The rise in fake medicines has led to greater regulatory scrutiny of supply chains. With new guidance on its way Ciarán Brady, PLS Pharma Logistics, looks at the potential impact on role of the Responsible Person.
In September 2011, Operation PANGEA IV closed down almost 13,500 websites that were selling fake medicines. Nearly 2.5m items of illegal or counterfeit medicines, worth US$6.3m (€4.7m), were seized worldwide by regulators and customs. According to Interpol, this was the largest operation of its kind, involving 81 countries in an international week of action targeting the sale of medicines on the Internet. The outcome of PANGEA IV demonstrates that from an enforcement perspective, governments and regulators are prepared more than ever to co-operate against the threat of fake and counterfeit medicines.
From a regulatory perspective also, changes are coming that will raise significantly expectations of the supply chain in the fight against fake medicines. In particular, the pending introduction of the Falsified Medicines Directive, and ongoing consultation on new ‘Commission Guidelines on Good Distribution Practice of Medicinal Products for Human Use’, both serve notice on the pharmaceutical industry that it is about to get much tougher to meet the standards required.
However, meet them it must, for while it may be impossible to stop every criminal producer from turning out fake drugs from an unknown factory and trading them over the Internet, the pharmaceutical industry must at least ensure that the legitimate supply chain is free of counterfeits and falsified medicines. At the same time, it has a responsibility to guarantee that its products are distributed in a carefully controlled manner so that drugs reach patients in a condition that is safe and fit for purpose.
While it may be impossible to stop every criminal producer from turning out fake drugs from an unknown factory and trading them over the Internet, the pharmaceutical industry must at least ensure that the legitimate supply chain is free of counterfeits and falsified medicines
The pharmaceutical supply chain is unique in that compliance at every point is essential. A manufacturer’s responsibility begins with sourcing materials from approved suppliers, continues through manufacturing under Good Manufacturing Practice (GMP) and on to delivery/distribution of the finished product to the final customer under Good Distribution Practice (GDP). The entire supply chain and the distribution network must be focused on supplying a quality product that complies at every point with regulatory requirements; any failings within the pharmaceutical supply chain can seriously compromise the quality of the product and patient safety.
This means the pharmaceutical supply chain extends well beyond the vehicles used to move bulk pharmaceutical materials, ingredients and components to the manufacturing facility and finished products from manufacturing facility to distributors/wholesalers worldwide. It also must ensure compliant delivery to hospitals, pharmacies and even supermarkets where the consumer can now purchase medicines.
As such, the supply chain inevitably involves partners who are far removed from the carefully controlled regime of the production facility. There are a myriad of drivers, freight forwarders/logistic providers, border control officials, warehousing operations, etc. that make up the distribution supply chain. Products are carried by land, sea and air, involving a wide variety of people with direct or indirect contact with product, and all of these people can have a positive or negative impact on product integrity and quality.
However, complexity is no excuse for lack of control, and the industry must aim for higher standards and compliance in the distribution chain. This is especially true since a greater number of new products require cold chain distribution, meaning that temperature-controlled transportation will be the standard required throughout the supply chain for the majority of pharma products in the future.
Complexity is no excuse for lack of control, and the industry must aim for higher standards and compliance in the distribution chain
GDP can be defined as the part of quality assurance that ensures the quality of a pharmaceutical product is maintained through adequate controls at the numerous stages of the distribution process. This definition could reasonably be extended to include sourcing, receipt, storage and transportation, encompassing the full supply chain that is necessary to make and sell pharmaceutical products. The critical need is to establish controls and manage risks at all points along the supply chain, so that all partners handling and transporting pharmaceuticals do so within compliance.
The importance of GDP is currently elaborated in the ‘EU Guidance on Distribution Practice’, but as noted above, this Guidance is presently under review. The consultation documents indicate that the new ‘Commission Guidelines on Good Distribution Practice of Medicinal Products for Human Use’, when published, will be far more prescriptive and demanding than the current one. Even a cursory glance proves this: the current Guidelines run to four pages whereas the consultation document is 33 pages. Whole new sections and demands are likely to be introduced and these are sure to have implications for those involved in pharmaceutical distribution.
Despite the fact that GDP in its current form has been promoted and practised for some time, European regulators continue to see deficiencies in pharmaceutical supply chains. Some of the key deficiencies found include:
- Inadequate temperature management for warehouses/vehicles and temperature excursions in storage and transportation of products
- Cold chain packaging and transport vehicles not properly approved to guarantee products remain within their approved temperature ranges for the duration of the delivery
- Training of key staff, in the full supply chain, not to an acceptable standard
- Bona fides of suppliers and customers were not established and maintained
- Unauthorised activities taking place
- Duties and responsibilities of staff not defined and/or not carried out in compliance with licence conditions
- Quality Systems not adequate, documentation not retained or available
- Drivers handling pharmaceutical products not trained in GDP
- Risk and due diligence in the supply chain not carried out correctly or at all
- Counterfeit awareness, procedures and processes not in place or inadequate.
Many of the failings referred to above fall specifically, or generally, under the heading of ‘human error’, which will come as no surprise to anyone. In some cases this will reflect a situation where an employee has not carried out a procedure as instructed, and in others, doubtless reflects a basic lack of understanding that what they are doing might damage pharmaceutical integrity. Whether the ‘fault’ lies with an individual employee, or within the organisation as whole, there is clearly a case for better education/training and more staff being aware of their personal responsibilities.
emphasis on personnel
It is interesting to note that the consultation document for the anticipated new Commission Guidelines on GDP devotes much more space to, and places more emphasis on, the role of personnel. In particular, it requires that ‘all personnel should be aware of the principles of GDP that affect them and should receive initial and continuing training relevant to their responsibilities’. The training requirement in the current guidelines is much looser i.e. ‘personnel should be trained in relation to the duties assigned to them and the training sessions recorded’.
Similarly, the consultation document suggests that it will inevitably place much greater emphasis on the roles and responsibilities of the Responsible Person (RP) and their deputies. The previous guidelines pre-date Article 79 of Directive 2001/83/EC, which required a RP to be appointed at a wholesale distributor, so it is no surprise that there will be specific reference to the RP’s role in the new Guidelines that was not made in the old.
The role of the RP within the distribution process mirrors that of QP in the manufacturing process. However, whereas there is a formal ‘examination’ for the QP, there is nothing similar as yet for the RP. Nevertheless, there is already specific RP training available, in courses that have the content, structure and assessment features that would be required for a formal qualification, when that eventually happens.
Even in the absence of a formal qualification, the value of training can clearly be demonstrated, not least because it appears that the RP’s actions are already receiving much greater scrutiny from the regulators. It is clear that the above-mentioned Guidelines and the Falsified Medicines Directive will both place greater emphasis on the role of the RP and their deputies, in keeping the supply chain free of false and counterfeit medicines.
Since, by definition, falsified medicines are fake medicines that pass themselves off as real, authorised medicines, one would not expect to see them in the legitimate supply chain. Unfortunately, experience has shown that this expectation is wrong.
The Falsified Medicines Directive will place greater emphasis on the role of the RP in keeping the supply chain free of false and counterfeit medicines
It is worth pointing out that the term ‘falsified’ medicine was chosen to be distinct from ‘counterfeit’, since the former term is more embracing of all kinds of fake medicines. The term ‘counterfeit’ describes only medicines that infringe intellectual property, whereas falsified medicines may not always be counterfeit.
It is also worth noting that as far as patients are concerned, a legitimate, genuine, authorised medicine that has been produced correctly, but then handled badly, thereby losing its efficacy, may be no better than a falsified medicine that has never contained an active ingredient. Whether taking a falsified medicine, or a genuine but degraded medicine, the patient does not benefit, and may actually be caused harm.
So while the Falsified Medicines Directive has one aim of preventing substandard products from entering the legitimate supply chain, it should not draw attention away from what needs to be done to prevent the good products from becoming substandard during distribution.
Good supply chain management coupled with best in class GDP is a minimum requirement in ensuring that patient safety is protected against all dangers, whether from counterfeits, falsified medicines or legitimate medicines that have been handled inappropriately.
changes ahead
The Falsified Medicines Directive, due to be enacted across Europe by early 2013, and the imminent arrival of new Commission Guide-lines on GDP of Medicinal Products for Human Use will require new standards from all involved in the supply chain. By this time next year, anyone working in the supply of pharmaceuticals who has not considered, never mind responded to, the new requirements should expect to find their working lives much harder, or possibly much quieter as their business moves elsewhere. If that sounds alarmist, it is a consequence the pharmaceutical industry must insist on to keep falsified, fake, counterfeit and low quality medicines out of the supply chain.
Patient safety requires all stakeholders to work in partnership to ensure supply chain integrity and compliance. It must be acknowledged that the majority of reported defective medicinal products have resulted from human error or carelessness. Sometimes these errors occur when individuals fail to follow procedures, and sometimes when they follow procedures that are inadequate. In either event, good training is needed for all employees in the principles of GDP, and for the RP and deputy RP in particular.
Ciarán M. Brady (PLS Pharma Logistics) is a consultant and trainer in GDP, RP and logistics at RSSL.
