalers and downstream to retailers. Inventories are large and expensive and move through the process like a medicinal hot potato. No one wants to maintain ownership any longer than they have to, forcing the drugs through the distribution process quickly.
Canada's geography, the lopsided dispersion of its population, and extreme climate, further complicate and challenge the safe transportation of temperature sensitive drug products. Canada is enormous, with a land mass of nearly 10,000,000 square kilometers (4,000,000 square miles) second only to Russia. Approximately 80% of Canada's 33.4 million inhabitants (equal to that of the State of California, which is 1/25th its size) live basically on an east-west line along a 4,000-mile stretch of its southern border, within 100 miles of the U.S.
o = Population greater than 1,000 n = Population less than 1,000 Source: Statistics Canada |
The nation's population is concentrated in four broad urban regions: the extended Golden Horseshoe in southern Ontario; Montral and environs; British Columbia's Lower Mainland and southern Vancouver Island; and the Calgary-Edmonton corridor. These areas can be reached effectively with regional distribution. However, this only accounts for 51% of the country's population.3
It is expected and we have an obligation that all parts of all provinces will be properly serviced," said Allan Reynolds, vice president of Industry & Member Relations for the Canadian Association of Pharmacy Distribution Management (CAPDM). "That means we must provide equal access to medicines and other health-care products whether it is in Montreal or Yellowknife [in the Northwest Territories]."
Although the range of temperatures across the length and breadth of this vast country is actually much less polarized than most people realize, it is still a matter of concern to the HPFB Inspectorate. Said Mr. Reynolds, "Rigorous demands are made by government inspectors regarding packaging and shipping conditions, temperature monitoring including certificates of calibration for data loggers and thermometers, temperature monitoring during transport and storage, profiling temperatures at known periods of summer and winter extremes, and many other procedures."
In addition to Guide-0069 requirements, Mr. Reynolds also cited federal law. "Canada's Food and Drug Act defines 'unsanitary conditions' as any condition(s) that may render a drug injurious to health. We thus have to interpret this to cover any degradation of products, microbial growth or other change that may adversely affect human health by exposure. Additionally, we must take into account changes in the product that may not render it harmful but render it ineffective. In other words, with the existing regulatory and legislative language, we -- as an industry -- have to be ready for anything, any time, anywhere," he said.