Issues in the interchangeability of generic drugs: part III

In the first two articles of this short series, we presented the results of a study on the problems encountered after switching between generic or innovator drugs in three hospitals.(1,2) The first article discussed problems regarding differences in the active substances and excipients, and the second discussed problems arising from differences in packaging, handling, preparations and instructions accompanying the drug. In this final article, we analyse the current process of purchasing drugs and problems encountered in our hospital pharmacy (Stichting Apotheek der Haarlemse Ziekenhuizen/Pharmacy Foundation of Haarlem Hospitals, The Netherlands), with the aim of improving the quality of the purchasing process and to prevent these problems in the future.

Our pharmacy contracts approximately 800 products annually, of which, on average, 70 products are switched to a different brand. These numbers partly explain why the problems described earlier in this series were not foreseen during the contracting process. Although these switches were performed with considerable caution, it is difficult to avoid every problem owing to the large number of switches involved.

It should be noted that problems described in the first two articles were derived from multiple hospitals over a number of years, and that the number of problems compared with the number of switches is relatively low. Nevertheless, these problems can cause serious harm to patients and should be avoided. Becker and colleagues devised a checklist that is a useful safety tool for comparing the drug in stock with similar drugs from competing manufacturers with regard to a number of safety and practical issues.(3) It includes checks on packaging, storage conditions, excipients, and consultation with clinicians. Using this list, the majority of issues detailed in the previous articles probably would have been foreseen.

Here, we will first discuss the process of purchasing drugs and contracting tenders by our hospital pharmacy. Second, we will discuss how we implemented this checklist in daily routine and the measures taken to prevent these problems in the future. Finally, we describe the role of the hospital pharmacist, who plays a key role in the process of purchasing drugs.

Contracting tenders in our hospital pharmacy can be carried out in two ways: either by a joint purchasing cooperative or through bilateral contracting. Contracting via the joint purchasing cooperative is the most important route. Ten non-academic hospitals participate in this foundation, in which each hospital is represented by one hospital pharmacist mandated by the board of the hospital for selecting, contracting and purchasing drugs.

The aim is to purchase drugs in a cost-effective manner by working as a larger group with increased market power compared with individual hospital pharmacies. Other advantages are shared secretarial support and bundling of the workforce to evaluate offers from different tenders. Each participating hospital pharmacist has a primary focus area, such as antibiotics or chemotherapeutics. This expert keeps his/her knowledge of the therapeutic field up to date and informs the other members on subjects such as new developments and presentations, new treatment guidelines, altering prescription numbers, patent expirations and the introduction of new drugs.

The first step in the annual contracting round is to evaluate the contracts for delivery and availability, and other potential safety issues of the contracted drugs. This process is called manufacturer rating. Drug availability is a particular concern,(4) and this aspect impacts strongly on the manufacturer rating. In the next step, each participating hospital decides individually and per medication (for example, diclofenac oral, doxorubicin IV, etc) whether it will participate during this contract round. Hospital pharmacies can decide not to participate for a number of reasons (for example, when a hospital uses a certain type of evaporator for sevoflurane or when a necessary mandate from clinicians or hospital formulary committee is lacking).

After each hospital has given its mandate, the cumulative dispensing numbers of the participating hospitals are calculated and offered to competing tenders. Offers from different tenders are evaluated by the field expert and the product offered for the lowest price that meets the specifications (for example, barcode; unit dose package etc)(1,2) is selected.

A second contract route is the bilateral route for products that are important for our hospitals but not for the other members of the purchasing foundation. The steps and process are similar to those in the purchasing cooperative.

To prevent the occurrence of problems after the introduction of a new brand, three main measures have been introduced in the process of contracting tenders:

The mandate is an important tool for individual hospital pharmacies. Generally, a mandate is given for each product that the individual hospital pharmacy does not think would cause problems switching to a (different) generic product. An example of a switch we did not mandate was potassium chloride ampoules. Potassium chloride is used at practically every hospital ward and can cause serious harm to a patient if used incorrectly.

Therefore, these ampoules should be clearly recognisable and switches should, in our view, be avoided as much as possible. Switching to a product that requires altered handling or dosing requires a mandate from a clinician. This is illustrated by the switch from Glypressin to Haemopressin. Both products contain terlipressin for the treatment of acute gastrointestinal bleeding. In Glypressin, the amount of terlipressin is given as terlipressin base whereas the dose in Haemopressin is given as terlipressin acetate 3-H20. This should be taken into account when calculating the required dose. Furthermore, Haemopressin required an extra preparation step because it is a powder for injection whereas Glypressin is a solution for injection. Considering the potential risks of this switch, the mandate was not given and despite the potential savings, we currently stock Glypressin.

The pharmacist eventually has to weigh-up the various products and product specifications. Comparisons have to be made between products that have different properties, which requires interpretation that could result in different weightings between hospitals. An example is a solution for injection compared with powder for injection. For the powder, more work is needed to prepare the drug, and a decision should be made as to whether this extra requirement outweighs the savings due to a lower price. Another example is extra costs for unit packages compared with blister packs. No general guidelines can be made on these decisions and weighting should be carried out by the field expert.

Some switches may result in extra costs because of required training of personnel and patients, which should also be taken into account when considering switching to a new label. An example is peritoneal dialysis fluids. There are three tenders that offer competing products in The Netherlands. The different products are therapeutically equivalent, although there are differences in appearance and handling. When switching, patients and personnel should be trained and be familiar with the new products. It is therefore recommended to contract these tenders for multiple years and to prepare a tender well in advance.

These examples illustrate that specific knowledge of products and hospital processes is essential when buying drugs. To further reduce the incidence of problems after the introduction of new drugs, we decided to introduce a fourth preventive measure and use the checklist mentioned previously.

We integrated the checklist presented by Becker et al with our registration form accompanying every change in our stock. The checklist serves as a risk analysis, and forces checking and recording of all potential differences between the originator and generic drug. Based on these differences, the most appropriate follow up is selected. Furthermore, the checklist foresees whether or not changes are required in hospital protocols, electronic prescribing records, and drug-handling instructions. All required follow-up actions are noted on the form, which is signed by the responsible pharmacist. The form is also used to note all communication with clinicians.

Communication is obviously the most important step in the process of contracting new drugs. Most drugs are registered and evaluated extensively by regulatory authorities and may be considered equally safe and effective as the branded drug; however, this is only true if the drug is administered correctly. Clinicians should therefore be well informed on handling and differences in appearance and labelling. This is also the legal duty of a pharmacist. In our hospital pharmacy, we send an e-mail to clinicians and managers and during the first period after switching, a letter accompanies each dispensed package. Furthermore, for parenterals, an updated handling instruction, including information on compatibilities and storage conditions, is easily accessible on the intranet.

Hence, the checklist serves as a final gateway and helps to identify any switches with the potential for problems before entering the clinic. Additionally, the checklist serves to accomplish a smooth introduction, including checks on communications with clinicians. It takes approximately five minutes to complete and could therefore easily be integrated in our daily routine.

The hospital pharmacy has the legal duty to inform other clinicians and patients when dispensing drugs. The hospital pharmacist should, therefore, be well informed about changes in the field and in charge of purchasing. Knowledge of chemical properties, indications, drug preparation, drug administration, hospital protocols and electronic prescribing records is essential for deciding whether eventual cost savings are outweighed by changes involved in switching to a different brand or drug.

For example, in the emergency situation, a ready-to-administer product is essential and cannot be substituted by a product that requires more complex handling. This information is essential to consider during the purchasing process.

The hospital pharmacy should be the key-player during purchasing. Furthermore, the hospital pharmacist is a member of the medical team and together with physicians is responsible for the treatment of patients, hospital formulary and treatment guidelines.

In these articles, we have not discussed the interchangeability of biosimilars. This issue is more complex and is beyond the scope of this series. For these products, more than for chemical entities, efficacy and safety need to be evaluated before considering a biosimilar drug.

Switching between different brands involves the risk of problems in the minority of cases and might involve patient safety issues. Measures should be taken to avoid these problems. The initial cost savings could easily be dampened if there are problems that should be solved, or if the switch involves the risk of patient harm. In this article, we have described the measures taken in our hospital pharmacy, one of which is the use of a checklist. The hospital pharmacy must have a key role in this process, because the hospital pharmacist has the knowledge that is essential for safe decision making.