The complex nature of cold chain management means a comprehensive approach is required to ensure all aspects of the supply chain comply with good manufacturing practice. Mike Meakin, DHL Exel Supply Chain, outlines how logistics service providers should use good cold chain management practice (GCCMP).
DHL continues to see an increase in the amount of cold chain storage and distribution required by the growing demands and complexity of clinical trial studies, biologics, blood products, diagnostic reagents and new nanotechnology products, which need refrigerated and deep-frozen solutions. DHL's healthcare sector covers human and veterinary medicines and their supply chains from manufacturing, primary and secondary distribution through local wholesalers and distributors to doctors, hospitals and pharmacies.
To enhance GCCMP capabilities, measures must be undertaken to ensure products are compliant with good manufacturing practice (GMP) and that the five key characteristics of safety, identity, strength, purity and quality (SISPQ) are maintained to ensure the product is not considered adulterated. For a logistics service provider (LSP), the focus concerns people, facilities and equipment, packaging and labelling, operational systems and transportation.
Accordingly, there are several key areas LSPs need to concentrate on: leadership, quality assurance, quality risk management, education and training, and auditing.
Corporate leadership 'compliance first' is the best approach to take, supported by coaching and sharing good practices. While a quality management system (QMS) is a basic requirement, DHL has reformatted its Quality Policy Manual by updating and referencing every section to the relevant international GxP clause. The manual is referred to as the 'yellow book', and covers the rules and guidance for good storage and distribution practices, thereby ensuring a compliance-first approach. The yellow book is underpinned by GxP directives and guidelines.
Quality directives on GCCMP, as well as quality guidelines on temperature-assured storage and transportation of medicinal products, temperature mapping, calibration, qualification and validation are a further part of DHL Healthcare's quality approach to give consistency across geographies. All use John Taylor's recommendations on the control of storage and transportation temperatures of medicinal products published in The Pharmaceutical Journal and in the MHRA's 2007 'orange guide'.
All the foregoing documents quote international regulations and guidelines together with standards such as ASTM, IATA, IMO, ISTA, NIST and PDA, to assist various country sites on requirements and good practice.
The quality directives are aimed at giving direction, clarifying policy and setting minimum standards. DHL employs over 20 pharmacists in its EMEA region to write, verify, approve and version control GxP guidelines. DHL policy links key standards such as IATA PCR chapter 17, USP 1079, processes such as PDA Technical Agreement 39 and ISTA 7D in line with EU Member States and FDA regulations, together with WHO guidelines under GCCMP.
The key elements of GCCMP within an LSP's quality management system (QMS) are change control, corrective action preventative action (CAPA), deviation reporting, qualification and validation, - and these are also key elements in DHL's QMS and those of its customers. By working with its clients, DHL ensures that responsibilities are defined within technical agreements. Accordingly, it is important that standards are set and agreed with by clients for completing reports, undertaking actions and obtaining appropriate sign-off.
LSPs should be aligning their QMS with ICH Q10, thereby linking their quality policy, quality plan, key objectives and quality risk management. DHL has found this approach germane to the GAMP 5 risk-based approach while ensuring patient safety along with product quality.
Logistics operations will find, from handling high risk medical devices in accordance with ISO 13485:2003 and 14971:2007, that cold chain requirements can be managed in a similar process to that of pharmaceuticals under ICH Q9 and EU GMP Annex 20. As the ISO 14971:2007 application of risk management has a similar process to EU GMP Annex 20, they all require science-based techniques such as PHA, FMEA and HAZOP. LSPs can have a GCCMP approach for all product groups.
As a consequence, LSPs can focus on the four cornerstones of their operations:
This will ensure LSPs understand their customers' requirements and appreciate the risks to patient safety where errors can be difficult to detect and where products are shipped direct.
DHL's quality risk management has been developed so it recognises the need to look at developing risk management plans and files of its process and actions.
In addition to LSP undertaking GxP induction and refresher training for their employees, additional training and awareness must be given in GCCMP. People need to understand the differences between active and passive shipments, what can go wrong, and how that will affect SISPQ and, ultimately, the patient.
One initiative launched following GAMP 5 in DHL has been its interactive e-learning module on qualification and validation. This was based on DHL's corporate approach as outlined in Chapter 18 of Validating Pharmaceutical Systems (edited by John Andrews; August 2005). This allows DHL employees to access the training via the internet during their own time, to work through the GMP requirements relating to qualification and validation, and undertake an assessment to confirm their understanding of the subject.
LSPs need to go beyond the basic GxP requirements for self-inspection. Having independent corporate compliance audits gives additional benefits such as ensuring compliance, improving quality and giving confidence to customers and regulators. They are also excellent for ensuring greater consistency across geographies.
DHL's compliance auditing strategy has been developed using guidelines from the Global Harmonization Task Force, for example, SG4/N30R20:2006 on Regulatory Auditing of Quality Management Systems, Part 2: Regulatory Auditing Strategy. This is a good way of planning, preparing and conducting regulatory audits and getting a balance between checklist-type questionnaires to understand how effective the QMS is.
LSPs must use independent, trained quality auditors. In its quality guidelines, DHL has specified minimum standards for different grades of internal auditors to conduct such audits. In addition, DHL conducts peer group audits where it operates an account in more than one country. The actual audit programme is also linked to a number of self-audit questionnaires on subjects such as GCCMP to identify potential areas of risk.
The audit process will benefit LSPs with learning while gaining GCCMP experience and maturity from internal, customer and regulator audits. This is also an opportunity for sites to share information with other pharmaceutical operations who have similar processes through regional GxP meetings and web calls between responsible persons and qualified persons.
An LSP's approach to quality standards within GCCMP needs to cover several key areas. 'The Yellow Book' sets out policy in DHL to meet GxP guidelines supported by quality directives and guidelines over and above standing operating procedures.
Key elements ensuring the quality assurance of products come through deviation reporting and CAPAs when things go wrong and change control management signed off by the client.
An integrated approach linking policy, plans and QRM will save duplication and enhance focus. Education and training backed up by CPD for key people and independent auditing complete the main areas of approach for LSPs to follow to ensure quality within the cold chain. It is important that standards are set and agreed with clients for completing reports, undertaking actions and getting sign-off.
Mike Meakin, vice president, Quality Assurance Regulatory Affairs for DHL Exel Supply Chain within EMEA, has more than 20 years' experience within healthcare and chemical logistics, including wholesale operations. Over the last ten years, he has focused on the healthcare industry covering biologics, medical devices and pharmaceuticals.