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Cool Guidance

Eric Newman at ProTecht Risk Solutions gives advice on a risk-based approach to cool chain management

Pharmaceutical manufacturers face a daunting challenge in today’s market. In addition to understanding the stringent government regulatory requirements and adherence to current Good Manufacturing Practices (cGMP), they must also bear the responsibility and burden of understanding the complexities and rigours involved in moving their sensitive products through the distribution chain. With more attention being given by regulators to the distribution of these products, manufacturers must ensure that their shipping and handling procedures are such that their products are adequately protected as they move through the distribution chain and are delivered to the end-user.

Manufacturers need to fully analyse all the potential risks that exist within the cold chain in order to develop and implement proper and effective shipping and handling procedures designed to protect the quality, integrity, efficacy, strength and potency of the product.

During the manufacturing and packaging process, manufacturers have the ability to maintain complete control of the product by adhering to well-defined processes and protocols that are mandated by government regulations and cGMP protocols. Conversely, the level of control sharply decreases when products enter the distribution chain and, as a result, the risk of loss or damage increases dramatically.

Despite this reduced level of control during distribution, the manufacturer still has a regulatory responsibility to ensure that the product is protected until its delivery in the state required by the end-user. Therefore it is imperative that manufacturers gain a firm understanding of the complexities involved within the supply chain so as to anticipate any circumstances and conditions that could potentially have deleterious effects on the product. In doing so, manufacturers can work with their logistics service providers to implement appropriate and effective shipping and handling procedures that are aligned with Good Distribution Practices (GDP) which will provide the required level of protection to the product throughout the distribution process.

Over the past few years, there have been several guidance documents published by industry organisations that address GDP. The ‘Good Storage & Shipping Practices’ was first published by the US Pharmacopeia (USP) in 2005 and provides guidance to manufacturers, wholesalers and transport logistic providers concerning the proper packaging, transport and storage of temperature-sensitive pharmaceutical products (the Packaging and Storage Expert Committee of the USP is currently revising the chapter) (1).

In 2005, the PDA published a report which provided industry guidance on the essential principles and practices of transporting temperature-sensitive medicinal products through the transportation environment (2). In 2007, the PDA published a revised version in order to harmonise with EU regulations (3). In 2009, the PDA published Technical Report 46 ‘Last Mile Guidance for Good Distribution Practices For Pharmaceutical Products To The End-User’ to provide guidance to all parties involved in the ‘last mile’ regarding the proper handling and storage of temperature-controlled medicinal products and devices (4).

The above mentioned documents (as well as other global regulatory documents and compendial standards) provide guidance to the pharmaceutical industry on the essential principles and practices involved with the distribution of temperaturesensitive pharmaceutical products. By performing diligent front-end risk analysis and implementing appropriate mitigation steps based on the results of that analysis, manufacturers can adhere to the principles and practices addressed in these guidance documents.

In order to develop an effective cold chain management programme that utilises this risk-based approach, manufacturers should take the following eight critical elements into consideration:

  • Pre-shipment planning and risk analysis
  • Standard operating procedures
  • Product packaging
  • Logistics service agreements
  • Service provider selection and monitoring
  • Shipment tracking
  • Transport security
  • Continuous improvement process


Manufacturers should perform diligent front-end mitigation analysis designed to identify any risk factors that could potentially pose a threat to the overall quality and integrity of the product during transit. This front-end mitigation analysis should include:

  • Pre-shipment route planning (to identify exact shipping lanes to be used)
  • Analysis of the carriers and subcontractors to be used, mode of conveyance and packaging requirements
  • The product temperature requirements
  • The product handling requirements (including stowage requirements)
  • Road transport issues
  • The security requirements
  • The anticipated climatic conditions throughout the entire transit
  • Customs clearance procedures
  • Shipment documentation
  • The availability of temperaturecontrolled vehicles
  • The storage areas needed

Proper pre-shipment planning should also include contingency planning for maintenance of product quality and integrity in the event of unscheduled stoppages or delays due to customs clearance procedures, government security inspections, and adverse weather conditions.


It is best practice for manufacturers to develop written cold chain management standard operating procedures (SOPs) that outline both the product- and lane-specific handling and safety procedures that must be followed by third-party logistics (3PL) service providers responsible for handling, transporting and storing temperaturesensitive products. A copy of the SOPs should be distributed to all service providers to ensure that they are not only familiar with the product handling and safety requirements, but that they also understand and appreciate the sensitivities and tolerances of the particular products being shipped.

The SOPs should outline specific instructions with regards to:

  • Handling and stowage requirements
  • Transportation service levels
  • Sub-contractor limitations
  • Routing
  • The length of transit time
  • In-transit temperature and humidity requirements
  • Temperature excursion threshold limits
  • Temperature and humidity monitoring procedures
  • The maximum amount of time a product can be exposed to non-climate controlled environments
  • The type of trucks required for transport
  • Equipment handling requirements
  • Storage requirements

Based on cost, need and feasibility, security requirements should also be considered for inclusion in the SOP for specified shipping lanes or highly valuable or particularly sensitive products that are being shipped.


Product packaging plays a critical role in ensuring that the condition and integrity of the product is maintained. In addition to product temperature requirements, the method of packing should be designed based on qualification studies that take into account the mode of conveyance, anticipated climatic conditions throughout the entire transit, routing, length of transit, conditions at interchange points or hubs, customs clearance and government inspection procedures.

The primary packaging should also be designed to provide adequate protection against any physical damage (even if only cosmetic in nature) that could compromise the overall quality or integrity of the product.

Packaging methods should not only be qualified based on the product requirements, but should also be qualified based on the mode of conveyance and the identified exposures along the intended shipping lane. The packaging design should also be monitored on an ongoing basis and revised as necessary to account for any changes that may occur with the product or the manner in which it is shipped.

When developing a packaging method for temperature-sensitive products, consideration should be given to consulting with qualified independent third-party packaging vendors and consultants that specialise in both product packaging design as well as shipping qualification studies. The data collected from shipping qualification studies (whether performed in-house or by an independent third party) should be used and included in the manufacturer’s master validation plan.


In many instances, carriers or logistic agents provide shippers with ‘boilerplate’ or standardised SOPs that are meant to be tailored to the particular products being shipped. Although the carrier or logistic agent’s SOP may address some of the necessary issues involving the product being shipped, the manufacturer’s SOP should be an overriding document that goes into much greater detail with the carrier being held accountable for the strict adherence to these requirements. In addition, both the manufacturer and shipper SOP should be effectively tied into the logistic service agreement, thereby making the carrier a committed stakeholder in the safe and on-time delivery of the shipment.

This could further be enforced by adding clauses to a service provider’s contract, holding them financially responsible in the event of loss or damage to product during transit where it could be demonstrated accurately that the shipping and handling SOP was not followed.

The manufacturer’s cold chain management SOP should be developed in collaboration with the 3PL service provider and reviewed on a regular and frequent basis, so as to allow for necessary revisions and updates to be made. In doing so, the relationship between manufacturer and service provider will be more of a partnership – both parties will be working together to continually refine and improve the process.

It is important to actively engage the 3PL service providers and hold them accountable for adherence to established shipping and handling procedures as well as safety requirements outlined in the SOP.


A vital element of an effective cold chain management programme is the choice of capable and qualified transportation and logistic service providers who are experienced in the handling, tracking, storage and transportation of temperaturesensitive pharmaceutical products.

Given the sensitivity of pharmaceutical products to temperature excursions, handling damage and delays in transit, it is important to consider the use of a ‘closed loop’ or single-source supply chain service provider that will maintain custody of the product and minimise handling throughout transit. Furthermore, the use of a singlesource supply chain service provider allows for tighter controls and monitoring of shipments. It also allows for proper performance monitoring of the carrier to ensure adherence to established and required shipping and handling procedures.

Service reviews of all 3PL service providers should be conducted on a regular basis to confirm that they meet the established SOPs on a shipment-toshipment basis. As part of the service provider review programme, consideration should be given to establishing a report card system that outlines quantifiable grading metrics or key performance indicators (KPIs) that will allow the manufacturer to effectively manage their carriers and logistic service providers.


Due to varying regulatory requirements throughout the world, there is increased likelihood of shipments being held up or delayed in transit for customs clearance, government security inspections and import and export documentation issues. Therefore, an important element of an effective cold chain management programme is tracking shipments throughout transit on a real-time active basis.

Real-time shipment tracking allows early detection of any stoppages or delays that may occur in transit and prompt investigation of the circumstances involved so that immediate action can be taken to locate the product and arrange for through delivery to the destination in a timely manner.

Rather than tracking shipments simply as a means to confirm delivery, manufacturers should actively track each individual shipment so that they are aware of its location at any given time. The tracking process should be fully documented so manufacturers can confirm to regulators and customers alike that the integrity of the product was not compromised at any point during transit.


The recent explosive growth in the pharmaceutical industry has resulted in an increased volume of high-value products being placed into the supply chain. An unfortunate by-product of this increased volume is the elevated risk of theft while the product moves through the distribution chain.

Cargo theft poses a serious challenge for pharmaceutical manufacturers and distributors who are ultimately responsible for protecting these products during transportation including the ‘last mile’ delivery to the end-user.

Manufacturers and distributors responsible for shipping high-value pharmaceutical products should perform risk evaluations of all of their shipping lanes in order to identify potential security gaps. This will enable them to prepare and implement appropriate loss prevention procedures that are aligned with industry best security practices to ensure their products are delivered to the end-user safely, intact and on time.

An important and effective best practice approach that will help reduce the risk of theft in transit is for manufacturers to collaborate with qualified and reputable transportation and logistic service providers that are capable of meeting all of their service level requirements. These requirements should be outlined in the shipping and handling SOP that is directly tied into a master service agreement, clearly defining the roles and responsibilities of all parties involved in the transportation of the shipment.

The shipping and handling SOP should contain specific security requirements such as:

  • Driver background checks
  • Driver training level requirements
  • Sub-contractor limitations
  • Approved routing
  • No-stopping requirements
  • In-transit communication
  • Escort requirements
  • Contingency planning
  • Escalation procedures
  • Use of upgraded trailer locks and seals

Another crucial element to any effective cold chain management programme is an active, real-time shipment tracking system that includes a layered approach using qualified electronic GPS tracking devices. This would make it difficult for would-be thieves to locate and disable the devices. Active real-time shipment tracking using electronic devices provides early detection of any stoppages, delays or route deviations that occur in transit, and allows for prompt investigation of the circumstances involved and coordination with local law enforcement to locate the goods in a timely manner.


Improving cold chain management is a cyclical and iterative process which starts with a comprehensive risk analysis that identifies and evaluates all exposures that exist within the cold chain. Once the exposures have been identified and evaluated, appropriate procedures and protocols designed to protect the product from those exposures need to be implemented (and outlined in a written SOP). Finally, there needs to be audit procedures established that will provide ongoing assessment and analysis to allow for necessary adjustments to be made so that the programme remains current and effective.


A risk-based approach to cold chain management that takes the eight critical elements discussed into account will allow manufacturers to not only meet their regulatory responsibility, but more importantly, their obligation to protect the health of the general public by ensuring their products remain safe as they move through the distribution chain to the end-user – the patient.


  1. US Pharmacopeia, General Guidance Chapter, 1079, Good Storage & Shipping Practices, 2005
  2. PDA Technical Report 39, Cold Chain Guidance for Medicinal Products, 2005
  3. PDA Technical Report 39, Guidance For Temperature-Controlled Medicinal Products, revised 2007
  4. PDA Technical Report 46, Last Mile: Guidance for Good Distribution Practices For Pharmaceutical Products to the End User, 2009

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Eric Newman is Vice President of ProTecht Risk Solutions, a division of Falvey Cargo Underwriting. As practice leader for life science and cold chain transportation and logistics, Eric provides consultative services in risk mitigation programs and practices. He is a member of the PDA’s Pharmaceutical Cold Chain Interest Group (PCCIG), Transport Packaging Committee of the Institute of Packaging Professionals (IoPP), Transported Asset Protection Association (TAPA) and the Pharmaceutical Cargo Security Coalition (PCSC). Eric also serves as an advisory board member of the International Maritime Business Department at the Massachusetts Maritime Academy, where he graduated with a BA in Marine Transportation.
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