GOOD DISTRIBUTION PRACTECES: THE NEW GUIDELINE AND ITS CONSEQUENCES FOR INDUSTRY
The pharmaceutical industry is highly regulated and, as a result there is a heavy emphasis on compliance with the various regulatory requirements. Historically, the key concerns of manufacturers have been compliance and GMP; every effort is made to ensure that the products manufactured are safe, effective and in compliance with the details registered and with GMP. Not so much emphasis however, was placed upon what happened to these, carefully manufactured products, once they left the site. Twenty to thirty years ago of course, pharmaceutical companies had multiple manufacturing facilities and distributed their products locally so travel distances and journey times were relatively short; international distribution across vast distances was relatively rare.
Little attention was paid to product storage and distribution; if the warehouse was dry, relatively clean and had a reasonable level of security, then the assumption was that all would be well. Similarly, companies simply ensured that the vehicles used were clean and dry, and avoided sharing the load with food stuffs and fertilisers. Introduction of the EU GDP Guidelines in 1994 (94/C63/03) was an important first step, both for the regulators and for the industry. The levels of control introduced brought about many changes and improvements in the storage and distribution of pharmaceutical products.
However, in light of the increased globalisation of the supply chain, the industry's drive to reduce costs and, more recently, the growing risk of counterfeiting and fraud, it was clear that these regulations were no longer adequate. Last year, the new EU directive on falsified medicines (2011/62/EU), signalled a shift of emphasis by describing the responsibilities of the QP with respect to the supply chain. The revised EU GMP Chapter 1 also defines the role and involvement of QPs in the supply chain; there is an expectation that the QP will approve 3rd party logistic service providers and ensure that quality agreements are in place which define the requirements with respect to supply chain security. Revision of the GDP guideline was therefore necessary and the new draft guideline (issued in July 2011 for public consultation) has taken into account the demands of the modern pharmaceutical supply chain.
The new document represents a major step forward in terms of the clarification of the requirements; it demonstrates the regulators' understanding of the business challenges as well as recognising the need to protect patients. However, it does introduce challenges for virtually all of the players in the pharmaceutical supply chain.
The new document is laid out in logical steps spanning 10 chapters; quality risk management within the supply chain is given the recognition it deserves and management responsibility/ ownership, in relation to product quality is clearly defined. None of this should require any additional work on the part of pharmaceutical wholesalers, and yet it should generate business improvements and bring about the sort of cost savings which are welcomed by all.
The role of the responsible person has been defined in more detail, but it is not clear whether there is requirement to have one in place permanently. Does this mean a full time employee? If so, the industry will face a major shortage of suitably experienced people, and the additional costs of employing a full-time RP may prove unsustainable for smaller companies.
Recommendation
Thursday, 13 June 2024 9 .00 - 17.30 h
GDP Audits - Live Online Training
Chapter 3, Premises and Equipment, details the need for temperature and environmental control in warehouses. This is not a new idea, but there are many warehouses across Europe, designed and built several years ago which will not be able to offer a controlled temperature environment for products. There is also a requirement to qualify and validate facilities and computer systems which brings the wholesalers' operations in to line with the manufacturing environment. Whilst many of the more modern facilities have been validated to current standards, the majority of the facilities, equipment and computer systems are several years old. Validation of the older facilities will take a long time, a large resource allocation and considerable planning as many will require major changes and updates. The industry will need to make a significant financial investment which, for some, will be a step too far.
Chapter 5, Operations, introduces the concept of qualification of suppliers and customers which goes hand in hand with the anti-falsification policy. However, not many wholesalers have the resource or experience to perform such tasks and this is an area where manufacturers will need to provide support to their chosen 3PL; enabling them to implement a supplier management process in their organisation. Destruction of unwanted goods (e.g. rejects, out of life and damaged stock) at wholesalers usually involves collation of the material for destruction until such time as a full load is accumulated. This is then shipped to a local incineration company for destruction. Very little, if any, information is retained on the contents of the load (i.e., product name, lot number, quantities, or the name of the manufacturer). This is a weak-link in terms of security which can easily be exploited by opportunists; better control of waste management is essential and it is no surprise that the new guideline demands it. Improved record keeping will be required, possibly updating of the warehouse management system and the auditing and approval of incineration facilities, which will require expert resource. So, inevitably, minimising the risk of unwanted product finding its way back into the supply chain by ongoing secure management of waste materials will increase costs.
Chapter 6 covers the requirements in relation to complaints, returned products, suspected falsified medicinal products and product recall. Nothing major has been added in this chapter compared to the existing regulations but the requirements regarding the handling of returned goods has been clarified by detailing the conditions which should be met before returned goods are put back into saleable stock.
To minimise the risk of falsified medicine entering the legitimate supply chain, there is now an expectation that wholesalers' staff are made aware of how falsified medicine can enter the supply chain. In addition the wholesalers are required to inform the competent authorities and where applicable, the marketing authorisation holders, of any medicinal products they identify as falsified or suspect to be falsified. These changes will require wholesalers to develop new procedures and ensure all their staff are trained.
The need to regularly evaluate effectiveness of the recall procedure brings the GDP requirements for recall in line with the cGMP expectations at manufacturing sites. This is an important aspect of the role of the wholesaler in providing information and support. There are many business benefits in ensuring the effectiveness of the recall process.
Contract Operations - covered in Chapter 7 - is an area which has developed rapidly in recent years, and the new requirements should not create too great a burden on resources. Most wholesalers have technical, quality and commercial agreements with their clients but these documents can always be improved, and the new document provides good guidance. However, there is currently a weakness in terms of a lack of contracts between wholesalers and smaller operators e.g. sub-contracted cleaning companies or pest control companies and more effort will be required to develop suitable contracts in such cases. Companies should see this as an opportunity to improve their relationships with their suppliers and embrace the opportunity to reap the business benefits. Clearly defined roles and responsibility in a contract agreement will help both the contract giver and the contract acceptor in the event of dispute. It will also allow the company to deliver a more cost effective service to their customers. None the less, one must recognise that for the first year of implementation there will be an additional need for resources to develop such agreements where none currently exist. The ongoing maintenance of the contracts will be important but it should not be resource intensive.
Chapter 8, Self Inspection, expands and emphasises the need for a robust self inspection programme. It recognises the need for independent assessment of the operations and their compliance with regulations and offers the opportunity to use external resources for this assessment. There is an emphasis on the need for audits of subcontractors to be included in the self inspection program and this is an area where wholesalers will need to make an investment, either by training and developing their personnel or employing external resource. In either case, there will be a need for collaborative audit programs otherwise the resource requirement for external audits will be unmanageable.
Chapter 9, Transportation, has been extensively revised. The requirement for transportation of medicinal products in accordance with the storage conditions indicated on the label has been re-emphasised, with transportation being viewed as an extension of product storage for the duration of the journey. Few products are transported directly from point A to point B, product handover and cross docking, are the norm in today's supply chains and the need for the use of storage hubs during transportation is not always avoidable. Whilst no specific limit has previously been stated, it has been widely accepted that provided that storage time at hubs did not exceed 72 hours there is no requirement for auditing, approval or licensing. The new GDP guideline specifies a time limit of 24 hours; where storage hubs are used to hold product for longer than 24 hours, they are deemed to be acting as storage facilities and hence should have wholesale dealer's licence. Furthermore, any storage hub used for storage of refrigerated products, for any period of time must hold a wholesale dealer's licence.
It is further stated that the premises used for unloading and reloading, e.g. at terminals and hubs, should be audited and approved prior to use. Particular attention should be paid to changes made to these facilities, and to the control and monitoring of the temperature.
The new requirements for auditing approval and licensing of storage hubs will place additional demands upon wholesalers, product manufacturers and member state competent authorities. None of the storage hubs currently used have been audited by regulators and, whilst some may hold storage licences, the vast majority do not fulfil the licensing requirements. The pharmaceutical industry will need to rethink its approach to product distribution with a view to rationalising their use of storage hubs and reducing storage times by better management of inventory. A large question mark remains as to where the resources required to implement this expectation (at regulators, wholesalers, 3PL's and manufacturers) will come from. This will probably be the greatest challenge for the industry and regulatory authorities arising from these new guidelines.
The need for control of temperature during transportation has been clarified, extending beyond the extensive investment and improvement made in cold chain distribution over the past 5- 10 years where industry has made. There is an expectation for refrigerated vehicles to have temperature monitoring in place using calibrated devices. It is also expected that such vehicles are temperature mapped, under representative conditions, taking into account seasonal variation. Considering the number of refrigerated vehicles in use across Europe and the inherent complexity of temperature mapping studies which account for seasonal variation, this is going to be an onerous task. Once again, an industry wide approach will be required if compliance with these requirements is to be achieved; this will take time.
Finally, Chapter 10 defines a specific provision for brokers. Brokers are involved in many activities which could impact product quality and yet this is an area which has never, previously, been regulated. Brokers are not normally involved in the physical handling of medicinal products; they operate independently and simply negotiate the sale or purchase of medicinal products on behalf of another organisation. Brokers are now to be subject to a requirement under which they will need to register a permanent address and contact details. As brokers do not handle product, the requirements regarding premises, installation and equipment as set out in Directive 2001/83/EC do not apply. However, all the other rules in Directive 2001/83/EC that apply to wholesalers, will also now apply to brokers, e.g. maintenance of a quality management system and the requirements pertaining to staff training and documentation management. This is a developing area, which will require input and support from the competent authorities to ensure the above requirements are incorporated to the brokers operations.
In summary, the new GDP guidelines represent a major step forward in terms of protecting patients through the introduction of better control within the supply chain. Emphasis has been placed on requirements which will minimise the risk of falsified medicines reaching the patient; whilst such risks cannot be eliminated, this represents a substantial improvement over what we have now. Auditing and approving the key players, putting contracts in place, and training all involved parties in the handling of medicinal products, will ultimately bring about enhanced security, reduced waste and improved patient safety. Maintaining of the appropriate storage temperature throughout our complex supply chains will ensure that products remain safe and effective. However, not all of this is achievable in the short term; the industry needs to have a hard look at supply strategies; rationalisation, consolidation and co-operation across and between companies will be required to achieve the required targets. This will come at a cost but, in time, everybody will benefit.
Recommendation
25/26 June 2024
Procurement and Purchase meet GMP - Live Online Training
If our industry has better controlled and more efficient supply chains, we will reap the benefit of reduced costs and patients will have the assurance that the medicine they are taking is safe and effective. Corporation between the wholesalers, manufacturers and the competent authorities is the key to achieving these shared goals.
Author:
Dr Afshin Hosseiny
... is Managing Director of Tabriz Consulting Ltd., providing consultancy services to the companies within the pharmaceutical and biotechnology supply chain. As an acknowledged expert in quality management system for pharmaceutical supply chain, he is currently advising companies on developing and validating Cold Chain Supply process.
